Barrels 36

Baltimore

Thursday, November 9

, 2023

9:00 to 9:10

Welcome

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9:10 to 10:10

INVITED TALK (30 minutes)

Randy Bruno, Oxford

Secondary Somatosensory and Visual Thalamus in Behavior

1. Short talk (15 minutes)

Learning induced neuronal identity switch in the superficial layers of the primary somatosensory cortex

J. Dai and Q.Q Sun. Univ. Wyoming

2. Short talk (15 minutes)

Input- and target-specific synaptic plasticity in neocortical layer 1 during sensory learning

Ajit Ray, Joseph C Christian, Alison L Barth, Carnegie Melon University

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Stretch Break 10 minutes

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10:20-11:20

INVITED TALK (30 minutes)

Anurag Pandey, Cardiff

Role of a feedback circuit from S2 to vS1 in learning-induced structural plasticity in vS1 cortex

3. Short talk (15 minutes)

Responses to cortical stimulation reveal thalamocortical state-dependent features in mice and humans

Simone Russo, Leslie Claar, Lydia Marks, Giulia Furregoni, Flavia Maria Zauli, Gabriel Hassan, Michela

Solbiati, Simone Sarasso, Mario Rosanova, Ivana Sartori, Andrea Pigorini, Christof Koch, Marcello

Massimini, Irene Rembado. Allen Brain Institute

4. Short talk (15 minutes)

Stimulus novelty uncovers coding diversity in visual cortical circuits

Farzaneh Najafi, Marina Garrett, Peter Groblewski, Alex Piet, Doug Ollerenshaw, Iryna Yavorska, Stefan

Mihalas, Anton Arkhipov, Christof Koch, Shawn R Olsen. Allen Institute

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Coffee Break 20 minutes

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11:40 to 12:40

INVITED TALK (30 minutes)

Jessica Cardin, Yale

Rhythm and flow in the cortex: flexible perceptual encoding by patterned activity

INVITED TALK (30 minutes)

Soohyun Lee, NIMH

Brainwide synaptic network of behavior-state dependent cortical neurons

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Lunch break

12:40 to 2:30

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2:30 to 3:30

INVITED TALK (30 minutes)

Solange Brown, Johns Hopkins

Neural activity in the claustrum during a cross-modal sensory selection task

5. Short talk (15 minutes)

Microglia-astrocyte crosstalk during synaptic remodeling in the barrel cortex

Travis E. Faust, Yi-Han Lee, Georgia Gunner, Ciara O’Connor, Margaret Boyle, Ana Badimon, Pinar

Ayata, Anne Schaefer, Dori Schafer. UMass Chan Medical School and Icahn School of Medicine at

Mount Sinai

6. Short talk (15 minutes)

Is paradoxical sleep a paradoxical state of sleep?

Flore BOSCHER and Nadia URBAIN

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Coffee Break 15 minutes

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3:45 to 5:00

INVITED TALK (30 minutes)

Aleena Garner, Harvard

A Cortical Circuit for Audio-Visual Predictions

7. Short talk (15 minutes)

Organizing principles of cortical interneurons

F. YÁÑEZ, F. MESSORE, G. QI, D. FELDMEYER, B. SAKMANN, M. OBERLAENDER Max Planck

Institute for Neurobiology of Behavior

8. Short talk (15 minutes)

Prrxl1 knockout – a non-invasive model of chronic pain

Ezekiel Willerson, Leah Kramer, Eliana Eichler, Jacob Zar, Kayla Wilamowsky, Giuseppe Cataldo,

Joshua C. Brumberg, Queens College, CUNY

9. Short talk (15 minutes)

Ultra-Flexible tentacle electrodes for months-long tracking of assemblies of single units simultaneously

from many brain areas

Tansel Baran Yasar, Peter Gombkoto, Eminhan Ozil, Alexei Vyssotski, Angeliki Vavladeli, Simon

Steffens, Orhun Caner, Eren, Wolfger von der Behrens, Mehmet Fatih Yanik.

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Posters and Dinner

5:00 to 9:00

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Friday, November 10

, 2023

Day 2

9:00 to 9:10

Announcements

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9:10 to 10:10 am

INVITED TALK (30 minutes)

Dan Feldman, UC Berkeley

History-based attentional cueing in the whisker system

11. Short talk (15 minutes)

Simulation tools for studying the vibrissal array

Mitra J Hartmann, Departments of Biomedical and Mechanical Engineering, Northwestern University

12. Short talk (15 minutes)

Cortical contributions to context-dependent sensorimotor transformation

Parviz Ghaderi, Sylvain Crochet and Carl Petersen

Swiss Federal Institute of Technology Lausanne

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Stretch Break 10 minutes

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10:20 to 11:20

INVITED TALK (30 minutes)

Florent Haiss, Institute Pasteur

Coexistence of state, choice, and sensory integration coding in barrel cortex

13. Short talk (15 minutes)

Connectomic analysis of astrocyte-synapse interactions in mouse barrel cortex

Yagmur Yener, Alessandro Motta, Moritz Helmstaedter

Max-Planck Institute for Brain Research

16. Short talk (15 minutes)

Joint representation of self-motion and touch in the Superior Colliculus

Suma Chinta & Scott R Pluta. Purdue University

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Coffee Break (20 minutes)

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11:40 to 12:40

INVITED TALK (30 minutes)

Rui Liu, UCSD

Spatiotemporal representation of rhythmicity by thalamocortical inputs during active sensing

INVITED TALK (30 minutes)

Nicholas Bush, U Washington

Brainstem populations that underlie breathing follow rotational, attractor-like dynamics

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Lunch break

12:40 to 2:30

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2:30 to 3:45

INVITED TALK (30 minutes)

Nuo Li, Baylor

A combinatorial code for motor memory

14. Short talk (15 minutes)

In-Vivo Recording of Optogenetically Identified Rapidly-Adapting Whisker Neurons

P. M. Thompson, Jun Takatoh, Seonmi Choi, Andrew Harahill, and Fan Wang. Massachusetts Institute

of Technology

15. Short talk (15 minutes)

Jaw muscle spindle afferents as multiplexed channels for sensing and guiding orofacial movement

William Olson, Varun Chokshi, Jeong Jun Kim, Montrell Vass, Noah Cowan, Daniel O’Connor. Johns

Hopkins University

16. Short talk (15 minutes)

What does motor cortex tell sensory cortex?

Edward Zagha. University of California Riverside

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Coffee Break (15 minutes)

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4:00 to 5:15

17. Short talk (15 minutes)

Functional network analysis of cortical dynamics seen with fast wide-field voltage imaging in a right/left

cued decision lick task

Dieter Jaeger, Yunmiao Wang. Emory University

18. Short talk (15 minutes)

Motor cortex modulation of nociception and movement through corticobulbar circuits

Nicole Mercer Lindsay, Simon Haziz, Thomas Baer, Mark Schnitzer & Grégory Scherrer. Stanford

University, University of North Carolina and New York Stem Cell Foundation

19. Short talk (15 minutes)

Sparse and distributed cortical populations mediate sensorimotor integration

Ravi Pancholi, Andrew Sun-Yan, Maya Laughton, Simon Peron. NYU

INVITED TALK (30 minutes)

Daniel O'Connor, Johns Hopkins

Rule-based modulation of a sensorimotor transformation across cortical areas

The End

ABSTRACTS FOR INVITED TALKS (in line with schedule)

Secondary Somatosensory and Visual Thalamus in Behavior

Randy Bruno

Oxford University, UK

Each sensory modality has its own primary and secondary thalamic nuclei. While primary thalamic nuclei

are well understood to relay sensory information from the periphery to the cortex, the function of

secondary sensory nuclei is elusive. One hypothesis has been that secondary nuclei may support

feature-based attention. If this is true, one would expect the activity in different nuclei to reflect the degree

to which modalities are or are not behaviorally relevant to a learned task. We trained head-fixed mice to

attend to one sensory modality while ignoring a second modality, namely attend to touch and ignore

vision (or vice versa). Arrays were used to record simultaneously from secondary somatosensory

thalamus (POm) and secondary visual thalamus (LP, the mouse homolog of primate visual pulvinar). In

mice trained to respond to tactile stimuli and ignore visual stimuli, POm was robustly activated by whisker

touches and largely unresponsive to visual stimuli. The reverse pattern was observed when mice were

trained to respond to visual stimuli and ignore touch, with POm now more robustly activated during visual

trials. This POm plasticity was not explained by differences in movements (i.e., whisking, licking) resulting

from the two tasks (respond to vision vs respond to touch). Post hoc histological reconstruction of array

tracks through POm revealed that subregions varied in their degree of plasticity. LP exhibited similar

phenomena. We conclude that behavioral training reshapes activity in secondary thalamic nuclei.

Secondary nuclei may then serve as “control knobs” on sensory processing and plasticity in their

corresponding sensory cortical areas, such as primary somatosensory and primary visual cortex.

Role of a feedback circuit from S2 to vS1 in learning-induced structural plasticity in vS1 cortex

Anurag Pandey, Sungmin Kang, Nicole Pacchiarini, Hanna Wyszynska, Aneesha Grewal, Alex Griffiths,

Imogen Healy-Millett, Zena Masseri, Neil Hardingham, Joseph O’Neill, Robert C. Honey and Kevin Fox

Cardiff University

Feedforward and feedback pathways are important for transfer and integration of information between

sensory cortical areas. Here we find that two closely connected cortical areas, the primary (S1) and

secondary (S2) somatosensory cortices are both required for mice to learn whisker-dependent texture

discrimination. Increased inhibition in either area (using excitatory DREADDs expressed in inhibitory

neurones) prevents learning. We find that learning the discrimination produces structural plasticity on

layer 2/3 pyramidal neurones in vibrissae S1 (vS1), that is restricted to the basal dendrites and leaves

dendritic spines on apical dendrites unchanged. As S2 projects to the apical dendrites of vS1 neurones,

we tested whether S2 affects LTP-induction in S1. We found that feedback projections from S2 to S1

gates LTP on feedforward pathways within S1. To test whether this feedback circuit might affect structural

plasticity in vivo, we inhibited S2 unilaterally during texture discrimination learning. We found plasticity to

be strongly attenuated in vS1 ipsilateral to the site of S2 inhibition, suggesting that feedback from S2 to

S1 controls plasticity during texture discrimination learning. Funding- BBSRC UK

Rhythm and flow in the cortex: flexible perceptual encoding by patterned activity.

Jessica A. Cardin

Department of Neuroscience, Kavli Institute for Neuroscience, Wu Tsai Institute, Yale University School of

Medicine, New Haven, CT, USA.

Cognitive processes underlying behavior are linked to specific spatiotemporal patterns of neural activity in

the neocortex. These patterns arise from synchronous synaptic activity and are often detected as

prominent peaks in particular frequency bands in the cortical field potential. Activity in a wide range of

frequencies (5-100Hz) generally occurs in correlation with cognitive behaviors such as navigation,

attention, perception, and memory. However, cortical activity is highly variable on multiple timescales

(milliseconds to hundreds of seconds), obscuring the fine temporal relationship between bouts of

patterned activity and behavior. Identifying discrete neural events underlying patterned activity within

highly dynamic cortical network fluctuations thus remains a critical challenge. We developed a novel

analytical method to track individual network events underlying state-dependent activity with single-cycle

precision. We find in mouse primary visual cortex (V1) that γ- (30-80Hz), but not β- (15-30Hz), range

events are associated with feedforward thalamocortical drive and can be selectively evoked by

thalamocortical stimulation in a biologically realistic pattern, but not by Poisson or regular stimulation. g,

but not b, events are associated with enhanced visual encoding by V1 neurons despite their neighboring

frequency bands.  event rate increases steadily prior to visually-cued behavior, accurately predicting

trial-by-trial visual detection performance. This relationship between cortical γ events and behavior is

sensory modality-specific and rapidly modulated by changes in task objectives, but unaffected by

behavioral state.  events thus selectively support flexible cortical encoding according to behavioral

context, suggesting a distinct role for transient patterns of cortical activity.

Brainwide synaptic network of behavior-state dependent cortical neurons

Ana R. Inácio, Ka Chun Lam, Yuan Zhao, Francisco Pereira, Charles R. Gerfen, and Soohyun Lee

National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

Neuronal connections provide the scaffolding for neuronal function. Revealing the connectivity of

functionally identified individual neurons is necessary to understand how activity patterns emerge and

support behavior. Yet, the brain-wide presynaptic wiring rules that lay the foundation for the functional

selectivity of individual neurons remain largely unexplored. Cortical neurons, even in primary sensory

cortex, are heterogeneous in their selectivity, not only to sensory stimuli but also to multiple aspects of

behavior. Here, to investigate presynaptic connectivity rules underlying the selectivity of pyramidal

neurons to behavioral state in primary somatosensory cortex (S1), we used two-photon calcium imaging,

neuropharmacology, single-cell based monosynaptic input tracing, and optogenetics. We show that

behavioral state-dependent neuronal activity patterns are stable over time. These are not determined by

neuromodulatory inputs but are instead driven by glutamatergic inputs. Analysis of brain-wide presynaptic

networks of individual neurons with distinct behavioral state-dependent activity profiles revealed

characteristic patterns of anatomical input. While both behavioral state-related and unrelated neurons had

a similar pattern of local inputs within S1, their long-range glutamatergic inputs differed. Our results

revealed distinct long-range glutamatergic inputs as a substrate for preconfigured network dynamics

associated with behavioral state. Funding: NIH IPR ZIAMH00295

Neural activity in the claustrum during a cross-modal sensory selection task

Solange Brown,

Johns Hopkins

Although the functions of the claustrum, a thin, elongated subcortical nucleus located between the

neocortex and striatum that forms extensive reciprocal connections with the neocortex, remain unclear, it

has recently been implicated in sensory selection. It has been proposed that claustrocortical activity

evoked by sensory input modulates the neocortex’s context-dependent responses to sensory stimuli. We

tested this hypothesis by recording from claustrum neurons in vivo while mice performed a crossmodal

sensory-selection task. We found that claustrum neurons, including putative claustrocortical neurons

projecting to primary somatosensory cortex, rarely responded solely to tactile or visual stimuli. We found

instead that neurons in anterior claustrum exhibited direction-tuned motor responses and encoded

upcoming lick direction during intertrial intervals. Anterograde and retrograde tracing studies confirmed

that the claustrum is interconnected with cortical motor areas such as ALM. Chemogenetic inhibition of

claustrocortical neurons significantly decreased lick responses to inappropriate sensory stimuli while

leaving the response rates to appropriate sensory stimuli unaffected. Together, these data suggest that

the claustrum is integrated into higher-order premotor circuits recently implicated in decision-making.

A Cortical Circuit for Audio-Visual Predictions

Aleena R. Garner

1,3

and Georg B. Keller

1,2

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland;

Faculty of Natural Sciences,

University of Basel, Basel, Switzerland;

Harvard Medical School Department of Neurobiology, Boston,

Massachusetts

Learned associations between stimuli in different sensory modalities can shape the way we perceive

these stimuli (Mcgurk and Macdonald, 1976). During audio-visual associative learning, auditory cortex

has been shown to underlie multi-modal plasticity in visual cortex (McIntosh et al., 1998; Zangenehpour

and Zatorre, 2010). However, how processing in visual cortex is altered when an auditory stimulus signals

a visual event and what the neural mechanisms are that mediate such experience-dependent audio-

visual associations is not well understood. Here we describe a neural mechanism that contributes to

shaping visual representations of behaviorally relevant stimuli through direct interactions between

auditory and visual cortices. We show that auditory association with a visual stimulus leads to an

experience-dependent suppression of visual responses in visual cortex. This suppression of the

predictable visual stimulus response is driven in part by input from auditory cortex. By recording from

auditory cortex axons in visual cortex, we find that these axons carry a mixture of auditory and

retinotopically matched visual input. Moreover, optogenetic stimulation of auditory cortex axons in visual

cortex selectively suppresses the neurons responsive to the associated visual stimulus after, but not

before, learning. Our results are consistent with the interpretation that cross-modal associations can be

stored in long-range cortical connections and that with learning these cross-modal connections function to

suppress the responses to predictable input.

History-based attention in the whisker system

DL Ramamurthy, L Rodriguez, DE Feldman

Attention flexibly selects specific sensory stimuli for prioritized processing, but the neurobiological

mechanisms remain poorly understood. We studied a common form of attention in which the history of

stimulus-reward association causes animals, including humans, to automatically attend to previously

rewarded stimuli. In a simple whisker detection task, mice rapidly shifted attention between specific

whiskers, based on the recent history of stimulus-reward association. A prior rewarded hit trial on a given

whisker elevated behavioral detectability (d-prime) for that whisker. This effect was somatotopically

specific, lasted ~10 sec, and was flexibly shifted between whiskers. Whisker stimulation alone, without

reward, did not trigger this effect. Reward delivery also generally elevated lickiness (i.e., reduces

criterion), which occurred in addition to this whisker-specific attentional effect. We tested for

neurobiological correlates of attention in S1, using 2p imaging from L2/3 pyramidal (PYR) cells during

behavior. Whisker-evoked DF/F for a given whisker was strongly increased when the prior trial was a

rewarded hit on that same whisker. This response amplification fell off with cortical distance in S1 from

the rewarded whisker's column, and thus was somatotopically organized. Prior reward also caused a

smaller, spatially non-specific ramping of PYR activity that may reflect general expectation. In ongoing

Neuropixels recordings, we confirmed that attention increases the gain of whisker-evoked spiking

responses by regular-spiking (presumed PYR) units. Thus, attention powerfully modulates the whisker

sensory code in S1. Funding: Supported by R01 NS092367 to DEF, and F32NS114327 and

K99NS129753 to DLR

Coexistence of state, choice, and sensory integration coding in barrel cortex

Pierre-Marie Gardères

1,2,

Sébastien Le Gal

, Charly Rousseau

, Alexandre Mamane

, Dan Alin

Ganea

2,3

, Florent Haiss

1: Institut Pasteur, Université Paris Cité, Unit of Neural Circuits Dynamics and Decision Making, 75015

Paris, France

2: IZKF Aachen, Medical School, RWTH Aachen University, 52074 Aachen, Germany

3: University of Basel, Department of Biomedicine, 4001 Basel, Switzerland

During perceptually guided decisions, correlates of choice are found as upstream as in the primary

sensory areas. However, how well these choice signals align with early sensory representations, a

prerequisite for their interpretation as feedforward substrates of perception, remains an open question.

We designed a two alternative forced choice task (2AFC) in which mice compared stimulation frequencies

applied to two adjacent vibrissae. The optogenetic silencing of individual columns in the primary

somatosensory cortex (wS1) resulted in predicted shifts of psychometric functions, demonstrating that

perception depends on focal, early sensory representations. Functional imaging of layer II/III single

neurons revealed sensory, choice and engagement coding. From trial to trial, these three varied

substantially, but independently from one another. Thus, coding of sensory and non-sensory variables co-

exist in orthogonal subspace of the population activity, suggesting that perceptual variability does not

originate from wS1 but rather from state or choice fluctuations in downstream areas.

Spatiotemporal representation of rhythmicity by thalamocortical inputs during active sensing

Rui Liu

, Karin Dekel

, Pan-tong Yao

, Abhi Aggarwal

, Kaspar Podgorski

, Daniel H. O'Connor

, David

Golomb

2,6,7

and David Kleinfeld

1,8

Department of Physics, University of California, San Diego, La Jolla, California, USA

Department of Physiology and Cell Biology, Ben Gurion University, Beer-Sheva, Israel

Neurosciences Graduate Program, University of California San Diego, La Jolla, California, USA

Allen Institute for Neural Dynamics, Seattle, Washington, USA

The Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore MD, USA

Department of Physics, Ben Gurion University, Beer-Sheva, Israel

Zlotowski Center for Neuroscience, Ben Gurion University, Beer-Sheva, Israel

Department of Neurobiology, University of California, San Diego, La Jolla, California, USA

In tactile active sensing, the swift shift from exploratory whisking to the state of "minimal impingement" plays

a crucial role in achieving optimal sensation when unexpectedly encountering objects. This rapid switching

necessitates prompt location-based perception. We consider the possibility that sensation is derived from

the mechanics of a sensorimotor plant and directly encoded by thalamocortical afferents, with limited

neuronal processing. Our study utilizes the rhythmically active rodent vibrissa system in combination with

high-resolution imaging of glutamate activities

on thalamocortical inputs in mouse layer 4 barrel cortex. We

employ adaptive optical two-photon microscopy to survey the activity of a substantial population of

thalamocortical boutons throughout one entire barrel while performing whisking dynamic pole contact task.

Our findings reveal, firstly, that in moving contacts, the torque upon touch, the azimuthal angle of contact

and the phase of contact onset are proportional to each other for small deflections. Next, the spiking at a

preferred phase in the free whisking cycle is a reliable and spatially-ordered metric to label thalamocortical

afferents. Thalamocortical boutons with similar phase preferences are spatially clustered. Further, the

strength of phase representation depends on the rhythmic regularity and setpoint of vibrissa movement.

Finally, the response probability to the contact location indicated by phase is in line with the preferred phase

of free whisking across a large number of thalamocortical boutons. This work is supported by NIH U19

NS107466 and U24 EB028942.

Brainstem populations that underlie breathing follow rotational, attractor-like dynamics

Nicholas Bush

Seattle Children's Research Institute; Jan-Marino Ramirez, University of Washington, Seattle Children's

Research Institute

Breathing is a vital, rhythmic motor behavior that persists throughout the life of an animal. Despite its

simplicity, the neural circuits that generate, pattern, and maintain breathing are embedded in a large

population of anatomically distributed and molecularly diverse neurons in the medulla called the Ventral

Respiratory Column (VRC). The populations in the VRC must not only generate rhythmic activity, but also

modulate breathing to maintain blood gas concentrations, and monitor mechanosensory signals that

represent lung state. We leverage Neuropixels probes to record simultaneously from a large spatial

extent of the VRC in anesthetized mice with intact neuro-respiratory systems while they breathe at

physiological rates. We record from over 15,000 units to characterize their respiratory related activity and

perform opto-tagging and histological analyses to map the cell-type and anatomical location of these

units. Through population-level analyses we uncover continuous rotational trajectories along a low-

dimensional neural manifold that target the offset of inspiration. Lastly, we disrupt the respiratory system

with opioids and hypoxic challenge. Opioids cause respiratory depression that results in diverse changes

in single unit activity, but the rotational population dynamics are preserved. In contrast, hypoxic challenge

induces gasping which eliminates the rotational dynamics and results in punctuated, one-phase

inspiratory efforts. Funding: NIH F32HL159904.

A combinatorial code for motor memory

Nuo Li

Baylor College of Medicine

In our lifetime we stably retain a repertoire of motor skills. How are learned actions stored in motor

memory? Moreover, how are motor memories maintained as we continuously acquire new motor skills?

To explore these questions, we used automated home-cage training to establish a continual learning

paradigm in mice. Mice learned to perform directional licking in multiple tasks. We combined this

paradigm with chronic two-photon imaging of anterior lateral motor cortex (ALM) to track the neural

representation of directional licking for up to 6 months and across continual learning. Within the same

task, activity driving directional licking was stably retained with little representational drift. When learning

new tasks, new preparatory activity emerged to drive the same licking actions. This created parallel new

motor memories while retaining the previous memories. Re-learning to make the same actions in the

previous task re-activated the previous preparatory activity, even 3 months later. Across multiple tasks,

distinct preparatory activities encoded the same action in a context-dependent manner. Our results show

that preparatory activity reflects motor memories that stably encode learned actions in combination with

their context, which we call a combinatorial code. Context-specific modular memories could reduce

interference of new learning on existing representations, enabling stable retention of motor repertoire in

the face of continual learning.

Rule-based modulation of a sensorimotor transformation across cortical areas

Yi-Ting Chang, Eric A. Finkel, Duo Xu, Daniel H. O’Connor

Johns Hopkins

Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic

environment. However, it remains unclear how the brain encodes rule information and uses this

information to guide behavioral responses to sensory stimuli. Here, we made single-unit recordings while

head-fixed mice performed a cross-modal sensory selection task in which they switched between two

rules in different blocks of trials: licking in response to tactile stimuli applied to a whisker while rejecting

visual stimuli, or licking to visual stimuli while rejecting the tactile stimuli. Along a cortical sensorimotor

processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial

(MM) and anterolateral (ALM) motor areas, the single-trial activity of individual neurons distinguished

between the two rules both prior to and in response to the tactile stimulus. Variable rule-dependent

responses to identical stimuli could in principle occur via appropriate configuration of pre-stimulus

preparatory states of a neural population, which would shape the subsequent response. We hypothesized

that neural populations in S1, S2, MM and ALM would show preparatory activity states that were set in a

rule-dependent manner to cause processing of sensory information according to the current rule. This

hypothesis was supported for the motor cortical areas by findings that (1) the current task rule could be

decoded from pre-stimulus population activity in ALM and MM; (2) neural subspaces containing the

population activity differed between the two rules both prior to the stimulus and during the stimulus-

evoked response; and (3) optogenetic disruption of pre-stimulus states within ALM and MM impaired task

performance. Our findings indicate that flexible selection of an appropriate action in response to a

sensory input can occur via configuration of preparatory states in the motor cortex.

ABSTRACTS FOR SHORT TALKS AND POSTERS (Alphabetically)

1. Short talk

Is paradoxical sleep a paradoxical state of sleep?

Flore BOSCHER and Nadia URBAIN

Paradoxical sleep (PS), coined as such by Jouvet in 1959 for the striking resemblance of its

electroencephalogram (EEG) to the one observed during the fundamentally different cognitive state of

wakefulness, is characterized by muscular atonia and the occurrence of rapid eye movements (REM). In

addition to REM, in mice, we observed rapid whisker movements. The whisker system therefore offers the

unique opportunity to study cortical and thalamic dynamics associated with whisker movements in both

wakefulness and REM sleep. We performed extra- and intracellular recordings of thalamic cells in head-

fixed mice, combined with local field potential (LFP) recordings in the primary somatosensory (S1) and

motor (M1) cortices, while simultaneously monitoring the EEG, the electromyogram and the whisker

movements with a high-speed camera. Our results show that self-generated movements are associated

with an increase in thalamic neuronal firing and a cortical activation in REM sleep, as in wakefulness.

Unexpectedly, our data further reveal a substate of REM, outside phasic events, which bears clear NREM

characteristics, opening a new insight into the function of REM sleep.

2. Short talk

Joint representation of self-motion and touch in the Superior Colliculus

Suma Chinta & Scott R Pluta, Department of Biology, Purdue University, West Lafayette, IN

In the absence of body movement, tactile localization is performed by mapping stimuli directly to

receptors on the body surface. However, in real life, tactile localization is active, whereby the position of

the body is constantly changing. Therefore, tactile localization requires the brain to combine its

somatotopic map of the body surface with an egocentric model of its position. Where in the brain does

this joint representation of somatotopic and egocentric space arise? We discovered neural activity in the

midbrain superior colliculus (SC) that is linearly related to volitional whisker position. A time-shifted

encoding model revealed that neural activity either accurately predicted or was predicted by specific

kinematic variables, ultimately revealing the proportion of sensory and motor information in individual SC

neurons. Active touch modulated the neural representation of self-motion by increasing the proportion of

sensory information in these neurons. A select group of neurons reliably fired action potentials

milliseconds before the start of whisker protraction, with greater spike rates preceding larger movements.

In these neurons (and others), tuning to whisker phase, amplitude and midpoint were combined to

generate an accurate representation of whisker position at high temporal resolution. Therefore, SC

neurons contain the full spectrum of afferent and efferent information needed to perform active tactile

localization. Funding:Whitehall Foundation grant

3. Short talk

Learning induced neuronal identity switch in the superficial layers of the primary somatosensory

cortex

J. Dai and Q.Q Sun, Univ. Wyoming, Wyoming Sensory Biology Center.

We studied the sensory cortical neuronal coding of trace eyeblink conditioning (TEC) learning in head-

fixed, freely running mice, where whisker deflection was used as a conditioned stimulus (CS) and an air

puff to the cornea delivered after an interval was used as unconditioned stimulus (US). GCaMP6 signals

were monitored by a two-photon microscope under a cranial window. The local blockade of S1 activities

with muscimol abolished the behavior learning suggesting that S1 is required for the TEC. In naive

animals, based on the response properties to the CS and US, identities of 20% of responsive primary

neurons (PNs) were divided into two subtypes: CR and UR neurons. After animals learned the task,

identity of CR and UR neurons changed: while the CR neurons are less responsive to CS, UR neurons

gain responsiveness to CS, a new phenomenon we defined as ‘learning induced neuronal identity switch

(LINIS)’. To explore the potential mechanisms underlying LINIS, we found that systemic and local (i.e. in

S1) administration of the nicotinic receptor antagonist during TEC training blocked the LINIS, and

concomitantly disrupted the behavior learning. Additionally, we monitored responses of two types of

cortical interneurons (INs) and observed that SST, but not PV contribute to the LINIS. Thus, we conclude

that L2/3 PNs in S1 encode perceptual learning by LINIS like mechanisms, and cholinergic pathways and

cortical SST interneurons are involved in the formation of LINIS. Funding: NIH.

4. Short talk

Microglia-astrocyte crosstalk during synaptic remodeling in the barrel cortex

Travis E. Faust1, Yi-Han Lee1, Georgia Gunner1, Ciara O’Connor1, Margaret Boyle1, Ana Badimon2,

Pinar Ayata2, Anne Schaefer2, Dori Schafer1 1-Department of Neurobiology, Brudnick Neuropsychiatric

Research Institute, UMass Chan Medical School, Worcester, MA 2-Fishberg Department of

Neuroscience, Department of Psychiatry, Friedman Brain Institute, Icahn School of Medicine at Mount

Sinai, New York, NY

Synapses remodel in response to changes in sensory experience and neural activity. Microglia and

astrocytes both contribute to activity-dependent synapse remodeling by engulfing and removing synapses

from less active neurons. Yet, how these two cell types communicate to remodel synapses, while sparing

others, remains an open question. Previously, we showed that microglia engulf and remove synapses in

neonate mouse barrel cortex following whisker lesioning and whisker trimming-induced reductions of

neural activity. This whisker lesioning-induced synapse removal was dependent on signaling between

neuronal fractalkine (CX3CL1) and its cognate microglial fractalkine receptor (CX3CR1). Using this

whisker lesioning paradigm, we are now exploring how astrocytes and microglia coordinate to regulate

synapse remodeling. Using cell type specific translating ribosome affinity purification followed by RNAseq

(TRAPseq), we are exploring transcriptional changes in microglia and astrocytes following whisker

lesioning. In the process, we have identified putative receptor-ligand signaling between these two cell

types. We are also now using expansion microscopy to assess how astrocytes modify their interactions

with synapses in a microglial CX3CR1 signaling-dependent manner. Together, our results provide a novel

mechanism by which microglia signal to astrocytes to facilitate synapse engulfment and remodeling of

cortical synapses in response to changes in neural activity.

5. Short talk

Cortical contributions to context-dependent sensorimotor transformation

Parviz Ghaderi, Sylvain Crochet and Carl Petersen . Swiss Federal Institute of Technology Lausanne

Flexible integration of sensory stimuli in a context-dependent manner is a key cognitive process required

to generate appropriate behavior. An intriguing question, then, is how the same sensory stimulus can be

interpreted differently according to context in order to generate different behavioral responses. We

designed a task in which mice were trained to lick for reward in response to a single whisker stimulus if it

was preceded 1 s earlier by a brief Go-Tone, but not if it was preceded by a NoGo-Tone.Optogenetic

inactivation of primary auditory cortex (A1), primary whisker somatosensory cortex (wS1), secondary

whisker somatosensory cortex (wS2), secondary whisker motor cortex (wM2), and anterior lateral motor

cortex (ALM) revealed prominent temporally-specific deficits in task performance for each area, whereas

inactivation of primary forepaw somatosensory cortex had no impact.We investigated neuronal correlates

of context-dependent sensorimotor transformation using high-density extracellular Neuropixels recordings

combined with high-speed video filming of facial movements. Neuronal activity in A1, wS1, wS2, wM2,

and ALM differed comparing Go-context hit trials to NoGo-context correct rejection trials.

6. Short talk

Simulation tools for studying the vibrissal array

Mitra J Hartmann, Departments of Biomedical and Mechanical Engineering, Northwestern University,

Evanston IL 60208

The rodent vibrissal array offers a tantalizing promise to neuroscientists: the ability to correlate whisking

behavior with neural activity throughout the trigeminal system. Yet once enticed, researchers often find

themselves daunted by limitations of this promise, alternately marveling at and cursing the whiskers’ small

size and rapid motions. The core problem lies in our inability to directly measure tactile input signals from

a whisker without disrupting the signals themselves. Even if we could measure signals from a single

whisker, it would be challenging to measure the signals from all ~50 whiskers. And even if we could

measure the signals from all whiskers in the anesthetized animal, it would be challenging to measure all

signals during active whisking behavior in a complex environment. In this presentation, I describe our

laboratory’s efforts to develop simulation tools to help tackle these problems. We aim to enable

researchers to estimate the tactile-input signals generated when stimulating the whiskers of an

anesthetized animal, as well as the tactile-input signals during active whisking. I will show one example in

which we simulate tactile inputs for all whiskers in the array during a ~2 second trial of active whisking of

a freely-moving rat. I will also describe an initial model of the facial musculature that controls whisker

movements, and discuss the next steps required to close the loop between simulations of tactile input and

muscle output.

7. Short talk

Functional network analysis of cortical dynamics seen with fast wide-field voltage imaging in a

right/left cued decision lick task

Dieter Jaeger, Yunmiao Wang

Population imaging of cortex‐wide activities can shed light on the cortical dynamics and functional

networks of motor control. We employed the fast genetically expressed voltage sensor JEDI-1P with

wide-field imaging. JEDI-1P was expressed cortex-wide in the cell bodies of excitatory neurons via a

soma–targeting Cre-dependent JEDI-1P AAV vector injection into the ventricles of neonatal EMX-1 Cre

mice. Imaging was performed through a cleared intact skull in adult head-fixed mice at a frame rate of

200 Hz. We trained mice expressing JEDI-1P in a left/right lick decision making task with a delay to follow

fast voltage dynamics throughout this behavioral task. We find that the contralateral S1 and M1 cortex

show clear lick related activity. Using Independent Component Analysis (ICA), a number of different task-

related functional networks with distinct voltage dynamics could be identified. These networks each follow

a distinct temporal dynamic during the task and reveal multiplexed task responses in different cortical

networks related to sensory processing, motor preparation, and motor execution. Additionally, a

coherence analysis in different frequencies showed that these networks in some cases are coupled

through oscillatory activity.Funding: NIH BRAIN Initiative 1R01NS111470

8. Short talk

Motor cortex modulation of nociception and movement through corticobulbar circuits

Mercer Lindsay, Nicole1-3,5-7; Haziza, Simon1-3; Baer, Thomas3,4*; Schnitzer, Mark1-3,8*; & Grégory

Scherrer5-7,9* 1Department of Biology, 2CNC program, 3Department of Applied Physics, 4Stanford

Photonics Research Center, Stanford University, 5Department of Cell Biology and Physiology, 6UNC

Neuroscience Center, 7Department of Pharmacology, The University of North Carolina at Chapel Hill,

8Howard Hughes Medical Institute, 9New York Stem Cell Foundation--Robertson Investigator, *Co-

corresponding authors

Motor cortex stimulation (MCS) reduces pain experience in humans suffering from chronic pain; however,

how motor cortex activity drives antinociception is poorly understood. This direct influence of motor

circuitry on sensory experience provides an ideal system to dissect feedforward motor circuits' impact on

sensory afferent signaling. Using mice as a model system, we sought to dissect the underlying

mechanisms of MCS by detailing response properties of key neurons in the stimulation site (i.e., motor

cortex) and in a downstream circuit responsible for modulating orofacial nociception during and following

MCS. Using a mouse-sized transcranial magnetic stimulation (TMS) device we built, we performed TMS

of the vibrissa motor cortex in mice with an infraorbital nerve constriction, a model of trigeminal

neuropathic pain. We observed a dose-dependent decline in pain behaviors for one week. We then used

voltage imaging, chemogenetics, pharmacology, and Neuropixels electrophysiological probes to reveal

that MCS activates layer 5 pyramidal neurons, which recruit a downstream opioidergic circuit in the

medulla to induce antinociception through direct projections to the spinal trigeminal nucleus caudalis.

Altogether, our data show that motor cortex feedforward circuits tune nociceptive sensory signaling, RVM

neurons drive these sensory modifications, and RVM endogenous opioid signaling regulates both MCS-

induced antinociception and movement. Funding: K99DE031802 - 01A1, R01NS106301

9. Short talk

Stimulus novelty uncovers coding diversity in visual cortical circuits

Farzaneh Najafi, Marina Garrett, Peter Groblewski, Alex Piet, Doug Ollerenshaw, Iryna Yavorska, Stefan

Mihalas, Anton Arkhipov, Christof Koch, Shawn R Olsen; Affiliations: Allen Institute

The detection of novel stimuli is critical to learn and survive in a dynamic environment. Though novel

stimuli powerfully affect brain activity, their impact on specific cell types and circuits is not well

understood. Disinhibition is one candidate mechanism for novelty-induced enhancements in activity. Here

we characterize the impact of stimulus novelty on disinhibitory circuit components using longitudinal 2-

photon calcium imaging of Vip, Sst, and excitatory populations in the mouse visual cortex. Mice learn a

behavioral task with stimuli that become highly familiar, then are tested on both familiar and novel stimuli.

Mice consistently perform the task with novel stimuli, yet responses to stimulus presentations and

stimulus omissions are dramatically altered. Further, we find that novelty modifies coding of visual as well

as behavioral and task information. At the population level, the direction of these changes is consistent

with engagement of the Vip-Sst disinhibitory circuit. At the single cell level, we identify separate clusters

of Vip, Sst, and excitatory cells with unique patterns of novelty-induced coding changes. This study and

the accompanying open-access dataset reveals the impact of novelty on sensory and behavioral

representations in visual cortical circuits and establishes novelty as a key driver of cellular functional

diversity.

10. Short talk

Jaw muscle spindle afferents as multiplexed channels for sensing and guiding orofacial

movement

William Olson, Varun Chokshi, Jeong Jun Kim, Montrell Vass, Noah Cowan, Daniel O’Connor; Johns

Hopkins University Kavli Neuroscience Discovery Institute, Johns Hopkins University

Muscle spindle afferents (MSAs) are muscle stretch sensors that provide real-time feedback to the

nervous system about body position and movement. While classic models proposed that MSAs are

‘kinematic encoder’ sensory neurons, more recent models highlight the dynamic tuning of these neurons

and propose they instead serve task-specific motor control functions. Here, we record from MSAs

innervating the jaw musculature (located in the mesencephalic trigeminal nucleus, MEV) in behaving mice

to test these competing hypotheses. In our task, head fixed mice lick a moving ‘port’ through an arc of

seven locations surrounding the mouse’s face to receive a water reward. MSA ensemble activity is

complex, evolving over single lick cycles as well as over entire licking sequences. While a large

component of MSA ensemble activity is correlated with jaw kinematics, major components of the activity

show clear decoupling from the kinematics. We find that (1) encoding of kinematics varies across the

MSA ensemble, with a small fraction of single MSAs showing strong encoding in a manner consistent

with classic models, (2) MSAs innervating jaw synergist muscles show distinct activity based on muscle of

innervation, with MSAs from one muscle (temporalis) showing the strongest kinematic encoding, and (3)

comparison of activity during active licking vs. passive movement under anesthesia reveals that MSA

kinematic tuning is actively set by the awake animal. Funding: NIH F32MH120873, Kavli Foundation

11. Short talk

Sparse and distributed cortical populations mediate sensorimotor integration

Pancholi, Ravi; Sun-Yan, Andrew; Laughton, Maya; Peron, Simon

Touch information is central to sensorimotor integration, yet little is known about how cortical touch and

movement representations interact. Touch- and movement-related activity is present in both

somatosensory and motor cortices, making both candidate sites for touch-motor interactions. We studied

touch-motor interactions in layer 2/3 of the primary vibrissal somatosensory and motor cortices of

behaving mice. Volumetric two-photon calcium imaging revealed robust responses to whisker touch,

whisking, and licking in both areas. Touch activity was dominated by a sparse population of broadly tuned

neurons responsive to multiple whiskers that exhibited longitudinal stability and disproportionately

influenced interareal communication. Movement representations were similarly dominated by sparse,

stable, reciprocally projecting populations. In both areas, many broadly tuned touch cells also produced

robust licking and/or whisking responses. These touch-licking and touch-whisking neurons showed

distinct dynamics suggestive of specific roles in shaping movement. Cortical touch-motor interactions are

thus mediated by specialized populations of highly responsive, broadly tuned neurons.

12. Short talk

Input- and target-specific synaptic plasticity in neocortical layer 1 during sensory learning

Ajit Ray, Joseph C Christian, Alison L Barth

Changes in higher-order thalamic inputs to cortical neurons are implicated in learning. These inputs

densely innervate layer 1 (L1), where excitatory synaptic changes in pyramidal neurons (Pyr) have been

demonstrated by anatomical and electrophysiological methods. However, L1 also houses dendrites from

several inhibitory populations including VIP interneurons, which are a critical circuit node controlling

computation across the cortical column. Here, we tested whether VIP dendrites in L1 also show input-

specific synaptic changes during learning. Using a high-throughput genetically-encoded fluorescence-

based synapse analysis pipeline that we previously used to show thalamocortical synaptic changes on L5

Pyr in a whisker-dependent learning task, we examined structural changes in thalamic (POm) synapses

on VIP interneurons in barrel cortex. Sensory association drove a rapid increase in the overall number

and size of excitatory synapses on VIP dendrites in L1, but not in their L2 dendrites. POm-specific

synapses showed a similar increase in size as non-thalamic synapses. Thus, learning triggers broad

synaptic changes across multiple long-range inputs to VIP neurons and are not restricted to thalamic

inputs. In contrast, we observed POm-specific plasticity in L1 dendrites of L2/3 Pyr in the same task. This

suggests that VIP neuron activity in the sensory cortex may sharply increase during early learning due to

stronger feedback from other cortical areas and higher-order thalamus.

13. Short talk

Responses to cortical stimulation reveal thalamocortical state-dependent features in mice and

humans

Simone Russo, Leslie Claar, Lydia Marks, Giulia Furregoni, Flavia Maria Zauli, Gabriel Hassan, Michela

Solbiati, Simone Sarasso, Mario Rosanova, Ivana Sartori, Andrea Pigorini, Christof Koch, Marcello

Massimini, Irene Rembado

Stimulating neocortex using a brief pulse is used in several experimental and clinical preparations. The

extent to which cortico-thalamo-cortical or cortico-cortical feedback circuits contribute to the late

responses is unclear. Stimulating secondary motor cortices with a single pulse while recording from head-

fixed mice using EEG and Neuropixels probes leads to a stereotyped tri-phasic EEG response that is

modulated by the state of the animal, such that movement leads to a smaller late response compared to

resting. We demonstrate that when optogenetically inhibiting the thalamus at different points in time, the

late EEG signal component likewise shifts in time, correlated to the degree of bursting and synchronicity

of thalamic neurons. Both factors can be modulated by movement, causing the observed modulation of

the EEG response. Intracranial stereo-encephalographic recordings of electrically evoked responses in

epileptic patients and EEG responses to transcranial magnetic stimulation in healthy subjects revealed a

similar modulation of the late responses with movement, here of the hand. These results identify a state-

dependent engagement of the cortico-thalamo-cortical loop at the origin of EEG responses to cortical

stimulation which is preserved across species and stimulation modalities.

14. Short talk

In-Vivo Recording of Optogenetically Identified Rapidly-Adapting Whisker Neurons

P. M. Thompson, Jun Takatoh, Seonmi Choi, Andrew Harahill, and Fan Wang. McGovern Institute for

Brain Research. Massachusetts Institute of Technology

The sensation of touch is constructed from multiple types of unique sensory receptors acting in parallel.

The functions of morphologically distinct mechanoreceptors in the whiskers during active touch remain

poorly understood with the exception of Merkel ending neurons. We describe how the genes NetrinG1

and Chondrolectin are selectively expressed in two specific types of touch receptors in the mouse whisker

follicle: club-like and lanceolate endings, respectively. We optogenetically-identified primary trigeminal

afferents with these endings in vivo and recorded their activities during behavior. We found that both

ending types were rapidly adapting to touch. While small number of neurons displayed an increased

spiking probability with the force of contact, most of these neurons only fired transiently at the onset of

contact during periods of relatively low whisker forces. These neurons were not refractory, however,

because the same units could be driven to fire at high rates in response to high-frequency stimulation.

Our results suggest that these neurons are ideally suited to detect the precise timing of contact, and that

the rapid adaptation in these neurons may be the result of receptive fields for high-frequency components

of mechanical stimuli, rather than being due to intrinsic neuronal accommodation.Funding: NS 077986

15. Short talk

Prrxl1 knockout – a non-invasive model of chronic pain

Ezekiel Willerson(4,2), Leah Kramer(1,2), Eliana Eichler(2), Jacob Zar(1,2), Kayla Wilamowsky(2),

Giuseppe Cataldo(1,2), Joshua C. Brumberg(1,2,3,4) 1. Neuroscience Major, Queens College, CUNY 2.

Department of Psychology, Queens College, CUNY 3. Neuroscience Subprogram, Biology PhD Program

in Biology, The Graduate Center, CUNY 4. Behavioral and Cognitive Neuroscience Training Area, PhD

Program in Psychology, The Graduate Center, CUNY

Prrxl1, a paired homeodomain transcription factor, is indispensable for development of patterning in the

trigeminal lemniscal pathway. In Prrxl1 knockout (KO) animals, somatotopic patterning is intact in the

spinal trigeminal nucleus (SpV) yet absent along the entire trigeminal lemniscal pathway from principal

sensory nucleus (PrV) to cortex. The PrV has been implicated in a variety of active sensing behaviors,

while the SpV is associated with transmission of noxious input. Prrxl1 KO animals were previously known

to be hypo-algesic to the body, yet here we show they are hyper-algesic in the orofacial region, as seen

by facial withdrawal (von Frey) and excessive facial grooming. Grooming was confirmed as pain behavior

by injecting histamine (which produces itch) and capsaicin (pain) into the whisker pad of wildtype mice.

Only capsaicin resulted in the stereotyped wiping seen in Prrxl1 KOs. Mice treated with capsaicin also

scored higher on the facial grimace scale. Next, we analyzed anatomical correlates of these behaviors.

Perineuronal nets (PNNs), extracellular matrix structures integral for synapse stability, are reportedly

degraded in chronic pain. When stained, we found that the PrV of Prrxl1s exhibit reduced PNNs.

Microglia activation has also been implicated in chronic pain. Upon staining and reconstruction, we found

Prrxl1 PrV microglial took on an “activated” phenotype. In sum, knockout of Prrxl1 results in a chronic

model of orofacial pain.Funding source: NS126987

16. Short talk

Organizing principles of cortical interneurons

F. Yáñez

, F. Messore

, G. Qi

, D. Feldmeyer

, B. Sakmann

, M. Oberlaender

1. MPI for Neurobiol. of Behav., Bonn, Germany

2. Univ. of Oxford, Oxford, UK

3. Res. Ctr. Juelich, Juelich, Germany

4. MPI for Biol. Intelligence, Martinsried, Germany

Cortical inhibitory neurons (INs) are diverse, including attributes such as morphology and intrinsic

physiology. Here we systematically assess the degree and character of the variability of these properties

across the entire cortical depth of rat S1. We analyzed 306 morphological reconstructions and current

injection responses, which were representative of the distribution of INs per depth. Each IN was

comprehensively characterized by morphoelectric features. We assigned INs into 13 e-, 20 m-, and 25

me-types using unsupervised multimodal clustering. These classes are consistent with previous reports in

mouse V1. Soma depth is the primary determinant for defining me-types. The spatial extent of both axons

and dendrites increases as a function of cortical depth, regardless of me-type. The spike-frequency also

increases with cortical depth, whereas the spike-frequency adaptation remains unaffected by it. A simple

depth-independent relationship, where the spike-frequency exceeds the spike-frequency adaptation,

delineates a class of INs resembling the distribution of Pvalb-INs, including small to large basket,

chandelier, and translaminar cells. The assignment based on depth-independent relationships shows a

strong correspondence with the distributions of Pvalb-, Sst-, and Vip-expressing INs in both rat S1 and

mouse V1. Thus, simple organizing principles may largely account for the diversity of INs through the

adjustment of their morphoelectric properties in cortex. Funding: DFG

17. Short talk

Ultra-Flexible tentacle electrodes for months-long tracking of assemblies of single units

simultaneously from many brain areas.

Tansel Baran Yasar, Peter Gombkoto, Eminhan Ozil, Alexei Vyssotski, Angeliki Vavladeli, Simon

Steffens, Orhun Caner, Eren, Wolfger von der Behrens, Mehmet Fatih Yanik

While the number of channels in the state-of-the-art in vivo electrophysiology systems is rapidly

increasing, these technologies do not cover simultaneously more than a few brain areas equally well and

the mismatch between these probes and the brain causes significant tissue damage, limiting the longevity

and quality of recordings. To address these challenges, we developed ultra-flexible intracortical

microelectrode arrays - Ultra-Flexible Tentacle Electrodes (UFTE). Unlike existing flexible electrode

technologies, we can rapidly adapt the spatial distribution of UFTE electrodes and deliver them

simultaneously into several brain areas at arbitrary locations with no depth limitations. Each channel is

mechanically independent in these arrays, ensuring optimal compatibility with brain tissue.

Immunostaining of the brain slices revealed no detectable long-term reaction/damage in the brain tissue

surrounding the UFTEs. Our UFTE recordings achieve 2-3x higher signal-to-noise ratio (SNR) with

respect to the state of the art. Our design allows packing hundreds of channels into each brain area with

a compact footprint. We were able to perform stable recordings of hundreds of single-units from each

area and track neuronal assemblies for many months simultaneously from the medial prefrontal cortex

(mPFC), retrosplenial cortex (RSC), dorsal hippocampus (dHPC), intermediate hippocampus (iHPC), and

orbitofrontal cortex (OFC) in freely moving rats using UFTEs. We also developed a second gen

18. Short talk

Connectomic analysis of astrocyte-synapse interactions in mouse barrel cortex

Yagmur Yener, Alessandro Motta, Moritz Helmstaedter

*Max-Planck Institute for Brain Research

Astrocytes express sensors for neurotransmitters released by synapses and are thought to release

chemicals associated with neuromodulation. Because of their complex morphology, each astrocyte can

contact thousands of synapses in its cellular territory. A systematic mapping of the glia-connectome

interaction in cortex is still lacking. Here, we developed classifiers for voxel-wise classification of

astrocytes using convolutional neural networks. This enabled us to quantify the nature of the contact

between synaptic elements and the peri-synaptic glial processes that partially wrap around synapses.

Using a previously published 3D EM dataset from mouse barrel cortex (Motta et al., 2019; n=200,507

synapses), we systematically analyzed the spatial relation between astrocytes and synapses. We

observed that there is a strong dependence of the fraction of astrocyte processes at the periphery of

dendritic spine synapses on synapse size. Importantly, this effect is absent in other synapse types and

does not occur for random non-synaptic interfaces. We furthermore found glial coverage to depend on

connectomic types, such as thalamocortical axons, smooth dendrites, inhibitory synapses, and

investigated its properties as a possible indicator of recent synaptic activity and synaptic plasticity.

Together, our data indicate the relevance of astrocytic coverage for synapse stability, and demonstrate a

surprising level of specificity for particular synaptic types.

19. Short talk

What does motor cortex tell sensory cortex?

Edward Zagha, Department of Psychology, University of California Riverside

Whisker motor cortex sends robust mono-synaptic and poly-synaptic projections to whisker sensory

cortex. These pathways have long been considered important in the context of active sensing and

corollary discharge. In this talk, I will develop the argument that these motor cortex to sensory cortex

pathways are well positioned to contribute to non-motor, cognitive processes. To support this argument, I

will present data from a recent study in our lab demonstrating a specific role for these pathways for

sensory discrimination in a passive sensing task: suppressing the propagation of non-target stimuli into

target-aligned response fields. By modulating sensory cortex excitability and receptive field properties,

motor cortex can modulate top-down context for motor and non-motor processes.Supported by:

NIH/NINDS R01NS107599

20. Short talk (Sponsor talk)

FemtoFiber ultra Lasers for Neuroscience

Joseph Mastron, TOPTICA Photonics, Inc.

TOPTICA is excited to introduce our FemtoFiber ultra lasers, tailored for applications in Neuroscience.

Our stable, low-maintenance laser systems at 780 nm, 920 nm, and 1050 nm offer exceptional pulse

quality comparable to Ti:Sapph lasers while maintaining the advantages of a fiber laser. With our

innovative design, these laser systems can be optically synchronized for multi-color experiments. In this

talk, I will discuss the underlying technologies that enable these capabilities, and briefly highlight some

applications.

POSTERS

Coding of sensorimotor variables in dysgranular vibrissal somatosensory cortices

Alisha Ahmed; Andy Garcia; Maya Laughton; Andrew Sun-Yan; Simon Peron

In the mouse whisker system, somatosensory thalamus outputs to primary and secondary vibrissal

somatosensory cortices (vS1 and vS2), as well as the dysgranular zone (Killackey et al. 1983), a strip of

cortex near the vibrissal and forepaw representations. Despite extensive studies of vS1 and vS2, the

dysgranular zone’s response to whisker touch remains poorly understood. Vibrissal S1 sends outputs to

three areas within the dysgranular zone: the anteromedial (AM), centromedial (CM), and posteromedial

(PM) areas (Yamashita et al. 2018). These areas may thus contribute to processing whisker touch. We

recorded activity in vS1, vS2, AM, CM, and PM using volumetric two-photon calcium imaging in

transgenic mice expressing GCaMP6s in cortical excitatory neurons. We trained mice trimmed to two or

three whiskers to actively palpate a pole with their whiskers, reporting touch of the pole with licks to one

of two lickports and no touch with licks to the other. We compared touch, whisking, and licking activity

across all areas. AM, CM, and vS2 had a larger fraction of touch neurons that were responsive to multiple

whiskers than vS1. We also found a higher fraction of lick responsive neurons in CM and a lower fraction

of whisking neurons in AM and CM than in vS1. These findings suggest that dysgranular areas may be

crucial for integrating touch information across multiple whiskers, likely combining touch information with

specific forms of motor information, such as licking and whisking.

Investigating the role of interneuron populations in whisking behavior through chemogenetics

Julien Guy, Jochen F. Staiger

UMG Institute for Neuroanatomy

Because of the precisely defined somatotopic map, the barrel cortex (wS1) is a favorable model for the

study of microcircuits and investigation of the roles of neuronal subtypes in the processing of sensory

information. Physiological mechanisms of wS1 of whisking behavior have mostly been investigated on

head-fixed animals to gain better control of stimuli and precise measurement. However, there is a limited

number of studies investigating whisker-based perceptual detection during natural behavioral conditions.

Also, the behavioral relevance of parvalbumin (PV) and vasoactive intestinal polypeptide (VIP) expressing

GABAergic neurons remains unclear. We aimed to define the contributions of PV and VIP expressing

populations within the wS1 towards texture discrimination on freely moving mice using chemogenetic

manipulation. To this extent, we have established a textured T-maze task, which is an operant

conditioning protocol for whisker-based tactile discrimination and to measure the perceptual detection

threshold of freely moving mice. In this protocol, food-restricted animals were trained for a 2-choice

reward task in a T-maze. Textured T-maze come out as a reliable measure for the discriminiation capacity

of mice. Furthermore, it can be safely combined with chemogenetic manipulation since neither intracranial

surgery nor IP injection of C21 impaired mice’s performance.

Cortical circuits for goal-directed cross-modal transfer learning

Maëlle Guyoton, Giulio Matteucci, Charlie G. Foucher, & Sami El-Boustani

University of Geneva

In an environment full of complex multisensory stimuli, flexible and effective behaviors rely on our ability

to transfer learned associations across sensory modalities. Here we explored the intertwined cortical

representations of visual and whisker tactile sensations in mice and their role in cross-modal transfer

learning. Mice trained to discriminate stimulations of two different whiskers seamlessly switched to the

discrimination of two visual cues only when reward contingencies were spatially congruent across

modalities. Using multi-scale calcium imaging over the dorsal cortex, we identified two distinct associative

domains within the ventral and dorsal streams displaying visuo-tactile integration. We observed

multimodal spatial congruency in visuo-tactile areas, both functionally and anatomically, for feedforward

and feedback projections with primary sensory regions. Single-cell responses in these domains were

tuned to congruent visuo-tactile stimuli. Suppressing synaptic transmission specifically in the dorsal

stream impaired transfer learning. Our results delineate the pivotal cortical pathway necessary for visuo-

tactile multisensory integration and goal-directed cross-modal transfer learning.

Modeling sensory perception with neurobiologically detailed artificial neural networks

Matthew Keaton; Rieke Fruengel; Marcel Oberlaender

Max Planck Institute for Neurobiology of Behavior

Unraveling cellular and circuit mechanisms that underlie perception is extremely challenging, because

even the simplest sensory stimulus activates hundreds of thousands of neurons distributed throughout

the entire brain. Yet, the brain is able to classify this noisy input across the hierarchy of cortical

processing stages, triggering flexible and nuanced behaviors - a hallmark of higher cognition. How the

brain accomplishes such robust perception is unclear. Here we introduce a novel computational modeling

approach that allows translating cellular and circuit mechanisms that represent neural substrates of

perception into design principles for artificial neural networks (ANNs). For this purpose, we motivate the

network architecture of ANNs with empirical anatomical data from both dense and sparse reconstructions

of local and long-range connectivity in the thalamocortical whisker system of the rat. Moreover, we inform

the activation functions of nodes in the ANNs with empirical physiological data to capture both the

perisomatic and nonlinear dendritic physiology of cortical pyramidal neurons. We provide first evidence

that our approach leads to an improved performance and ability of such ANNs to generalize across tasks,

and less reliance on large training datasets. These results indicate that neurobiologically detailed ANNs

could facilitate dissecting the neural basis of perception, and showcase how higher brain functions

emerge from their neurobiological implementations.

A combinatorial code for learned motor actions

Jae-Hyun Kim, Nuo Li

Department of Neuroscience, Baylor College of Medicine, Houston, TX

Motor cortex neurons exhibit preparatory activity that instructs specific future movements. It remains

unclear whether activity producing the same movement is stably maintained oveer time and across

different sensorimotor contexts. To explore these questions, we used automated home-cage training and

in-cage optogenetics to establish a cortex-dependent continual learning paradigm. Mice learned to

perform directional licking in different tasks for up to 10 months. We combined this paradigm with chronic

2-photon imaging of anterior lateral motor cortex (ALM) to track the representation of learned actions

across extended time and over continual learning. Within the same task context, the pattern of activity

around movement was stably retained for 2 months with little representational drift. As mice learned to

make the same licking actions under new task contexts, new preparatory states emerged, while activity

related to sensory stimulus and movement execution remained surprisingly stable. Yet, the old

preparatory states are not lost, re-learning to make the same actions under the previous context re-

activated the previous preparatory states, even 3 months later. These data show that learned motor

actions are stored in multiple representations in conjunction with its sensorimotor context, which we call a

combinatorial code. These results suggest motor cortex exhibit high-capacity storage for context-specific

motor memories. Funding: R01NS131229, R01NS112312

Alterations in homeostatic plasticity in Fmr1 KO mice following unilateral whisker deprivation

Lakhani, A & Wenner, P.

Emory University

Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability. It is caused by a

loss-of-function of the FMR1 gene on the X chromosome, resulting in the absence of FMRP. Altered

cortical activity is an underlying pathology of FXS that is associated with sensory hypersensitivity and

epileptic vulnerability. Previous work suggests that homeostatic mechanisms are impaired in FXS models.

Unilateral whisker deprivation has been shown to trigger homeostatic responses in the barrel cortex. This

has been expressed as an increase in whisker-evoked responses in L4 and L2/3 regular spiking (RS)

excitatory neurons. In order to determine if and how homeostatic plasticity was altered in the Fmr1 KO

mouse model of FXS, we trimmed whiskers every other day from postnatal day 14-21 (PD 14-21).

Whiskers were deflected using a 3x3 array of piezoelectric actuators to stimulate the principal/most

responsive whisker and surrounding whiskers at multiple velocities. Spiking activity was recorded using a

64-channel probe in the somatosensory cortex of lightly anesthetized mice. Preliminary results suggested

that spiking in L5/6 RS neurons in control mice was reduced in the KO compared to WT littermates. In

addition, following 7 days of whisker deprivation, the sensitivity to whisker stimulation was very different in

the whisker-deprived KO compared to whisker-deprived WT littermates.

Behavioral role of individual mouse vibrissal somatosensory cortex barrels in discriminating

between touch by distinct whiskers

Laughton Maya, Sun-Yan Andrew, Ryan Lauren, Peron Simon

NYU

As nocturnal mammals, mice use tactile sensation from facial whiskers to probe their surroundings. The

mouse primary vibrissal somatosensory cortex is partitioned into a topographic map of well-defined

columns (‘barrels’) receiving input from a single primary whisker. Prior loss-of-function studies established

columnar scale lesions of the barrel of interest, in a single whisker behavior task, degrade tactile

discrimination but not object detection. In two whisker behavior tasks, mice discriminate between stimuli

at distinct locations of the sensory epithelium. It is unclear if this is more like a detection task with distinct

sites or a discrimination task. In mice with cranial windows, doing a two whisker behavior task, we

lesioned barrels using a femtosecond laser. Dual barrel lesions transiently impacted performance of mice

using adjacent whiskers, without disrupting vibrissal kinematics. Single barrel lesions also transiently

impacted performance of mice using adjacent whiskers. We analyzed if performance decline was whisker

specific or the same across both whiskers. To ensure effects were not a result of degrading neighboring

tissue, we performed single barrel lesions in mice using more distal whiskers to solve the task. Post-

lesion, the resulting decline in this behavior was smaller and mice tended to recover within the same

session rather than across multiple sessions. Thus, tactile information is being integrated across distinct

locations of the sensory epithelium.

Poster

Astrocytes modulate a critical window of microglia-mediated synapse remodeling in the barrel

cortex

Yi-Han Lee#, Travis Faust#, Ciara O’Connor, Margaret Boyle, Dorothy Schafer

Department of Neurobiology, UMass Chan Medical School, Worcester, MA, USA

Neuroplasticity is required for learning and adaptation to the ever-changing environment. During early

development, changes in neuronal activity lead to removal of less active synapses. Microglia and

astrocytes participate in the activity-dependent synapse remodeling by engulfing the synapse from less

active neurons. However, the clearance of synapses is less robust after specific “critical windows” of

development. How these two glial cells precisely clear up specific synapses and regulate the closure of

the critical window remains an open question. In mice, the activity-dependent synaptic remodeling can be

studied by whisker manipulation. Decreased sensory input from the whiskers results in pruning of

thalamocortical presynaptic terminals in the whisker barrel region of the somatosensory cortex. Previously

in our study, we demonstrate that microglia are responsible for the removal of thalamocortical synapses

in somatosensory cortex upon whisker lesioning. Yet astrocytes do not engulf the synapses but decrease

their contact with the synapses in advance of synaptic pruning when whiskers are lesioned at early

postnatal stage. Interestingly, when whisker lesioning occurs at later developmental stage, astrocytes no

longer retract their processes and synaptic pruning is dramatically reduced. We hypothesize that

astrocyte-synapse contacts might be a key modulator that determines the closure of developmental

critical window for activity-dependent synaptic pruning. 2R01MH113743

Diverse, state-dependent coupling between cortical activity patterns and the activity of

hippocampal and thalamic neuron

Chris Lewis

, Adrian Hoffmann

1,2

, Stewart Berry

1,2

, Linus Meienberg

1,2

, T. Baran Yasar

2,3

, M. Fatih

Yanik

2,3

, Fritjof Helmchen

1,2

1)Brain Research Institute, University of Zurich

2)Neuroscience Center Zurich, University of Zurich and ETH Zurich

3)Institute for Neuroinformatics, University of Zurich and ETH Zurich

Adaptive behavior is enabled by the dynamic coordination of diverse signals across spatial and temporal

scales. We combined extracellular recording of subcortical activity using flexible multi-electrode arrays

with wide-field or 2-photon calcium imaging of cortex to reveal aspects of large-scale dynamics invisible to

standard, single-modality approaches. We investigated the relationship between fast dynamics recorded

with chronically implanted multi-electrode arrays with simultaneously acquired cortical activity patterns

monitored via the expression of GCaMP6f in transgenic animals. We find diverse state-dependent

patterns of coupling between concurrently acquired hippocampal and thalamic spiking activity and

calcium dynamics across dorsal cortex. The repertoire of activity patterns in single hippocampal and

thalamic neurons is stable across days. However, within a recording session the activity of subcortical

neurons exhibits distinct patterns of brain-wide coupling dependent on changes in behavioral state, as

well as ongoing, intrinsic variations in brain state. The topographical patterns of coupling between the

activity of subcortical neurons and cortex activation are anatomically specific and fluctuate over long time

scales (10s of seconds to minutes) in a frequency-dependent manner. We believe that these diverse,

dynamic activity patterns reflect shifts in functional connectivity that underlie distinct modes of brain-wide

coordination and communication.

Connectomic traces of Hebbian plasticity in mouse and human cortex

S. LOOMBA1, A. KHALIFA1, A. MOTTA1, J. GEMPT2, H.-S. MEYER2, M. HELMSTAEDTER1; 1Max

Planck Inst. For Brain Res., Frankfurt Am Main, Germany; 2Universitätsklinikums Hamburg-Eppendorf,

Hamburg, Germany

Synaptic plasticity plays a crucial role in the organization of neuronal circuits and refinement of their

connectivity during learning and development. Our current knowledge of the mechanisms that underlie

synaptic plasticity is primarily based on laboratory animal models, in particular rodents. Recent

advancements in the accessibility of human tissue have made it feasible to perform physiological studies

on human tissue slices, enabling the investigation of synaptic plasticity in human. However, how the

principles of synaptic plasticity apply to the human brain remains poorly understood. In this study, we

employed 3-dimensional electron microscopy of human, non-human primate and mouse supragranular

cortical samples to identify the structural effects of Hebbian plasticity in connectomic data. We quantified

the rate of excitatory spines undergoing synaptic weight adaptation consistent with Hebbian learning. The

human cortex shows abundance of spines with large synaptic weights, a feature absent in both the

mouse and non-human primate cortex. Additionally, the synaptic weights consistent with Hebbian

plasticity show stronger correlations in human cortex compared to the mouse and non-human primate

cortex. These results suggest that the Hebbian plasticity may be quantitatively different in the human

cortex from other species. Together this opens new avenues for future exploration into the functional

significance and influence of these distinct plasticity characteristics.