BARRELS
XXXIV
Wednesday, November 3
rd
Thursday, November 4
th
Friday, November 5
th
, 2021
Table of Contents
BARRELS XXXIV – 2021
Contents…………………………………………………………………………1
A Special Thanks……………………………………………………………….2
Barrels Program, Overview………..…………………………………………..3
Barrels Program/Invited Speakers & Platform Talks………………………..8
Poster Abstracts…………………………………….…………………………..22
Participant List…………………………………………………………………..30
2
A SPECIAL THANK YOU to:
The Organizing Committee:
Solange Brown, MD, Ph.D., Johns Hopkins University
Joshua C. Brumberg, Ph.D., The Graduate Center and Queens College, CUNY
Randy Bruno, Ph.D., Columbia University
Mitra Hartmann, Ph.D., Northwestern University
David Kleinfeld, Ph.D., University of California, San Diego
Dan O’Connor, Ph.D., Johns Hopkins University
Robert Sachdev, Ph.D., Humboldt University, Germany
Gordon Shepherd, MD, Ph.D., Northwestern University
Jochen Staiger, M.D., Georg-August-Universirtaet
WELCOME TO Barrels XXXIV – 2021!
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BARRELS XXXIV Program
November 3
rd
- November 5
th
2021
The 34
th
Annual Barrels Society Meeting
Wednesday, November 3 (All times ET)
10:00 10:05 Welcome: Randy Bruno
Zuckerman Institute, Columbia University
10:05 10:10 Introduction of keynote speaker: David Kleinfeld
UC San Diego
10:10 – 11:00 Keynote 1: Alipasha Vaziri
Rockefeller University
Towards cortex-wide volumetric recording of neuroactivity at cellular resolution
Session 1: Cortical Layer 1
11:0011:10 Introduction: Gordon Arbuthnott
Okinawa Institute of Science & Technology
11:1011:40 Naoya Takahashi
University of Bordeaux
Under cortical L1, active dendritic mechanism for touch detection
11:40 12:10 Anne E Takesian
Mass Eye and Ear/ Harvard Medical School
Diverse layer 1 circuits for auditory cortical processing and plasticity
12:1012:40 Naoki Yamawaki
Aarhus University
Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by
apical tuft-targeting CA1 neurons
12:40 – 12:50 Discussion
12:50 1:00 Break
Short Platform Talks (10 min including questions)
Moderated by Solange Brown, Johns Hopkins University
1:00 1:10 Katayun Cohen-Kashi Malina
Weizmann Institute of Science
NDNF interneurons in layer 1 gain-modulate whole cortical columns according to
an animal’s behavioral state
1:10 1:20 Matthew Larkum
Humboldt University Berlin
Neocortical layer 1 the memory layer?
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1:20 1:30 Qian-Quan Sun
National Institute of Health
A long-range, recurrent neuronal network linking the emotion regions with the
somatic motor cortex
1:30 1:40 Break
1:40 1:50 Julia Ledderose
Humboldt University Berlin
Local input to Layer 1 numerically outweighs long-range input and can drive
layer 1 interneurons
1:50 2:00 Gordon H. Petty
Columbia University
Effects of arousal and movement on secondary somatosensory and visual
thalamus
2:00 2:10 Christina Mo
University of Chicago
A transthalamic pathway via the posterior medial nucleus is necessary for whisker
discrimination
2:10 2:20 Jia Qi
National Institute of Health
Higher-order thalamic nucleus contributes to sensory perception during active
sensing
2:30 4:00 Virtual Poster Session
Thursday, November 4 (All times ET)
10:00 10:05 Convene/Welcome to Day 2
Short Platform Talks (10 min including questions)
Moderated by Fritjof Helmchen, University of Zurich
10:0510:15 Oliver M. Gauld
University College London
All-optical interrogation of barrel cortex during sensory discrimination
10:1510:25 Rikki Rabinovich
Columbia University
Learning enhances encoding of time and temporal surprise in primary sensory
cortex
10:2510:35 William Zeiger
University of California, Los Angeles
Plasticity of local L2/3 pyramidal neurons after a focal lesion of the barrel cortex
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10:3510:45 Adam M. Packer
University of Oxford
All-optical interrogation of neural code transmission between primary and
secondary somatosensory cortex
10:4510:55 Yunmiao Wang
Emory University
Wide-field imaging with JEDI, a novel and fast genetically encoded voltage sensor
10:5511:05 Xin Ye
Boston University
Multi-beam ultra-fast two-photon microscope for population-level voltage imaging
in mouse cortex
Session 2: Navigating and Locomotion
11:0511:15 Introduction: Robert Sachdev
Humboldt University Berlin
11:15 11:45 Diana Amaro
MPI for Neurobiology
Source identity shapes spatial preference in primary auditory cortex during active
navigation
11:45 – 12:15 Asli Ayaz
National Institute of Mental Health
Layer-specific processing of touch during locomotion
12:15 – 12:45 John Issa
Northwestern University
Neural circuits supporting navigation through space and time in the medial
entorhinal cortex and beyond
12:4512:55 Discussion
12:55 1:10 Break
Short Platform Talks (10 min including questions)
Moderated by Daniel O’Connor
1:10 – 1:20 Sevgi Öztürk
Boğaziçi University
Relationship between psychophysical sensitivity index and Bayesian prediction
accuracty in behaving rats
1:20 – 1:30 Zhaoran Zhang
University of California, Riverside
Proactive and context-dependent motor to sensory cortical feedback regulation of
network excitability
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1:30 – 1:40 Gregorio L. Galiñanes
University of Geneva
Modular organization of motor cortex activity in a multi-directional reaching task
1:40 1:50 Break
1:50 – 2:00 Sam Kwon
University of Michigan
Role of somatosensory cortex in control of paw movement during locomotion
2:00 – 2:10 John M Barrett
Northwestern University
Cortico-kinematic coupling during dexterous food-handling
2:10 – 2:20 Krista Marrero
University of California, Riverside
Global, low-amplitude cortical state predicts response outcomes in a selective
detection task in mice
2:20 2:30 Break
2:30 – 2:40 Maxime Chevée
Johns Hopkins University School of Medicine
Neural activity in the mouse claustrum in a cross-modal sensory selection task
2:40 – 2:50 Lisa Meyer-Baese
Georgia Institute of Technology & Emory University
Spatiotemporal patterns of cortical coupling to pupil fluctuations during
spontaneous behavior
2:50 – 3:00 Krithiga Aruljothi
University of California, Riverside
Cortical feedback activity under anesthesia is pathway dependent
Friday, November 5 (All times ET)
10:00 – 10:05 Convene/Welcome
10:05 10:10 Introduction of keynote speaker: Randy Bruno
Columbia University
10:10 – 11:00 Keynote 2: Dorothy Schafer
University of Massachusetts
Leveraging the power of the barrel cortex circuit to study microglia function
Short Platform Talks (10 min including questions)
Moderated by Mitra Hartmann, Northwestern University
11:0011:10 Jim McBurney-Lin
University of California, Riverside
Pupil diameter is not an accurate real-time readout of locus coeruleus activity
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11:10 11:20 Keerthi Krishnan
University of Tennessee
Elucidating the molecular and cellular mechanisms of cerebral lateralization
11:20 11:30 Marcel Oberlaender
Caesar Institute
Ion channel distributions in cortical neurons are optimized for energy-efficient
active dendritic computations
Session 3: Psychedelics and Perception
11:30 11:40 Introduction: Yi Zuo
University of Southern California
11:40 12:10 Carine Becamel
Universite de Montpellier
Effect of serotonin 5-HT2A receptor activation on plasticity gating and fear
processing
12:10 12:40 Ju Lu
University of Southern California
An analog of psychedelics restores functional neural circuits disrupted by
unpredictable stress
12:40 1:10 Da-Ting Lin
National Institute of Health
Deep Behavior Mapping reveals the formation of neural ensembles across
learning
1:10 1:40 Cris Niell
University of Oregon
The impact of a serotonergic hallucinogen on cortical visual processing and
dynamics
1:401:50 Discussion
1:50 – 2:30 Group Photo, Meeting Feedback
ADJOURN
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BARRELS XXXIV Program
November 3
rd
- November 5
th
2021
The 34
th
Annual Barrels Society Meeting
Wednesday, November 3 (All times ET)
10:00 10:05 Welcome: Randy Bruno
Zuckerman Institute, Columbia University
10:05 10:10 Introduction of keynote speaker: David Kleinfeld
UC San Diego
10:10 – 11:00 Keynote 1: Alipasha Vaziri
Rockefeller University
Towards cortex-wide volumetric recording of neuroactivity at cellular resolution
Understanding how sensory information is represented, processed, and leads to generation of complex
behavior from the activity of neurons is the major goal of systems neuroscience. However, the ability to detect
and manipulate such large-scale functional circuits has been hampered by the lack of appropriate tools and
methods that allow parallel and spatiotemporally specific manipulation of neuronal population activity while
capturing the dynamic activity of the entire network at high spatial and temporal resolutions.
A central focus of my lab is the development and application of new optics-based neurotechnologies for large-
scale, high-speed, and single-cell resolution interrogation of neuroactivity across model systems. Through
these, we have consistently pushed the limits on speed, volume size, and depth at which neuronal population
activity can be optically recorded at cellular resolution. Amongst others, we have have demonstrated whole-
brain recording of neuroactivity at cellular resolution in small model systems as well as more recently, near-
simultaneous recording from over one million neurons distributed across both hemispheres and different layers
of the mouse cortex at cellular resolution.
I will present on our efforts on neurotechnology development and how the application of some of these optical
neurotechnologies will enable solving a qualitatively new range of neurobiological questions that are beyond
reach of current methods. Ultimately, our aim is to uncover some of the computational principles underlying
representation of sensory information at different levels, its processing across the mammalian brain, and how
its interaction with internal states generates behavior.
Session 1: Cortical Layer 1
11:00 11:10 Introduction: Gordon Arbuthnott
Okinawa Institute of Science & Technology
11:1011:40 Naoya Takahashi
University of Bordeaux
Under cortical L1, active dendritic mechanism for touch detection
The output of cortical columns is routed to different downstream targets via distinct pathways: cortico-cortical
and cortico-subcortical. It is as yet unclear what roles these pathways play in perception of sensory stimuli, and
which cellular and circuit mechanisms regulate their gating. We previously showed that activation of the apical
dendrites of layer 5 (L5) pyramidal neurons in the primary somatosensory cortex correlates with the threshold
for detecting whisker deflections in mice. L5 neurons come in two classes that target either other cortical or
subcortical areas. By taking advantage of transgenic mouse lines for these L5 subclasses, we found that the
activation of apical dendrites in subcortically-projecting L5 neurons almost exclusively determined the detection
of tactile stimuli in mice. Our results suggest that dendritic activation drives context-dependent interactions
between cortex and subcortical regions, including the higher-order thalamus, superior colliculus, and striatum,
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which are crucial for perception.
11:40 12:10 Anne E Takesian
Mass Eye and Ear/ Harvard Medical School
Diverse layer 1 circuits for auditory cortical processing and plasticity
The primary auditory cortex (A1) is a central site of convergence for projections arising from diverse sensory
and neuromodulatory regions. These inputs influence moment-to-moment cortical activity and drive long-
lasting changes in synaptic connections that may underlie auditory behavioral learning. Recent work from our
laboratory and others implicates layer 1 (L1) of A1 as a hub for integrating both tuned sensory signals from the
auditory thalamus and neuromodulatory inputs from cholinergic and serotonergic brain regions. The
interneurons that populate L1 are heterogenous and can be subdivided into at least two major classes defined
by the expression of either neuron-derived neurotrophic factor (NDNF) or vasoactive intestinal peptide
(VIP). However, the mechanisms by which these diverse interneuron subtypes participate in unique circuits to
control cortical state and plasticity are not fully understood. Combining anatomical and in
vitro electrophysiological approaches, we have begun elucidating the distinct pre and post-synaptic partners of
NDNF and VIP L1 interneurons in mouse A1. Parallel experiments using two-photon imaging in awake,
behaving mice are revealing differences in the in vivo activity patterns of these interneuron subtypes in
response to a range of sound and behaviorally-relevant stimuli. These results reveal a wide diversity of
responses within the VIP and NDNF L1 interneuron populations; many interneurons are selectively activated
by specific, complex sounds or behavioral cues. Finally, ongoing behavioral experiments are identifying the
function of these L1 interneuron subtypes in auditory perception and learning. Together, our results suggest
that the distinct connectivity patterns of the NDNF and VIP interneurons may underlie specialized functions in
sensory encoding and cortical plasticity. The results of this research may identify L1 circuit mechanisms to
promote auditory plasticity in adulthood, advancing treatments following neurodevelopmental disorders, injury
or peripheral hearing loss.
12:10 12:40 Naoki Yamawaki
Aarhus University
Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by
apical tuft-targeting CA1 neurons
Hippocampus, granular retrosplenial cortex (RSCg), and anterior thalamic nuclei (ATN) interact to mediate
diverse cognitive functions. To identify cellular mechanisms underlying hippocampothalamoretrosplenial
interactions, we investigated the potential circuit suggested by projections to RSCg layer 1 (L1) from
GABAergic CA1 neurons and ATN. We find that CA1→RSCg projections stem from GABAergic neurons with a
distinct morphology, electrophysiology, and molecular profile. Their longrange axons inhibit L5 pyramidal
neurons in RSCg via potent synapses onto apical tuft dendrites in L1. These inhibitory inputs intercept L1-
targeting thalamocortical excitatory inputs from ATN to coregulate RSCg activity. Subicular axons, in contrast,
excite proximal dendrites in deeper layers. Short-term plasticity differs at each connection. Chemogenetically
abrogating CA1→RSCg or ATN→RSCg connections oppositely affects the encoding of contextual fear
memory. Our findings establish retrosplenial-projecting CA1 neurons as a distinct class of long-range dendrite-
targeting GABAergic neuron and delineate an unusual cortical circuit specialized for integrating long-range
inhibition and thalamocortical excitation. This research was supported by NIH grants NS061963 (G.M.G.S.),
EB017695 (G.M.G.S.), and MH108837 (J.R.).
12:40 – 12:50 Discussion
12:50 1:00 Break
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Short Platform Talks (10 min including questions)
Moderated by Solange Brown, Johns Hopkins University
1:00 1:10 Katayun Cohen-Kashi Malina
Weizmann Institute of Science
NDNF interneurons in layer 1 gain-modulate whole cortical columns according to
an animal’s behavioral state
Processing of sensory information in neural circuits is modulated by an animal’s behavioral state, but the
underlying cellular mechanisms are not well understood. Focusing on the mouse visual cortex, here we
analyze the role of GABAergic interneurons that are located in layer 1 and express Ndnf (L1 NDNF INs) in the
state dependent control over sensory processing. We find that the ongoing and sensory-evoked activity of L1
NDNF INs is strongly enhanced when an animal is aroused and that L1 NDNF INs gain-modulate local
excitatory neurons selectively during high-arousal states by inhibiting their apical dendrites while disinhibiting
their somata via Parvalbumin-expressing interneurons. Because active NDNF INs are evenly spread in L1 and
can affect excitatory neurons across all cortical layers, this indicates that the state-dependent activation of L1
NDNF INs and the subsequent shift of inhibition in excitatory neurons toward their apical dendrites gain
modulate sensory processing in whole cortical columns. Funding: This work was supported by a Minna James
Heineman grant (712566-01 to I.S.), an Israel Science Foundation (ISF) Israeli Centers for Research
Excellence (I-CORE) grant (1916/12 to I.S.), a Deutsche Forschungsgemeinschaft (DFG)-
Sonderforschungsbereiche (SFB) grant (1089 to I.L.), an ISF grant (1539/17 to I.L.), and a Minerva Foundation
grant (to I.L.).
1:10 1:20 Matthew Larkum
Humboldt University Berlin
Neocortical layer 1 the memory layer?
Accumulating evidence in rodents suggests that neocortical layer 1 might be a key site for long-term plasticity
and learning. Several laboratories have observed that subcortical memory structures predominantly target this
layer. For instance, higher-order thalamic input targets layer 1 in the sensory cortex where it has also been
associated with learning and enhanced activity in the tuft dendrites of pyramidal neurons. Similarly, it was
shown that projections from the amygdala to layer 1 are crucial for fear memory formation. More recently, it
was shown that the hippocampus also targets neocortical layer 1 of the barrel cortex via parahippocampal
structures and is crucial for associative learning. This short talk will present the hypothesis that layer 1 is the
locus of memory formation and storage in the neocortex and discuss the mechanisms that might underlie this.
Funding: Deutsche Forschungsgemeinschaft, Human Brain Project, NeuroCure
1:20 1:30 Qian-Quan Sun
National Institute of Health
A long-range, recurrent neuronal network linking the emotion regions with the
somatic motor cortex
Recurrent neural networks (RNNs) are designed to learn sequential patterns in silico, but it is unclear whether
and how an RNN forms in the native networks of the mammalian brain. Here, we report an innate RNN, which
is formed by the unidirectional connections from three basic units: input units arriving from emotion regions, a
hidden unit in the medial prefrontal cortex (mPFC), and output units located at the somatic motor cortex (sMO).
Specifically, the neurons from basal lateral amygdala (BLA) and the insular cortex (IC) project to the mPFC
motor-cortex-projecting (MP) neurons. These MP neurons form a local self-feedback loop and target major
projecting neurons of the sMO. Within the sMO, the neurons in the infragranular layers receive stronger input
than the neurons in supragranular layers. Finally, we show in vivo evidence that the communications from the
emotion regions to the sMO are abolished when MP neurons are chemogenetically silenced. This work is
funded by NIH grants 5R01NS094550, 3P20GM121310-04S2, and P20GM121310 to Q.-Q.S. This paper is in
presss in Cell Report.
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1:30 1:40 Break
1:40 1:50 Julia Ledderose
Humboldt University Berlin
Local input to Layer 1 numerically outweighs long-range input and can drive
layer 1 interneurons
Neocortical layer (L) 1 is a locus for interactions between long-range inputs, L1 interneurons and apical tuft
dendrites of pyramidal neurons. Here we characterized the input to L1 of mouse somatosensory cortex using
anatomical tracing techniques and optogenetics. Our work using fast blue shows that most of the input to L1 is
local, and that both local and long-range inputs to this layer arise predominantly from L2/3 and L5 neurons.
Subtypes of L5 and L6b neurons project to the overlying L1 with different probabilities. VIP and SST
interneurons in L2/3 and L5 also innervate L1. A subset of local L5, the intratelencephalic, pyramidal neurons,
drive L1 interneurons but have no effect on L5 apical tuft dendrites. When fast blue application was combined
with rabies virus, we found only a fraction of local and long-range neurons were presynaptic to L5 neurons and
projected to L1. These results demonstrate that L1 receives a large proportion of its input from local neurons,
and that some of these inputs specifically target interneurons. We conclude that L1 is not just where long-
range feedback inputs connect to the apical tuft dendrites; instead L1 is a site for complex modulation of
pyramidal neurons by local and long-range inputs.
1:50 2:00 Gordon H. Petty
Columbia University
Effects of arousal and movement on secondary somatosensory and visual
thalamus
Neocortical sensory areas have associated primary and secondary thalamic nuclei. While primary nuclei
transmit sensory information to cortex, secondary nuclei remain poorly understood. We recorded juxtasomally
from secondary somatosensory (POm) and visual (LP) nuclei of awake mice while tracking whisking and pupil
size. POm activity correlated with whisking, but not precise whisker kinematics. This coarse movement
modulation persisted after facial paralysis and thus was not due to sensory reafference. This phenomenon also
continued during optogenetic silencing of somatosensory and motor cortex and after lesion of superior
colliculus, ruling out a motor efference copy mechanism. Whisking and pupil dilation were strongly correlated,
possibly reflecting arousal. Indeed LP, which is not part of the whisker system, tracked whisking equally well,
further indicating that POm activity does not encode whisker movement per se. What appears to be
movement-related activity is instead a global effect of arousal on both nuclei. We conclude that secondary
thalamus monitors behavioral state, rather than movement, and may exist to alter cortical activity accordingly.
2:00 2:10 Christina Mo
University of Chicago
A transthalamic pathway via the posterior medial nucleus is necessary for whisker
discrimination
In sensory systems, pathways from primary to secondary cortex can arrive directly (cortico-cortical) or
indirectly through higher order thalamus (cortico-thalamo-cortical). The function of the transthalamic route is
unknown, despite its ubiquity and driver-type glutamatergic synapses. In the somatosensory system in the
mouse, we inactivated the transthalamic pathway by expressing the Jaws inhibitory opsin in left S1 layer 5 of
Rbp4-Cre x GCAMP6S mice and directed a 633nm laser through an optic fiber implanted in POm. Mice were
trained in a head-fixed, delayed go/no-go task to discriminate between panels of textured grating presented to
the right whisker field. Jaws inhibition during the texture presentation period severely impaired discrimination
performance, and, inhibition during the 1-sec delay period increased the threshold of discriminability (n=7
mice). Concurrent imaging of GCAMP6S activity in layer 2/3 of either S1 or S2 showed that S2 cells could
discriminate texture trials better than S1 cells, and laser inhibition suppressed texture-responsive S2 cells more
than S1 cells. TdTomato-expressing mice (n=2) and Jaws-expressing mice with a fiber implanted away from
POm (n=3) did not show any effects of laser activation. Our results suggest that the layer 5 S1 - POm - S2
transthalamic pathway propagates complex sensory information such as texture features.
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2:10 2:20 Jia Qi
National Institute of Health
Higher-order thalamic nucleus contributes to sensory perception during active
sensing
Higher-order sensory thalamic nuclei are densely connected with multiple cortical and subcortical areas, yet
the role of these nuclei remains elusive. The posteromedial thalamic nucleus (POm), the higher-order thalamic
nucleus in the rodent somatosensory system, is a critical network hub integrating sensory-motor processing,
yet weakly responds to sensory stimulation. We developed a self-initiated, two-alternative forced-choice task
for freely moving mice to test whisker-dependent sensory perception during active sensing. Using optogenetic
and chemogenetic manipulation, we show that POm thalamic nucleus significantly contributes to sensory
perception and the projection from the primary somatosensory cortex to POm is critical for the contribution of
POm in sensory perception during active sensing.
2:30 4:00 Virtual Poster Session
Thursday, November 4 (All times ET)
10:00 10:05 Convene/Welcome to Day 2
Short Platform Talks (10 min including questions)
Moderated by Fritjof Helmchen, University of Zurich
10:05 10:15 Oliver M. Gauld
University College London
All-optical interrogation of barrel cortex during sensory discrimination
Understanding how neural circuit activity drives perceptual computations is a major goal in neuroscience. We
combined behavioural psychophysics, optogenetic manipulations and two-photon calcium imaging to study the
relationship between sensory input, neural activity in barrel cortex layer 2/3 (L2/3) and behavioural responses.
Head-fixed mice discriminated contralateral vs ipsilateral whisker deflections and reported decisions after a
short delay via a two-choice lickport. We used an all-optical combination of simultaneous calcium imaging and
targeted photostimulation to selectively manipulate small groups of excitatory neurons based on stimulus
tuning, and measured the resulting impact on behaviour and network activity. Photostimulation evoked a
perceptual choice bias that correlated with the number, but not tuning, of activated target neurons consistent
with an intrahemispheric spike count code for contralateral whisker deflection. Reading out the efficacy of
patterned photostimulation with simultaneous calcium imaging revealed strong and widespread recruitment of
inhibition in the network during task performance. Our results demonstrate that perceptual readout of cortical
activity is exquisitely sensitive to changes in the balance between L2/3 excitation and inhibition, with strong
recruitment of inhibition likely playing a dominant role in enforcing sparse and reliable perceptual coding of
whisker stimuli.
10:15 10:25 Rikki Rabinovich
Columbia University
Learning enhances encoding of time and temporal surprise in primary sensory
cortex
Primary sensory cortex has long been believed to play a straightforward role in the initial processing of sensory
information. Yet, the superficial layers of cortex overall are sparsely active, even during sensory stimulation;
moreover, cortical activity is influenced by other modalities, task context, reward, and behavioral state. Our
study demonstrates that reinforcement learning dramatically alters representations among longitudinally
imaged neurons in superficial layers of mouse primary somatosensory cortex. Learning an object detection
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task recruits previously unresponsive neurons, enlarging the neuronal population sensitive to touch and
behavioral choice. In contrast, cortical responses decrease upon repeated exposure to unrewarded stimuli.
Moreover, training improved population encoding of the passage of time, and unexpected deviations in trial
timing elicited even stronger responses than touch did. In conclusion, the superficial layers of sensory cortex
exhibit a high degree of learning-dependent plasticity and are strongly modulated by non-sensory but
behaviorally-relevant features, such as timing and surprise. NIH/NINDS R01 NS069679; NSF GRFP
10:25 10:35 William Zeiger
University of California, Los Angeles
Plasticity of local L2/3 pyramidal neurons after a focal lesion of the barrel cortex
Circuit plasticity is well established in the barrel cortex, for instance after peripheral sensory deprivation
induced by whisker trimming. It has been widely hypothesized that after cortical injury, circuits will remap with
spared neurons assuming the functionality of those lost to injury. Direct evidence supporting this hypothesis is
lacking, so here we tested this question directly by precisely targeting photothrombotic lesions to an individual
barrel (C1) in the barrel cortex. Using longitudinal in vivo two-photon calcium imaging before and after
lesioning the C1 barrel, we did not find any increase in the number of C1 whisker-responsive neurons in
adjacent, spared barrels. Spared C1 whisker-responsive neurons showed diminished sensory-evoked neuronal
responses for 2 months after lesioning. To promote plasticity, we employed a forced-use paradigm and
plucked all whiskers except C1 after lesioning. This led to an increase in the reliability of sensory-evoked
responses in C1 whisker-responsive neurons, but did not increase numbers of C1 whisker-responsive neurons
in spared surround barrels. These data suggest that maladaptive circuit changes occur that limit, rather than
promote, recovery after a focal cortical lesion. We are now investigating the mechanisms underlying these
changes, with a specific interest in the role of GABAergic parvalbumin-expressing (PV) interneurons. Funding -
NIH: R01 NS076942-04, R25 NS065723, 1 K08 NS114165-01A1. Academy of Neurology NRTS 2199.
10:35 10:45 Adam M. Packer
University of Oxford
All-optical interrogation of neural code transmission between primary and
secondary somatosensory cortex
The brains of higher organisms are composed of anatomically and functionally distinct regions performing
specialised tasks. However, individual regions do not operate in isolation. Hence, the orchestration of complex
behaviours requires communication between brain regions and reliable transmission of information between
them. We study this process directly by generating neural activity that propagates between brain regions and
drives behaviour, allowing us to assess how populations of neurons in sensory cortex act in concert to transmit
information. We achieved this by imaging two hierarchically organised and densely interconnected regions, the
primary and secondary somatosensory cortex (S1 and S2) in mice while performing two-photon
photostimulation of S1 neurons and assigning behavioural salience to the photostimulation. We found that the
probability of perception is determined by both the variance of the S1 network and the strength of the
photostimulation. Conceptually this means that maximising the signal-to-noise ratio of an incoming stimulus is
critical to its continued propagation downstream. Further, we show that propagated, behaviourally salient
activity elicits balanced, persistent and generalised activation of the downstream region, consistent with
inhibitory stabilised network models with dense recurrent connectivity. Hence, our work adds to existing
understanding of cortical function by identifying how population activity is formatted to ensure robust
transmission.
10:45 10:55 Yunmiao Wang
Emory University
Wide-field imaging with JEDI, a novel and fast genetically encoded voltage sensor
Wide-field imaging allows monitoring population neural activities on a large spatial scale. While calcium
indicators are the most commonly used sensors for population imaging, the measurement of calcium
concentration as a proxy for voltage signals has posed challenges and limitations. Here, we present in vivo
wide-field imaging with a newly developed voltage indicator, Jellyfish-derived Electricity-reporting Designer
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Indicator (JEDI), which shows high temporal resolution, and improved signal-to-noise ratio and photostability
over previous generations of genetically expressed voltage sensors. We show the verification of the voltage-
dependency of the sensor with simultaneous imaging and local field potential recording. The presentation will
demonstrate the feasibility of subtracting hemodynamics from voltage signals using an independent fluorescent
channel and a single excitation light source. The talk will also highlight the reliable ability of JEDI to follow fast
whisker and visual stimulation up to 50Hz in awake behaving mice.
10:55 11:05 Xin Ye
Boston University
Multi-beam ultra-fast two-photon microscope for population-level voltage imaging
in mouse cortex
Understanding the complexity of neural networks in vivo requires simultaneous recordings of neuronal
populations with action potential resolution. Genetically-encoded voltage indicators (GEVIs) provide direct and
reliable optical readouts of neural activity with high temporal resolution. Existing high-speed 2P microscopes
scan restricted field of views (FOVs), limiting the number of simultaneously imaged neurons. We developed an
Ultra-Fast 2-Photon (UF2P) microscope which is capable of full-frame high-speed imaging of a
400x400µm2 FOV of up to ~300 microns deep in mouse cortex at a kilohertz scan rate. We used a
combination of spatial and temporal beam multiplexing to achieve parallel resonance frame scanning of 8
beams at up to 1 kHz framerate. Spatially multiplexed beams were resolved using a multi-anode
photomultiplier tube. For temporal demultiplexing, a fixed 920nm-wavelength, low repetition rate laser was
used to deliver interleaved laser pulses and emitted photons were digitized and temporally de-multiplexed. We
compared the photobleaching performance and neural activity readouts of two-photon compatible GEVIs in the
primary somatosensory cortex of awake mice. Using a self-supervised deep-learning-based denoising
algorithm, sensory-evoked action potentials could be identified from neurons imaged at resolutions near
1µm2/pixel. This microscope system demonstrates the capacity to perform two-photon voltage imaging across
larger neuronal populations.
Session 2: Navigating and Locomotion
11:05 – 11:15 Introduction: Robert Sachdev
Humboldt University Berlin
11:15 – 11:45 Diana Amaro
MPI for Neurobiology
Source identity shapes spatial preference in primary auditory cortex during active
navigation
In the auditory system, spatial information is computed in the brain based on the position of the sound source
relative to the observer and thus assumed to be egocentric throughout the auditory pathway. This assumption
is largely based on studies lacking self-motion and selective listening - fundamental components of natural
sensing that may crucially impact the nature of spatial coding and sensory object representation. We
incorporated these factors by training gerbils on a behavioral foraging paradigm that required localization and
identification of sound sources during free navigation. Chronic tetrode recordings in primary auditory cortex
during task performance revealed previously unreported sensory object representations. Strikingly, the
egocentric angle preference of the majority of spatially sensitive neurons changed significantly depending on
the task-specific identity (outcome association) of the sound source. Spatial tuning also exhibited large
temporal complexity. Moreover, we encountered egocentrically untuned neurons whose response magnitude
differed between source identities. We show that, together, neuronal response ensembles provide
spatiotemporally co-existent information about both the egocentric location and the identity of individual
sensory objects during self-motion, revealing a novel cortical computation principle for naturalistic sensing.
Project funded by Deutsche Forschungsgemeinschaft DFG (PE2251/2-1 and d SFB 870, #118803580, project
B02).
15
11:45 – 12:15 Asli Ayaz
National Institute of Mental Health
Layer-specific processing of touch during locomotion
We perceive the outside world as a result of continuous interactions between sensory inputs and motor
actions. During navigation, rodents continually sample the environment with their whiskers. However, whisking
behavior, not running, has been the main focus of studies on sensorimotor integration in the barrel cortex.
Somatosensory processing is likely to vary between running and stationary states because behavioral
requirements are different: During locomotion, mice need to monitor their location while remaining sensitive to
sudden changes in the environment, such as encountering an obstacle on their way. However, while being
stationary and exploring an object in detail, mice may screen more subtle aspects of tactile processing such as
shape or texture. Here, we investigated whether Layer 2/3 and Layer 5 neurons of barrel cortex integrate
sensory and motor signals differently. We applied two-photon calcium imaging in head-restrained mice running
along a “virtual tactile wall.” This setting allowed us to study the integration of two motor behaviors‘whisking’
and ‘running’with prolonged sensory touches. About one-third of neurons in both layers increased activity
during running and concomitant whisking in the absence of touch. Fewer neurons were modulated by whisking
alone. Whereas L5 neurons responded transiently to wall-touching during running, L2/3 neurons showed
sustained activity after touch onset. Consistently, neurons encoding running-with-touch were more abundant in
L2/3 compared to L5. Few neurons across layers were also sensitive to abrupt perturbations of tactile flow. We
propose that L5 neurons mainly report changes in touch conditions, whereas L2/3 neurons continually monitor
ongoing tactile stimuli during running.
12:15 – 12:45 John Issa
Northwestern University
Neural circuits supporting navigation through space and time in the medial
entorhinal cortex and beyond
The neural circuits that support spatial navigation have been well-described by work over the past few
decades. Another dimension relevant for memory and behavior is time. Recent work has begun to implicate
the hippocampal formation as involved in both space and time, but how this hub interfaces with larger
brainwide networks is not understood. In this talk, I will cover work from our lab to develop an interval timing
task in rodents. Using this task, we have discovered that cells in the medial entorhinal cortex code for the
passage of time. More recently, we have employed mesoscale imaging to search for networks across the brain
that also participate in time coding. These large-scale methods will allow us to address the question of whether
and how different brain regions coordinate to synchronize interval timing signals. This work is supported by
NIH R01MH101297, the Hartwell Foundation Postdoctoral Fellowship, and a NARSAD Young Investigator
Grant from the Brain & Behavior Research Foundation.
12:45 – 12:55 Discussion
12:55 1:10 Break
Short Platform Talks (10 min including questions)
Moderated by Daniel O’Connor
1:10 1:20 Sevgi Öztürk
Boğaziçi University
Relationship between psychophysical sensitivity index and Bayesian prediction
accuracty in behaving rats
This study focuses on modeling psychophysical responses of awake behaving rats in a Bayesian framework.
Multiunit spike activity was recorded from the hindlimb area of the sensorimotor cortex by using 16-channel
16
microwire array electrodes during a psychophysical yes/no detection task. The vibrotactile stimuli consisted of
40-Hz sinusoidal mechanical displacements (amplitude: 200 µm, duration: 0.5 s) applied on the glabrous skin
of the hindpaws. Ten rats were conditioned to press the right lever for the stimulus-on condition and the left
lever for the stimulus-off condition to get water reward. Average firing rates of the sorted units were used as
features in a Bayesian network including the stimulus presentation, population activity, and right/left lever
selection as random variables. Each subject was represented as a separate Bayesian model and its lever
presses were predicted trial-by-trial. Although there were prominent within-subject and between-subject
variance in the neural data, the Bayesian models showed good overall accuracy (0.60-0.91). Furthermore, rats
which had lower psychophysical sensitivity (A’) were predicted better by the models. This result may be
significant for the training and rehabilitation stages of brain-computer interfaces (BCIs).
1:20 1:30 Zhaoran Zhang
University of California, Riverside
Proactive and context-dependent motor to sensory cortical feedback regulation of
network excitability
Cortical feedback, the anatomical pathways from higher-order to lower-order cortices, is believed to modulate
sensory processing according to internal and behavioral context. Current studies on cortical feedback focus
primarily on resolving how it shapes post-stimulus activity of lower-order cortex, with the assumption that
cortical feedback regulation requires a stimulus-triggered bottom-up signal. In this study, we recorded single
unit activity in the mouse whisker primary somatosensory cortex (lower-order), while conducting interleaved
inhibition in the whisker motor cortex (higher-order) to assess the impacts of cortical feedback under different
contexts. We found that cortical feedback strongly influences spontaneous (pre-stimulus) activity. We found
that cortical feedback modulates spontaneous network excitability differently under different behavioral
contexts, and that these modulations of excitability can, at least in part, account for changes in post-stimulus
responses. Overall, our study emphasizes the importance of cortical feedback as proactive regulators of
feedforward signal processing.
1:30 1:40 Gregorio L. Galiñanes
University of Geneva
Modular organization of motor cortex activity in a multi-directional reaching task
We studied the activity of motor cortex neurons in mice performing a multi-directional reaching task. We found
that task-related neurons were modulated at different phases of the task, from target presentation to reach
onset and reward consumption. Interestingly all task-task related neurons displayed a very strong selectivity for
the reaching target location. However, neuron activity was insensitive to changes in arm trajectories suggesting
that these neurons don't encode kinematic parameters of reaching but spatial information of the reaching
target. We analyzed how fine-grained this spatial representation was and found that neurons could be
clustered into three segregated groups representing reaching targets located on the left, center or right of the
animal, suggesting a coarse spatial representation. Taken together, the data indicate that different subsets of
layer 2/3 neurons represent specific combinations of spatial and temporal aspects of the task. We speculated
that these subsets of neurons form functional modules that can be dynamically recruited depending on the task
demands. To evaluate this possibility we analyzed neuron activity during trials in which the reaching target was
suddenly moved from one location to another after the mouse had initiated reaching towards the first location.
According to our speculation, we found that the activity of neuronal modules was consistently updated to match
the novel target location and the subsequent task phases.
1:40 1:50 Break
1:50 – 2:00 Sam Kwon
University of Michigan
Role of somatosensory cortex in control of paw movement during locomotion
The primary somatosensory cortex (S1) is important for the control of movement as it encodes sensory input
from the body periphery and external environment during ongoing movement. Mouse S1 consists of several
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distinct sensorimotor subnetworks that receive topographically organized cortico-cortical inputs from distant
sensorimotor areas, including the secondary somatosensory cortex (S2) and primary motor cortex (M1). The
role of the vibrissal S1 area and associated cortical connections during active sensing is well documented, but
whether (and if so, how) non-whisker S1 areas are involved in movement control remains relatively
unexplored. Here, we demonstrate that unilateral silencing of the non-whisker S1 area in both male and female
mice disrupts hind paw movement during locomotion on a rotarod and a runway. S2 and M1 provide major
long-range inputs to this S1 area. Silencing S2 to non-whisker S1 projections alters the hind paw orientation
during locomotion while manipulation of the M1 projection has little effect. Using patch-clamp recordings in
brain slices from male and female mice, we show that S2 projection preferentially innervates inhibitory
interneuron subtypes. We conclude that interneuron-mediated S2S1 cortico-cortical interactions are critical for
efficient locomotion.
2:00 2:10 John M Barrett
Northwestern University
Cortico-kinematic coupling during dexterous food-handling
Food-handling offers unique opportunities to investigate how cortical activity relates to forelimb movements in
an especially natural, ethologically essential, and kinematically rich form of manual dexterity. We recorded unit
activity in mouse forelimb motor cortex (M1) along with close-up kilohertz video to determine these
relationships. Spiking correlated with oromanual events, rising briskly as mice raised food to the mouth and
tapering during further manipulation before falling to baseline at event offset. Such phasic-tonic activity in
forelimb M1 contrasted with tonic oromanual-associated activity in tongue/jaw M1, and an intermediate pattern
in forelimb somatosensory cortex (S1). Cluster analysis identified phasic and tonic activity classes among
active units, present in each area but with area-specific proportions that accounted for the different overall
firing patterns. Cortical activity during food-handling thus exhibits robust area- and submovement-specific
relationships with the fast kinematic hallmarks of this form of complex object-handling manual dexterity.
Funded by NIH grants R01NS061963 and R21NS116886.
2:10 2:20 Krista Marrero
University of California, Riverside
Global, low-amplitude cortical state predicts response outcomes in a selective
detection task in mice
Spontaneous neuronal activity strongly impacts stimulus encoding and behavioral responses. We sought to
determine the effects of neocortical prestimulus activity on stimulus detection. We trained mice in a selective
whisker detection task, in which they learned to respond (lick) to target stimuli in one whisker field and ignore
distractor stimuli in the contralateral whisker field. During expert task performance, we used widefield calcium
imaging to assess prestimulus and post-stimulus neuronal activity broadly across frontal and parietal cortices.
We found that lower prestimulus activity correlated with enhanced stimulus detection: lower prestimulus activity
predicted response versus no response outcomes and faster reaction times. The activity predictive of trial
outcome was distributed through dorsal neocortex, rather than being restricted to whisker or licking regions.
Using principal component analysis, we demonstrate that response trials are associated with a distinct and
less variable prestimulus neuronal subspace. For single units, prestimulus choice probability was weak yet
distributed broadly, with lower than chance choice probability correlating with stronger sensory and motor
encoding. These findings support low amplitude and low variability as an optimal prestimulus cortical state for
stimulus detection that presents globally and predicts response outcomes for both target and distractor stimuli.
2:20 2:30 Break
2:30 2:40 Maxime Chevée
Johns Hopkins University School of Medicine
Neural activity in the mouse claustrum in a cross-modal sensory selection task
The claustrum, a subcortical nucleus forming extensive connections with the neocortex, has been implicated in
sensory selection. Sensory-evoked claustrum activity is thought to modulate the neocortex’s context-
18
dependent response to sensory input. To test this hypothesis, we recorded from neurons in anterior claustrum,
including putative, optotagged claustrocortical (ClaC) neurons projecting to S1, while mice performed a tactile-
visual sensory-selection task. We found few neurons modulated by sensory input. Rather, claustrum neurons,
including putative S1-projecting ClaC neurons, exhibited direction-tuned responses reflecting upcoming
movement, including activity during inter-trial intervals reflecting upcoming lick direction. We further found that
pairs of claustrum neurons exhibiting synchronous firing were enriched for pairs preferring contralateral lick
directions, suggesting that ensembles of similarly tuned claustrum neurons may modulate cortical activity.
Finally, using chemogenetics to test the contribution of ClaC neurons to task performance, we found that
inhibition of ClaC neurons decreased lick responses to inappropriate sensory stimuli while not affecting the
number of inter-trial licks or correct detection-associated licks. Together, our data indicate that the claustrum is
integrated into higher-order premotor circuits implicated in decision-making and may regulate premotor circuits
involved in suppressing unwanted movements in response to inappropriate stimuli.
2:40 2:50 Lisa Meyer-Baese
Georgia Institute of Technology & Emory University
Spatiotemporal patterns of cortical coupling to pupil fluctuations during
spontaneous behavior
Cerebral cortex exists in a state of constant activity, even in the absence of external sensory input. This
spontaneous activity has been proposed to encode ongoing behavioral and cognitive variables. Recent studies
using awake spontaneously behaving mice have demonstrated that changes in pupil diameter closely
resembles sub-threshold voltage activity and arousal levels. What remains unknown is how arousal signals as
measured by pupil diameter are represented spatially and temporally within spontaneous changes in cortical
activity. To reveal these spatiotemporal dynamics, we used wide-field voltage imaging in VSFP-Butterfly 1.2
mice while simultaneously tracking changes in pupil diameter. We found that pupil diameter is tightly coupled
to global changes in cortical voltage with distinct coupling patterns across different cortical regions and
frequency bands.
2:50 3:00 Krithiga Aruljothi
University of California, Riverside
Cortical feedback activity under anesthesia is pathway dependent
'Top-down processing' refers to the use of prior knowledge and internal context to bias sensation, perception,
and action. Studies of cortical anatomy and physiology support that top-down processing is mediated, in part,
by cortical feedback pathways, which connect higher order to lower order cortical regions. Given the
importance of top-down processing during wakefulness, a long-standing assumption with some experimental
evidence is that cortical feedback is not active under anesthesia. In this study, we measure the spontaneous
activity of two cortical feedback pathways during slow wave anesthesia. We demonstrate that under
anesthesia the retrosplenial cortex to primary visual cortex feedback pathway is not active, yet the whisker
motor cortex to whisker primary somatosensory cortex feedback pathway is active. These findings suggest that
the functions of cortical feedback are not limited to wakefulness. Ongoing studies are attempting to determine
the mechanisms underlying these activity differences.
Friday, November 5 (All times ET)
10:00 10:05 Convene/Welcome
10:05 10:10 Introduction of keynote speaker: Joshua Brumberg
Queens College and The Graduate Center, CUNY
19
10:10 – 11:00 Keynote 2: Dorothy Schafer
University of Massachusetts
Leveraging the power of the barrel cortex circuit to study microglia function
Microglia, resident central nervous system macrophages, dynamically survey their neuronal environment and
prune away less active synaptic connections. Using the mouse barrel cortex circuit, we identified that microglia
engulf and eliminate synapses in the primary somatosensory cortex following early postnatal (postnatal day 4)
unilateral lesioning of the whiskers. We found this early life microglial synaptic remodeling requires chemokine
signaling between neurons and microglia. We are now determining whether there is a critical window for
microglia-induced synapse remodeling in the barrel cortex and we are using cell type-specific molecular
genetic approaches to explore the crosstalk between microglia and astrocytes in this process.
Short Platform Talks 3 (10 min including questions)
Moderated by Mitra Hartmann, Northwestern University
11:00 11:10 Jim McBurney-Lin
University of California, Riverside
Pupil diameter is not an accurate real-time readout of locus coeruleus activity
Pupil diameter is often treated as a non-invasive readout of activity in the locus coeruleus (LC). However, how
accurately it can be used to index LC activity is not known. To address this question, we established a graded
relationship between pupil size changes and LC spiking activity, where pupil dilation increased monotonically
with the number of LC spikes. However, this relationship exists with substantial variability such that pupil
diameter can only be used to accurately predict a small fraction of LC activity on a moment-by-moment basis.
In addition, pupil exhibited large session-to-session fluctuations in response to identical optical stimulation in
the LC. The variations in the pupil-LC relationship were strongly correlated with decision bias-related
behavioral variables. Together, our data show that substantial variability exists in an overall graded relationship
between pupil diameter and LC activity, and further suggest that the pupil-LC relationship is dynamically
modulated by brain states.
11:10 11:20 Keerthi Krishnan
University of Tennessee
Elucidating the molecular and cellular mechanisms of cerebral lateralization
Cortical asymmetry or cerebral lateralization which allows for functional specialization of bilateral brain regions
in humans and other species has been a subject of long-standing interest. This subject has basic and clinical
implications, as atypical structural and functional asymmetry has been identified in patients with
neuropsychiatric disorders. However, cortical asymmetry is rarely considered in rodent studies. We recently
discovered that perineuronal nets (PNNs), specialized extracellular matrix structures that restrict synaptic
plasticity, are lateralized in expression in different sub-regions of the adult primary somatosensory cortex.
PNNs are historically thought to signal the end of early postnatal sensory critical periods, and function as static
inhibitors of synaptic plasticity, particularly on cortical parvalbumin+ GABAergic interneurons which generate
gamma oscillations in the adult brain. However, their roles in adult plasticity is unclear. Our overarching
general hypothesis states that mature PNNs contribute to cerebral lateralization in the rodent brain, ultimately
impacting behavioral efficiency. I will present our ongoing work in the context of tactile and pup retrieval
behaviors.
11:20 – 11:30 Marcel Oberlaender
Caesar Institute
Ion channel distributions in cortical neurons are optimized for energy-efficient
active dendritic computations
The mammalian brain uses more than 20% of the energy consumed by the entire body. This enormous
demand for energy is thought to impose strong selective pressure by which neurons evolve in ways that
ensure robust function at minimal energy cost. Here we found that the distributions of ion channels by which
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pyramidal tract neurons the major output cell type of the cerebral cortex could implement their complex
intrinsic physiology is extremely widespread. Surprisingly, this wide spectrum does not reflect variations in
dendritic morphology, but instead the energy cost required for the generation of dendritic calcium spikes.
Energy-efficient implementations of calcium spikes require a steep decay of potassium channels towards the
distal dendrites, an empirical observation whose significance remained unclear for more than a decade. Thus,
cortical neurons do not utilize all theoretically possible ways to implement their functions, but instead select
those optimized for energy-efficient active dendritic computations.
Session 3: Psychedelics and Perception
11:30 – 11:40 Introduction: Yi Zuo
University of Southern California
11:40 – 12:10 Carine Becamel
Universite de Montpellier
Effect of serotonin 5-HT2A receptor activation on plasticity gating and fear
processing
5-HT2A receptors are a principal G protein-coupled receptor subtype mediating the excitatory effects of
serotonin. 5-HT2A receptors mediate the psychotropic effects of psychedelic hallucinogens but their impact on
glutamatergic transmission and synaptic plasticity as well as their role in fear processing remains poorly
characterized. In the present studies, we first examined the impact of postsynaptic 5-HT2A receptor activation
on AMPA-mediated glutamatergic transmission at layer I/V synapses of the median prefrontal cortex (mPFC).
We provided evidence that a prolonged activation of 5-HT2A receptors using 2,5-dimethoxy-4-
iodoamphetamine (DOI), a psychedelic agonist, gates the induction of LTD by promoting the phosphorylation
of GluA2-containing receptors through a PKC (Protein Kinase C)-dependent mechanism. We also investigated
the impact of a sub-chronic treatment of mice with fluoxetine, one of the most prescribed selective serotonin
reuptake inhibitor (SSRI) antidepressants, on AMPA transmission at layer I/V synapses of mPFC. Finally, we
investigated the effect of DOI on fear expression in WT and 5-HT2A receptor-deficient mice mice.
12:10 – 12:40 Ju Lu
University of Southern California
An analog of psychedelics restores functional neural circuits disrupted by
unpredictable stress
Stress pervades modern life. It affects various brain functions, posing risks for many psychiatric disorders.
However, few therapeutics are available to combat such deleterious effects of stress. One class of candidate
drugs are psychedelics. With potent and fascinating effects on the human mind, these drugs have received
renewed research interest in recent years. However, their hallucinogenic effects remain a concern for clinical
applications. Using a mouse model of unpredictable mild stress, we investigated a novel compound called
tabernanthalog (TBG), which is similar in structure to the psychedelic drug ibogaine but free from its
hallucinogenic and toxic effects. We found that a single low dose of TBG can correct stress-induced behavioral
deficits including anxiety, cognitive inflexibility, and defective sensory processing. In the stressed brain, TBG
promotes the regrowth of stress-disrupted connections between cortical neurons and normalizes their activity
patterns. Our study highlights the potential of using analogs of psychedelics to treat stress-related brain
disorders, and provides novel insights into the neural mechanisms underlying their therapeutic effects.
12:401:10 Da-Ting Lin
National Institute of Health
Deep Behavior Mapping reveals the formation of neural ensembles across
learning
We previously showed that Psychedelics phencyclidine (PCP) interfered with mice social behavior by altering
prelimbic (PrL) neural ensembles coding social exploration. Yet better understanding of how Psychedelics
interferes with neural correlates of animal behavior likely requires more in-depth mapping of animal behavior.
21
To this end, we recently developed deep behavior mapping (DBM) to identify behavioral microstates in video
recordings. We combined DBM with longitudinal calcium imaging to quantify behavioral tuning in PrL neurons
as mice learned an operant task. We found that a subset of PrL neurons were strongly tuned to highly specific
behavioral microstates, both task and non-task related. Overlapping neural ensembles were tiled across
consecutive microstates in the response-reinforcer sequence, forming a continuous map. As mice learned the
operant task, weakly tuned neurons were recruited into new ensembles, with a bias towards behaviors similar
to their initial tuning. DBM combined with in vivo neural recording will open a new avenue to examine the
impact of Psychedelics on neural coding of animal behavior.
1:101:40 Cris Niell
University of Oregon
The impact of a serotonergic hallucinogen on cortical visual processing and
dynamics
Our perception of the visual world arises from a complex interplay of sensory input with top-down expectations
(priors) and behavioral state. This perceptual experience is drastically altered by hallucinogenic drugs,
including serotonergic agonists such as LSD and psilocybin. However, little is known about the effect of
serotonergic hallucinogens on neural coding and dynamics that could underlie this altered perception. I will
present our results using a range of methods to measure neural activity in mouse V1, from large-scale
organization with widefield calcium imaging, down to single unit activity with silicon probes, following
administration of the hallucinogenic, selective 5-HT
2A
R agonist DOI (2,5-Dimethoxy-4-iodoamphetamine).
These results demonstrate that basic aspects of neural coding in V1, such as retinotopy and orientation
selectivity, are not affected by DOI. However, we observe a dramatic decrease in the amplitude of visually-
evoked responses, along with changes in the temporal dynamics of responses, supporting a model in which
hallucinations result from an imbalance between bottom-up and top-down inputs. In addition, I will present new
computational and experimental approaches to explore the impact of hallucinogens on cortical visual
processing.
1:401:50 Discussion
1:502:30 Group Photo, Meeting Feedback
ADJOURN
BARRELS XXXIV POSTER ABSTRACTS
22
Krithiga Aruljothi (1), A. Lam (2), E. Zagha (1)
[1] Department of Psychology; [2] Biomedical Sciences, University of California, Riverside
Cortical Feedback Activity Under Anesthesia is Pathway Dependent
'Top-down processing' refers to the use of prior knowledge and internal context to bias sensation, perception, and action.
Studies of cortical anatomy and physiology support that top-down processing is mediated, in part, by cortical feedback
pathways, which connect higher order to lower order cortical regions. Given the importance of top-down processing during
wakefulness, a long-standing assumption with some experimental evidence is that cortical feedback is not active under
anesthesia. In this study, we measure the spontaneous activity of two cortical feedback pathways during slow wave
anesthesia. We demonstrate that under anesthesia the retrosplenial cortex to primary visual cortex feedback pathway is
not active, yet the whisker motor cortex to whisker primary somatosensory cortex feedback pathway is active. These
findings suggest that the functions of cortical feedback are not limited to wakefulness. Ongoing studies are attempting to
determine the mechanisms underlying these activity differences.
Funding: NIH/NNDS R01 Grant NS107599 Whitehall Foundation Grant 2017-05-71
Jason M. Guest*, Arco Bast*, Rajeevan T. Narayanan, Marcel Oberlaender
Max Planck Group: In Silico Brain Sciences, Center of Advanced European Studies and Research (caesar),
Thalamus gates active dendritic computations in cortex during sensory processing
Perception is causally linked to a calcium-dependent spiking mechanism that is built into the distal dendrites of layer 5
pyramidal tract neurons the major output cell type of the cerebral cortex. It is yet unclear which circuits activate this
cellular mechanism upon sensory stimulation. Here we found that the same thalamocortical axons that relay sensory
signals to layer 4 also densely target the dendritic domain by which pyramidal tract neurons initiate calcium spikes. Distal
dendritic inputs, which normally appear greatly attenuated at the cell body, thereby generate bursts of action potentials in
cortical output during sensory processing. Our findings indicate that thalamus gates an active dendritic mechanism to
facilitate the combination of sensory signals with top-down information streams into cortical output. Thus, in addition to
being the central hub for sensory signals, thalamus is also likely to ensure that the signals it relays to cortex are perceived
by the animal.
Funding: Advanced European Studies and Research, the European Research Council under the European Union’s
Horizon 2020 research and innovation program (grant 633428, to M.O.), the Deutsche Forschungsgemeinschaft (SFB
1089 and SPP 2041, to M.O.), and the German Federal Ministry of Education and Research (grant 01IS18052, to M.O.).
A. Barrientos, S. Mroziuk, A. Lahijani, I. Uddin, J. C. Brumberg
Queens College and The Graduate Center, CUNY
Sensory deprivation impacts microglia morphology and perineuronal net integrity in a manner that varies from
that of chronic LPS challenge in early development
Limited studies focused on how microglia interact with perineuronal nets (PNNs) in the developing brain. We examined
how chronic lipopolysaccharide (LPS) or minocycline administration alone or in conjunction with sensory deprivation
impact microglia in the primary somatosensory cortex (S1). We also examined how microglia’s reactive state as
characterized by their morphology correlate to changes to the PNN in S1. Litters were randomly assigned to be given IP
injections of saline, minocycline or LPS. A separate cohort of litters underwent sensory deprivation in addition to receiving
saline, minocycline or LPS. We found that microglia morphology is impacted in a treatment-specific manner. Minocycline
results in hyper ramification of microglial processes, while LPS resulted in smaller microglia somas and retracted
processes. Sensory deprivation tapers these effects. LPS in conjunction with sensory deprivation results in a reduction of
PNN density and diminished staining intensity. Sensory deprived mice had reduced surface area of WFA+ somas relative
to controls and those of minocycline and LPS-treated mice. A regression analysis shows that microglia density as well as
specific features correlated with fewer PNNs following sensory deprivation. Both minocycline and LPS treatment disrupt
this relationship. These studies suggest that sensory deprivation may render the developing brain more vulnerable to
factors that influence microglia which shape the PNN.
Funding: NIH/NIGMS GM122657
BARRELS XXXIV POSTER ABSTRACTS
23
Thomas Burnett, Daniel O'Connor, Kristina Nielsen
Johns Hopkins University
Ferrets as a model of whisker-based somatosensory processing
Rodent and primate models of somatosensation have enabled key insights into neural mechanisms of touch, but
translating findings across species poses a major challenge due to differences in sensory organs (whiskers vs. hands)
and cortical organization. An additional model system that relies on whiskers but has a cortical organization more similar
to that of primates will aid in placing findings from rodents and primates into a common framework. Ferrets (Mustela
putorius furo), an established animal model in vision and auditory research, could serve this role. Similar to mice, ferrets
possess whiskers, and research suggests a cortical organization typical of carnivores, including multiple somatosensory
areas beyond S1, similar to primates. While previous research has shown conservation of the lemniscal touch pathway in
ferrets, our current knowledge of ferret somatosensory cortex (S1) is incomplete with respect to the somatotopy, response
properties, and cortical borders. We address these knowledge gaps with the aim of establishing the ferret as a new model
for investigating touch processing. In this project, we used tungsten electrodes and cytochrome oxidase staining to
investigate the organization and borders of S1. We detail the bodily and facial receptive fields, as well as whisker
response properties. Together, out work serves as a foundation to establish the ferret as a new model of whisker
somatosensation.
Giuseppe Cataldo (1), Paul Feinstein (2, 4), H. Philip Zeigler (3, 4), Joshua C. Brumberg (1, 4),
[1] Department of Psychology, Queens College, CUNY; [2] Department of Biological Sciences, Hunter College; [3]
Department of Psychology, Hunter College, CUNY; [4] The Graduate Center, CUNY.
Orofacial hyperalgesia (is) associated with selective deletion of trigeminal lemniscal patterning in Prrxl1 mutant
mouse
Trigeminal neuropathic pain, a frequently debilitating orofacial pain, is difficult to manage and contributes significantly to a
poor quality of life. Prrxl1 is indispensable for the development of patterning in the trigeminal lemniscal pathway and is
also expressed by primary sensory neurons in dorsal root ganglia and their central targets in the dorsal horn. In Prrxl1
knockout (KO) mice, disrupted patterning of primary sensory afferent fibers into the dorsal horn is associated with
significantly attenuated responses to noxious stimuli applied to the hind paws. In contrast, observations suggest that
Prrxl1 KOs exhibit orofacial hyperalgesia as well as significantly extended periods of orofacial grooming making the role
for Prrxl1 in pain unclear. The rodent trigeminal system has been implicated in a variety of active sensing as well as
ingestive behavior. Although absence of patterning is associated with disruption of these behaviors, its involvement in
nociception and the impact of nociception on these behaviors is poorly understood. It was found that Prrxl1 KO mice
exhibited hypoalgesia of the hind paws while displaying hyperalgesia of the orofacial region which was significantly
attenuated by subcutaneous administration of Carprofen. Prrxl1 mice also displayed significantly more grooming bouts
and groomed for a longer duration. These results suggest that the disruption of patterning in Prrxl1 KO mice is selectively
associated with the expression of orofacial pain.
Suma Chinta, Scott Pluta
Purdue University
The superior colliculus combines tactile cues with self-motion to localize objects
Navigating the environment is an active process that requires animals to localize and respond to changes in the scene.
The midbrain superior colliculus (SC) is hypothesized to be essential for localizing and orienting towards tactile cues.
Despite this expectation, the sensorimotor features encoded by SC neurons during tactile localization are largely
unknown. To address this gap, we performed large-scale SC recordings and high-speed behavioral tracking while
locomoting mice explored a dynamically moving surface with their whiskers. We discovered that whisker-activated SC
neurons contain a complex representation of tactile space that enables accurate decoding of surface location. Decoder
accuracy was greatest when surface movements engaged novel whiskers, causing transient and persistent changes in
spike rate that accentuated movement direction. When comparing surface locations that engaged the same whiskers, we
observed significant differences in spike timing, relative to the phase of self-motion, but only modest or no change in
mean spike rate. The spike rate of many SC neurons was linearly related to the speed of locomotion and the position of
the whiskers in space. Neurons combined these motor variables with tactile cues to form a dynamic representation of
surface location. These results establish the mouse SC as a sensorimotor hub specialized for localizing novel tactile cues.
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Elaida D. Dimwamwa, Aurélie Pala, & Garrett B. Stanley
Georgia Institute of Technology
Synchrony dependent corticothalamic gating of thalamocortical sensory responses
There are numerous feedback processes within the neuronal pathways that enable us to perceive the world through our
senses. Corticothalamic feedback neurons from layer 6 of the cortex (L6CT) is one such process that provides extensive
inputs back to the thalamus, outnumbering thalamocortical (TC) projections 10:1 (Deschênes, P. et al., 1998). Our
objective is to elucidate the role of L6CT feedback in sensory coding and processing. Using the vibrissal system of awake,
NTSR1-cre mice selectively expressing ChR2 in L6CT neurons, we conduct simultaneous extracellular recordings of
populations of individual neurons in the primary somatosensory cortex (S1) and Ventral Posteromedial nucleus (VPm) of
thalamus. While optically driving the spiking activity of ChR2-expressing L6CT neurons, we investigate how L6CT neurons
modulate VPm neuronal activity. We find that the ongoing firing rates of VPm neurons can be enhanced or suppressed
depending on the rate of synchronous L6CT inputs, in turn suppressing and enhancing, respectively, the signal-to-noise
ratio of VPm sensory responses. Taken together, we hypothesize a synchrony dependent L6CT excitatory window of
integration (WOI), akin to the well-characterized WOI in the feedforward TC pathway, as the underlying mechanism gating
net enhancement/suppression of VPm. This may emerge as a fundamental principle underlying sensory processing
throughout the sensory hierarchy.
Funding: NIH/NINDS BRAIN R01NS104928 and NINDS R21NS112783.
Rieke Fruengel (1), Daniel Udvary (1), Philipp Harth (2), Daniel Baum (2), Marcel Oberlaender (1)
[1] Max Planck Research Group: In Silico Brain Sciences, Center of Advanced European Studies and Research (caesar);
[2] Visual and Data-centric Computing, Zuse Institute Berlin
Neurobiological design principles for artificial perception
Unlike animals, which are born with innate behavioural abilities, artificial neural networks (ANNs) generally require
extensive training on large datasets before they can perform even simple tasks. It has been suggested that specific wiring
properties may emerge in biological neural circuits during an animal’s development which provide the scaffolding for
learning. This would be a major difference from conventional ANNs, which are usually initialised randomly and do not
contain any predetermined structure. To investigate whether brain networks may have wiring properties particularly
adapted for innate performance and rapid learning, we apply structural constraints from a biological neural network to
ANNs. Specifically, we use the connectome from an anatomically detailed reconstruction of a cortical column in rat barrel
cortex to initialize the weights in ANNs prior to learning. Because of the highly recurrent wiring patterns between cortical
layers in the biological system, we chose a recurrent ANN architecture and are evaluating it with an image classification
task, in which each image was encoded as a time series of grayscale values. We assess whether these ANNs can
perform tasks with less training, with the aim of elucidating the design principles underlying the brain’s computational
properties.
Funding: Center of Advanced European Studies and Research, European Research Council, German Federal Ministry of
Education and Research, Deutsche Forschungsgemeinschaft.
Jacob T. Gable, *Shuonan He, Kelsey Tyssoski, Jenny Chen and Hopi E. Hoekstra.
Department of Molecular & Cellular Biology, Department of Organismic & Evolutionary Biology, Museum of Comparative
Zoology- Harvard University; Howard Hughes Medical Institute
Understanding the genetic basis of whisker evolution in the deer mice, Peromyscus maniculatus
Whiskers (Mystacial vibrissae) are specialized tactile sensory hairs that constitute a crucial component of the mammalian
somatosensory pathway. Morphological variation of whiskers can be observed in mammals that are adapted to different
ecological niches, yet the genetic basis of such variation remains unexplored. Here we focus on two subpopulations of
deer mice (Peromyscus maniculatus) from distinct habitats to investigate genetic basis and functional significance of
whisker length differences. At the morphological level, forest-dwelling deer mice have whiskers that are on average 40%
longer than those from a prairie habitat. We demonstrated that the length variation is not due to different growth rate
between subspecies, but a prolonged growth phase (anagen) in the whisker follicles of forest mice. At the behavioral
level, whisker length significantly affects the performance of deer mice in the gap crossing assay, as the long-whiskered
forest mice are capable of crossing larger gaps than prairie mice in the absence of visual input. At the molecular level,
RNA-seq of whisker pads from both forest and prairie mice revealed distinct temporal expression patterns of Tgf-b
signaling components and cell cycle related genes. We are currently performing quantitative trait locus (QTL) analysis by
crossing forest and prairie subspecies to pinpoint the genetic cause underlying the whisker length difference.
Funding: Howard Hughes Medical Institute.
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A. R. Inacio, K. Lam, F. Pereira, C. R. Gerfen, S. Lee
NIMH, NIH
Brain-wide networks for functionally-distinct principal neurons in the primary somatosensory cortex
Principal neurons in primary sensory cortices exhibit heterogeneous patterns of activity, not only in response to sensory
stimuli but also, during spontaneous movements. How these heterogeneous, behavioral state-dependent patterns of
activity arise is largely unknown. Longitudinal 2-photon Ca2+ imaging uncovered a remarkably stable correlation between
the activity of principal neurons in layer II/III of primary somatosensory cortex (S1) and spontaneous movements. This
population activity could reliably predict spontaneous movements, with a subset of neurons accounting for most of the
prediction accuracy. The activity of movement-encoding neurons could not be explained by direct sensory feedback, as
paralysis of contralateral whisker pad did not disrupt correlation with ipsilateral whisker motion and locomotion. During
pharmacological blockade of neuromodulators, activity levels were altered, but the correlation of neuronal activity with
spontaneous movements was largely maintained. By contrast, glutamatergic transmission blockers nearly abolished this
correlation. Single cell-initiated monosynaptic retrograde tracing and whole-brain presynaptic network analysis revealed
that movement-encoding neurons receive characteristic subcortical inputs. Finally, optogenetic silencing of identified
inputs during spontaneous movements altered activity patterns in S1. Our study provides a connectivity rule that supports
the representation of spontaneous movements in S1.
Funding: NIH IRP.
Hyein Park(1), *Hayagreev Keri(2), Scott Pluta(1).
[1] Department of Life Sciences, Purdue University; [2] Weldon School of Biomedical Engineering, Purdue University
Goal-directed bilateral integration flexibly enhances spike synchrony within and between the somatosensory
cortices
Bilateral tactile integration is crucial for everyday survival. Performing simple tasks such as tying our shoes to executing
complicated tasks like playing the piano require precisely coordinated bilateral movements guided by a delicate balance of
pressure between our hands. Similarly, mice must quickly maneuver through dense woodland brush, guided by their
ability to decode the bilateral relationship between objects around their face. How does the brain encode and interpret
bilateral sensory signals to guide goal-directed movements? While naive models of processing might assume that bilateral
integration only occurs at higher cortical levels, interhemispheric (IH) connections are also prevalent in the primary
sensory cortex. Despite their proven necessity for behavior, the impact of these IH connections on the coding properties
of cortical neurons, their downstream targets, and ultimately perception remains unknown.   Here we take advantage of
the mouse whisker system to decipher the spatial principles of bilateral integration while mice decode the somatotopic
relationship between objects on each side of their face. During the task, we recorded single-unit activity simultaneously
from the relevant barrels of both hemispheres using high-density silicon probes. Contrary to literature findings, our
preliminary data and analyses argue that the impact of bilateral integration is flexibly controlled by reward context, not a
strict anatomical rule.
D. Lee (1,2), G. House (3), A. Carey (3,2), D. Lamay (3,4), J. L. Chen (3,1,2)
[1] Biomedical Engineering, [2] Neurophotonics Center, [3] Biology, Boston University; [4] Northeastern University
Automated home-cage mouse training of a whisker-based tactile working memory task
Understanding the neural correlates of task learning requires unbiased observation of learning behavior. Human-guided
mouse training of complex goal-directed tasks is a time-consuming process. This method limits the number of animals
which can be trained in a given period of time and may introduce human error and biases in the training of subjects. To
increase training throughput and assess variability in learning in an unbiased manner, we have designed an automated
training system which allows mice to learn a whisker-based tactile working memory task from their home cage. The
system contains components to deliver whisker and auditory stimuli, deliver rewarding and aversive stimuli, and monitor
animal entry and licking behavior. Multiple animal cages can be connected to a shared training system where singly
housed mice gain scheduled access to the training module. This enables simultaneous training of multiple animals while
controlling for social interactions. We have developed software that intelligently tracks mouse performance and adjusts
settings across multiple stages of training on a two-alternative forced choice delayed match to sample task. Mice can
successfully be trained to expert performance within three to four weeks. The learning trajectory of individual animals can
be analyzed using a dynamic model of sensory decision-making fit to behavioral data. Through this, variability in learning
and behavior strategies are observed across inbred and outbred mouse strains.
BARRELS XXXIV POSTER ABSTRACTS
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Sarah Lutchman (1), Kathleen Berta (1), Michelle Nanatova (2), Raj Vaidya (3), Joshua C. Brumberg (1, 2, 4)
[1] Behavioral Neuroscience MA Program, Queens College, CUNY; [2] Department of Psychology, Queens College,
CUNY; [3] CUNY Macaulay Honors College, Queens College, CUNY; [4] Biology and Psychology PhD Programs, The
Graduate Center, CUNY
Offspring of Calorically Restricted Mothers Exhibited Neuroanatomical and Behavioral Alterations
Calorie consumption during prenatal development has been shown to impact postnatal health, and inadequate prenatal
caloric intake in particular has been linked with later physical and mental health issues. To better study this, adult female
CD-1 mice were placed on a calorically restricted diet before and throughout pregnancy. Pups birthed to calorically
restricted mothers were assayed for their behavior, microglia, neuronal morphology along with perineuronal net density in
the barrel cortex was accessed to gauge the impact of a restricted prenatal diet. An open field paradigm was conducted to
examine anxiety levels in the resulting pups through analysis of locomotor activity. Female prenatally restricted pups also
expressed less willingness to explore in the open field compared to control pups. Mice that were calorically restricted in
utero had significantly fewer perineuronal nets compared to non-restricted mice. There was also a sex difference with
female offspring being more affected by maternal caloric restriction than male offspring. Neuron somata were significantly
smaller and the microglia of prenatally restricted mice were more ramified, a difference which was specific to certain
layers of the barrel field. From studying the impact of food restriction in mice, this data can be used to better understand
the effects of inadequate caloric intake on children born to mothers during times of food shortage.
Funding: NIH Grant GM122657
Aman Maharjan (1), Jean-Alban Rathelot (2), Jason M. Guest (3), Mythreya Seetharama (1), Peter L. Strick (4) and
Marcel Oberlaender (1)
[1] Caesar; [2] Aix-Marseille Université; [3] Max Planck Florida Institute of Neuroscience; [4] University of Pittsburg
Muscle representation in the rat cerebral cortex: an anatomical perspective
How are the neurons that influence movements of a muscle distributed in the cerebral cortex? To address this question
quantitatively, we used retrograde transneuronal transport of rabies virus from single muscles in rats. This enabled us to
identify cortical motor neurons (CD cells) that make monosynaptic connections with the premotor neurons that connect to
the motoneurons of the injected muscle. We examined the distributions of CMNs for a facial muscle involved in
movements of a single vibrissa and a muscle in the forepaw. We found that CMNs for both muscles display remarkably
widespread distributions that span across secondary motor, primary motor, primary sensory and secondary sensory
cortices. Surprisingly, the numbers of CMNs in sensory areas rival those in motor areas. In contrast to motor areas,
however, the sensory areas occupied by CMNs are largely disjoint. The CMNs for the injected facial muscle are located in
vibrissa-related sensory areas, e.g. the barrel cortex. The CMNs for the injected hand muscle are located in areas that
represent the forepaw. Our findings indicate a topographic organization of CMNs across sensory cortex.
Fernando Messore (1), Felipe Yáñez (1), Jason M Guest (1,2), Marcel Oberlaender (1).
[1] Center of Advance European Studies and Research; [2] Current adress: Max Planck Florida Institute for Neuroscience
Single cell properties and in-vivo activity of feed-forward and feedback inhibitory circuits in the Neocortex
GABAergic neurons in the neocortex play a crucial role in regulating the flow of sensory information and signal modulation
in cortical microcircuits. Synaptic inhibition can be described as being mediated by mainly two circuit configurations,
feedforward and feedback. Feedforward inhibition occurs when thalamocortical axons synapse directly into inhibitory
interneurons, inhibiting their downstream targets. On the contrary, feedback inhibition occurs when excitatory neurons
synapse with these inhibitory interneurons which in turn project back to inhibit them, creating a feedback inhibition. Recent
In-vitro studies have shown that Parvalbumin positive cells in Layer 2/3 of the somatosensory cortex have stronger and
faster innervation from the thalamus when compared with other interneurons. We focus on how the thalamocortical inputs
are organized onto the inhibitory neuron population in the deeper layers on rat‘s somatosensory cortex. In this study, we
explore the role of cellular properties in shaping a neuronal in-vivo spiking activity and their particular embedding in the
neocortical microcircuitry
Ravi Pancholi, Lauren Ryan, Bettina Voelcker, Simon P. Peron
New York University
Cortical dynamics during optical microstimulation task training
Theoretical studies of cortical plasticity have predicted that repeated activation of a group of neurons should drive a host
of changes in primary sensory cortex. However, technical limitations with stimulation and recording techniques, as well as
noise and plasticity introduced at processing stages prior to cortex, have made it difficult to interpret cortical network
changes resulting from sensory stimulation. Here, we train transgenic mice expressing GCaMP6s in cortical pyramidal
BARRELS XXXIV POSTER ABSTRACTS
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neurons to perform an optogenetic pulse count discrimination task. Mice must use activity evoked in layer 2/3 of primary
vibrissal somatosensory cortex (vS1) to report whether the number of optogenetic LED pulses presented to cortex was
high or low. As mice learn to perform this task, we use two-photon calcium imaging to track vS1 neural dynamics across
learning. We find distinct populations of neurons whose activity declines, remains stable, or increases over the course of
training. These changes are consistent with theoretical models of repeated cortical stimulation showing increased
feedback inhibition for highly responsive neurons. A decoding analysis further allows us to track choice-related activity
dynamics across learning and reveals neurons whose activity is highly correlated with animal choice. Future experiments
will explore the behavioral impact of neurons with varying levels of stimulus-evoked and choice-related activity.
Funding: NINDS 5R01NS117536-02
Eunsol Park, Dika. A. Kuljis, Alison. L. Barth
Department of Biological Sciencies, Carnegie Mellon University
Layer-specific regulation of SST inhibition in mouse barrel cortex during whisker-dependent sensory learning
Somatostatin (SST)-expressing GABAergic neurons comprise a major class of inhibitory interneurons in the cerebral
cortex. Previous studies have suggested that inhibition from SST neurons may be regulated during sensory experiences
and learning. However, whether changes in SST neurons are state-dependent or manifested as changes in synaptic
weights, as well as the cellular target of these changes, remain unclear. Here we investigated whether SST output onto
pyramidal (PYR) neurons in the primary somatosensory cortex was altered during sensory association training, using
analysis of SST-IPSCs in acute brain slices from trained animals. Because downregulation of SST interneurons is
hypothesized to be critical for gating synaptic plasticity, we hypothesize that reduction in SST-neuronal output might
facilitate the potentiation of excitatory synapses that has been detected in previous studies. We found that SST-neuronal
output is reduced on layer 2/3 PYR neurons but not on layer 5 PYR neurons after sensory association training.
Furthermore, the reduction of SST input was not apparent when the water reward was decoupled from the whisker
stimulation. Our results suggest that the depression of SST output onto PYR neurons is a layer-specific modification
selectively engaged during reinforcement learning but not sensory exposure.
Funding: AFOSR GRANT13022629
Alyse Thomas (1), Sri Laasya Tipparaju (1), Guang Chen (1), Weiguo Yang (1), Kylie Swiekatowski (1), Mahima Tatam
(1), Charles Gerfen (2), and Nuo Li (1)
[1] Department of Neuroscience Baylor College of Medicine; [2] Laboratory of Systems Neuroscience National Institute of
Mental Health
Local and long-range mechanisms of action selection across a cortico-collicular circuit
Prior to movement, competing motor representations are intermingled and distributed across a multi-regional circuit,
including frontal cortex and superior colliculus (SC). Preparatory activity in these regions is considered a correlate of
action selection, yet the circuit mechanisms mediating this process remain poorly understood. Traditional models posit
that cortex selects upcoming behaviors, then sends a motor command to SC. However, recent data implicate SC
feedback in action selection. We employed anatomical tracing, optogenetic manipulation and electrophysiological
recordings to investigate action selection mechanisms in mice. Our anatomical tracing experiments reveal that the lateral
SC receives direct input from ipsilateral frontal cortex (anterior lateral motor cortex, ALM) and projects back to ALM
through medio-dorsal and ventral-medial thalamus, forming a loop. To define SC contributions to behavior, we performed
optogenetic manipulation during a delayed response task. Animals used their whiskers to discriminate the position of an
object during a sample period. After a delay period (1.3 s), the animals reported their choice via directional licking (left or
right). Unilateral activation of SC evoked contralateral licking, and bilateral inactivation blocked licking
altogether. Unilateral inactivation of the SC during the delay and response periods (but not the sample period) produced
ipsilateral choice biases. Even transient inactivation of SC during the early delay was sufficient to bias upcoming licking,
suggesting that the SC participates in the selection of future movements. Electrophysiological recordings revealed
topographically organized action representations where SC preparatory activity is localized to the ALM projection zone.
Intermingled neurons in both SC and ALM encoded competing representations for ipsilateral and contralateral licking prior
to movement. Combined SC inactivation and ALM recording reveal that a local SC mechanism was sufficient to drive
action selection dynamics across the ALM-SC loop prior to movement. Optrode tagging experiments within SC show that
SC inhibitory neurons preferentially encoded ipsilateral licking and locally inhibited contralateral licking representations.
This local inhibition was sufficient to mediate the competition between motor representations. Our findings argue against
action selection models that relegate SC function to a motor relay. Instead, the SC is implicated as a locus for competition
and a driver of cortical action selection dynamics.
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Daniel Udvary (1), Philipp Harth (2), Jakob H. Macke (3), Hans-Christian Hege (2), Christiaan P.J. de Kock (4), Bert
Sakmann (5) and Marcel Oberlaender (1)
[1] Max Planck Group: In Silico Brain Sciences, Center of Advanced European Studies and Research (caesar);
[2] Department of Visual and Data-centric Computing, Zuse Institute Berlin; [3] Machine Learning in Science, Tübingen
University; [4] Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU
Amsterdam; [5] Max Planck Institute of Neurobiology, Martinsried
The Impact of Neuron Morphology on Cortical Network Architecture
It has become increasingly clear that the neurons in the cerebral cortex are not randomly interconnected. This wiring
specificity can result from synapse formation mechanisms that interconnect neurons depending on their activity or
genetically defined identity. Here we report that in addition to these synapse formation mechanisms, the structural
composition of the neuropil provides a third prominent source by which wiring specificity emerges in cortical networks.
This structurally determined wiring specificity reflects the packing density, morphological diversity and similarity of the
dendritic and axonal processes. The higher these three factors are, the more recurrent the topology of the networks.
Conversely, low density, diversity and similarity yield feedforward networks. These principles predict connectivity patterns
from subcellular to network scales that are remarkably consistent with empirical observations from a rich body of
literature. Thus, cortical network architectures reflect the specific morphological properties of their constituents to much
larger degrees than previously thought.
Funding: Center of Advanced European Studies and Research, Max Planck Institute for Biological Cybernetics, Center for
Neurogenomics and Cognitive Research, European Research Council under the European Union’s Horizon 2020
research and innovation program, German Federal Ministry of Education and Research, Deutsche
Forschungsgemeinschaft
K. Hu, A. Armstrong, *Y. Vlasov
University of Illinois Urbana-Champaign
Cortical processing dynamics during sensory-guided behavior using a tactile virtual-reality task
Our goal is to determine how neuronal populations in the mice barrel cortex are organized in dynamic functional networks
that guide behavioral choices downstream during a whisker-dependent task. To enrich the number of activity states that
neuronal populations encounter during a task trial, we designed naturalistic tactile virtual reality behavioral experiments
that load cortical circuits with difficult yet manageable cognitive tasks and, at the same time, elicit an ethologically relevant
behavior. To record from large neuronal populations during active navigation in a tactile VR, 64channel multi electrode
arrays are acutely implanted into the principle whisker barrel thus recording massive single unit spiking activity across all
cortical layers. We observed distinct layer-dependent stratification of spiking activity of neuronal populations recorded
simultaneously during naturalistic whisker-dependent behavior in our VR.
*Courtney Michelle Whilden, Maxime Chevée, *Seong Yeol An, Solange Pezon Brown
Johns Hopkins University
The synaptic inputs and thalamic projections of two classes of layer 6 corticothalamic neurons in primary
somatosensory cortex of the mouse
Though corticothalamic neurons (CThNs) represent the major input to the thalamus, their role in sensory processing
remains unclear. CThNs are historically divided into two classes: layer 5 CThNs projecting to higher-order thalamic nuclei
and other subcortical structures and layer 6 CThNs projecting to first-order thalamic nuclei, but L6CThNs exhibit additional
diversity. For example, in rodent S1, one subtype projects to the ventral posterior medial nucleus (VPM-only L6CThNs)
while another projects to both VPM and the posterior medial nucleus (VPM/POm L6CThNs). These two subtypes also
differ in their transcriptional identities and local intracortical connectivity. However, whether each subtype receives distinct
long-range inputs is not clear. Using rabies-based tracing, we found that both types receive inputs from S1, VPM, and
POm. VPM/POm L6CThNs, however, receive additional inputs from cortical areas including S2, motor and retrosplenial
cortex, higher-order thalamic nuclei such as the parafascicular nucleus, and subcortical structures such as the basolateral
amygdala. We also found that VPM-only and VPM/POm L6CThNs project to distinct sectors of the thalamic reticular
nucleus (TRN) associated with VPM and POm circuits respectively. Our results indicate that L6CThN subtypes represent
two information streams and suggest that VPM/POm L6CThNs integrate more contextual information while VPM-only
L6CThNs modulate sensory responses via more restricted synaptic relationships.
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Felipe Yáñez (1), Fernando Messore (1), Guanxiao Qi (2), Bert Sakmann (3), Dirk Feldmeyer (2), Marcel Oberlaender (1)
[1] Research Center caesar, Bonn, Germany. [2] FZ Jülich, Jülich, Germany. [3] MPI of Neurobiology, Martinsried,
Germany.
A systematic assessment of single cell properties of cortical GABAergic interneurons
The vast diversity of GABAergic interneurons (INs) has been shown throughout the entire neocortex. At the single cell
level, attributes such as intrinsic physiology, morphology, and molecular identity exhibit complex patterns of variation,
making them difficult to characterize. Here, we systematically assess the degree and character of the variability of these
properties across the entire cortical depth of the rat barrel cortex. First, we extract descriptive features of 306 INs based
on (i) their spiking patterns in response to somatic current injections, (ii) reconstructions of their axon and dendrite
morphology, as well as somatic depth location, and (iii) their respective molecular identity. Second, we cluster the
extracted features, perform a sensitivity analysis, and evaluate classification accuracy in order to obtain robust morpho-
electrical types. Third, we determine the absolute number and density distribution of the three most predominant
molecular marker classes throughout the entire barrel cortex. We compare the relative abundances across the cortical
depth of molecularly defined IN types, with those determined by morpho-electrical properties. Our results provide
quantitative insight into the relationships between the three main attributes that are currently used to group INs, and
reveal the degree to which somatic depth location in combination with molecular identity is predictive of an IN’s intrinsic
physiological and/or morphological type, and vice versa.
Behzad Zareian (1), Angelina Lam (2), Edward Zagha (1)
[1] Department of Psychology, University of California, Riverside; [2] Department of Biomedical Sciences, University of
California, Riverside
Differential Contributions of Neocortex and Striatum to Sensory Selection and Attenuation in a Selective
Detection Task in Mice
A learned sensory-motor behavior engages multiple brain regions, including the neocortex and basal ganglia. How these
brain regions coordinate to effect sensory selection (for target stimuli) and attenuation (for distractor stimuli) remains
unknown. Here, we aimed to determine the coordination of sensory-motor flow between cortex and basal ganglia using
laminar electrophysiological recordings and muscimol inactivations during a selective detection task in mice. Whisker
motor cortex (wMC) has been shown to be important in lateralized attenuation of sensory information and sensory-motor
transformation (Aruljothi et al. 2020, Zareian et al. 2021). Striatum has been suggested to be important in habituated
sensory-motor tasks (Fernandez-Ruiz et al. 2001). We first localize attenuation of the sensory stream to striatum and the
infragranular layers of wMC for target- and distractor- aligned hemispheres, rendering both regions functionally
downstream of primary somatosensory cortex. We then show that inactivation of target-aligned striatum severely impairs
task execution, substantially reducing behavioral responses to all stimuli. In contrast, contributions of wMC appear to be
context-dependent: target-aligned wMC contributes to early sensory- and choice- encoding, whereas distractor-aligned
wMC suppresses responses to distractor stimuli. Overall, these data suggest a cortex to basal ganglia direction of
sensory-motor flow in a selective detection task.