Developmental and evolutionary perspectives on thalamic function

Brain organization and function is a complex topic. We are good at establishing correlates of perception and behavior across forebrain circuits, as well as manipulating activity in these circuits to affect behavior. However, we still lack good models for the large-scale organization and function of the forebrain. What are the contributions of the cortex, basal ganglia, and thalamus to behavior? In addressing these questions, we often ascribe function to each area as if it were an independent processing unit. However, we know from the anatomy that the cortex, basal ganglia, and thalamus, are massively interconnected in a large network. One way to generate insight into these questions is to consider the evolution and development of forebrain systems. In this talk, I will discuss the developmental and evolutionary (comparative anatomy) data on the thalamus, and how it fits within forebrain networks. I will address questions including, when did the thalamus appear in evolution, how is the thalamus organized across the vertebrate lineage, and how can the change in the organization of forebrain networks affect behavioral repertoires.

Neural Signal Propagation Atlas of C. elegans

In the age of connectomics, it is increasingly important to understand how the nodes and edges of a brain's anatomical network, or "connectome," gives rise to neural signaling and neural function. I will present the first comprehensive brain-wide cell-resolved causal measurements of how neurons signal to one another in response to stimulation in the nematode C. elegans. I will compare this signal propagation atlas to the worm's known connectome to address fundamental questions of structure and function in the brain.

Cognitive maps as expectations learned across episodes – a model of the two dentate gyrus blades

How can the hippocampal system transition from episodic one-shot learning to a multi-shot learning regime and what is the utility of the resultant neural representations? This talk will explore the role of the dentate gyrus (DG) anatomy in this context. The canonical DG model suggests it performs pattern separation. More recent experimental results challenge this standard model, suggesting DG function is more complex and also supports the precise binding of objects and events to space and the integration of information across episodes. Very recent studies attribute pattern separation and pattern integration to anatomically distinct parts of the DG (the suprapyramidal blade vs the infrapyramidal blade). We propose a computational model that investigates this distinction. In the model the two processing streams (potentially localized in separate blades) contribute to the storage of distinct episodic memories, and the integration of information across episodes, respectively. The latter forms generalized expectations across episodes, eventually forming a cognitive map. We train the model with two data sets, MNIST and plausible entorhinal cortex inputs. The comparison between the two streams allows for the calculation of a prediction error, which can drive the storage of poorly predicted memories and the forgetting of well-predicted memories. We suggest that differential processing across the DG aids in the iterative construction of spatial cognitive maps to serve the generation of location-dependent expectations, while at the same time preserving episodic memory traces of idiosyncratic events.

Vision for perception versus vision for action: dissociable contributions of visual sensory drives from primary visual cortex and superior colliculus neurons to orienting behaviors

The primary visual cortex (V1) directly projects to the superior colliculus (SC) and is believed to provide sensory drive for eye movements. Consistent with this, a majority of saccade-related SC neurons also exhibit short-latency, stimulus-driven visual responses, which are additionally feature-tuned. However, direct neurophysiological comparisons of the visual response properties of the two anatomically-connected brain areas are surprisingly lacking, especially with respect to active looking behaviors. I will describe a series of experiments characterizing visual response properties in primate V1 and SC neurons, exploring feature dimensions like visual field location, spatial frequency, orientation, contrast, and luminance polarity. The results suggest a substantial, qualitative reformatting of SC visual responses when compared to V1. For example, SC visual response latencies are actively delayed, independent of individual neuron tuning preferences, as a function of increasing spatial frequency, and this phenomenon is directly correlated with saccadic reaction times. Such “coarse-to-fine” rank ordering of SC visual response latencies as a function of spatial frequency is much weaker in V1, suggesting a dissociation of V1 responses from saccade timing. Consistent with this, when we next explored trial-by-trial correlations of individual neurons’ visual response strengths and visual response latencies with saccadic reaction times, we found that most SC neurons exhibited, on a trial-by-trial basis, stronger and earlier visual responses for faster saccadic reaction times. Moreover, these correlations were substantially higher for visual-motor neurons in the intermediate and deep layers than for more superficial visual-only neurons. No such correlations existed systematically in V1. Thus, visual responses in SC and V1 serve fundamentally different roles in active vision: V1 jumpstarts sensing and image analysis, but SC jumpstarts moving. I will finish by demonstrating, using V1 reversible inactivation, that, despite reformatting of signals from V1 to the brainstem, V1 is still a necessary gateway for visually-driven oculomotor responses to occur, even for the most reflexive of eye movement phenomena. This is a fundamental difference from rodent studies demonstrating clear V1-independent processing in afferent visual pathways bypassing the geniculostriate one, and it demonstrates the importance of multi-species comparisons in the study of oculomotor control.

Analyzing Network-Level Brain Processing and Plasticity Using Molecular Neuroimaging

Behavior and cognition depend on the integrated action of neural structures and populations distributed throughout the brain. We recently developed a set of molecular imaging tools that enable multiregional processing and plasticity in neural networks to be studied at a brain-wide scale in rodents and nonhuman primates. Here we will describe how a novel genetically encoded activity reporter enables information flow in virally labeled neural circuitry to be monitored by fMRI. Using the reporter to perform functional imaging of synaptically defined neural populations in the rat somatosensory system, we show how activity is transformed within brain regions to yield characteristics specific to distinct output projections. We also show how this approach enables regional activity to be modeled in terms of inputs, in a paradigm that we are extending to address circuit-level origins of functional specialization in marmoset brains. In the second part of the talk, we will discuss how another genetic tool for MRI enables systematic studies of the relationship between anatomical and functional connectivity in the mouse brain. We show that variations in physical and functional connectivity can be dissociated both across individual subjects and over experience. We also use the tool to examine brain-wide relationships between plasticity and activity during an opioid treatment. This work demonstrates the possibility of studying diverse brain-wide processing phenomena using molecular neuroimaging.

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.

Updating our models of the basal ganglia using advances in neuroanatomy and computational modeling

Learning representations of specifics and generalities over time

There is a fundamental tension between storing discrete traces of individual experiences, which allows recall of particular moments in our past without interference, and extracting regularities across these experiences, which supports generalization and prediction in similar situations in the future. One influential proposal for how the brain resolves this tension is that it separates the processes anatomically into Complementary Learning Systems, with the hippocampus rapidly encoding individual episodes and the neocortex slowly extracting regularities over days, months, and years. But this does not explain our ability to learn and generalize from new regularities in our environment quickly, often within minutes. We have put forward a neural network model of the hippocampus that suggests that the hippocampus itself may contain complementary learning systems, with one pathway specializing in the rapid learning of regularities and a separate pathway handling the region’s classic episodic memory functions. This proposal has broad implications for how we learn and represent novel information of specific and generalized types, which we test across statistical learning, inference, and category learning paradigms. We also explore how this system interacts with slower-learning neocortical memory systems, with empirical and modeling investigations into how the hippocampus shapes neocortical representations during sleep. Together, the work helps us understand how structured information in our environment is initially encoded and how it then transforms over time.

Memory: types and neuroanatomical basis

Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions

Understanding how macroscale brain dynamics are shaped by microscale mechanisms is crucial in neuroscience. We investigate this relationship in animal models by directly manipulating cellular properties and measuring whole-brain responses using resting-state fMRI. Specifically, we explore the impact of chemogenetically neuromodulating D1 medium spiny neurons in the dorsomedial caudate putamen (CPdm) on BOLD dynamics within a striato-thalamo-cortical circuit in mice. Our findings indicate that CPdm neuromodulation alters BOLD dynamics in thalamic subregions projecting to the dorsomedial striatum, influencing both local and inter-regional connectivity in cortical areas. This study contributes to understanding structure–function relationships in shaping inter-regional communication between subcortical and cortical levels.

From primate anatomy to human neuroimaging: insights into the circuits underlying psychiatric disease and neuromodulation; Large-scale imaging of neural circuits: towards a microscopic human connectome

On Thursday, October 26th, we will host Anastasia Yendiki and Suzanne Haber. Anastasia Yendiki, PhD, is an Associate Professor in Radiology at the Harvard Medical School and an Associate Investigator at the Massachusetts General Hospital and Athinoula A. Martinos Center. Suzanne Haber, PhD, is a Professor at the University of Rochester and runs a lab at McLean hospital at Harvard Medical School in Boston. She has received numerous awards for her work on neuroanatomy. Beside her scientific presentation, she will give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!

Location, time and type of epileptic activity influence how sleep modulates epilepsy

Sleep and epilepsy are tightly interconnected: On the one hand disturbed sleep is known to negatively affect epilepsy, whereas on the other hand epilepsy negatively impacts sleep. In this talk, we leverage on the unique opportunity provided by simultaneous stereo-EEG and sleep recordings to disentangle these relationships. We will discuss latest evidence on if anatomy (temporal vs. extratemporal), time (early vs. late sleep), and type of epileptic activity (ictal vs. interictal) influence how epileptic activity is modulated by sleep. After this talk, attendees will have a more nuanced understanding of the contributions of location, time and type of epileptic activity in the relationship between sleep and epilepsy.

Brain Connectivity Workshop

Founded in 2002, the Brain Connectivity Workshop (BCW) is an annual international meeting for in-depth discussions of all aspects of brain connectivity research. By bringing together experts in computational neuroscience, neuroscience methodology and experimental neuroscience, it aims to improve the understanding of the relationship between anatomical connectivity, brain dynamics and cognitive function. These workshops have a unique format, featuring only short presentations followed by intense discussion. This year’s workshop is co-organised by Wellcome, putting the spotlight on brain connectivity in mental health disorders. We look forward to having you join us for this exciting, thought-provoking and inclusive event.

Obesity and Brain – Bidirectional Influences

The regulation of body weight relies on homeostatic mechanisms that use a combination of internal signals and external cues to initiate and terminate food intake. Homeostasis depends on intricate communication between the body and the hypothalamus involving numerous neural and hormonal signals. However, there is growing evidence that higher-level cognitive function may also influence energy balance. For instance, research has shown that BMI is consistently linked to various brain, cognitive, and personality measures, implicating executive, reward, and attentional systems. Moreover, the rise in obesity rates over the past half-century is attributed to the affordability and widespread availability of highly processed foods, a phenomenon that contradicts the idea that food intake is solely regulated by homeostasis. I will suggest that prefrontal systems involved in value computation and motivation act to limit food overconsumption when food is scarce or expensive, but promote over-eating when food is abundant, an optimum strategy from an economic standpoint. I will review the genetic and neuroscience literature on the CNS control of body weight. I will present recent studies supporting a role of prefrontal systems in weight control. I will also present contradictory evidence showing that frontal executive and cognitive findings in obesity may be a consequence not a cause of increased hunger. Finally I will review the effects of obesity on brain anatomy and function. Chronic adiposity leads to cerebrovascular dysfunction, cortical thinning, and cognitive impairment. As the most common preventable risk factor for dementia, obesity poses a significant threat to brain health. I will conclude by reviewing evidence for treatment of obesity in adults to prevent brain disease.

Prox2+ and Runx3+ vagal sensory neurons regulate esophageal motility

Sensory neurons of the vagus nerve monitor distention and stretch in the gastrointestinal tract. We used genetically guided anatomical tracing, optogenetics and electrophysiology to identify and characterize two vagal sensory neuronal subtypes expressing Prox2 and Runx3. We show that these neuronal subtypes innervate the esophagus where they display regionalized innervation patterns. Electrophysiological analyses showed that they are both low threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis and swallowing in freely behaving animals. Our work reveals the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.

Hippocampal network dynamics during impaired working memory in epileptic mice

Memory impairment is a common cognitive deficit in temporal lobe epilepsy (TLE). The hippocampus is severely altered in TLE exhibiting multiple anatomical changes that lead to a hyperexcitable network capable of generating frequent epileptic discharges and seizures. In this study we investigated whether hippocampal involvement in epileptic activity drives working memory deficits using bilateral LFP recordings from CA1 during task performance. We discovered that epileptic mice experienced focal rhythmic discharges (FRDs) while they performed the spatial working memory task. Spatial correlation analysis revealed that FRDs were often spatially stable on the maze and were most common around reward zones (25 ‰) and delay zones (50 ‰). Memory performance was correlated with stability of FRDs, suggesting that spatially unstable FRDs interfere with working memory codes in real time.

Connecting performance benefits on visual tasks to neural mechanisms using convolutional neural networks

Behavioral studies have demonstrated that certain task features reliably enhance classification performance for challenging visual stimuli. These include extended image presentation time and the valid cueing of attention. Here, I will show how convolutional neural networks can be used as a model of the visual system that connects neural activity changes with such performance changes. Specifically, I will discuss how different anatomical forms of recurrence can account for better classification of noisy and degraded images with extended processing time. I will then show how experimentally-observed neural activity changes associated with feature attention lead to observed performance changes on detection tasks. I will also discuss the implications these results have for how we identify the neural mechanisms and architectures important for behavior.

Gut Feelings: The Microbiome as a Key Regulator of Brain & Behaviour Across the Lifespan

Building System Models of Brain-Like Visual Intelligence with Brain-Score

Research in the brain and cognitive sciences attempts to uncover the neural mechanisms underlying intelligent behavior in domains such as vision. Due to the complexities of brain processing, studies necessarily had to start with a narrow scope of experimental investigation and computational modeling. I argue that it is time for our field to take the next step: build system models that capture a range of visual intelligence behaviors along with the underlying neural mechanisms. To make progress on system models, we propose integrative benchmarking – integrating experimental results from many laboratories into suites of benchmarks that guide and constrain those models at multiple stages and scales. We show-case this approach by developing Brain-Score benchmark suites for neural (spike rates) and behavioral experiments in the primate visual ventral stream. By systematically evaluating a wide variety of model candidates, we not only identify models beginning to match a range of brain data (~50% explained variance), but also discover that models’ brain scores are predicted by their object categorization performance (up to 70% ImageNet accuracy). Using the integrative benchmarks, we develop improved state-of-the-art system models that more closely match shallow recurrent neuroanatomy and early visual processing to predict primate temporal processing and become more robust, and require fewer supervised synaptic updates. Taken together, these integrative benchmarks and system models are first steps to modeling the complexities of brain processing in an entire domain of intelligence.

Odd dynamics of living chiral crystals

The emergent dynamics exhibited by collections of living organisms often shows signatures of symmetries that are broken at the single-organism level. At the same time, organism development itself encompasses a well-coordinated sequence of symmetry breaking events that successively transform a single, nearly isotropic cell into an animal with well-defined body axis and various anatomical asymmetries. Combining these key aspects of collective phenomena and embryonic development, we describe here the spontaneous formation of hydrodynamically stabilized active crystals made of hundreds of starfish embryos that gather during early development near fluid surfaces. We describe a minimal hydrodynamic theory that is fully parameterized by experimental measurements of microscopic interactions among embryos. Using this theory, we can quantitatively describe the stability, formation and rotation of crystals and rationalize the emergence of mechanical properties that carry signatures of an odd elastic material. Our work thereby quantitatively connects developmental symmetry breaking events on the single-embryo level with remarkable macroscopic material properties of a novel living chiral crystal system.

Binocular combination of light

The brain combines signals across the eyes. This process is well-characterized for the perceptual anatomical pathway through V1 that primarily codes contrast, where interocular normalization ensures that responses are approximately equal for monocular and binocular stimulation. But we have much less understanding of how luminance is combined binocularly, both in the cortex and in subcortical structures that govern pupil diameter. Here I will describe the results of experiments using a novel combined EEG and pupillometry paradigm to simultaneously index binocular combination of luminance flicker in parallel pathways. The results show evidence of a more linear process than for spatial contrast, that may reflect different operational constraints in distinct anatomical pathways.

The functional architecture of the human entorhinal-hippocampal circuitry

Cognitive functions like episodic memory require the formation of cohesive representations. Critical for that process is the entorhinal-hippocampal circuitry’s interaction with cortical information streams and the circuitry’s inner communication. With ultra-high field functional imaging we investigated the functional architecture of the human entorhinal-hippocampal circuitry. We identified an organization that is consistent with convergence of information in anterior and lateral entorhinal subregions and the subiculum/CA1 border while keeping a second route specific for scene processing in a posterior-medial entorhinal subregion and the distal subiculum. Our findings agree with information flow along information processing routes which functionally split the entorhinal-hippocampal circuitry along its transversal axis. My talk will demonstrate how ultra-high field imaging in humans can bridge the gap between anatomical and electrophysiological findings in rodents and our understanding of human cognition. Moreover, I will point out the implications that basic research on functional architecture has for cognitive and clinical research perspectives.

Feedforward and feedback processes in visual recognition

Progress in deep learning has spawned great successes in many engineering applications. As a prime example, convolutional neural networks, a type of feedforward neural networks, are now approaching – and sometimes even surpassing – human accuracy on a variety of visual recognition tasks. In this talk, however, I will show that these neural networks and their recent extensions exhibit a limited ability to solve seemingly simple visual reasoning problems involving incremental grouping, similarity, and spatial relation judgments. Our group has developed a recurrent network model of classical and extra-classical receptive field circuits that is constrained by the anatomy and physiology of the visual cortex. The model was shown to account for diverse visual illusions providing computational evidence for a novel canonical circuit that is shared across visual modalities. I will show that this computational neuroscience model can be turned into a modern end-to-end trainable deep recurrent network architecture that addresses some of the shortcomings exhibited by state-of-the-art feedforward networks for solving complex visual reasoning tasks. This suggests that neuroscience may contribute powerful new ideas and approaches to computer science and artificial intelligence.

The 15th David Smith Lecture in Anatomical Neuropharmacology: Professor Tim Bliss, "Memories of long term potentiation

The David Smith Lectures in Anatomical Neuropharmacology, Part of the 'Pharmacology, Anatomical Neuropharmacology and Drug Discovery Seminars Series', Department of Pharmacology, University of Oxford. The 15th David Smith Award Lecture in Anatomical Neuropharmacology will be delivered by Professor Tim Bliss, Visiting Professor at UCL and the Frontier Institutes of Science and Technology, Xi’an Jiaotong University, China, and is hosted by Professor Nigel Emptage. This award lecture was set up to celebrate the vision of Professor A David Smith, namely, that explanations of the action of drugs on the brain requires the definition of neuronal circuits, the location and interactions of molecules. Tim Bliss gained his PhD at McGill University in Canada. He joined the MRC National Institute for Medical Research in Mill Hill, London in 1967, where he remained throughout his career. His work with Terje Lømo in the late 1960’s established the phenomenon of long-term potentiation (LTP) as the dominant synaptic model of how the mammalian brain stores memories. He was elected as a Fellow of the Royal Society in 1994 and is a founding fellow of the Academy of Medical Sciences. He shared the Bristol Myers Squibb award for Neuroscience with Eric Kandel in 1991, the Ipsen Prize for Neural Plasticity with Richard Morris and Yadin Dudai in 2013. In May 2012 he gave the annual Croonian Lecture at the Royal Society on ‘The Mechanics of Memory’. In 2016 Tim, with Graham Collingridge and Richard Morris shared the Brain Prize, one of the world's most coveted science prizes. Abstract: In 1966 there appeared in Acta Physiologica Scandinavica an abstract of a talk given by Terje Lømo, a PhD student in Per Andersen’s laboratory at the University of Oslo. In it Lømo described the long-lasting potentiation of synaptic responses in the dentate gyrus of the anaesthetised rabbit that followed repeated episodes of 10-20Hz stimulation of the perforant path. Thus, heralded and almost entirely unnoticed, one of the most consequential discoveries of 20th century neuroscience was ushered into the world. Two years later I arrived in Oslo as a visiting post-doc from the National Institute for Medical Research in Mill Hill, London. In this talk I recall the events that led us to embark on a systematic reinvestigation of the phenomenon now known as long-term potentiation (LTP) and will then go on to describe the discoveries and controversies that enlivened the early decades of research into synaptic plasticity in the mammalian brain. I will end with an observer’s view of the current state of research in the field, and what we might expect from it in the future.

What the fly’s eye tells the fly’s brain…and beyond

Fly Escape Behaviors: Flexible and Modular We have identified a set of escape maneuvers performed by a fly when confronted by a looming object. These escape responses can be divided into distinct behavioral modules. Some of the modules are very stereotyped, as when the fly rapidly extends its middle legs to jump off the ground. Other modules are more complex and require the fly to combine information about both the location of the threat and its own body posture. In response to an approaching object, a fly chooses some varying subset of these behaviors to perform. We would like to understand the neural process by which a fly chooses when to perform a given escape behavior. Beyond an appealing set of behaviors, this system has two other distinct advantages for probing neural circuitry. First, the fly will perform escape behaviors even when tethered such that its head is fixed and neural activity can be imaged or monitored using electrophysiology. Second, using Drosophila as an experimental animal makes available a rich suite of genetic tools to activate, silence, or image small numbers of cells potentially involved in the behaviors. Neural Circuits for Escape Until recently, visually induced escape responses have been considered a hardwired reflex in Drosophila. White-eyed flies with deficient visual pigment will perform a stereotyped middle-leg jump in response to a light-off stimulus, and this reflexive response is known to be coordinated by the well-studied giant fiber (GF) pathway. The GFs are a pair of electrically connected, large-diameter interneurons that traverse the cervical connective. A single GF spike results in a stereotyped pattern of muscle potentials on both sides of the body that extends the fly's middle pair of legs and starts the flight motor. Recently, we have found that a fly escaping a looming object displays many more behaviors than just leg extension. Most of these behaviors could not possibly be coordinated by the known anatomy of the GF pathway. Response to a looming threat thus appears to involve activation of numerous different neural pathways, which the fly may decide if and when to employ. Our goal is to identify the descending pathways involved in coordinating these escape behaviors as well as the central brain circuits, if any, that govern their activation. Automated Single-Fly Screening We have developed a new kind of high-throughput genetic screen to automatically capture fly escape sequences and quantify individual behaviors. We use this system to perform a high-throughput genetic silencing screen to identify cell types of interest. Automation permits analysis at the level of individual fly movements, while retaining the capacity to screen through thousands of GAL4 promoter lines. Single-fly behavioral analysis is essential to detect more subtle changes in behavior during the silencing screen, and thus to identify more specific components of the contributing circuits than previously possible when screening populations of flies. Our goal is to identify candidate neurons involved in coordination and choice of escape behaviors. Measuring Neural Activity During Behavior We use whole-cell patch-clamp electrophysiology to determine the functional roles of any identified candidate neurons. Flies perform escape behaviors even when their head and thorax are immobilized for physiological recording. This allows us to link a neuron's responses directly to an action.

Translation at the Synapse

The complex morphology of neurons, with synapses located hundreds of microns from the cell body, necessitates the localization of important cell biological machines, including ribosomes, within dendrites and axons. Local translation of mRNAs is important for the function and plasticity of synapses. Using advanced sequencing and imaging techniques we have updated our understanding of the local transcriptome and identified the local translatome- identifying over 800 transcripts for which local translation is the dominant source of protein. In addition, we have explored the unique mechanisms neurons use to meet protein demands at synapses, identifying surprising features of neuronal and synaptic protein synthesis.

Unchanging and changing: hardwired taste circuits and their top-down control

The taste system detects 5 major categories of ethologically relevant stimuli (sweet, bitter, umami, sour and salt) and accordingly elicits acceptance or avoidance responses. While these taste responses are innate, the taste system retains a remarkable flexibility in response to changing external and internal contexts. Taste chemicals are first recognized by dedicated taste receptor cells (TRCs) and then transmitted to the cortex via a multi-station relay. I reasoned that if I could identify taste neural substrates along this pathway, it would provide an entry to decipher how taste signals are encoded to drive innate response and modulated to facilitate adaptive response. Given the innate nature of taste responses, these neural substrates should be genetically identifiable. I therefore exploited single-cell RNA sequencing to isolate molecular markers defining taste qualities in the taste ganglion and the nucleus of the solitary tract (NST) in the brainstem, the two stations transmitting taste signals from TRCs to the brain. How taste information propagates from the ganglion to the brain is highly debated (i.e., does taste information travel in labeled-lines?). Leveraging these genetic handles, I demonstrated one-to-one correspondence between ganglion and NST neurons coding for the same taste. Importantly, inactivating one ‘line’ did not affect responses to any other taste stimuli. These results clearly showed that taste information is transmitted to the brain via labeled lines. But are these labeled lines aptly adapted to the internal state and external environment? I studied the modulation of taste signals by conflicting taste qualities in the concurrence of sweet and bitter to understand how adaptive taste responses emerge from hardwired taste circuits. Using functional imaging, anatomical tracing and circuit mapping, I found that bitter signals suppress sweet signals in the NST via top-down modulation by taste cortex and amygdala of NST taste signals. While the bitter cortical field provides direct feedback onto the NST to amplify incoming bitter signals, it exerts negative feedback via amygdala onto the incoming sweet signal in the NST. By manipulating this feedback circuit, I showed that this top-down control is functionally required for bitter evoked suppression of sweet taste. These results illustrate how the taste system uses dedicated feedback lines to finely regulate innate behavioral responses and may have implications for the context-dependent modulation of hardwired circuits in general.

The Standard Model of the Retina

The science of the retina has reached an interesting stage of completion. There exists now a consensus standard model of this neural system - at least in the minds of many researchers - that serves as a baseline against which to evaluate new claims. The standard model links phenomena from molecular biophysics, cell biology, neuroanatomy, synaptic physiology, circuit function, and visual psychophysics. It is further supported by a normative theory explaining what the purpose is of processing visual information this way. Most new reports of retinal phenomena fit squarely within the standard model, and major revisions seem increasingly unlikely. Given that our understanding of other brain circuits with comparable complexity is much more rudimentary, it is worth considering an example of what success looks like. In this talk I will summarize what I think are the ingredients that led to this mature understanding of the retina. Equally important, a number of practices and concepts that are currently en vogue in neuroscience were not needed or indeed counterproductive. I look forward to debating how these lessons might extend to other areas of brain research.

Neural Representations of Social Homeostasis

How does our brain rapidly determine if something is good or bad? How do we know our place within a social group? How do we know how to behave appropriately in dynamic environments with ever-changing conditions? The Tye Lab is interested in understanding how neural circuits important for driving positive and negative motivational valence (seeking pleasure or avoiding punishment) are anatomically, genetically and functionally arranged. We study the neural mechanisms that underlie a wide range of behaviors ranging from learned to innate, including social, feeding, reward-seeking and anxiety-related behaviors. We have also become interested in “social homeostasis” -- how our brains establish a preferred set-point for social contact, and how this maintains stability within a social group. How are these circuits interconnected with one another, and how are competing mechanisms orchestrated on a neural population level? We employ optogenetic, electrophysiological, electrochemical, pharmacological and imaging approaches to probe these circuits during behavior.

A draft connectome for ganglion cell types of the mouse retina

The visual system of the brain is highly parallel in its architecture. This is clearly evident in the outputs of the retina, which arise from neurons called ganglion cells. Work in our lab has shown that mammalian retinas contain more than a dozen distinct types of ganglion cells. Each type appears to filter the retinal image in a unique way and to relay this processed signal to a specific set of targets in the brain. My students and I are working to understand the meaning of this parallel organization through electrophysiological and anatomical studies. We record from light-responsive ganglion cells in vitro using the whole-cell patch method. This allows us to correlate directly the visual response properties, intrinsic electrical behavior, synaptic pharmacology, dendritic morphology and axonal projections of single neurons. Other methods used in the lab include neuroanatomical tracing techniques, single-unit recording and immunohistochemistry. We seek to specify the total number of ganglion cell types, the distinguishing characteristics of each type, and the intraretinal mechanisms (structural, electrical, and synaptic) that shape their stimulus selectivities. Recent work in the lab has identified a bizarre new ganglion cell type that is also a photoreceptor, capable of responding to light even when it is synaptically uncoupled from conventional (rod and cone) photoreceptors. These ganglion cells appear to play a key role in resetting the biological clock. It is just this sort of link, between a specific cell type and a well-defined behavioral or perceptual function, that we seek to establish for the full range of ganglion cell types. My research concerns the structural and functional organization of retinal ganglion cells, the output cells of the retina whose axons make up the optic nerve. Ganglion cells exhibit great diversity both in their morphology and in their responses to light stimuli. On this basis, they are divisible into a large number of types (>15). Each ganglion-cell type appears to send its outputs to a specific set of central visual nuclei. This suggests that ganglion cell heterogeneity has evolved to provide each visual center in the brain with pre-processed representations of the visual scene tailored to its specific functional requirements. Though the outline of this story has been appreciated for some time, it has received little systematic exploration. My laboratory is addressing in parallel three sets of related questions: 1) How many types of ganglion cells are there in a typical mammalian retina and what are their structural and functional characteristics? 2) What combination of synaptic networks and intrinsic membrane properties are responsible for the characteristic light responses of individual types? 3) What do the functional specializations of individual classes contribute to perceptual function or to visually mediated behavior? To pursue these questions, we label retinal ganglion cells by retrograde transport from the brain; analyze in vitro their light responses, intrinsic membrane properties and synaptic pharmacology using the whole-cell patch clamp method; and reveal their morphology with intracellular dyes. Recently, we have discovered a novel ganglion cell in rat retina that is intrinsically photosensitive. These ganglion cells exhibit robust light responses even when all influences from classical photoreceptors (rods and cones) are blocked, either by applying pharmacological agents or by dissociating the ganglion cell from the retina. These photosensitive ganglion cells seem likely to serve as photoreceptors for the photic synchronization of circadian rhythms, the mechanism that allows us to overcome jet lag. They project to the circadian pacemaker of the brain, the suprachiasmatic nucleus of the hypothalamus. Their temporal kinetics, threshold, dynamic range, and spectral tuning all match known properties of the synchronization or "entrainment" mechanism. These photosensitive ganglion cells innervate various other brain targets, such as the midbrain pupillary control center, and apparently contribute to a host of behavioral responses to ambient lighting conditions. These findings help to explain why circadian and pupillary light responses persist in mammals, including humans, with profound disruption of rod and cone function. Ongoing experiments are designed to elucidate the phototransduction mechanism, including the identity of the photopigment and the nature of downstream signaling pathways. In other studies, we seek to provide a more detailed characterization of the photic responsiveness and both morphological and functional evidence concerning possible interactions with conventional rod- and cone-driven retinal circuits. These studies are of potential value in understanding and designing appropriate therapies for jet lag, the negative consequences of shift work, and seasonal affective disorder.

Crystallinity characterization of white matter in the human brain

White matter microstructure underpins cognition and function in the human brain through the facilitation of neuronal communication, and the non-invasive characterization of this structure remains an elusive goal in the neuroscience community. Efforts to assess white matter microstructure are hampered by the sheer amount of information needed for characterization. Current techniques address this problem by representing white matter features with single scalars that are often not easy to interpret. Here, we address these issues by introducing tools from soft matter for the characterization of white matter microstructure. We investigate structure on a mesoscopic scale by analyzing its homogeneity and determining which regions of the brain are structurally homogeneous, or ``crystalline" in the context of materials science. We find that crystallinity is a reliable metric that varies across the brain along interpretable lines of anatomical difference. We also parcellate white matter into ``crystal grains," or contiguous sets of voxels of high structural similarity, and find overlap with other white matter parcellations. Our results provide new means of assessing white matter microstructure on multiple length scales, and open new avenues of future inquiry.

The evolution and development of visual complexity: insights from stomatopod visual anatomy, physiology, behavior, and molecules

Bioluminescence, which is rare on land, is extremely common in the deep sea, being found in 80% of the animals living between 200 and 1000 m. These animals rely on bioluminescence for communication, feeding, and/or defense, so the generation and detection of light is essential to their survival. Our present knowledge of this phenomenon has been limited due to the difficulty in bringing up live deep-sea animals to the surface, and the lack of proper techniques needed to study this complex system. However, new genomic techniques are now available, and a team with extensive experience in deep-sea biology, vision, and genomics has been assembled to lead this project. This project is aimed to study three questions 1) What are the evolutionary patterns of different types of bioluminescence in deep-sea shrimp? 2) How are deep-sea organisms’ eyes adapted to detect bioluminescence? 3) Can bioluminescent organs (called photophores) detect light in addition to emitting light? Findings from this study will provide valuable insight into a complex system vital to communication, defense, camouflage, and species recognition. This study will bring monumental contributions to the fields of deep sea and evolutionary biology, and immediately improve our understanding of bioluminescence and light detection in the marine environment. In addition to scientific advancement, this project will reach K-college aged students through the development and dissemination of educational tools, a series of molecular and organismal-based workshops, museum exhibits, public seminars, and biodiversity initiatives.

Emergence of homochirality in large molecular systems

The question of the origin of homochirality of living matter, or the dominance of one handedness for all molecules of life across the entire biosphere, is a long-standing puzzle in the research on the Origin of Life. In the fifties, Frank proposed a mechanism to explain homochirality based on the properties of a simple autocatalytic network containing only a few chemical species. Following this work, chemists struggled to find experimental realizations of this model, possibly due to a lack of proper methods to identify autocatalysis [1]. In any case, a model based on a few chemical species seems rather limited, because prebiotic earth is likely to have consisted of complex ‘soups’ of chemicals. To include this aspect of the problem, we recently proposed a mechanism based on certain features of large out-of-equilibrium chemical networks [2]. We showed that a phase transition towards an homochiral state is likely to occur as the number of chiral species in the system becomes large or as the amount of free energy injected into the system increases. Through an analysis of large chemical databases, we showed that there is no need for very large molecules for chiral species to dominate over achiral ones; it already happens when molecules contain about 10 heavy atoms. We also analyzed the various conventions used to measure chirality and discussed the relative chiral signs adopted by different groups of molecules [3]. We then proposed a generalization of Frank’s model for large chemical networks, which we characterized using random matrix theory. This analysis includes sparse networks, suggesting that the emergence of homochirality is a robust and generic transition. References: [1] A. Blokhuis, D. Lacoste, and P. Nghe, PNAS (2020), 117, 25230. [2] G. Laurent, D. Lacoste, and P. Gaspard, PNAS (2021) 118 (3) e2012741118. [3] G. Laurent, D. Lacoste, and P. Gaspard, Proc. R. Soc. A 478:20210590 (2022).

Functional segregation of rostral and caudal hippocampus in associative memory

It has long been established that the hippocampus plays a crucial role for episodic memory. As opposed to the modular approach, now it is generally assumed that being a complex structure, the HC performs multiplex interconnected functions, whose hierarchical organization provides basis for the higher cognitive functions such as semantics-based encoding and retrieval. However, the «where, when and how» properties of distinct memory aspects within and outside the HC are still under debate. Here we used a visual associative memory task as a probe to test the hypothesis about the differential involvement of the rostral and caudal portions of the human hippocampus in memory encoding, recognition and associative recall. In epilepsy patients implanted with stereo-EEG, we show that at retrieval the rostral HC is selectively active for recognition memory, whereas the caudal HC is selectively active for the associative memory. Low frequency desynchronization and high frequency synchronization characterize the temporal dynamic in encoding and retrieval. Therefore, we describe here anatomical segregation in the hippocampal contributions to associative and recognition memory.

Human visual cortex as a window into the developing brain

Remembering immunity: Neuronal representation of immune responses

Accumulating data indicate that the brain can affect immunity, as evidenced, for example, by the effects of stress, stroke, and reward system activity on the peripheral immune system. However, our understanding of this neuroimmune interaction is still limited. Importantly, we do not know how the brain evaluates and represents the state of the immune system. In this talk, I will present our latest study from our lab, designed to test the existence of immune-related information in the brain and determine its relevance to immune regulation. We hypothesized that the InsCtx, specifically the posterior InsCtx (as a primary cortical site of interoception in the brain), is especially suited to contain such a representation of the immune system. Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (dextran sulfate sodium [DSS]-induced colitis and zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Moreover, using retrograde neuronal tracing, we found an anatomical efferent pathway linking these InsCtx neurons to the inflamed peripheral sites. Taken together, we show that the brain can store and retrieve specific immune responses, extending the classical concept of immunological memory to neuronal representations of inflammatory information.

Orbitofrontal cortex and the integrative approach to functional neuroanatomy

The project of functional neuroanatomy typically considers single brain areas as the core functional unit of the brain. Functional neuroanatomists typically use specialized tasks that are designed to isolate hypothesized functions from other cognitive processes. Our lab takes a broader view; specifically, we consider brain regions as parts of larger circuits and we take cognitive processes as part of more complex behavioral repertoires. In my talk, I will discuss the ramifications of this perspective for thinking about the role of the orbitofrontal cortex. I will discuss results of recent experiments from my lab that tackle the question of OFC function within the context of larger brain networks and in freely moving foraging tasks. I will argue that this perspective challenges conventional accounts of the role of OFC and invites new ones. I will conclude by speculating on implications for the practice of functional neuroanatomy.

Flexible motor sequence generation by thalamic control of cortical dynamics through low-rank connectivity perturbations

One of the fundamental functions of the brain is to flexibly plan and control movement production at different timescales to efficiently shape structured behaviors. I will present a model that clarifies how these complex computations could be performed in the mammalian brain, with an emphasis on the learning of an extendable library of autonomous motor motifs and the flexible stringing of these motifs in motor sequences. To build this model, we took advantage of the fact that the anatomy of the circuits involved is well known. Our results show how these architectural constraints lead to a principled understanding of how strategically positioned plastic connections located within motif-specific thalamocortical loops can interact with cortical dynamics that are shared across motifs to create an efficient form of modularity. This occurs because the cortical dynamics can be controlled by the activation of as few as one thalamic unit, which induces a low-rank perturbation of the cortical connectivity, and significantly expands the range of outputs that the network can produce. Finally, our results show that transitions between any motifs can be facilitated by a specific thalamic population that participates in preparing cortex for the execution of the next motif. Taken together, our model sheds light on the neural network mechanisms that can generate flexible sequencing of varied motor motifs.

Integrators in short- and long-term memory

The accumulation and storage of information in memory is a fundamental computation underlying animal behavior. In many brain regions and task paradigms, ranging from motor control to navigation to decision-making, such accumulation is accomplished through neural integrator circuits that enable external inputs to move a system’s population-wide patterns of neural activity along a continuous attractor. In the first portion of the talk, I will discuss our efforts to dissect the circuit mechanisms underlying a neural integrator from a rich array of anatomical, physiological, and perturbation experiments. In the second portion of the talk, I will show how the accumulation and storage of information in long-term memory may also be described by attractor dynamics, but now within the space of synaptic weights rather than neural activity. Altogether, this work suggests a conceptual unification of seemingly distinct short- and long-term memory processes.

Emotions are constructed of more basic networks

It has long been assumed that certain “basic” emotions emerge from anatomically ingrained circuits. Yet growing research suggests that emotions emerge from more basic networks that comprise the brain’s basic functional architecture. In this talk, I’ll discuss evidence that human emotional experiences are associated with the co-activation of broadscale networks subserving psychological functions that are not specific to emotion.

Frontal circuit specialisations for information search and decision making

During primate evolution, prefrontal cortex (PFC) expanded substantially relative to other cortical areas. The expansion of PFC circuits likely supported the increased cognitive abilities of humans and anthropoids to sample information about their environment, evaluate that information, plan, and decide between different courses of action. What quantities do these circuits compute as information is being sampled towards and a decision is being made? And how can they be related to anatomical specialisations within and across PFC? To address this, we recorded PFC activity during value-based decision making using single unit recording in non-human primates and magnetoencephalography in humans. At a macrocircuit level, we found that value correlates differ substantially across PFC subregions. They are heavily shaped by each subregion’s anatomical connections and by the decision-maker’s current locus of attention. At a microcircuit level, we found that the temporal evolution of value correlates can be predicted using cortical recurrent network models that temporally integrate incoming decision evidence. These models reflect the fact that PFC circuits are highly recurrent in nature and have synaptic properties that support persistent activity across temporally extended cognitive tasks. Our findings build upon recent work describing economic decision making as a process of attention-weighted evidence integration across time.

Brain chart for the human lifespan

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight. Here, we built an interactive resource to benchmark brain morphology, www.brainchart.io, derived from any current or future sample of magnetic resonance imaging (MRI) data. With the goal of basing these reference charts on the largest and most inclusive dataset available, we aggregated 123,984 MRI scans from 101,457 participants aged from 115 days post-conception through 100 postnatal years, across more than 100 primary research studies. Cerebrum tissue volumes and other global or regional MRI metrics were quantified by centile scores, relative to non-linear trajectories of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones; showed high stability of individual centile scores over longitudinal assessments; and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared to non-centiled MRI phenotypes, and provided a standardised measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In sum, brain charts are an essential first step towards robust quantification of individual deviations from normative trajectories in multiple, commonly-used neuroimaging phenotypes. Our collaborative study proves the principle that brain charts are achievable on a global scale over the entire lifespan, and applicable to analysis of diverse developmental and clinical effects on human brain structure.

How does seeing help listening? Audiovisual integration in Auditory Cortex

Multisensory responses are ubiquitous in so-called unisensory cortex. However, despite their prevalence, we have very little understanding of what – if anything - they contribute to perception. In this talk I will focus on audio-visual integration in auditory cortex. Anatomical tracing studies highlight visual cortex as one source of visual input to auditory cortex. Using cortical cooling we test the hypothesis that these inputs support audiovisual integration in ferret auditory cortex. Behavioural studies in humans support the idea that visual stimuli can help listeners to parse an auditory scene. This effect is paralleled in single units in auditory cortex, where responses to a sound mixture can be determined by the timing of a visual stimulus such that sounds that are temporally coherent with a visual stimulus are preferentially represented. Our recent data therefore support the idea that one role for the early integration of auditory and visual signals in auditory cortex is to support auditory scene analysis, and that visual cortex plays a key role in this process.

NMC4 Short Talk: Synchronization in the Connectome: Metastable oscillatory modes emerge from interactions in the brain spacetime network

The brain exhibits a rich repertoire of oscillatory patterns organized in space, time and frequency. However, despite ever more-detailed characterizations of spectrally-resolved network patterns, the principles governing oscillatory activity at the system-level remain unclear. Here, we propose that the transient emergence of spatially organized brain rhythms are signatures of weakly stable synchronization between subsets of brain areas, naturally occurring at reduced collective frequencies due to the presence of time delays. To test this mechanism, we build a reduced network model representing interactions between local neuronal populations (with damped oscillatory response at 40Hz) coupled in the human neuroanatomical network. Following theoretical predictions, weakly stable cluster synchronization drives a rich repertoire of short-lived (or metastable) oscillatory modes, whose frequency inversely depends on the number of units, the strength of coupling and the propagation times. Despite the significant degree of reduction, we find a range of model parameters where the frequencies of collective oscillations fall in the range of typical brain rhythms, leading to an optimal fit of the power spectra of magnetoencephalographic signals from 89 heathy individuals. These findings provide a mechanistic scenario for the spontaneous emergence of frequency-specific long-range phase-coupling observed in magneto- and electroencephalographic signals as signatures of resonant modes emerging in the space-time structure of the Connectome, reinforcing the importance of incorporating realistic time delays in network models of oscillatory brain activity.

NMC4 Short Talk: A mechanism for inter-areal coherence through communication based on connectivity and oscillatory power

Inter-areal coherence between cortical field-potentials is a widespread phenomenon and depends on numerous behavioral and cognitive factors. It has been hypothesized that inter-areal coherence reflects phase-synchronization between local oscillations and flexibly gates communication. We reveal an alternative mechanism, where coherence results from and is not the cause of communication, and naturally emerges as a consequence of the fact that spiking activity in a sending area causes post-synaptic inputs both in the same area and in other areas. Consequently, coherence depends in a lawful manner on oscillatory power and phase-locking in a sending area and inter-areal connectivity. We show that changes in oscillatory power explain prominent changes in fronto-parietal beta-coherence with movement and memory, and LGN-V1 gamma-coherence with arousal and visual stimulation. Optogenetic silencing of a receiving area and E/I network simulations demonstrate that afferent synaptic inputs rather than spiking entrainment are the main determinant of inter-areal coherence. These findings suggest that the unique spectral profiles of different brain areas automatically give rise to large-scale inter-areal coherence patterns that follow anatomical connectivity and continuously reconfigure as a function of behavior and cognition.

Neural representations of space in the hippocampus of a food-caching bird

Spatial memory in vertebrates requires brain regions homologous to the mammalian hippocampus. Between vertebrate clades, however, these regions are anatomically distinct and appear to produce different spatial patterns of neural activity. We asked whether hippocampal activity is fundamentally different even between distant vertebrates that share a strong dependence on spatial memory. We studied tufted titmice – food-caching birds capable of remembering many concealed food locations. We found mammalian-like neural activity in the titmouse hippocampus, including sharp-wave ripples and anatomically organized place cells. In a non-food-caching bird species, spatial firing was less informative and was exhibited by fewer neurons. These findings suggest that hippocampal circuit mechanisms are similar between birds and mammals, but that the resulting patterns of activity may vary quantitatively with species-specific ethological needs.

From aura to neuroinflammation: Has imaging resolved the puzzle of migraine pathophysiology?

In this talk I will present data from imaging studies that we have been conducting for the past 20 years trying to shed light on migraine physiopathology, from anatomical and functional MRI to positron emission tomography.

Transdiagnostic approaches to understanding neurodevelopment

Macroscopic brain organisation emerges early in life, even prenatally, and continues to develop through adolescence and into early adulthood. The emergence and continual refinement of large-scale brain networks, connecting neuronal populations across anatomical distance, allows for increasing functional integration and specialisation. This process is thought crucial for the emergence of complex cognitive processes. But how and why is this process so diverse? We used structural neuroimaging collected from a large diverse cohort, to explore how different features of macroscopic brain organisation are associated with diverse cognitive trajectories. We used diffusion-weighted imaging (DWI) to construct whole-brain white-matter connectomes. A simulated attack on each child's connectome revealed that some brain networks were strongly organized around highly connected 'hubs'. The more children's brains were critically dependent on hubs, the better their cognitive skills. Conversely, having poorly integrated hubs was a very strong risk factor for cognitive and learning difficulties across the sample. We subsequently developed a computational framework, using generative network modelling (GNM), to model the emergence of this kind of connectome organisation. Relatively subtle changes within the wiring rules of this computational framework give rise to differential developmental trajectories, because of small biases in the preferential wiring properties of different nodes within the network. Finally, we were able to use this GNM to implicate the molecular and cellular processes that govern these different growth patterns.

What is the function of auditory cortex when it develops in the absence of acoustic input?

Cortical plasticity is the neural mechanism by which the cerebrum adapts itself to its environment, while at the same time making it vulnerable to impoverished sensory or developmental experiences. Like the visual system, auditory development passes through a series of sensitive periods in which circuits and connections are established and then refined by experience. Current research is expanding our understanding of cerebral processing and organization in the deaf. In the congenitally deaf, higher-order areas of "deaf" auditory cortex demonstrate significant crossmodal plasticity with neurons responding to visual and somatosensory stimuli. This crucial cerebral function results in compensatory plasticity. Not only can the remaining inputs reorganize to substitute for those lost, but this additional circuitry also confers enhanced abilities to the remaining systems. In this presentation we will review our present understanding of the structure and function of “deaf” auditory cortex using psychophysical, electrophysiological, and connectional anatomy approaches and consider how this knowledge informs our expectations of the capabilities of cochlear implants in the developing brain.

CNStalk: Anatomo-functional organisation of the grasping network in the primate brain

Cortical functions result from the conjoint activity of different, reciprocally connected areas working together as large-scale functionally specialized networks. In the macaque brain, neural tracers and functional data have provided evidence for functionally specialized large-scale cortical networks involving temporal, parietal, and frontal areas. One of these networks, the lateral grasping network, appears to play a primary role in controlling hand action organization and recognition. Available functional and tractograpy data suggest the existence of a human counterpart of this network.

In search of me: a theoretical approach to identify the neural substrate of consciousness

A major neuroscientific challenge is to identify the neural mechanisms that support consciousness. Though experimental studies have accumulated evidence about the location of the neural substrate of consciousness, we still lack a full understanding of why certain brain areas, but not others, can support consciousness. In this talk, I will give an overview of our approach, taking advantage of the theoretical framework provided by Integrated Information Theory (IIT). First, I will introduce results showing that a maximum of integrated information within the human brain matches our best evidence concerning the location of the NSC, supporting the IIT’s prediction. Furthermore, I will discuss the possibility that the NSC can change its location and even split into two depending on the task demand. Finally, based on some graph-theoretical analyses, I will argue that the ability of different brain regions to contribute or not to consciousness depends on specific properties of their anatomical connectivity, which determines their ability to support high integrated information.

Cholinergic modulation of the cerebellum

Many studies have investigated the major glutamatergic inputs to the cerebellum, mossy fibres and climbing fibres, however far less is known about its neuromodulatory inputs. In particular, anatomical studies have described cholinergic input to the cerebellum, yet little is known about its role(s). In this talk, I will present our recent findings which demonstrate that manipulating acetylcholine receptors in the cerebellum causes effects at both a cellular and behavioural level. Activating acetylcholine receptors alters the intrinsic properties and synaptic inputs of cerebellar output neurons, and blocking these receptors results in deficits in a range of behavioural tasks.

“From the Sublime to the Stomatopod: the story from beginning to nowhere near the end.”

“Call me a marine vision scientist. Some years ago - never mind how long precisely - having little or no money in my purse, and nothing particular to interest me on shore, I thought I would sail about a little and see what animals see in the watery part of the world. It is a way I have of dividing off the spectrum, and regulating circular polarisation.” Sometimes I wish I had just set out to harpoon a white whale as it would have been easier than studying stomatopod (mantis shrimp) vision. Nowhere near as much fun of course and certainly less dangerous so in this presentation I track the history of discovery and confusion that stomatopods deliver in trying to understand what the do actually see. The talk unashamedly borrows from that of Mike Bok a few weeks ago (April 13th 2021 “The Blurry Beginnings: etc” talk) as an introduction to the system (do go look at his talk again, it is beautiful!) and goes both backwards and forwards in time, trying to provide an explanation for the design of this visual system. The journey is again one of retinal anatomy and physiology, neuroanatomy, electrophysiology, behaviour and body ornaments but this time focusses more on polarisation vision (Mike covered the colour stuff well). There is a comparative section looking at the cephalopods too and by the end, I hope you will understand where we are at with trying to understand this extraordinary way of seeing the world and why we ‘pod-people’ wave our arms around so much when asked to explain; what do stomatopods see? Maybe, to butcher another quote: “mantis shrimp have been rendered visually beautiful for vision’s sake.”

Tectal and Pretectal Circuits of the Visual Thalamus

A fresh look at the bird retina

I am working on the vertebrate retina, with a main focus on the mouse and bird retina. Currently my work is focused on three major topics: Functional and molecular analysis of electrical synapses in the retina Circuitry and functional role of retinal interneurons: horizontal cells Circuitry for light-dependent magnetoreception in the bird retina Electrical synapses Electrical synapses (gap junctions) permit fast transmission of electrical signals and passage of metabolites by means of channels, which directly connect the cytoplasm of adjoining cells. A functional gap junction channel consists of two hemichannels (one provided by each of the cells), each comprised of a set of six protein subunits, termed connexins. These building blocks exist in a variety of different subtypes, and the connexin composition determines permeability and gating properties of a gap junction channel, thereby enabling electrical synapses to meet a diversity of physiological requirements. In the retina, various connexins are expressed in different cell types. We study the cellular distribution of different connexins as well as the modulation induced by transmitter action or change of ambient light levels, which leads to altered electrical coupling properties. We are also interested in exploiting them as therapeutic avenue for retinal degeneration diseases. Horizontal cells Horizontal cells receive excitatory input from photoreceptors and provide feedback inhibition to photoreceptors and feedforward inhibition to bipolar cells. Because of strong electrical coupling horizontal cells integrate the photoreceptor input over a wide area and are thought to contribute to the antagonistic organization of bipolar cell and ganglion cell receptive fields and to tune the photoreceptor–bipolar cell synapse with respect to the ambient light conditions. However, the extent to which this influence shapes retinal output is unclear, and we aim to elucidate the functional importance of horizontal cells for retinal signal processing by studying various transgenic mouse models. Retinal circuitry for light-dependent magnetoreception in the bird We are studying which neuronal cell types and pathways in the bird retina are involved in the processing of magnetic signals. Likely, magnetic information is detected in cryptochrome-expressing photoreceptors and leaves the retina through ganglion cell axons that project via the thalamofugal pathway to Cluster N, a part of the visual wulst essential for the avian magnetic compass. Thus, we aim to elucidate the synaptic connections and retinal signaling pathways from putatively magnetosensitive photoreceptors to thalamus-projecting ganglion cells in migratory birds using neuroanatomical and electrophysiological techniques.

Thalamocortical circuits from neuroanatomy to mental representations

In highly volatile environments, performing actions that address current needs and desires is an ongoing challenge for living organisms. For example, the predictive value of environmental signals needs to be updated when predicted and actual outcomes differ. Furthermore, organisms also need to gain control over the environment through actions that are expected to produce specific outcomes. The data to be presented will show that these processes are highly reliant on thalamocortical circuits wherein thalamic nuclei make a critical contribution to adaptive decision-making, challenging the view that the thalamus only acts as a relay station for the cortical stage. Over the past few years, our work has highlighted the specific contribution of multiple thalamic nuclei in the ability to update the predictive link between events or the causal link between actions and their outcomes via the combination of targeted thalamic interventions (lesion, chemogenetics, disconnections) with behavioral procedures rooted in experimental psychology. We argue that several features of thalamocortical architecture are consistent with a prominent role for thalamic nuclei in shaping mental representations.

Frontal circuit specialisations for decision making

During primate evolution, prefrontal cortex (PFC) expanded substantially relative to other cortical areas. The expansion of PFC circuits likely supported the increased cognitive abilities of humans and anthropoids to plan, evaluate, and decide between different courses of action. But what do these circuits compute as a decision is being made, and how can they be related to anatomical specialisations within and across PFC? To address this, we recorded PFC activity during value-based decision making using single unit recording in non-human primates and magnetoencephalography in humans. At a macrocircuit level, we found that value correlates differ substantially across PFC subregions. They are heavily shaped by each subregion’s anatomical connections and by the decision-maker’s current locus of attention. At a microcircuit level, we found that the temporal evolution of value correlates can be predicted using cortical recurrent network models that temporally integrate incoming decision evidence. These models reflect the fact that PFC circuits are highly recurrent in nature and have synaptic properties that support persistent activity across temporally extended cognitive tasks. Our findings build upon recent work describing economic decision making as a process of attention-weighted evidence integration across time.

Distinct limbic-hypothalamic circuits for the generation of social behaviors

The main pillars of social behaviors involve (1) mating, where males copulate with female partners to reproduce, and (2) aggression, where males fight conspecific male competitors in territory guarding. Decades of study have identified two key regions in the hypothalamus, the medial preoptic nucleus (MPN) and the ventrolateral part of ventromedial hypothalamus (VMHvl) , that are essential for male sexual and aggressive behaviors, respectively. However, it remains ambiguous what area directs excitatory control of the hypothalamic activity and generates the initiation signal for social behaviors. Through neural tracing, in vivo optical recording and functional manipulations, we identified the estrogen receptor alpha (Esr1)-expressing cells in the posterior amygdala (PA) as a main source of excitatory inputs to the MPN and VMHvl, and key hubs in mating and fighting circuits in males. Importantly, two spatially-distinct populations in the PA regulate male sexual and aggressive behaviors, respectively. Moreover, these two subpopulations in the PA display differential molecular phenotypes, projection patterns and in vivo neural responses. Our work also observed the parallels between these social behavior circuits and basal ganglia circuits to control motivated behaviors, which Larry Swanson (2000) originally proposed based on extensive developmental and anatomical evidence.

Anatomical and functional characterization of the neuronal circuits underlying ejaculation

During sexual behavior, copulation related sensory information and modulatory signals from the brain must be integrated and converted into the motor and secretory outputs that characterize ejaculation (Lenschow and Lima, Current Opinion in Neurobiology, 2020). Studies in humans and rats suggest the existence of interneurons in the lumbar spinal cord that mediates that step: the spinal ejaculation generator (SEG). My work aimed at gaining mechanistic insights about the neuronal circuits controlling ejaculation thereby applying cutting-edge techniques. More specifically, we mapped anatomically and functionally the spinal circuit for ejaculation starting from the main muscle being involved in sperm expulsion: the bulbospongiosus muscle (BSM). Combining viral tracing strategies with electrophysiology, we specifically show that the BSM motoneurons receive direct synaptic input from a group of interneurons located in between lumbar segment 2 and 3 and expressing the peptide galanin. Electrically and optogenetically activating the galanin positive cells (the SEG) lead to the activation of the motoneurons innervating the BSM and the muscle itself. Finally, inhibition of SEG cells using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in sexual behaving animals is currently conducted to reveal whether ejaculation can be prevented.

Anatomically-aligned neural processing of the IBL task

Bernstein Conference 2024

Cortex-wide high density ECoG recordings from rat reveal diverse generators of sleep-spindles with characteristic anatomical topographies and non-stationary subcycle dynamics

Bernstein Conference 2024

Functional inter-subject alignment of MEG data outperforms anatomical alignment

Bernstein Conference 2024

Quantitative evaluation of T-Bar anatomic structure influence upon calcium concentration enhancement

Bernstein Conference 2024

An anatomically accurate circuit for short- and long-term motivational learning in fruit flies

COSYNE 2022

Predicting proprioceptive cortical anatomy and neural coding with topographic autoencoders

COSYNE 2023

Traveling UP states in the post-subiculum reveal an anatomical gradient of intrinsic properties

COSYNE 2023

Anatomically resolved oscillatory bursts orchestrate visual thalamocortical activity during naturalistic stimulus viewing

COSYNE 2025

An Anatomical Explanation of the Inverted Face Effect

COSYNE 2025

Anatomical projection atlas of the periaqueductal gray

FENS Forum 2024

Anatomical, electrophysiological, and functional characterization of lateral septal cholinergic neurons

FENS Forum 2024

Anatomical and functional dissection of orbitofrontal cortex neurons' contributions to decision confidence

FENS Forum 2024

Anatomical organization of genetically-defined prefrontal projections to sensory cortices

FENS Forum 2024

Anatomically heterogeneous pyramidal cells in supragranular layers of the dorsal cortex show the surface-to-deep firing frequency increase during natural sleep

FENS Forum 2024

Anatomofunctional characterization of the tail of the ventral tegmental area (tVTA/RMTg) in mice

FENS Forum 2024

Anatomo-functional diversity of medullary V2a neurons for limb and cranial nerve-mediated movements

FENS Forum 2024

Characterizing the fasciola cinerea: An anatomical and physiological investigation in the mouse hippocampus

FENS Forum 2024

Comparison of histological procedures and antigenicity of human postmortem brains fixed with solutions used in gross-anatomy laboratories

FENS Forum 2024

Estrogen effects on neuritogenesis of NGF-differentiated PC12 neuronal cells via genomic versus non-genomic pathways: A microanatomical analysis

FENS Forum 2024

From anatomy to functions in locomotion: An optogenetic investigation on the organisation of V2a-derived reticulospinal neurons

FENS Forum 2024

Functional and anatomical modifications of peritumoral tissue that occur along with glioma progression

FENS Forum 2024

CSF leak presenting as recurrent bilateral subdural hematoma in an adult Asian male: A case report

FENS Forum 2024

Neuroanatomical basis for the anti-nociceptive role of the relaxin-3/RXFP3 peptidergic system

FENS Forum 2024

Neuroanatomical characterisation of the cell adhesion molecule IgSF9b reveals heterogeneous synaptic localization across different regions of the mouse brain

FENS Forum 2024

NGF-sensitive interpeduncular nucleus (IPN) neurons in circuits shaping social behaviour: Anatomical and functional studies of the nucleus incertus–IPN–ventral hippocampus axis

FENS Forum 2024

Novel astrocytic translatome isolation pipeline uncovers regional and sex-specific differences in mouse brain cortex

FENS Forum 2024

O2L-001, an innovative thrombolytic to evacuate intracerebral haematoma

FENS Forum 2024

Regulation of the axonal translatome in dopaminergic circuits during development

FENS Forum 2024

The role of noradrenaline in medial forebrain bundle deep brain stimulation: A physiological and anatomical approach

FENS Forum 2024

Shared anatomical principles of the projections from the higher-order thalamus to the cortex

FENS Forum 2024

Subpopulation of thalamic neurons possesses distinct anatomical connectivities and electrophysiological properties in the anterior thalamic nucleus

FENS Forum 2024

Unraveling the complexity of stress and reward processing: Nucleus incertus responses to noxious stimulus – electrophysiological, anatomical and immediate early gene expression studies

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

Deep Reinforcement Learning for anatomically accurate musculoskeletal models to investigate neural control of movement across animal species

Neuromatch 5