Developmental emergence of personality

The Nature versus Nurture debate has generally been considered from the lens of genome versus experience dichotomy and has dominated our thinking about behavioral individuality and personality traits. In contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using the Drosophila melanogaster visual system, I will discuss our efforts to dissect how individuality in circuit wiring emerges during development, and how that helps generate individual behavioral variation.

High Stakes in the Adolescent Brain: Glia Ignite Under THC’s Influence

Restoring Sight to the Blind: Effects of Structural and Functional Plasticity

Visual restoration after decades of blindness is now becoming possible by means of retinal and cortical prostheses, as well as emerging stem cell and gene therapeutic approaches. After restoring visual perception, however, a key question remains. Are there optimal means and methods for retraining the visual cortex to process visual inputs, and for learning or relearning to “see”? Up to this point, it has been largely assumed that if the sensory loss is visual, then the rehabilitation focus should also be primarily visual. However, the other senses play a key role in visual rehabilitation due to the plastic repurposing of visual cortex during blindness by audition and somatosensation, and also to the reintegration of restored vision with the other senses. I will present multisensory neuroimaging results, cortical thickness changes, as well as behavioral outcomes for patients with Retinitis Pigmentosa (RP), which causes blindness by destroying photoreceptors in the retina. These patients have had their vision partially restored by the implantation of a retinal prosthesis, which electrically stimulates still viable retinal ganglion cells in the eye. Our multisensory and structural neuroimaging and behavioral results suggest a new, holistic concept of visual rehabilitation that leverages rather than neglects audition, somatosensation, and other sensory modalities.

Contentopic mapping and object dimensionality - a novel understanding on the organization of object knowledge

Our ability to recognize an object amongst many others is one of the most important features of the human mind. However, object recognition requires tremendous computational effort, as we need to solve a complex and recursive environment with ease and proficiency. This challenging feat is dependent on the implementation of an effective organization of knowledge in the brain. Here I put forth a novel understanding of how object knowledge is organized in the brain, by proposing that the organization of object knowledge follows key object-related dimensions, analogously to how sensory information is organized in the brain. Moreover, I will also put forth that this knowledge is topographically laid out in the cortical surface according to these object-related dimensions that code for different types of representational content – I call this contentopic mapping. I will show a combination of fMRI and behavioral data to support these hypotheses and present a principled way to explore the multidimensionality of object processing.

Mapping the neural dynamics of dominance and defeat

Social experiences can have lasting changes on behavior and affective state. In particular, repeated wins and losses during fighting can facilitate and suppress future aggressive behavior, leading to persistent high aggression or low aggression states. We use a combination of techniques for multi-region neural recording, perturbation, behavioral analysis, and modeling to understand how nodes in the brain’s subcortical “social decision-making network” encode and transform aggressive motivation into action, and how these circuits change following social experience.

Decision and Behavior

This webinar addressed computational perspectives on how animals and humans make decisions, spanning normative, descriptive, and mechanistic models. Sam Gershman (Harvard) presented a capacity-limited reinforcement learning framework in which policies are compressed under an information bottleneck constraint. This approach predicts pervasive perseveration, stimulus‐independent “default” actions, and trade-offs between complexity and reward. Such policy compression reconciles observed action stochasticity and response time patterns with an optimal balance between learning capacity and performance. Jonathan Pillow (Princeton) discussed flexible descriptive models for tracking time-varying policies in animals. He introduced dynamic Generalized Linear Models (Sidetrack) and hidden Markov models (GLM-HMMs) that capture day-to-day and trial-to-trial fluctuations in choice behavior, including abrupt switches between “engaged” and “disengaged” states. These models provide new insights into how animals’ strategies evolve under learning. Finally, Kenji Doya (OIST) highlighted the importance of unifying reinforcement learning with Bayesian inference, exploring how cortical-basal ganglia networks might implement model-based and model-free strategies. He also described Japan’s Brain/MINDS 2.0 and Digital Brain initiatives, aiming to integrate multimodal data and computational principles into cohesive “digital brains.”

Brain-Wide Compositionality and Learning Dynamics in Biological Agents

Biological agents continually reconcile the internal states of their brain circuits with incoming sensory and environmental evidence to evaluate when and how to act. The brains of biological agents, including animals and humans, exploit many evolutionary innovations, chiefly modularity—observable at the level of anatomically-defined brain regions, cortical layers, and cell types among others—that can be repurposed in a compositional manner to endow the animal with a highly flexible behavioral repertoire. Accordingly, their behaviors show their own modularity, yet such behavioral modules seldom correspond directly to traditional notions of modularity in brains. It remains unclear how to link neural and behavioral modularity in a compositional manner. We propose a comprehensive framework—compositional modes—to identify overarching compositionality spanning specialized submodules, such as brain regions. Our framework directly links the behavioral repertoire with distributed patterns of population activity, brain-wide, at multiple concurrent spatial and temporal scales. Using whole-brain recordings of zebrafish brains, we introduce an unsupervised pipeline based on neural network models, constrained by biological data, to reveal highly conserved compositional modes across individuals despite the naturalistic (spontaneous or task-independent) nature of their behaviors. These modes provided a scaffolding for other modes that account for the idiosyncratic behavior of each fish. We then demonstrate experimentally that compositional modes can be manipulated in a consistent manner by behavioral and pharmacological perturbations. Our results demonstrate that even natural behavior in different individuals can be decomposed and understood using a relatively small number of neurobehavioral modules—the compositional modes—and elucidate a compositional neural basis of behavior. This approach aligns with recent progress in understanding how reasoning capabilities and internal representational structures develop over the course of learning or training, offering insights into the modularity and flexibility in artificial and biological agents.

Emergence of behavioural individuality from global microstructure of the brain and learning

Influence of the context of administration in the antidepressant-like effects of the psychedelic 5-MeO-DMT

Psychedelics like psilocybin have shown rapid and long-lasting efficacy on depressive and anxiety symptoms. Other psychedelics with shorter half-lives, such as DMT and 5-MeO-DMT, have also shown promising preliminary outcomes in major depression, making them interesting candidates for clinical practice. Despite several promising clinical studies, the influence of the context on therapeutic responses or adverse effects remains poorly documented. To address this, we conducted preclinical studies evaluating the psychopharmacological profile of 5-MeO-DMT in contexts previously validated in mice as either pleasant (positive setting) or aversive (negative setting). Healthy C57BL/6J male mice received a single intraperitoneal (i.p.) injection of 5-MeO-DMT at doses of 0.5, 5, and 10 mg/kg, with assessments at 2 hours, 24 hours, and one week post-administration. In a corticosterone (CORT) mouse model of depression, 5-MeO-DMT was administered in different settings, and behavioral tests mimicking core symptoms of depression and anxiety were conducted. In CORT-exposed mice, an acute dose of 0.5 mg/kg administered in a neutral setting produced antidepressant-like effects at 24 hours, as observed by reduced immobility time in the Tail Suspension Test (TST). In a positive setting, the drug also reduced latency to first immobility and total immobility time in the TST. However, these beneficial effects were negated in a negative setting, where 5-MeO-DMT failed to produce antidepressant-like effects and instead elicited an anxiogenic response in the Elevated Plus Maze (EPM).Our results indicate a strong influence of setting on the psychopharmacological profile of 5-MeO-DMT. Future experiments will examine cortical markers of pre- and post-synaptic density to correlate neuroplasticity changes with the behavioral effects of 5-MeO-DMT in different settings.

The multi-phase plasticity supporting winner effect

Aggression is an innate behavior across animal species. It is essential for competing for food, defending territory, securing mates, and protecting families and oneself. Since initiating an attack requires no explicit learning, the neural circuit underlying aggression is believed to be genetically and developmentally hardwired. Despite being innate, aggression is highly plastic. It is influenced by a wide variety of experiences, particularly winning and losing previous encounters. Numerous studies have shown that winning leads to an increased tendency to fight while losing leads to flight in future encounters. In the talk, I will present our recent findings regarding the neural mechanisms underlying the behavioral changes caused by winning.

Characterizing the causal role of large-scale network interactions in supporting complex cognition

Neuroimaging has greatly extended our capacity to study the workings of the human brain. Despite the wealth of knowledge this tool has generated however, there are still critical gaps in our understanding. While tremendous progress has been made in mapping areas of the brain that are specialized for particular stimuli, or cognitive processes, we still know very little about how large-scale interactions between different cortical networks facilitate the integration of information and the execution of complex tasks. Yet even the simplest behavioral tasks are complex, requiring integration over multiple cognitive domains. Our knowledge falls short not only in understanding how this integration takes place, but also in what drives the profound variation in behavior that can be observed on almost every task, even within the typically developing (TD) population. The search for the neural underpinnings of individual differences is important not only philosophically, but also in the service of precision medicine. We approach these questions using a three-pronged approach. First, we create a battery of behavioral tasks from which we can calculate objective measures for different aspects of the behaviors of interest, with sufficient variance across the TD population. Second, using these individual differences in behavior, we identify the neural variance which explains the behavioral variance at the network level. Finally, using covert neurofeedback, we perturb the networks hypothesized to correspond to each of these components, thus directly testing their casual contribution. I will discuss our overall approach, as well as a few of the new directions we are currently pursuing.

Mitochondrial diversity in the mouse and human brain

The basis of the mind, of mental states, and complex behaviors is the flow of energy through microscopic and macroscopic brain structures. Energy flow through brain circuits is powered by thousands of mitochondria populating the inside of every neuron, glial, and other nucleated cell across the brain-body unit. This seminar will cover emerging approaches to study the mind-mitochondria connection and present early attempts to map the distribution and diversity of mitochondria across brain tissue. In rodents, I will present convergent multimodal evidence anchored in enzyme activities, gene expression, and animal behavior that distinct behaviorally-relevant mitochondrial phenotypes exist across large-scale mouse brain networks. Extending these findings to the human brain, I will present a developing systematic biochemical and molecular map of mitochondrial variation across cortical and subcortical brain structures, representing a foundation to understand the origin of complex energy patterns that give rise to the human mind.

Stability of visual processing in passive and active vision

The visual system faces a dual challenge. On the one hand, features of the natural visual environment should be stably processed - irrespective of ongoing wiring changes, representational drift, and behavior. On the other hand, eye, head, and body motion require a robust integration of pose and gaze shifts in visual computations for a stable perception of the world. We address these dimensions of stable visual processing by studying the circuit mechanism of long-term representational stability, focusing on the role of plasticity, network structure, experience, and behavioral state while recording large-scale neuronal activity with miniature two-photon microscopy.

The quest for brain identification

In the 17th century, physician Marcello Malpighi observed the existence of distinctive patterns of ridges and sweat glands on fingertips. This was a major breakthrough, and originated a long and continuing quest for ways to uniquely identify individuals based on fingerprints, a technique massively used until today. It is only in the past few years that technologies and methodologies have achieved high-quality measures of an individual’s brain to the extent that personality traits and behavior can be characterized. The concept of “fingerprints of the brain” is very novel and has been boosted thanks to a seminal publication by Finn et al. in 2015. They were among the firsts to show that an individual’s functional brain connectivity profile is both unique and reliable, similarly to a fingerprint, and that it is possible to identify an individual among a large group of subjects solely on the basis of her or his connectivity profile. Yet, the discovery of brain fingerprints opened up a plethora of new questions. In particular, what exactly is the information encoded in brain connectivity patterns that ultimately leads to correctly differentiating someone’s connectome from anybody else’s? In other words, what makes our brains unique? In this talk I am going to partially address these open questions while keeping a personal viewpoint on the subject. I will outline the main findings, discuss potential issues, and propose future directions in the quest for identifiability of human brain networks.

Tracking subjects' strategies in behavioural choice experiments at trial resolution

Psychology and neuroscience are increasingly looking to fine-grained analyses of decision-making behaviour, seeking to characterise not just the variation between subjects but also a subject's variability across time. When analysing the behaviour of each subject in a choice task, we ideally want to know not only when the subject has learnt the correct choice rule but also what the subject tried while learning. I introduce a simple but effective Bayesian approach to inferring the probability of different choice strategies at trial resolution. This can be used both for inferring when subjects learn, by tracking the probability of the strategy matching the target rule, and for inferring subjects use of exploratory strategies during learning. Applied to data from rodent and human decision tasks, we find learning occurs earlier and more often than estimated using classical approaches. Around both learning and changes in the rewarded rules the exploratory strategies of win-stay and lose-shift, often considered complementary, are consistently used independently. Indeed, we find the use of lose-shift is strong evidence that animals have latently learnt the salient features of a new rewarded rule. Our approach can be extended to any discrete choice strategy, and its low computational cost is ideally suited for real-time analysis and closed-loop control.

Modeling the Navigational Circuitry of the Fly

Navigation requires orienting oneself relative to landmarks in the environment, evaluating relevant sensory data, remembering goals, and convert all this information into motor commands that direct locomotion. I will present models, highly constrained by connectomic, physiological and behavioral data, for how these functions are accomplished in the fly brain.

Consciousness in the cradle: on the emergence of infant experience

Although each of us was once a baby, infant consciousness remains mysterious and there is no received view about when, and in what form, consciousness first emerges. Some theorists defend a ‘late-onset’ view, suggesting that consciousness requires cognitive capacities which are unlikely to be in place before the child’s first birthday at the very earliest. Other theorists defend an ‘early-onset’ account, suggesting that consciousness is likely to be in place at birth (or shortly after) and may even arise during the third trimester. Progress in this field has been difficult, not just because of the challenges associated with procuring the relevant behavioral and neural data, but also because of uncertainty about how best to study consciousness in the absence of the capacity for verbal report or intentional behavior. This review examines both the empirical and methodological progress in this field, arguing that recent research points in favor of early-onset accounts of the emergence of consciousness.

A recurrent network model of planning predicts hippocampal replay and human behavior

When interacting with complex environments, humans can rapidly adapt their behavior to changes in task or context. To facilitate this adaptation, we often spend substantial periods of time contemplating possible futures before acting. For such planning to be rational, the benefits of planning to future behavior must at least compensate for the time spent thinking. Here we capture these features of human behavior by developing a neural network model where not only actions, but also planning, are controlled by prefrontal cortex. This model consists of a meta-reinforcement learning agent augmented with the ability to plan by sampling imagined action sequences drawn from its own policy, which we refer to as `rollouts'. Our results demonstrate that this agent learns to plan when planning is beneficial, explaining the empirical variability in human thinking times. Additionally, the patterns of policy rollouts employed by the artificial agent closely resemble patterns of rodent hippocampal replays recently recorded in a spatial navigation task, in terms of both their spatial statistics and their relationship to subsequent behavior. Our work provides a new theory of how the brain could implement planning through prefrontal-hippocampal interactions, where hippocampal replays are triggered by -- and in turn adaptively affect -- prefrontal dynamics.

Decoding mental conflict between reward and curiosity in decision-making

Humans and animals are not always rational. They not only rationally exploit rewards but also explore an environment owing to their curiosity. However, the mechanism of such curiosity-driven irrational behavior is largely unknown. Here, we developed a decision-making model for a two-choice task based on the free energy principle, which is a theory integrating recognition and action selection. The model describes irrational behaviors depending on the curiosity level. We also proposed a machine learning method to decode temporal curiosity from behavioral data. By applying it to rat behavioral data, we found that the rat had negative curiosity, reflecting conservative selection sticking to more certain options and that the level of curiosity was upregulated by the expected future information obtained from an uncertain environment. Our decoding approach can be a fundamental tool for identifying the neural basis for reward–curiosity conflicts. Furthermore, it could be effective in diagnosing mental disorders.

A recurrent network model of planning explains hippocampal replay and human behavior

When interacting with complex environments, humans can rapidly adapt their behavior to changes in task or context. To facilitate this adaptation, we often spend substantial periods of time contemplating possible futures before acting. For such planning to be rational, the benefits of planning to future behavior must at least compensate for the time spent thinking. Here we capture these features of human behavior by developing a neural network model where not only actions, but also planning, are controlled by prefrontal cortex. This model consists of a meta-reinforcement learning agent augmented with the ability to plan by sampling imagined action sequences drawn from its own policy, which we refer to as 'rollouts'. Our results demonstrate that this agent learns to plan when planning is beneficial, explaining the empirical variability in human thinking times. Additionally, the patterns of policy rollouts employed by the artificial agent closely resemble patterns of rodent hippocampal replays recently recorded in a spatial navigation task, in terms of both their spatial statistics and their relationship to subsequent behavior. Our work provides a new theory of how the brain could implement planning through prefrontal-hippocampal interactions, where hippocampal replays are triggered by - and in turn adaptively affect - prefrontal dynamics.

Mechanisms Underlying the Persistence of Cancer-Related Fatigue

Cancer-related fatigue is a prominent and debilitating side effect of cancer and its treatment. It can develop prior to diagnosis, generally peaks during cancer treatment, and can persist long after treatment completion. Its mechanisms are multifactorial, and its expression is highly variable. Unfortunately, treatment options are limited. Our research uses syngeneic murine models of cancer and cisplatin-based chemotherapy to better understand these mechanisms. Our data indicate that both peripherally and centrally processes may contribute to the developmental of fatigue. These processes include metabolic alterations, mitochondrial dysfunction, pre-cachexia, and inflammation. However, our data has revealed that behavioral fatigue can persist even after the toxicity associated with cancer and its treatment recover. For example, running during cancer treatment attenuates kidney toxicity while also delaying recovery from fatigue-like behavior. Additionally, administration of anesthetics known to disrupt memory consolidation at the time treatment can promote recovery, and treatment-related cues can re-instate fatigue after recovery. Cancer-related fatigue can also promote habitual behavioral patterns, as observed using a devaluation task. We interpret this data to suggest that limit metabolic resources during cancer promote the utilization of habit-based behavioral strategies that serve to maintain fatigue behavior into survivorship. This line of work is exciting as it points us toward novel interventional targets for the treatment of persistent cancer-related fatigue.

Why are we consistently inconsistent? On the neural mechanisms of behavioural inconsistency

Precise spatio-temporal spike patterns in cortex and model

The cell assembly hypothesis postulates that groups of coordinated neurons form the basis of information processing. Here, we test this hypothesis by analyzing massively parallel spiking activity recorded in monkey motor cortex during a reach-to-grasp experiment for the presence of significant ms-precise spatio-temporal spike patterns (STPs). For this purpose, the parallel spike trains were analyzed for STPs by the SPADE method (Stella et al, 2019, Biosystems), which detects, counts and evaluates spike patterns for their significance by the use of surrogates (Stella et al, 2022 eNeuro). As a result we find STPs in 19/20 data sets (each of 15min) from two monkeys, but only a small fraction of the recorded neurons are involved in STPs. To consider the different behavioral states during the task, we analyzed the data in a quasi time-resolved analysis by dividing the data into behaviorally relevant time epochs. The STPs that occur in the various epochs are specific to behavioral context - in terms of neurons involved and temporal lags between the spikes of the STP. Furthermore we find, that the STPs often share individual neurons across epochs. Since we interprete the occurrence of a particular STP as the signature of a particular active cell assembly, our interpretation is that the neurons multiplex their cell assembly membership. In a related study, we model these findings by networks with embedded synfire chains (Kleinjohann et al, 2022, bioRxiv 2022.08.02.502431).

A sense without sensors: how non-temporal stimulus features influence the perception and the neural representation of time

Any sensory experience of the world, from the touch of a caress to the smile on our friend’s face, is embedded in time and it is often associated with the perception of the flow of it. The perception of time is therefore a peculiar sensory experience built without dedicated sensors. How the perception of time and the content of a sensory experience interact to give rise to this unique percept is unclear. A few empirical evidences show the existence of this interaction, for example the speed of a moving object or the number of items displayed on a computer screen can bias the perceived duration of those objects. However, to what extent the coding of time is embedded within the coding of the stimulus itself, is sustained by the activity of the same or distinct neural populations and subserved by similar or distinct neural mechanisms is far from clear. Addressing these puzzles represents a way to gain insight on the mechanism(s) through which the brain represents the passage of time. In my talk I will present behavioral and neuroimaging studies to show how concurrent changes of visual stimulus duration, speed, visual contrast and numerosity, shape and modulate brain’s and pupil’s responses and, in case of numerosity and time, influence the topographic organization of these features along the cortical visual hierarchy.

Relations and Predictions in Brains and Machines

Humans and animals learn and plan with flexibility and efficiency well beyond that of modern Machine Learning methods. This is hypothesized to owe in part to the ability of animals to build structured representations of their environments, and modulate these representations to rapidly adapt to new settings. In the first part of this talk, I will discuss theoretical work describing how learned representations in hippocampus enable rapid adaptation to new goals by learning predictive representations, while entorhinal cortex compresses these predictive representations with spectral methods that support smooth generalization among related states. I will also cover recent work extending this account, in which we show how the predictive model can be adapted to the probabilistic setting to describe a broader array of generalization results in humans and animals, and how entorhinal representations can be modulated to support sample generation optimized for different behavioral states. In the second part of the talk, I will overview some of the ways in which we have combined many of the same mathematical concepts with state-of-the-art deep learning methods to improve efficiency and performance in machine learning applications like physical simulation, relational reasoning, and design.

Self-perception: mechanosensation and beyond

Brain-organ communications play a crucial role in maintaining the body's physiological and psychological homeostasis, and are controlled by complex neural and hormonal systems, including the internal mechanosensory organs. However, the progress has been slow due to technical hurdles: the sensory neurons are deeply buried inside the body and are not readily accessible for direct observation, the projection patterns from different organs or body parts are complex rather than converging into dedicate brain regions, the coding principle cannot be directly adapted from that learned from conventional sensory pathways. Our lab apply the pipeline of "biophysics of receptors-cell biology of neurons-functionality of neural circuits-animal behaviors" to explore the molecular and neural mechanisms of self-perception. In the lab, we mainly focus on the following three questions: 1, The molecular and cellular basis for proprioception and interoception. 2, The circuit mechanisms of sensory coding and integration of internal and external information. 3, The function of interoception in regulating behavior homeostasis.

Behavioural Basis of Subjective Time Distortions

Precisely estimating event timing is essential for survival, yet temporal distortions are ubiquitous in our daily sensory experience. Here, we tested whether the relative position, duration, and distance in time of two sequentially-organized events—standard S, with constant duration, and comparison C, with duration varying trial-by-trial—are causal factors in generating temporal distortions. We found that temporal distortions emerge when the first event is shorter than the second event. Importantly, a significant interaction suggests that a longer inter-stimulus interval (ISI) helps to counteract such serial distortion effect only when the constant S is in the first position, but not if the unpredictable C is in the first position. These results imply the existence of a perceptual bias in perceiving ordered event durations, mechanistically contributing to distortion in time perception. Our results clarify the mechanisms generating time distortions by identifying a hitherto unknown duration-dependent encoding inefficiency in human serial temporal perception, something akin to a strong prior that can be overridden for highly predictable sensory events but unfolds for unpredictable ones.

Hallucinating mice, dopamine and immunity; towards mechanistic treatment targets for psychosis

Hallucinations are a core symptom of psychotic disorders and have traditionally been difficult to study biologically. We developed a new behavioral computational approach to measure hallucinations-like perception in humans and mice alike. Using targeted neural circuit manipulations, we identified a causal role for striatal dopamine in mediating hallucination-like perception. Building on this, we currently investigate the neural and immunological upstream regulators of these dopaminergic circuits with the goal to identify new biological treatment targets for psychosis

Applying Structural Alignment theory to Early Verb Learning

Learning verbs is difficult and critical to learning one's native language. Children appear to benefit from seeing multiple events and comparing them to each other, and structural alignment theory provides a good theoretical framework to guide research into how preschool children may be comparing events as they learn new verbs. The talk will include 6 studies of early verb learning that make use of eye-tracking procedures as well as other behavioral (pointing) procedures, and that test key predictions from SA theory including the prediction that seeing similar examples before more varied examples helps observers learn how to compare (progressive alignment) and the prediction that when events have very low alignability with other events, that is one cue that the events should be ignored. Whether or how statistical learning may also be at work will be considered.

Analyzing artificial neural networks to understand the brain

In the first part of this talk I will present work showing that recurrent neural networks can replicate broad behavioral patterns associated with dynamic visual object recognition in humans. An analysis of these networks shows that different types of recurrence use different strategies to solve the object recognition problem. The similarities between artificial neural networks and the brain presents another opportunity, beyond using them just as models of biological processing. In the second part of this talk, I will discuss—and solicit feedback on—a proposed research plan for testing a wide range of analysis tools frequently applied to neural data on artificial neural networks. I will present the motivation for this approach as well as the form the results could take and how this would benefit neuroscience.

Motor contribution to auditory temporal predictions

Temporal predictions are fundamental instruments for facilitating sensory selection, allowing humans to exploit regularities in the world. Recent evidence indicates that the motor system instantiates predictive timing mechanisms, helping to synchronize temporal fluctuations of attention with the timing of events in a task-relevant stream, thus facilitating sensory selection. Accordingly, in the auditory domain auditory-motor interactions are observed during perception of speech and music, two temporally structured sensory streams. I will present a behavioral and neurophysiological account for this theory and will detail the parameters governing the emergence of this auditory-motor coupling, through a set of behavioral and magnetoencephalography (MEG) experiments.

Versatile treadmill system for measuring locomotion and neural activity in head-fixed mice

Here, we present a protocol for using a versatile treadmill system to measure locomotion and neural activity at high temporal resolution in head-fixed mice. We first describe the assembly of the treadmill system. We then detail surgical implantation of the headplate on the mouse skull, followed by habituation of mice to locomotion on the treadmill system. The system is compact, movable, and simple to synchronize with other data streams, making it ideal for monitoring brain activity in diverse behavioral frameworks. https://dx.doi.org/10.1016/j.xpro.2022.101701

Protocols for the social transfer of pain and analgesia in mice

We provide protocols for the social transfer of pain and analgesia in mice. We describe the steps to induce pain or analgesia (pain relief) in bystander mice with a 1-h social interaction with a partner injected with CFA (complete Freund’s adjuvant) or CFA and morphine, respectively. We detail behavioral tests to assess pain or analgesia in the untreated bystander mice. This protocol has been validated in mice and rats and can be used for investigating mechanisms of empathy. Highlights • A protocol for the rapid social transfer of pain in rodents • Detailed requirements for handling and housing conditions • Procedures for habituation, social interaction, and pain induction and assessment • Adaptable for social transfer of analgesia and may be used to study empathy in rodents https://doi.org/10.1016/j.xpro.2022.101756

Prefrontal top-down projections control context-dependent strategy selection

The rules governing behavior often vary with behavioral contexts. As a result, an action rewarded in one context may be discouraged in another. Animals and humans are capable of switching between behavioral strategies under different contexts and acting adaptively according to the variable rules, a flexibility that is thought to be mediated by the prefrontal cortex (PFC). However, how the PFC orchestrates the context-dependent switch of strategies remains unclear. Here we show that pathway-specific projection neurons in the medial PFC (mPFC) differentially contribute to context-instructed strategy selection. In mice trained in a decision-making task in which a previously established rule and a newly learned rule are associated with distinct contexts, the activity of mPFC neurons projecting to the dorsomedial striatum (mPFC-DMS) encodes the contexts and further represents decision strategies conforming to the old and new rules. Moreover, mPFC-DMS neuron activity is required for the context-instructed strategy selection. In contrast, the activity of mPFC neurons projecting to the ventral midline thalamus (mPFC-VMT) does not discriminate between the contexts, and represents the old rule even if mice have adopted the new one. Furthermore, these neurons act to prevent the strategy switch under the new rule. Our results suggest that mPFC-DMS neurons promote flexible strategy selection guided by contexts, whereas mPFC-VMT neurons favor fixed strategy selection by preserving old rules.

Modern Approaches to Behavioural Analysis

The goal of neuroscience is to understand how the nervous system controls behaviour, not only in the simplified environments of the lab, but also in the natural environments for which nervous systems evolved. In pursuing this goal, neuroscience research is supported by an ever-larger toolbox, ranging from optogenetics to connectomics. However, often these tools are coupled with reductionist approaches for linking nervous systems and behaviour. This course will introduce advanced techniques for measuring and analysing behaviour, as well as three fundamental principles as necessary to understanding biological behaviour: (1) morphology and environment; (2) action-perception closed loops and purpose; and (3) individuality and historical contingencies [1]. [1] Gomez-Marin, A., & Ghazanfar, A. A. (2019). The life of behavior. Neuron, 104(1), 25-36

Early life adversity, inflammation, and depression-onset: Results from the Teen Resilience Project

My research focuses broadly on the lifelong health disparities associated with experiences of adversity early in life. In this talk I will present the results of our recently completed Teen Resilience Project, a prospective and longitudinal study of first onset depression during adolescence. First, I will present the results on whether and how inflammatory processes may be shaped by early life adversity. Second, I will present data on the role of stress-induced inflammation in reward-related psychological processes. Finally, I will discuss the biobehavioral predictors of first-onset depression in this sample.

Mouse visual cortex as a limited resource system that self-learns an ecologically-general representation

Studies of the mouse visual system have revealed a variety of visual brain areas in a roughly hierarchical arrangement, together with a multitude of behavioral capacities, ranging from stimulus-reward associations, to goal-directed navigation, and object-centric discriminations. However, an overall understanding of the mouse’s visual cortex organization, and how this organization supports visual behaviors, remains unknown. Here, we take a computational approach to help address these questions, providing a high-fidelity quantitative model of mouse visual cortex. By analyzing factors contributing to model fidelity, we identified key principles underlying the organization of mouse visual cortex. Structurally, we find that comparatively low-resolution and shallow structure were both important for model correctness. Functionally, we find that models trained with task-agnostic, unsupervised objective functions, based on the concept of contrastive embeddings were substantially better than models trained with supervised objectives. Finally, the unsupervised objective builds a general-purpose visual representation that enables the system to achieve better transfer on out-of-distribution visual, scene understanding and reward-based navigation tasks. Our results suggest that mouse visual cortex is a low-resolution, shallow network that makes best use of the mouse’s limited resources to create a light-weight, general-purpose visual system – in contrast to the deep, high-resolution, and more task-specific visual system of primates.

Inter-tissue signals modify food-seeking behavior in C. elegans

Animals modify their behavioral outputs in response to changes in external and internal environments. We use the nematode, C. elegans to probe the pathways linking changes in internal states like hunger with behavior. We find that acute food deprivation alters the localization of two transcription factors, likely releasing an insulin-like peptide from the intestine, which in turn modifies chemosensory neurons and alters behavior. These results present a model for how inter-tissue signals to generate flexible behaviors via gut-brain signaling.

Behavioural probing of learned statistical structure in humans

COSYNE 2022

Adolescent stress impairs behavioural flexibility in adults through population-specific alterations to ventral hippocampal circuits

FENS Forum 2024

Analysis of gaze control neuronal circuits combining behavioural experiments with a novel virtual reality platform

FENS Forum 2024

Investigating behavioural and neural alterations in zebrafish seizure and epilepsy models

FENS Forum 2024

Behavioural characterization of the CAG-hACE2 transgenic mice

FENS Forum 2024

Behavioural hypersensitivity to CO2 is associated with increased engagement of the insula in subjects with high trait anxiety

FENS Forum 2024

A behavioural assessment to characterize different stages of memory impairment in humanized APP knock-in mouse models across various ages

FENS Forum 2024

Behavioural control training promotes antidepressant/anxiolytic-like reversal of chronic stress-induced behavioural deficits: Endocannabinoidergic and prolactinergic mechanisms

FENS Forum 2024

Behavioural and multi-omic characterization of lrrtm4l1-/- zebrafish

FENS Forum 2024

Behavioural and neural influences of social partner’s motivational type on food preference

FENS Forum 2024

Cerebral malaria leads to persistent microglial activation, long-term behavioural changes and electrographic seizures in mice

FENS Forum 2024

Changes in frequency and amplitude of hippocampal theta modulate firing across neurons with respect to behavioural context

FENS Forum 2024

Chemogenetic activation of oligodendrocytes modulates behavioural processes

FENS Forum 2024

Cognitive behavioural deficits in a knock-in mouse model with a human schizophrenia-associated mutation in the CACNG2 gene

FENS Forum 2024

New data in an animal model for schizophrenia: Ketamine-induced locomotor activity and repetitive behavioural responses are higher after neonatal functional blockade of the prefrontal cortex

FENS Forum 2024

Decreased brain serotonin in RBFOX1 mutant zebrafish and partial reversion of behavioural alterations by the SSRI fluoxetine

FENS Forum 2024

The dynamic state of a prefrontal-hypothalamic-midbrain circuit commands behavioural transitions

FENS Forum 2024

Effects of non-invasive electrical stimulation on neural and behavioural changes following photothrombotic ischemic stroke

FENS Forum 2024

The estrogen-immune axis: A key regulator of behavioural inflexibility

FENS Forum 2024

Examination of adolescent cannabinoid vapour exposure effects on behavioural predictors of addiction and alcohol use disorder features in adult male and female rats

FENS Forum 2024

Functional, behavioural and molecular characterization of a presymptomatic model of Parkinson disease expressing α-synuclein in the locus coeruleus

FENS Forum 2024

Light-dependent cAMP modulation in astrocytes triggers synaptic potentiation, hemodynamic responses, and behavioural changes in mice: Role in Huntington’s disease

FENS Forum 2024

Modelling cognitive and psychiatric behavioural traits in a mouse model of neurofibromatosis type I

FENS Forum 2024

Molecular and neuronal mechanisms of behavioural integration in the extended amygdala

FENS Forum 2024

Neuronal discrimination of visual environments differentially depends on behavioural context in the hippocampus and neocortex

FENS Forum 2024

Novel DVC interlinking home cage monitoring system facilitates social behavioural testing in mice

FENS Forum 2024

Orbitofrontal cortical contributions to behavioural strategies during tactile reversal learning

FENS Forum 2024

Overtraining enhances behavioural flexibility on a serial reversal learning task

FENS Forum 2024

Oxytocin's role in behavioural prioritization: Examining competing social and food needs in mice

FENS Forum 2024

Paternal exposure to voluntary exercise or corticosterone modifies the sperm long noncoding RNA profile, and their microinjection alters adult behavioural endophenotypes

FENS Forum 2024

The pesticide glyphosate induces sex-dependent behavioural changes in mice: A role for the gut microbiota?

FENS Forum 2024

Prediction errors elicit faster and more accurate behavioural responses

FENS Forum 2024

Prefrontal-tDCS rescues hippocampal dopamine signalling, resulting in cellular, functional and behavioural improvements and amyloid-β reduction in a mouse model of Alzheimer’s disease

FENS Forum 2024

Pubertal immune challenge differentially modulates LPS-induced molecular and behavioural sequelae in adult male and female mice

FENS Forum 2024

Rate of representational drift correlates with information theoretic measures of neural and behavioural coupling

FENS Forum 2024

Shared genetics between addiction, aggression, and related behavioural traits

FENS Forum 2024

Stratification of ALS progression by a combined motor and behavioural tracking approach for preclinical drug validation

FENS Forum 2024

Temperature-driven neural and behavioural responses in Hydra vulgaris

FENS Forum 2024

Thorough behavioural characterization of zebrafish models across Parkinson's disease progression

FENS Forum 2024

Unravelling the complexity of stress and reward processing: The innervation of midbrain nuclei by the nucleus incertus – Anatomical, electrophysiological and behavioural studies in rats

FENS Forum 2024