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Digital Minds: Brain Development in the Age of Technology
Digital Minds: Brain Development in the Age of Technology examines how our increasingly connected world shapes mental and cognitive health. From screen time and social media to virtual interactions, this seminar delves into the latest research on how technology influences brain development, relationships, and emotional well-being. Join us to explore strategies for harnessing technology's benefits while mitigating its potential challenges, empowering you to thrive in a digital age.
Learning and Memory
This webinar on learning and memory features three experts—Nicolas Brunel, Ashok Litwin-Kumar, and Julijana Gjorgieva—who present theoretical and computational approaches to understanding how neural circuits acquire and store information across different scales. Brunel discusses calcium-based plasticity and how standard “Hebbian-like” plasticity rules inferred from in vitro or in vivo datasets constrain synaptic dynamics, aligning with classical observations (e.g., STDP) and explaining how synaptic connectivity shapes memory. Litwin-Kumar explores insights from the fruit fly connectome, emphasizing how the mushroom body—a key site for associative learning—implements a high-dimensional, random representation of sensory features. Convergent dopaminergic inputs gate plasticity, reflecting a high-dimensional “critic” that refines behavior. Feedback loops within the mushroom body further reveal sophisticated interactions between learning signals and action selection. Gjorgieva examines how activity-dependent plasticity rules shape circuitry from the subcellular (e.g., synaptic clustering on dendrites) to the cortical network level. She demonstrates how spontaneous activity during development, Hebbian competition, and inhibitory-excitatory balance collectively establish connectivity motifs responsible for key computations such as response normalization.
Unmotivated bias
In this talk, I will explore how social affective biases arise even in the absence of motivational factors as an emergent outcome of the basic structure of social learning. In several studies, we found that initial negative interactions with some members of a group can cause subsequent avoidance of the entire group, and that this avoidance perpetuates stereotypes. Additional cognitive modeling discovered that approach and avoidance behavior based on biased beliefs not only influences the evaluative (positive or negative) impressions of group members, but also shapes the depth of the cognitive representations available to learn about individuals. In other words, people have richer cognitive representations of members of groups that are not avoided, akin to individualized vs group level categories. I will end presenting a series of multi-agent reinforcement learning simulations that demonstrate the emergence of these social-structural feedback loops in the development and maintenance of affective biases.
Cell-type-specific plasticity shapes neocortical dynamics for motor learning
How do cortical circuits acquire new dynamics that drive learned movements? This webinar will focus on mouse premotor cortex in relation to learned lick-timing and explore high-density electrophysiology using our silicon neural probes alongside region and cell-type-specific acute genetic manipulations of proteins required for synaptic plasticity.
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.
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.
Sensory Consequences of Visual Actions
We use rapid eye, head, and body movements to extract information from a new part of the visual scene upon each new gaze fixation. But the consequences of such visual actions go beyond their intended sensory outcomes. On the one hand, intrinsic consequences accompany movement preparation as covert internal processes (e.g., predictive changes in the deployment of visual attention). On the other hand, visual actions have incidental consequences, side effects of moving the sensory surface to its intended goal (e.g., global motion of the retinal image during saccades). In this talk, I will present studies in which we investigated intrinsic and incidental sensory consequences of visual actions and their sensorimotor functions. Our results provide insights into continuously interacting top-down and bottom-up sensory processes, and they reify the necessity to study perception in connection to motor behavior that shapes its fundamental processes.
How what you do shapes what you see
Prosody in the voice, face, and hands changes which words you hear
Speech may be characterized as conveying both segmental information (i.e., about vowels and consonants) as well as suprasegmental information - cued through pitch, intensity, and duration - also known as the prosody of speech. In this contribution, I will argue that prosody shapes low-level speech perception, changing which speech sounds we hear. Perhaps the most notable example of how prosody guides word recognition is the phenomenon of lexical stress, whereby suprasegmental F0, intensity, and duration cues can distinguish otherwise segmentally identical words, such as "PLAto" vs. "plaTEAU" in Dutch. Work from our group showcases the vast variability in how different talkers produce stressed vs. unstressed syllables, while also unveiling the remarkable flexibility with which listeners can learn to handle this between-talker variability. It also emphasizes that lexical stress is a multimodal linguistic phenomenon, with the voice, lips, and even hands conveying stress in concert. In turn, human listeners actively weigh these multisensory cues to stress depending on the listening conditions at hand. Finally, lexical stress is presented as having a robust and lasting impact on low-level speech perception, even down to changing vowel perception. Thus, prosody - in all its multisensory forms - is a potent factor in speech perception, determining what speech sounds we hear.
The embodied brain
Understanding the brain is not only intrinsically fascinating, but also highly relevant to increase our well-being since our brain exhibits a power over the body that makes it capable both of provoking illness or facilitating the healing process. Bearing in mind this dark force, brain sciences have undergone and will undergo an important revolution, redefining its boundaries beyond the cranial cavity. During this presentation, we will discuss about the communication between the brain and other systems that shapes how we feel the external word and how we think. We are starting to unravel how our organs talk to the brain and how the brain talks back. That two-way communication encompasses a complex, body-wide system of nerves, hormones and other signals that will be discussed. This presentation aims at challenging a long history of thinking of bodily regulation as separate from "higher" mental processes. Four centuries ago, René Descartes famously conceptualized the mind as being separate from the body, it is time now to embody our mind.
Explaining an asymmetry in similarity and difference judgments
Explicit similarity judgments tend to emphasize relational information more than do difference judgments. In this talk, I propose and test the hypothesis that this asymmetry arises because human reasoners represent the relation different as the negation of the relation same (i.e., as not-same). This proposal implies that processing difference is more cognitively demanding than processing similarity. Both for verbal comparisons between word pairs, and for visual comparisons between sets of geometric shapes, participants completed a triad task in which they selected which of two options was either more similar to or more different from a standard. On unambiguous trials, one option was unambiguously more similar to the standard, either by virtue of featural similarity or by virtue of relational similarity. On ambiguous trials, one option was more featurally similar (but less relationally similar) to the standard, whereas the other was more relationally similar (but less featurally similar). Given the higher cognitive complexity of assessing relational similarity, we predicted that detecting relational difference would be particularly demanding. We found that participants (1) had more difficulty accurately detecting relational difference than they did relational similarity on unambiguous trials, and (2) tended to emphasize relational information more when judging similarity than when judging difference on ambiguous trials. The latter finding was captured by a computational model of comparison that weights relational information more heavily for similarity than for difference judgments. These results provide convergent evidence for a representational asymmetry between the relations same and different.
Asymmetric signaling across the hierarchy of cytoarchitecture within the human connectome
Cortical variations in cytoarchitecture form a sensory-fugal axis that shapes regional profiles of extrinsic connectivity and is thought to guide signal propagation and integration across the cortical hierarchy. While neuroimaging work has shown that this axis constrains local properties of the human connectome, it remains unclear whether it also shapes the asymmetric signaling that arises from higher-order topology. Here, we used network control theory to examine the amount of energy required to propagate dynamics across the sensory-fugal axis. Our results revealed an asymmetry in this energy, indicating that bottom-up transitions were easier to complete compared to top-down. Supporting analyses demonstrated that asymmetries were underpinned by a connectome topology that is wired to support efficient bottom-up signaling. Lastly, we found that asymmetries correlated with differences in communicability and intrinsic neuronal time scales and lessened throughout youth. Our results show that cortical variation in cytoarchitecture may guide the formation of macroscopic connectome topology.
The embodied brain
Understanding the brain is not only intrinsically fascinating, but also highly relevant to increase our well-being since our brain exhibits a power over the body that makes it capable both of provoking illness or facilitating the healing process. Bearing in mind this dark force, brain sciences have undergone and will undergo an important revolution, redefining its boundaries beyond the cranial cavity. During this presentation, we will discuss about the communication between the brain and other systems that shapes how we feel the external word and how we think. We are starting to unravel how our organs talk to the brain and how the brain talks back. That two-way communication encompasses a complex, body-wide system of nerves, hormones and other signals that will be discussed. This presentation aims at challenging a long history of thinking of bodily regulation as separate from "higher" mental processes. Four centuries ago, René Descartes famously conceptualized the mind as being separate from the body, it is time now to embody our mind.
What shapes the transcriptional identity of a neuron?
Within the vertebrate neocortex and other telencephalic structures, molecularly-defined neurons tend to segregate at first order into GABAergic types and glutamatergic types. Two fundamental questions arise: (1) do non-telencephalic neurons similarly segregate by neurotransmitter status, and (2) do GABAergic (or glutamatergic) types sampled in different structures share many molecular features in common, beyond the few genes directly responsible for neurotransmitter synthesis and release? To address these questions, we used single-nucleus RNA sequencing, analyzing over 2.4 million brain cells sampled from 16 locations in a primate (the common marmoset). Unexpectedly, we find the answer to both is “no”. I will discuss implications for generalizing associations between neurotransmitter utilization and other phenotypes, and share ongoing efforts to map the biodistributions of cell types in the primate brain.
The brain: A coincidence detector between sensory experiences and internal milieu
Understanding the brain is not only intrinsically fascinating, but also highly relevant to increase our well-being since our brain exhibits a power over the body that makes it capable both of provoking illness or facilitating the healing process. Bearing in mind this dark force, brain sciences have undergone and will undergo an important revolution, redefining its boundaries beyond the cranial cavity. During this presentation, we will discuss about the communication between the brain and other systems that shapes how we feel the external word and how we think. We are starting to unravel how our organs talk to the brain and how the brain talks back. That two-way communication encompasses a complex, bodywide system of nerves, hormones and other signals that we will discussed. This presentation aims at challenging a long history of thinking of bodily regulation as separate from "higher" mental processes. Four centuries ago, René Descartes famously conceptualized the mind as being separate from the body, it is time now to embody our mind.
Peripersonal space (PPS) as a primary interface for self-environment interactions
Peripersonal space (PPS) defines the portion of space where interactions between our body and the external environment more likely occur. There is no physical boundary defining the PPS with respect to the extrapersonal space, but PPS is continuously constructed by a dedicated neural system integrating external stimuli and tactile stimuli on the body, as a function of their potential interaction. This mechanism represents a primary interface between the individual and the environment. In this talk, I will present most recent evidence and highlight the current debate about the neural and computational mechanisms of PPS, its main functions and properties. I will discuss novel data showing how PPS dynamically shapes to optimize body-environment interactions. I will describe a novel electrophysiological paradigm to study and measure PPS, and show how this has been used to search for a basic marker of potentials of self-environment interaction in newborns and patients with disorders of consciousness. Finally, I will discuss how PPS is also involved in, and in turn shaped by, social interactions. Under these acceptances, I will discuss how PPS plays a key role in self-consciousness.
Membrane mechanics meet minimal manifolds
Changes in the geometry and topology of self-assembled membranes underlie diverse processes across cellular biology and engineering. Similar to lipid bilayers, monolayer colloidal membranes studied by the Sharma (IISc Bangalore) and Dogic (UCSB) Labs have in-plane fluid-like dynamics and out-of-plane bending elasticity, but their open edges and micron length scale provide a tractable system to study the equilibrium energetics and dynamic pathways of membrane assembly and reconfiguration. First, we discuss how doping colloidal membranes with short miscible rods transforms disk-shaped membranes into saddle-shaped minimal surfaces with complex edge structures. Theoretical modeling demonstrates that their formation is driven by increasing positive Gaussian modulus, which in turn is controlled by the fraction of short rods. Further coalescence of saddle-shaped surfaces leads to exotic topologically distinct structures, including shapes similar to catenoids, tri-noids, four-noids, and higher order structures. We then mathematically explore the mechanics of these catenoid-like structures subject to an external axial force and elucidate their intimate connection to two problems whose solutions date back to Euler: the shape of an area-minimizing soap film and the buckling of a slender rod under compression. A perturbation theory argument directly relates the tensions of membranes to the stability properties of minimal surfaces. We also investigate the effects of including a Gaussian curvature modulus, which, for small enough membranes, causes the axial force to diverge as the ring separation approaches its maximal value.
Reprogramming the nociceptive circuit topology reshapes sexual behavior in C. elegans
In sexually reproducing species, males and females respond to environmental sensory cues and transform the input into sexually dimorphic traits. Yet, how sexually dimorphic behavior is encoded in the nervous system is poorly understood. We characterize the sexually dimorphic nociceptive behavior in C. elegans – hermaphrodites present a lower pain threshold than males in response to aversive stimuli, and study the underlying neuronal circuits, which are composed of the same neurons that are wired differently. By imaging receptor expression, calcium responses and glutamate secretion, we show that sensory transduction is similar in the two sexes, and therefore explore how downstream network topology shapes dimorphic behavior. We generated a computational model that replicates the observed dimorphic behavior, and used this model to predict simple network rewirings that would switch the behavior between the sexes. We then showed experimentally, using genetic manipulations, artificial gap junctions, automated tracking and optogenetics, that these subtle changes to male connectivity result in hermaphrodite-like aversive behavior in-vivo, while hermaphrodite behavior was more robust to perturbations. Strikingly, when presented with aversive cues, rewired males were compromised in finding mating partners, suggesting that the network topology that enables efficient avoidance of noxious cues would have a reproductive "cost". To summarize, we present a deconstruction of a sex-shared neural circuit that affects sexual behavior, and how to reprogram it. More broadly, our results are an example of how common neuronal circuits changed their function during evolution by subtle topological rewirings to account for different environmental and sexual needs.
How are nervous systems remodeled in complex metazoans?
Early in development the nervous system is constructed with far too many neurons that make an excessive number of synaptic connections. Later, a wave of neuronal remodeling radically reshapes nervous system wiring and cell numbers through the selective elimination of excess synapses, axons and dendrites, and even whole neurons. This remodeling is widespread across the nervous system, extensive in terms of how much individual brain regions can change (e.g. in some cases 50% of neurons integrated into a brain circuit are eliminated), and thought to be essential for optimizing nervous system function. Perturbations of neuronal remodeling are thought to underlie devastating neurodevelopmental disorders including autism spectrum disorder, schizophrenia, and epilepsy. This seminar will discuss our efforts to use the relatively simple nervous system of Drosophila to understand the mechanistic basis by which cells, or parts of cells, are specified for removal and eliminated from the nervous system.
How Attention Shapes Perception
Lifestyle, cardiovascular health, and the brain
Lifestyle factors such as sleep, diet, stress, and exercise, profoundly influence cardiovascular health. Seeking to understand how lifestyle affects our biology is important for at least two reasons. First, it can expose a particular lifestyle’s biological impact, which can be leveraged for adopting specific public health policies. Second, such work may identify crucial molecular mechanisms central to how the body adapts to our environments. These insights can then be used to improve our lives. In this talk, I will focus on recent work in the lab exploring how lifestyle factors influence cardiovascular health. I will show how combining tools of neuroscience, hematology, immunology, and vascular biology helps us better understand how the brain shapes leukocytes in response to environmental perturbations. By “connecting the dots” from the brain to the vessel wall, we can begin to elucidate how lifestyle can both maintain and perturb salutogenesis.
Connecting structure and function in early visual circuits
How does the brain interpret signals from the outside world? Walking through a park, you might take for granted the ease with which you can understand what you see. Rather than seeing a series of still snapshots, you are able to see simple, fluid movement — of dogs running, squirrels foraging, or kids playing basketball. You can track their paths and know where they are headed without much thought. “How does this process take place?” asks Rudy Behnia, PhD, a principal investigator at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute. “For most of us, it’s hard to imagine a world where we can’t see motion, shapes, and color; where we can’t have a representation of the physical world in our head.” And yet this representation does not happen automatically — our brain has no direct connection with the outside world. Instead, it interprets information taken in by our senses. Dr. Behnia is studying how the brain builds these representations. As a starting point, she focuses on how we see motion
How Migration Policy Shapes the Subjective Well-Being of the Non-immigrant Population in European Countries
Existing studies show that there is a positive association between pro-migrant integration policies and the subjective well-being of immigrants. However, there is a lack of research elucidating the relations between migrant integration policies and the subjective well-being of the host (i.e., non-migrant) population. This study is based on European data and uses multilevel analysis to clarify the relations between migrant integration policy (both as a whole and its 8 separate components such as: Labour market mobility and Family reunion) and the subjective well-being of the non-immigrant population in European countries. We examined relations between the Migrant Integration Policy Index (MIPEX) for 22 countries in Europe and subjective well-being, as assessed by the European Social Survey (ESS) data. The results demonstrated that there is a positive relation between the MIPEX and subjective well-being for non-immigrants. Considering different components of the MIPEX separately, we found most of them being positively related to the subjective well-being of non-immigrants. As no negative relationship was identified between any of the eight MIPEX components and subjective well-being, policies in favour of immigrant integration also seem to benefit the non-immigrant population.
Separable pupillary signatures of perception and action during perceptual multistability
The pupil provides a rich, non-invasive measure of the neural bases of perception and cognition, and has been of particular value in uncovering the role of arousal-linked neuromodulation, which alters cortical processing as well as pupil size. But pupil size is subject to a multitude of influences, which complicates unique interpretation. We measured pupils of observers experiencing perceptual multistability -- an ever-changing subjective percept in the face of unchanging but inconclusive sensory input. In separate conditions the endogenously generated perceptual changes were either task-relevant or not, allowing a separation between perception-related and task-related pupil signals. Perceptual changes were marked by a complex pupil response that could be decomposed into two components: a dilation tied to task execution and plausibly indicative of an arousal-linked noradrenaline surge, and an overlapping constriction tied to the perceptual transient and plausibly a marker of altered visual cortical representation. Constriction, but not dilation, amplitude systematically depended on the time interval between perceptual changes, possibly providing an overt index of neural adaptation. These results show that the pupil provides a simultaneous reading on interacting but dissociable neural processes during perceptual multistability, and suggest that arousal-linked neuromodulation shapes action but not perception in these circumstances. This presentation covers work that was published in e-life
Input and target-selective plasticity in sensory neocortex during learning
Behavioral experience shapes neural circuits, adding and subtracting connections between neurons that will ultimately control sensation and perception. We are using natural sensory experience to uncover basic principles of information processing in the cerebral cortex, with a focus on how sensory learning can selectively alter synaptic strength. I will discuss recent findings that differentiate reinforcement learning from sensory experience, showing rapid and selective plasticity of thalamic and inhibitory synapses within primary sensory cortex.
Nonlinear spatial integration in retinal bipolar cells shapes the encoding of artificial and natural stimuli
Vision begins in the eye, and what the “retina tells the brain” is a major interest in visual neuroscience. To deduce what the retina encodes (“tells”), computational models are essential. The most important models in the retina currently aim to understand the responses of the retinal output neurons – the ganglion cells. Typically, these models make simplifying assumptions about the neurons in the retinal network upstream of ganglion cells. One important assumption is linear spatial integration. In this talk, I first define what it means for a neuron to be spatially linear or nonlinear and how we can experimentally measure these phenomena. Next, I introduce the neurons upstream to retinal ganglion cells, with focus on bipolar cells, which are the connecting elements between the photoreceptors (input to the retinal network) and the ganglion cells (output). This pivotal position makes bipolar cells an interesting target to study the assumption of linear spatial integration, yet due to their location buried in the middle of the retina it is challenging to measure their neural activity. Here, I present bipolar cell data where I ask whether the spatial linearity holds under artificial and natural visual stimuli. Through diverse analyses and computational models, I show that bipolar cells are more complex than previously thought and that they can already act as nonlinear processing elements at the level of their somatic membrane potential. Furthermore, through pharmacology and current measurements, I illustrate that the observed spatial nonlinearity arises at the excitatory inputs to bipolar cells. In the final part of my talk, I address the functional relevance of the nonlinearities in bipolar cells through combined recordings of bipolar and ganglion cells and I show that the nonlinearities in bipolar cells provide high spatial sensitivity to downstream ganglion cells. Overall, I demonstrate that simple linear assumptions do not always apply and more complex models are needed to describe what the retina “tells” the brain.
Untitled Seminar
Laura Fenlon (Australia): Time shapes all brains: timing of a conserved transcriptional network underlies divergent cortical connectivity routes in mammalian brain development and evolution; Laurent Nguyen (Belgium): Regulation of cerebral cortex morphogenesis by migrating cells; Carol Ann Mason (USA): Wiring the eye to brain for binocular vision: lessons from the albino visual system. Thomas Perlmann (Sweden): Interrogating dopamine neuron development at the single cell level
Learning to see Stuff
Materials with complex appearances, like textiles and foodstuffs, pose challenges for conventional theories of vision. How does the brain learn to see properties of the world—like the glossiness of a surface—that cannot be measured by any other senses? Recent advances in unsupervised deep learning may help shed light on material perception. I will show how an unsupervised deep neural network trained on an artificial environment of surfaces that have different shapes, materials and lighting, spontaneously comes to encode those factors in its internal representations. Most strikingly, the model makes patterns of errors in its perception of material that follow, on an image-by-image basis, the patterns of errors made by human observers. Unsupervised deep learning may provide a coherent framework for how many perceptual dimensions form, in material perception and beyond.
Themes and Variations: Circuit mechanisms of behavioral evolution
Animals exhibit extraordinary variation in their behavior, yet little is known about the neural mechanisms that generate this diversity. My lab has been taking advantage of the rapid diversification of male courtship behaviors in Drosophila to glean insight into how evolution shapes the nervous system to generate species-specific behaviors. By translating neurogenetic tools from D. melanogaster to closely related Drosophila species, we have begun to directly compare the homologous neural circuits and pinpoint sites of adaptive change. Across species, P1 neurons serve as a conserved node in regulating male courtship: these neurons are selectively activated by the sensory cues indicative of an appropriate mate and their activation triggers enduring courtship displays. We have been examining how different sensory pathways converge onto P1 neurons to regulate a male’s state of arousal, honing his pursuit of a prospective partner. Moreover, by performing cross-species comparison of these circuits, we have begun to gain insight into how reweighting of sensory inputs to P1 neurons underlies species-specific mate recognition. Our results suggest how variation at flexible nodes within the nervous system can serve as a substrate for behavioral evolution, shedding light on the types of changes that are possible and preferable within brain circuits.
Encoding local stimulus attributes and higher visual functions in V1 of behaving monkeys
In this lecture, I will present our recent progress on three aspects of population responses in the primary visual cortex: encoding local stimulus attributes, electrical microstimulation and higher visual function. In the first part I will focus on population encoding and reconstruction of contour shapes in V1 and the comparison between monkey and mouse visual responses. In the second part of the talk I will present the effects of microstimulation on neural population in V1 and the relation to evoked saccades. In the final part of the talk I will discuss top-down influences in V1 and their relation to higher visual functions.
Swimming and crawling of Euglena gracilis: a tale with many twists
Euglena gracilis is an interesting unicellular protist, also because it can adopt different motility strategies: swimming by flagellar propulsion, or crawling thanks to large amplitude shape changes of the whole body (a behavior known as “metaboly”, or “amoeboid motion”). Swimming trajectories are helical. The are powered by the beating of a single emerging flagellum, which spans non-planar waveforms in the shape of a twisted lasso. Finally the harmoniously coordinated shape changes that make metaboly possible, reminiscent of peristaltic waves, arise form the relative sliding of its pellicle strips, resulting in twisted helical bundles. We will report on the most recent findings on these interconnected topics, for which helical shapes provide a striking fil rouge.
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.
Frustrated Self-Assembly of Non-Euclidean Crystals of Nanoparticles
Self-organized complex structures in nature, e.g., viral capsids, hierarchical biopolymers, and bacterial flagella, offer efficiency, adaptability, robustness, and multi-functionality. Can we program the self-assembly of three-dimensional (3D) complex structures using simple building blocks, and reach similar or higher level of sophistication in engineered materials? Here we present an analytic theory for the self-assembly of polyhedral nanoparticles (NPs) based on their crystal structures in non-Euclidean space. We show that the unavoidable geometrical frustration of these particle shapes, combined with competing attractive and repulsive interparticle interactions, lead to controllable self-assembly of structures of complex order. Applying this theory to tetrahedral NPs, we find high-yield and enantiopure self-assembly of helicoidal ribbons, exhibiting qualitative agreement with experimental observations. We expect that this theory will offer a general framework for the self-assembly of simple polyhedral building blocks into rich complex morphologies with new material capabilities such as tunable optical activity, essential for multiple emerging technologies.
How the immune system shapes synaptic functions
The synapse is the core component of the nervous system and synapse formation is the critical step in the assembly of neuronal circuits. The assembly and maturation of synapses requires the contribution of secreted and membrane-associated proteins, with neuronal activity playing crucial roles in regulating synaptic strength, neuronal membrane properties, and neural circuit refinement. The molecular mechanisms of synapse assembly and refinement have been so far largely examined on a gene-by-gene basis and with a perspective fully centered on neuronal cells. However, in the last years, the involvement of non-neuronal cells has emerged. Among these, microglia, the resident immune cells of the central nervous system, have been shown to play a key role in synapse formation and elimination. Contacts of microglia with dendrites in the somatosensory cortex were found to induce filopodia and dendritic spines via Ca2+ and actin-dependent processes, while microglia-derived BDNF was shown to promote learning-dependent synapse formation. Microglia is also recognized to have a central role in the widespread elimination (or pruning) of exuberant synaptic connections during development. Clarifying the processes by which microglia control synapse homeostasis is essential to advance our current understanding of brain functions. Clear answers to these questions will have important implications for our understanding of brain diseases, as the fact that many psychiatric and neurological disorders are synaptopathies (i.e. diseases of the synapse) is now widely recognized. In the last years, my group has identified TREM2, an innate immune receptor with phagocytic and antiinflammatory properties expressed in brain exclusively by microglia, as essential for microglia-mediated synaptic refinement during the early stages of brain development. The talk will describe the role of TREM2 in synapse elimination and introduce the molecular actors involved. I will also describe additional pathways by which the immune system may affect the formation and homeostasis of synaptic contacts.
A developmental-cognitive perspective on the impact of adolescent social media use
Concerns about the impact of social media use on adolescent well-being and mental health are common. While the amount of research in this area has increased rapidly over the last 5 years, most outputs are still marred by a multitude of limitations. These shortcomings have left our understanding of social media effects severely limited, holding back both scientific discovery and policy interventions. This talk discusses how developmental, cognitive and neuroscientific approaches might provide a new and improved way of studying social media effects. It will detail new studies in support of this idea, and raise potential avenues for collaborative work across the Cambridge Neuroscience community. As the digital world now (re)shapes what it means for us to live, communicate and develop, only an interdisciplinary approach will allow us to truly understand its impacts.
Global AND Scale-Free? Spontaneous cortical dynamics between functional networks and cortico-hippocampal communication
Recent advancements in anatomical and functional imaging emphasize the presence of whole-brain networks organized according to functional and connectivity gradients, but how such structure shapes activity propagation and memory processes still lacks asatisfactory model. We analyse the fine-grained spatiotemporal dynamics of spontaneous activity in the entire dorsal cortex. through simultaneous recordings of wide-field voltage sensitive dye transients (VS), cortical ECoG, and hippocampal LFP in anesthetized mice. Both VS and ECoG show cortical avalanches. When measuring avalanches from the VS signal, we find a major deviation of the size scaling from the power-law distribution predicted by the criticality hypothesis and well approximated by the results from the ECoG. Breaking from scale-invariance, avalanches can thus be grouped in two regimes. Small avalanches consists of a limited number of co-activation modes involving a sub-set of cortical networks (related to the Default Mode Network), while larger avalanches involve a substantial portion of the cortical surface and can be clustered into two families: one immediately preceded by Retrosplenial Cortex activation and mostly involving medial-posterior networks, the other initiated by Somatosensory Cortex and extending preferentially along the lateral-anterior region. Rather than only differing in terms of size, these two set of events appear to be associated with markedly different brain-wide dynamical states: they are accompaniedby a shift in the hippocampal LFP, from the ripple band (smaller) to the gamma band (larger avalanches), and correspond to opposite directionality in the cortex-to-hippocampus causal relationship. These results provide a concrete description of global cortical dynamics, and shows how cortex in its entirety is involved in bi-directional communication in the hippocampus even in sleep-like states.
Linking dimensionality to computation in neural networks
The link between behavior, learning and the underlying connectome is a fundamental open problem in neuroscience. In my talk I will show how it is possible to develop a theory that bridges across these three levels (animal behavior, learning and network connectivity) based on the geometrical properties of neural activity. The central tool in my approach is the dimensionality of neural activity. I will link animal complex behavior to the geometry of neural representations, specifically their dimensionality; I will then show how learning shapes changes in such geometrical properties and how local connectivity properties can further regulate them. As a result, I will explain how the complexity of neural representations emerges from both behavioral demands (top-down approach) and learning or connectivity features (bottom-up approach). I will build these results regarding neural dynamics and representations starting from the analysis of neural recordings, by means of theoretical and computational tools that blend dynamical systems, artificial intelligence and statistical physics approaches.
How Memory Guides Value-Based Decisions
From robots to humans, the ability to learn from experience turns a rigid response system into a flexible, adaptive one. In this talk, I will discuss emerging findings regarding the neural and cognitive mechanisms by which learning shapes decisions. The lecture will focus on how multiple brain regions interact to support learning, what this means for how memories are built, and the consequences for how decisions are made. Results emerging from this work challenge the traditional view of separate learning systems and advance understanding of how memory biases decisions in both adaptive and maladaptive ways.
Dynamically relevant motifs in inhibition-dominated networks
Many networks in the nervous system possess an abundance of inhibition, which serves to shape and stabilize neural dynamics. The neurons in such networks exhibit intricate patterns of connectivity whose structure controls the allowed patterns of neural activity. In this work, we examine inhibitory threshold-linear networks whose dynamics are constrained by an underlying directed graph. We develop a set of parameter-independent graph rules that enable us to predict features of the dynamics, such as emergent sequences and dynamic attractors, from properties of the graph. These rules provide a direct link between the structure and function of these networks, and may provide new insights into how connectivity shapes dynamics in real neural circuits.
Endless forms most beautiful: how to program materials using geometry, topology and singularities
The dream of programmable matter is to create materials whose physical properties (shape, moduli, response to perturbations, etc.) can be changed on the fly. For many years, my group has been thinking about how to program flat sheets that fold up into three dimensional shapes, most recently by exploiting the principles of origami design. Unfortunately, a combinatorial explosion of folding pathways makes robust folding particularly challenging. In this talk, I will discuss how this pluripotency arises from the topology of the configuration space. This suggests a broader understanding of a larger class of materials spanning from folding forms to spring networks to mechanical structures that perform computational logic.
“Biophysics of Structural Plasticity in Postsynaptic Spines”
The ability of the brain to encode and store information depends on the plastic nature of the individual synapses. The increase and decrease in synaptic strength, mediated through the structural plasticity of the spine, are important for learning, memory, and cognitive function. Dendritic spines are small structures that contain the synapse. They come in a variety of shapes (stubby, thin, or mushroom-shaped) and a wide range of sizes that protrude from the dendrite. These spines are the regions where the postsynaptic biochemical machinery responds to the neurotransmitters. Spines are dynamic structures, changing in size, shape, and number during development and aging. While spines and synapses have inspired neuromorphic engineering, the biophysical events underlying synaptic and structural plasticity of single spines remain poorly understood. Our current focus is on understanding the biophysical events underlying structural plasticity. I will discuss recent efforts from my group — first, a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation and a series of spatial models to study the role of spine geometry and organelle location within the spine for calcium and cyclic AMP signaling. Second, I will discuss how mechanics of membrane-cytoskeleton interactions can give insight into spine shape region. And I will conclude with some new efforts in using reconstructions from electron microscopy to inform computational domains. I will conclude with how geometry and mechanics plays an important role in our understanding of fundamental biological phenomena and some general ideas on bio-inspired engineering.
Multiple maps for navigation
Over the last several decades, the tractable response properties of parahippocampal neurons have provided a new access key to understanding the cognitive process of self-localization: the ability to know where you are currently located in space. Defined by functionally discrete response properties, neurons in the medial entorhinal cortex and hippocampus are proposed to provide the basis for an internal neural map of space, which enables animals to perform path-integration based spatial navigation and supports the formation of spatial memories. My lab focuses on understanding the mechanisms that generate this neural map of space and how this map is used to support behavior. In this talk, I’ll discuss how learning and experience shapes our internal neural maps of space to guide behavior.
Natural visual stimuli for mice
During the course of evolution, a species’ environment shapes its sensory abilities, as individuals with more optimized sensory abilities are more likely survive and procreate. Adaptations to the statistics of the natural environment can be observed along the early visual pathway and across species. Therefore, characterising the properties of natural environments and studying the representation of natural scenes along the visual pathway is crucial for advancing our understanding of the structure and function of the visual system. In the past 20 years, mice have become an important model in vision research, but the fact that they live in a different environment than primates and have different visual needs is rarely considered. One particular challenge for characterising the mouse’s visual environment is that they are dichromats with photoreceptors that detect UV light, which the typical camera does not record. This also has consequences for experimental visual stimulation, as the blue channel of computer screens fails to excite mouse UV cone photoreceptors. In my talk, I will describe our approach to recording “colour” footage of the habitat of mice – from the mouse’s perspective – and to studying retinal circuits in the ex vivo retina with natural movies.
Is Rule Learning Like Analogy?
Humans’ ability to perceive and abstract relational structure is fundamental to our learning. It allows us to acquire knowledge all the way from linguistic grammar to spatial knowledge to social structures. How does a learner begin to perceive structure in the world? Why do we sometimes fail to see structural commonalities across events? To begin to answer these questions, I attempt to bridge two large, yet somewhat separate research traditions in understanding human’s structural abstraction: rule learning (Marcus et al., 1999) and analogical learning (Gentner, 1989). On the one hand, rule learning research has shown humans’ domain-general ability and ease—as early as 7-month-olds—to abstract structure from a limited experience. On the other hand, analogical learning works have shown robust constraints in structural abstraction: young learners prefer object similarity over relational similarity. To understand this seeming paradox between ease and difficulty, we conducted a series of studies using the classic rule learning paradigm (Marcus et al., 1999) but with an analogical (object vs. relation) twist. Adults were presented with 2-minute sentences or events (syllables or shapes) containing a rule. At test, they had to choose between rule abstraction and object matches—the same syllable or shape they saw before. Surprisingly, while in the absence of object matches adults were perfectly capable of abstracting the rule, their ability to do so declined sharply when object matches were present. Our initial results suggest that rule learning ability may be subject to the usual constraints and signatures of analogical learning: preference to object similarity can dampen rule generalization. Humans’ abstraction is also concrete at the same time.
Theme and variations: circuit mechanisms of behavioural evolution
Animals exhibit extraordinary variation in their behaviour, yet little is known about the neural mechanisms that generate this diversity. My lab has been taking advantage of the rapid diversification of male courtship behaviours in Drosophila to gain insight into how evolution shapes the nervous system to generate species-specific behaviours. By translating neurogenetic tools from D. melanogaster to closely related Drosophila species, we have begun to directly compare the homologous neural circuits and pinpoint sites of adaptive change. Across species, P1 interneurons serve as a conserved and key node in regulating male courtship: these neurons are selectively activated by the sensory cues carried by an appropriate mate and their activation triggers enduring courtship displays. We have been examining how different sensory pathways converge onto P1 neurons to regulate a male’s state of arousal, honing his pursuit of a prospective partner. Moreover, by performing cross-species comparison of these circuits, we have begun to gain insight into how reweighting of sensory inputs to P1 neurons underlies species-specific mate recognition. Our results suggest how variation at flexible nodes within the nervous system can serve as a substrate for behavioural evolution, shedding light on the types of changes that are possible and preferable within brain circuits.
Cortical plasticity
Plasticity shapes the brain during development, and mechanisms of plasticity continue into adulthood to enable learning and memory. Nearly all brain functions are influenced by past events, reinforcing the view that the confluence of plasticity and computation in the same circuit elements is a core component of biological intelligence. My laboratory studies plasticity in the cerebral cortex during development, and plasticity during behaviour that is manifest as cortical dynamics. I will describe how cortical plasticity is implemented by learning rules that involve not only Hebbian changes and synaptic scaling but also dendritic renormalization. By using advanced techniques such as optical measurements of single-synapse function and structure in identified neurons in awake behaving mice, we have recently demonstrated locally coordinated plasticity in dendrites whereby specific synapses are strengthened and adjacent synapses with complementary features are weakened. Together, these changes cooperatively implement functional plasticity in neurons. Such plasticity relies on the dynamics of activity-dependent molecules within and between synapses. Alongside, it is increasingly clear that risk genes associated with neurodevelopmental disorders disproportionately target molecules of plasticity. Deficits in renormalization contribute fundamentally to dysfunctional neuronal circuits and computations, and may be a unifying mechanistic feature of these disorders.
How connection probability shapes fluctuations of neural population dynamics
Bernstein Conference 2024
Cortical feedback shapes high order structure of population activity to improve sensory coding
Bernstein Conference 2024
How the presynapse shapes its molecular composition in an energetically optimal manner
Bernstein Conference 2024
Short-term adaptation reshapes retinal ganglion cell selectivity to natural scenes
Bernstein Conference 2024
Top-down modulation shapes timescales via synaptic plasticity in cortical circuits with multiple interneuron types
Bernstein Conference 2024
Unsupervised clustering of burst shapes reveals the increasing complexity of developing networks in vitro
Bernstein Conference 2024
Divisive normalization shapes evidence accumulation during dynamic decision-making
COSYNE 2022
Long-term motor learning creates structure within neural space that shapes motor adaptation
COSYNE 2022
Long-term motor learning creates structure within neural space that shapes motor adaptation
COSYNE 2022
Natural scene expectation shapes the structure of trial to trial variability in mid-level visual cortex
COSYNE 2022
Natural scene expectation shapes the structure of trial to trial variability in mid-level visual cortex
COSYNE 2022
Sex-specific network topology of the nociceptive circuit shapes dimorphic behavior in C. elegans
COSYNE 2022
Sex-specific network topology of the nociceptive circuit shapes dimorphic behavior in C. elegans
COSYNE 2022
Dendritic low pass filtering shapes midbrain neural responses to behaviorally relevant stimuli
COSYNE 2023
Uncertainty differentially shapes premotor and primary motor activity during movement planning
COSYNE 2023
Beneficial effects of alternative stimulation pulse shapes for sensory prostheses: insights from vestibular prosthesis-evoked reflexes and population neural activity
COSYNE 2025
How connection probability shapes fluctuations of neural population dynamics
COSYNE 2025
A family of synaptic plasticity rules shapes triplet motifs in recurrent networks
COSYNE 2025
Top-down modulation shapes the timescales of cortical circuits via synaptic plasticity
COSYNE 2025
Astroglial control of prefrontal dopamine tone shapes behavior
FENS Forum 2024
Disynaptic inhibition shapes tuning of OFF-motion detectors in Drosophila
FENS Forum 2024
Hierarchy of prediction errors shapes context-dependent sensory representations
FENS Forum 2024
Metabolic dynamics shapes neural activity: A framework for control of epilepsy
FENS Forum 2024
Microglial TREM2 receptor signaling shapes neuronal bioenergetics during development
FENS Forum 2024
Passive versus active novelty detection: How volition shapes olfactory representations in the medial temporal lobe
FENS Forum 2024
Posterior parietal cortex oscillatory activity shapes persistent spatial memory impairments induced by soluble amyloid-β oligomers
FENS Forum 2024
Predictive learning shapes the representational geometry of the human brain
FENS Forum 2024
In vitro treatment of rat primary hippocampal neurons with 17-α-ethinyl estradiol shapes synaptic spines: molecular, morphological and functional effects
FENS Forum 2024