=2022=
 
=2022=
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==June==
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Date: 03 June 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Jackie Giovanniello'''
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<h4>Title: “ Opposing amygdala-striatal pathways enable chronic stress to hasten habit formation” </h4>
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<u>Abstract:</u> A balance in behavioral control strategies between goal-directed actions and habits allows for adaptive and efficient decision making. However, chronic stress tips this balance toward habits, which can become maladaptive. Over-reliance on habits is an endophenotype of a number of psychiatric conditions which are also exacerbated by stress. Despite this, the neural mechanisms that allow stress to promote habit formation remain unclear. We believe direct projections from the basolateral (BLA) and central (CeA) subregions of the amygdala to the dorsomedial striatum (DMS) are well-positioned to differentially regulate the ability of stress to influence behavioral control. To test this, we developed a task to model chronic stress-induced acceleration of instrumental habits in mice and couple it with in vivo pathway-specific neural activity monitoring and chemogenetic manipulation techniques. These data establish a function for both the BLA-DMS and the newly identified CeA-DMS pathways in flexible and inflexible behavior.  Our findings have important implications for psychiatric conditions exacerbated by stress and characterized by maladaptive habits, such as obsessive-compulsive disorder and substance use disorder.
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<u>Relevant Papers:</u>  https://pubmed.ncbi.nlm.nih.gov/29571524/
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https://pubmed.ncbi.nlm.nih.gov/19644122/
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==May==
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Date: 27 May 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Felix Schweizer'''
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<h4>Title: “  Does structure matter and are synapses real?” </h4>
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<u>Abstract:</u> Dopaminergic (DA) neurons exert profound influences on behavior including addiction. However, how DA axons communicate with target neurons and how those communications change with drug exposure remains poorly understood. We leverage cell type-specific labeling with large volume serial electron microscopy to detail DA connections in the nucleus accumbens (NAc) of the mouse (Mus musculus) before and after exposure to cocaine. We find that individual DA axons contain different varicosity types based on their vesicle contents. Spatially ordering along individual axons further suggests that varicosity types are non-randomly organized. DA axon varicosities rarely make specific synapses (<2%, 6/410), but instead are more likely to form spinule-like structures (15%, 61/410) with neighboring neurons. Days after a brief exposure to cocaine, DA axons were extensively branched relative to controls, formed blind-ended 'bulbs' filled with mitochondria, and were surrounded by elaborated glia. Finally, mitochondrial lengths increased by ~2.2 times relative to control only in DA axons and NAc spiny dendrites after cocaine exposure. We conclude that DA axonal transmission is unlikely to be mediated via classical synapses in the NAc and that the major locus of anatomical plasticity of DA circuits after exposure to cocaine are large-scale axonal re-arrangements with correlated changes in mitochondria.
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<u>Relevant Papers:</u>  https://pubmed.ncbi.nlm.nih.gov/34965204/
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Date: 13 May 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Douglas Vormstein-Schneider'''
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<h4>Title: “  Geometry of sequence working memory in macaque prefrontal cortex ” </h4>
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<u>Abstract:</u> How the brain stores a sequence in memory remains largely unknown. We investigated the neural code underlying sequence working memory using two-photon calcium imaging to record thousands of neurons in the prefrontal cortex of macaque monkeys memorizing and then reproducing a sequence of locations after a delay. We discovered a regular geometrical organization: The high-dimensional neural state space during the delay could be decomposed into a sum of low-dimensional subspaces, each storing the spatial location at a given ordinal rank, which could be generalized to novel sequences and explain monkey behavior. The rank subspaces were distributed across large overlapping neural groups, and the integration of ordinal and spatial information occurred at the collective level rather than within single neurons. Thus, a simple representational geometry underlies sequence working memory.
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<u>Relevant Papers:</u>  https://www.science.org/doi/10.1126/science.abm0204
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Date: 06 May 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Ana Sias'''
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<h4>Title: “ Dopamine projections to the basolateral amygdala mediate the encoding of outcome-specific reward memories.  ” </h4>
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<u>Abstract:</u> To make adaptive decisions, we often use cues in our environment to retrieve detailed memories of associated rewards and choose accordingly. Emerging evidence suggests ventral tegmental area (VTA) dopamine might be involved in learning the relationship between a cue and the identifying features of the specific reward it predicts (i.e., model-based learning). But the projections through which dopamine does this are unknown. Using optical imaging and manipulation methods coupled with the outcome-specific Pavlovian-to-instrumental transfer task, we investigate the contribution of dopaminergic projections to the basolateral amygdala in forming these detailed associative reward memories.
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<u>Relevant Papers:</u> https://elifesciences.org/articles/68617
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==April==
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Date: 29 April 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Katsushi Arisaka'''
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<h4>Title: “ Grand Unified Theory of Mind and Brain: Space-Time Approach to Visual Perception and Memory of 3D Space.  ” </h4>
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<u>Abstract:</u> Animals have a remarkable ability to perceive, navigate, and memorize allocentric 3D space, primarily based on egocentric 2D visual stimulation. How can we effortlessly reconstruct and maintain a stable representation of allocentric space despite constant motion of the eyes, head, and body, which results in a seemingly chaotic dynamic visual input?
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According to our Grand Unified Theory, external allocentric space is holographically reconstructed in the frequency-time domain by multi-frequency brainwaves. 3D visual perception is constructed by alpha waves, despite the constant saccades and head motions that continuously change egocentric visual input. Likewise, 3D navigational-space is constructed by theta waves, while maintaining allocentric place fields. Following a navigation event, an episodic memory is encoded as an engram using the principles of a new concept we call the Holographic Ring Attractor Lattice (HAL).
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In my talk, I will present the concept of Neural Holographic Tomography (NHT), and apply it to Hippocampus-based navigation, learning, and memory.
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Date: 22 April 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Chris Gabriel'''
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<h4>Title: “ BehaviorDEPOT: a simple, flexible tool for automated behavioral classification based on markerless pose tracking. ” </h4>
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<u>Abstract:</u> Quantitative descriptions of animal behavior are essential to study the neural substrates of cognitive and emotional processes. Analyses of naturalistic behaviors are often performed by hand or with expensive, inflexible commercial software. Recently, machine learning methods for markerless pose estimation enabled automated tracking of freely moving animals, even in labs with limited coding expertise. However, classifying specific behaviors based on pose data requires additional computational analyses and remains a significant challenge for many groups. We developed BehaviorDEPOT (DEcoding behavior based on POsitional Tracking), a simple, flexible software program that can classify behavior from video time series and also analyze the results of experimental assays. BehaviorDEPOT calculates kinematic and postural statistics from keypoint tracking data and classifies behavior algorithmically. It requires no programming experience and is applicable to a wide range of behaviors and experimental designs. We provide several hard-coded classifiers. Our freezing classifier achieves above 90% accuracy in videos of mice and rats, including those wearing tethered head-mounts. BehaviorDEPOT also helps researchers develop their own classifiers and incorporate them into the software’s graphical interface. Behavioral data is stored framewise for easy alignment with neural data. We demonstrate the immediate utility and flexibility of BehaviorDEPOT using popular assays including fear conditioning, decision making in a T-maze, open field, elevated plus maze, and novel object exploration.
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<u>Relevant Papers:</u>  https://www.biorxiv.org/content/10.1101/2021.06.20.449150v2
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Date: 15 April 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Austin Coley'''
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<h4>Title: “ Investigating mPFC valence-specific neuronal populations during anhedonia ” </h4>
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<u>Abstract:</u> Anhedonia is the inability to experience pleasure and is a core symptom in neuropsychiatric disorders, such as major depressive disorder (MDD) and schizophrenia (SCZ). The prefrontal cortex (PFC) is implicated in anhedonia due to imbalances in dopamine (DA) concentrations. Dopamine in the PFC has been implicated in processing negatively valence stimuli (Vander Weele et al., 2018a), and can produce avoidance (Gunaydin et al., 2014), but is suggested to be a major component in reward prediction (Schultz et al., 1997), indicating that DA modulates mPFC encoding of both positive and negative valence in behavior. However, it remains unknown how DA modulates mPFC valence-specific neurons during anhedonia. We hypothesize that mPFC valence-specific neuronal populations are differentially regulated via DA transmission and are altered during stress-induced anhedonia. To study this, we implemented depression induced protocols such as learned helplessness (LH) and chronic mild stress (CMS) paradigms to induce anhedonia within mice. Using in vivo 2-photon Ca2+ imaging and behavioral phenotypic classification techniques, we examined mPFC-valence specific neuronal population activity within anhedonic mice. These findings will provide a greater understanding of the activity and dynamics in mPFC valence-specific neuronal populations during anhedonia.
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Date: 08 April 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Alessandro Luchetti'''
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<h4>Title: “ Compartment-specific tuning of dendritic feature selectivity by intracellular Ca2+ release. ” </h4>
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<u>Abstract:</u> What is the role of intracellular calcium release from the endoplasmatic reticulum in neuronal signal processing and in the formation of hippocampal place fields? O’Hare et al. used single-cell viral delivery techniques, optogenetics, and in vivo calcium imaging to simultaneously record dendritic and somatic activity of area CA1 pyramidal neurons. Increasing intracellular calcium release increased spatial tuning in apical and, to a lesser extent, in basal CA1 pyramidal cell dendrites. This activity in turn changed place cell responses during learning and memory storage. Intracellular calcium release in concert with circuit-level anatomical features thus shapes and promotes somatic feature selectivity in vivo.
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<u>Relevant Papers:</u> https://www.science.org/doi/10.1126/science.abm1670
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Date: 01 April 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Charltien Long'''
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<h4>Title: “ What Does Dopamine Do? ” </h4>
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<u>Abstract:</u> Striatal function is strongly regulated by midbrain dopaminergic (DA) neuron input. Previous work suggests that, in addition to regulating synaptic plasticity, DA neurons can rapidly regulate striatal spiking activity on short (subsecond to second) timescales. Such rapid modulatory effects are believed to be important for controlling imminent or ongoing behaviors such as responses to rewards or initiation of movement. Here we focus on one of the main projection sites of midbrain DA neurons: the nucleus accumbens (NAc), and a prominent type of signal in this pathway: unexpected rewards. DA neurons, as well as DA release in the NAc, strongly signal unexpected reward events, which are thought to play a critical role in the learning and performance of motivated actions. Neural firing rates in the NAc are similarly modulated by rewards. The temporal coincidence of reward-evoked DA signals with NAc spiking has led to the view that rapid DA signaling is a key driver of reward activity in NAc neurons. However, this hypothesis has not been rigorously tested. Furthermore, it is unclear how varying levels of DA differentially impact NAc firing. To facilitate a systematic study of these questions, here we present an approach combining in vivo electrophysiology, fluorescence DA sensing, and optogenetics. We use a silicon microprobe to record spiking activity from dozens of NAc neurons, and an integrated optical fiber to concurrently monitor local DA signaling with the fluorescent sensor dLight. In parallel, we perform optogenetic manipulations of VTA DA neurons in DAT-Cre mice, to transiently raise or reduce DA levels in the NAc.
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We find that optogenetically evoked DA release has minimal effects on NAc firing rates unless the level of DA release is multiple-times higher than the level corresponding to reward delivery. We also find that optogenetic suppression of DA neurons has minimal effect on NAc firing rates during reward delivery. Taken together, these findings suggest that NAc neural responses to rewards on rapid timescales are largely uncoupled from physiological, but not supraphysiological DA activity. These results challenge the current dogma that DA neurons normally play an important role in rapidly modulating striatal activity to influence imminent or ongoing behaviors. Finally, they suggest a critical need for the field to distinguish between what DA neurons normally do in the brain, and what they are capable of doing under supraphysiological conditions.
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==March==
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Date: 18 March 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Zachary Zeidler  '''
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<h4>Title: “ Memory organization in the amygdala across time and re-exposure. ” </h4>
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<u>Abstract:</u> I will discuss and synthesize two recent papers examining amygdalar activity during fear memory across time and memory re-exposure. The papers emphasize different aspects of amygdala dynamics. One paper (Liu...Maren Jan 2022 Biol Psych) focuses on overlap in activity representing both recent and remote memory. The other (Cho...Han Dec 2021 Curr Bio) emphasizes turnover in amygdalar ensembles following memory re-exposure. Together, they show the persistent yet dynamic activity of amygdalar ensembles in fear memory.
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<u>Relevant Papers:</u>  1) Liu, J., Totty, M. S., Melissari, L., Bayer, H. & Maren, S. Convergent coding of recent and remote fear memory in the basolateral amygdala. Biol Psychiat (2022) doi:10.1016/j.biopsych.2021.12.018.
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2) Cho, H.-Y. et al. Turnover of fear engram cells by repeated experience. Curr Biol (2021) doi:10.1016/j.cub.2021.10.004.
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Date: 11 March 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Ayal Lavi '''
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<h4>Title: “ A retrograde mechanism coordinates recruitment of memory ensembles across brain regions. ” </h4>
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<u>Abstract:</u> Memories are stored in ensembles of neurons in different brain regions. However, it is unclear whether and how the allocation of a memory to these ensembles is coordinated across brain regions. To address this question, we developed a novel approach that uses CREB expression to bias memory allocation in one brain region, and rabies retrograde tracing to study memory allocation in connected presynaptic neurons in other brain regions. Together with mathematical simulations, this approach revealed a universal retrograde mechanism that coordinates the recruitment of memory ensembles across cortical and subcortical regions, and in multiple behavioral paradigms, including conditioned taste aversion and auditory fear conditioning. We leveraged this retrograde mechanism to increase memory ensemble connectivity between brain regions, and show that this enhanced memory. These results uncovered a novel retrograde mechanism that coordinates the recruitment of memory ensembles across brain regions, and demonstrate its importance for memory formation.
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<u>Relevant Papers:</u> ttps://www.biorxiv.org/content/10.1101/2021.10.28.466361v1
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Date: 04 March 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Peyman Golshani'''
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<h4>Title: “ Local circuit amplification of spatial selectivity in the hippocampus ” </h4>
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<u>Abstract:</u>  Local circuit architecture facilitates the emergence of feature selectivity in the cerebral cortex1. In the hippocampus, it remains unknown whether local computations supported by specific connectivity motifs2 regulate the spatial receptive fields of pyramidal cells3. Here we developed an in vivo electroporation method for monosynaptic retrograde tracing4 and optogenetics manipulation at single-cell resolution to interrogate the dynamic interaction of place cells with their microcircuitry during navigation. We found a local circuit mechanism in CA1 whereby the spatial tuning of an individual place cell can propagate to a functionally recurrent subnetwork5 to which it belongs. The emergence of place fields in individual neurons led to the development of inverse selectivity in a subset of their presynaptic interneurons, and recruited functionally coupled place cells at that location. Thus, the spatial selectivity of single CA1 neurons is amplified through local circuit plasticity to enable effective multi-neuronal representations that can flexibly scale environmental features locally without degrading the feedforward input structure.
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<u>Relevant Papers:</u> https://www.nature.com/articles/s41586-021-04169-9
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==February==
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Date: 18 February 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Saray Soldado Magraner '''
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<h4>Title: “ What is the dynamic regime of the cerebral cortex? ” </h4>
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<u>Blurb:</u> In which regime does the cerebral cortex operate? This is a fundamental question for understanding cortical function. Decades of theoretical and experimental studies have converged into a model where strong recurrent excitation--unstable by itself--is balanced by recurrent inhibition. Circuits operating in this regime are known as Inhibition Stabilized Networks (ISN). However, it has been unclear whether the cortex operates as an ISN 'by default' or just under certain circumstances (for example, under strong sensory input). In this talk, I will introduce what ISN are and how we can prove them experimentally. I will then present the most compelling experimental study to date supporting that ISN may be the default dynamic regime of the cortex.
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<u>Abstract:</u>    Many cortical network models use recurrent coupling strong enough to require inhibition for stabilization. Yet it has been experimentally unclear whether inhibition-stabilized network (ISN) models describe cortical function well across areas and states. Here, we test several ISN predictions, including the counterintuitive (paradoxical) suppression of inhibitory firing in response to optogenetic inhibitory stimulation. We find clear evidence for ISN operation in mouse visual, somatosensory, and motor cortex. Simple two-population ISN models describe the data well and let us quantify coupling strength. Although some models predict a non-ISN to ISN transition with increasingly strong sensory stimuli, we find ISN effects without sensory stimulation and even during light anesthesia. Additionally, average paradoxical effects result only with transgenic, not viral, opsin expression in parvalbumin (PV)-positive neurons; theory and expression data show this is consistent with ISN operation. Taken together, these results show strong coupling and inhibition stabilization are common features of the cortex.
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<u>Relevant papers:</u> https://elifesciences.org/articles/54875 https://www.nature.com/articles/s41583-020-00390-z https://www.sciencedirect.com/science/article/pii/S0896627321005754
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Date: 11 February 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Lukas Oesch '''
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<h4>Title: “ Mouse prefrontal cortex represents learned rules for categorization ” </h4>
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<u>Abstract:</u>  How animals learn to classify a set of stimuli into discrete categories that can guide the selection of adequate behavioral responses remains poorly understood. One of the major challenges in identifying the neural representation of such categories is that they might partially overlap with other representations, such as stimulus identity or chosen actions. In their study Reinert and colleagues recorded neural activity in the mouse prefrontal cortex while animals were learning a visual Go/NoGo task. They demonstrate the presence of category selective neurons by changing either the categorization rule on a constant set of stimuli or the way animals reported their choice. They further show that category selectivity for Go-associated stimuli arises earlier in learning than NoGo-category selectivity.
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<u>Relevant papers:</u>  https://www.nature.com/articles/s41586-021-03452-z
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Date: 04 February 2022
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Time: 09:30 am
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<u>Speaker:</u> '''Emily Wu '''
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<h4>Title: “ Neural control of affiliative touch in prosocial interaction ” </h4>
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<u>Abstract:</u>  The ability to help and care for others fosters social cohesiveness and is vital to the physical and emotional well-being of social species, including humans1-3. Affiliative social touch, such as allogrooming (grooming behaviour directed towards another individual), is a major type of prosocial behaviour that provides comfort to others1-6. Affiliative touch serves to establish and strengthen social bonds between animals and can help to console distressed conspecifics. However, the neural circuits that promote prosocial affiliative touch have remained unclear. Here we show that mice exhibit affiliative allogrooming behaviour towards distressed partners, providing a consoling effect. The increase in allogrooming occurs in response to different types of stressors and can be elicited by olfactory cues from distressed individuals. Using microendoscopic calcium imaging, we find that neural activity in the medial amygdala (MeA) responds differentially to naive and distressed conspecifics and encodes allogrooming behaviour. Through intersectional functional manipulations, we establish a direct causal role of the MeA in controlling affiliative allogrooming and identify a select, tachykinin-expressing subpopulation of MeA GABAergic (γ-aminobutyric-acid-expressing) neurons that promote this behaviour through their projections to the medial preoptic area. Together, our study demonstrates that mice display prosocial comforting behaviour and reveals a neural circuit mechanism that underlies the encoding and control of affiliative touch during prosocial interactions.
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<u>Relevant papers:</u>  https://pubmed.ncbi.nlm.nih.gov/34646019/
    
==January==
 
==January==
 
<u>Speaker:</u> '''Mimi La-Vu '''
 
<u>Speaker:</u> '''Mimi La-Vu '''