development

Developmental emergence of personality

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

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

Cellular Crosstalk in Brain Development, Evolution and Disease

Cellular crosstalk is an essential process during brain development and is influenced by numerous factors, including cell morphology, adhesion, the local extracellular matrix and secreted vesicles. Inspired by mutations associated with neurodevelopmental disorders, we focus on understanding the role of extracellular mechanisms essential for the proper development of the human brain. Therefore, we combine 2D and 3D in vitro human models to better understand the molecular and cellular mechanisms involved in progenitor proliferation and fate, migration and maturation of excitatory and inhibitory neurons during human brain development and tackle the causes of neurodevelopmental disorders.

Development of an Optical and Colorimetric Biosensor for the Quantification of Microrna 184 for Late Life Depression

Understanding reward-guided learning using large-scale datasets

Understanding the neural mechanisms of reward-guided learning is a long-standing goal of computational neuroscience. Recent methodological innovations enable us to collect ever larger neural and behavioral datasets. This presents opportunities to achieve greater understanding of learning in the brain at scale, as well as methodological challenges. In the first part of the talk, I will discuss our recent insights into the mechanisms by which zebra finch songbirds learn to sing. Dopamine has been long thought to guide reward-based trial-and-error learning by encoding reward prediction errors. However, it is unknown whether the learning of natural behaviours, such as developmental vocal learning, occurs through dopamine-based reinforcement. Longitudinal recordings of dopamine and bird songs reveal that dopamine activity is indeed consistent with encoding a reward prediction error during naturalistic learning. In the second part of the talk, I will talk about recent work we are doing at DeepMind to develop tools for automatically discovering interpretable models of behavior directly from animal choice data. Our method, dubbed CogFunSearch, uses LLMs within an evolutionary search process in order to "discover" novel models in the form of Python programs that excel at accurately predicting animal behavior during reward-guided learning. The discovered programs reveal novel patterns of learning and choice behavior that update our understanding of how the brain solves reinforcement learning problems.

“Brain theory, what is it or what should it be?”

n the neurosciences the need for some 'overarching' theory is sometimes expressed, but it is not always obvious what is meant by this. One can perhaps agree that in modern science observation and experimentation is normally complemented by 'theory', i.e. the development of theoretical concepts that help guiding and evaluating experiments and measurements. A deeper discussion of 'brain theory' will require the clarification of some further distictions, in particular: theory vs. model and brain research (and its theory) vs. neuroscience. Other questions are: Does a theory require mathematics? Or even differential equations? Today it is often taken for granted that the whole universe including everything in it, for example humans, animals, and plants, can be adequately treated by physics and therefore theoretical physics is the overarching theory. Even if this is the case, it has turned out that in some particular parts of physics (the historical example is thermodynamics) it may be useful to simplify the theory by introducing additional theoretical concepts that can in principle be 'reduced' to more complex descriptions on the 'microscopic' level of basic physical particals and forces. In this sense, brain theory may be regarded as part of theoretical neuroscience, which is inside biophysics and therefore inside physics, or theoretical physics. Still, in neuroscience and brain research, additional concepts are typically used to describe results and help guiding experimentation that are 'outside' physics, beginning with neurons and synapses, names of brain parts and areas, up to concepts like 'learning', 'motivation', 'attention'. Certainly, we do not yet have one theory that includes all these concepts. So 'brain theory' is still in a 'pre-newtonian' state. However, it may still be useful to understand in general the relations between a larger theory and its 'parts', or between microscopic and macroscopic theories, or between theories at different 'levels' of description. This is what I plan to do.

“Development and application of gaze control models for active perception”

Gaze shifts in humans serve to direct high-resolution vision provided by the fovea towards areas in the environment. Gaze can be considered a proxy for attention or indicator of the relative importance of different parts of the environment. In this talk, we discuss the development of generative models of human gaze in response to visual input. We discuss how such models can be learned, both using supervised learning and using implicit feedback as an agent interacts with the environment, the latter being more plausible in biological agents. We also discuss two ways such models can be used. First, they can be used to improve the performance of artificial autonomous systems, in applications such as autonomous navigation. Second, because these models are contingent on the human’s task, goals, and/or state in the context of the environment, observations of gaze can be used to infer information about user intent. This information can be used to improve human-machine and human robot interaction, by making interfaces more anticipative. We discuss example applications in gaze-typing, robotic tele-operation and human-robot interaction.

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.

Understanding reward-guided learning using large-scale datasets

Understanding the neural mechanisms of reward-guided learning is a long-standing goal of computational neuroscience. Recent methodological innovations enable us to collect ever larger neural and behavioral datasets. This presents opportunities to achieve greater understanding of learning in the brain at scale, as well as methodological challenges. In the first part of the talk, I will discuss our recent insights into the mechanisms by which zebra finch songbirds learn to sing. Dopamine has been long thought to guide reward-based trial-and-error learning by encoding reward prediction errors. However, it is unknown whether the learning of natural behaviours, such as developmental vocal learning, occurs through dopamine-based reinforcement. Longitudinal recordings of dopamine and bird songs reveal that dopamine activity is indeed consistent with encoding a reward prediction error during naturalistic learning. In the second part of the talk, I will talk about recent work we are doing at DeepMind to develop tools for automatically discovering interpretable models of behavior directly from animal choice data. Our method, dubbed CogFunSearch, uses LLMs within an evolutionary search process in order to "discover" novel models in the form of Python programs that excel at accurately predicting animal behavior during reward-guided learning. The discovered programs reveal novel patterns of learning and choice behavior that update our understanding of how the brain solves reinforcement learning problems.

Harnessing Big Data in Neuroscience: From Mapping Brain Connectivity to Predicting Traumatic Brain Injury

Neuroscience is experiencing unprecedented growth in dataset size both within individual brains and across populations. Large-scale, multimodal datasets are transforming our understanding of brain structure and function, creating opportunities to address previously unexplored questions. However, managing this increasing data volume requires new training and technology approaches. Modern data technologies are reshaping neuroscience by enabling researchers to tackle complex questions within a Ph.D. or postdoctoral timeframe. I will discuss cloud-based platforms such as brainlife.io, that provide scalable, reproducible, and accessible computational infrastructure. Modern data technology can democratize neuroscience, accelerate discovery and foster scientific transparency and collaboration. Concrete examples will illustrate how these technologies can be applied to mapping brain connectivity, studying human learning and development, and developing predictive models for traumatic brain injury (TBI). By integrating cloud computing and scalable data-sharing frameworks, neuroscience can become more impactful, inclusive, and data-driven..

Constructing and deconstructing the human nervous system to study development and disease

Pharmacological exploitation of neurotrophins and their receptors to develop novel therapeutic approaches against neurodegenerative diseases and brain trauma

Neurotrophins (NGF, BDNF, NT-3) are endogenous growth factors that exert neuroprotective effects by preventing neuronal death and promoting neurogenesis. They act by binding to their respective high-affinity, pro-survival receptors TrkA, TrkB or TrkC, as well as to p75NTR death receptor. While these molecules have been shown to significantly slow or prevent neurodegeneration, their reduced bioavailability and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic compounds which selectively resemble neurotrophins’ effects, presenting preferable pharmacological properties and promoting neuroprotection and repair against neurodegeneration. In addition, the combination of these molecules with 3D cultured human neuronal cells, and their targeted delivery in the brain ventricles through soft robotic systems, could offer novel therapeutic approaches against neurodegenerative diseases and brain trauma.

Regulation of cortical circuit maturation and plasticity by oligodendrocytes and myelin

Structural & Functional Neuroplasticity in Children with Hemiplegia

About 30% of children with cerebral palsy have congenital hemiplegia, resulting from periventricular white matter injury, which impairs the use of one hand and disrupts bimanual co-ordination. Congenital hemiplegia has a profound effect on each child's life and, thus, is of great importance to the public health. Changes in brain organization (neuroplasticity) often occur following periventricular white matter injury. These changes vary widely depending on the timing, location, and extent of the injury, as well as the functional system involved. Currently, we have limited knowledge of neuroplasticity in children with congenital hemiplegia. As a result, we provide rehabilitation treatment to these children almost blindly based exclusively on behavioral data. In this talk, I will present recent research evidence of my team on understanding neuroplasticity in children with congenital hemiplegia by using a multimodal neuroimaging approach that combines data from structural and functional neuroimaging methods. I will further present preliminary data regarding functional improvements of upper extremities motor and sensory functions as a result of rehabilitation with a robotic system that involves active participation of the child in a video-game setup. Our research is essential for the development of novel or improved neurological rehabilitation strategies for children with congenital hemiplegia.

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.

Brain macrophage transplantation for research and therapy development

Gene regulatory mechanisms of neocortex development and evolution

The neocortex is considered to be the seat of higher cognitive functions in humans. During its evolution, most notably in humans, the neocortex has undergone considerable expansion, which is reflected by an increase in the number of neurons. Neocortical neurons are generated during development by neural stem and progenitor cells. Epigenetic mechanisms play a pivotal role in orchestrating the behaviour of stem cells during development. We are interested in the mechanisms that regulate gene expression in neural stem cells, which have implications for our understanding of neocortex development and evolution, neural stem cell regulation and neurodevelopmental disorders.

Rett syndrome, MECP2 and therapeutic strategies

The development of the iPS cell technology has revolutionized our ability to study development and diseases in defined in vitro cell culture systems. The talk will focus on Rett Syndrome and discuss two topics: (i) the use of gene editing as an approach to therapy and (ii) the role of MECP2 in gene expression (i) The mutation of the X-linked MECP2 gene is causative for the disease. In a female patient, every cell has a wt copy that is, however, in 50% of the cells located on the inactive X chromosome. We have used epigenetic gene editing tools to activate the wt MECP2 allele on the inactive X chromosome. (ii) MECP2 is thought to act as repressor of gene expression. I will present data which show that MECP2 binds to Pol II and acts as an activator for thousands of genes. The target genes are significantly enriched for Autism related genes. Our data challenge the established model of MECP2’s role in gene expression and suggest novel therapeutic approaches.

Screen Savers : Protecting adolescent mental health in a digital world

In our rapidly evolving digital world, there is increasing concern about the impact of digital technologies and social media on the mental health of young people. Policymakers and the public are nervous. Psychologists are facing mounting pressures to deliver evidence that can inform policies and practices to safeguard both young people and society at large. However, research progress is slow while technological change is accelerating.My talk will reflect on this, both as a question of psychological science and metascience. Digital companies have designed highly popular environments that differ in important ways from traditional offline spaces. By revisiting the foundations of psychology (e.g. development and cognition) and considering digital changes' impact on theories and findings, we gain deeper insights into questions such as the following. (1) How do digital environments exacerbate developmental vulnerabilities that predispose young people to mental health conditions? (2) How do digital designs interact with cognitive and learning processes, formalised through computational approaches such as reinforcement learning or Bayesian modelling?However, we also need to face deeper questions about what it means to do science about new technologies and the challenge of keeping pace with technological advancements. Therefore, I discuss the concept of ‘fast science’, where, during crises, scientists might lower their standards of evidence to come to conclusions quicker. Might psychologists want to take this approach in the face of technological change and looming concerns? The talk concludes with a discussion of such strategies for 21st-century psychology research in the era of digitalization.

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.

Virtual and experimental approaches to the pathogenicity of SynGAP1 missense mutations

Understanding the complex behaviors of the ‘simple’ cerebellar circuit

Every movement we make requires us to precisely coordinate muscle activity across our body in space and time. In this talk I will describe our efforts to understand how the brain generates flexible, coordinated movement. We have taken a behavior-centric approach to this problem, starting with the development of quantitative frameworks for mouse locomotion (LocoMouse; Machado et al., eLife 2015, 2020) and locomotor learning, in which mice adapt their locomotor symmetry in response to environmental perturbations (Darmohray et al., Neuron 2019). Combined with genetic circuit dissection, these studies reveal specific, cerebellum-dependent features of these complex, whole-body behaviors. This provides a key entry point for understanding how neural computations within the highly stereotyped cerebellar circuit support the precise coordination of muscle activity in space and time. Finally, I will present recent unpublished data that provide surprising insights into how cerebellar circuits flexibly coordinate whole-body movements in dynamic environments.

↗ Clonal analysis at single cell level helps to understand neural crest development

Clonal analysis at single cell level helps to understand neural crest development

Recent research on the neural crest has revealed the multipotency and plasticity of nerve-associated Schwann cell precursors, which can differentiate into diverse cell types, including parasympathetic neurons, neuroendocrine cells, and mesenchymal stem cells. These findings challenge the traditional view of peripheral nerves, highlighting their role as niches for migratory progenitor cells that contribute to tissue formation and regeneration.

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.

Targeting gamma oscillations to improve cognition

Untitled Seminar

Prosocial Learning and Motivation across the Lifespan

2024 BACN Early-Career Prize Lecture Many of our decisions affect other people. Our choices can decelerate climate change, stop the spread of infectious diseases, and directly help or harm others. Prosocial behaviours – decisions that help others – could contribute to reducing the impact of these challenges, yet their computational and neural mechanisms remain poorly understood. I will present recent work that examines prosocial motivation, how willing we are to incur costs to help others, prosocial learning, how we learn from the outcomes of our choices when they affect other people, and prosocial preferences, our self-reports of helping others. Throughout the talk, I will outline the possible computational and neural bases of these behaviours, and how they may differ from young adulthood to old age.

SYNGAP1 Natural History Study/ Multidisciplinary Clinic at Children’s Hospital Colorado

Development of a small molecule to promote neuroprotection and repair in progressive multiple sclerosis

Frequency tagging: a powerful method to investigate neurocognitive development with EEG

Beyond the synapse: SYNGAP1 in primary and motile cilia

The multi-phase plasticity supporting winner effect

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

The Roles of Distinct Functions of SynGAP1 in SYNGAP1-Related Disorders

Investigating dynamiCa++l mechanisms underlying cortical development and disease

Charting the fetal development of neural complexity

Vision Unveiled: Understanding Face Perception in Children Treated for Congenital Blindness

Modeling human brain development and disease: the role of primary cilia

Neurodevelopmental disorders (NDDs) impose a global burden, affecting an increasing number of individuals. While some causative genes have been identified, understanding the human-specific mechanisms involved in these disorders remains limited. Traditional gene-driven approaches for modeling brain diseases have failed to capture the diverse and convergent mechanisms at play. Centrosomes and cilia act as intermediaries between environmental and intrinsic signals, regulating cellular behavior. Mutations or dosage variations disrupting their function have been linked to brain formation deficits, highlighting their importance, yet their precise contributions remain largely unknown. Hence, we aim to investigate whether the centrosome/cilia axis is crucial for brain development and serves as a hub for human-specific mechanisms disrupted in NDDs. Towards this direction, we first demonstrated species-specific and cell-type-specific differences in the cilia-genes expression during mouse and human corticogenesis. Then, to dissect their role, we provoked their ectopic overexpression or silencing in the developing mouse cortex or in human brain organoids. Our findings suggest that cilia genes manipulation alters both the numbers and the position of NPCs and neurons in the developing cortex. Interestingly, primary cilium morphology is disrupted, as we find changes in their length, orientation and number that lead to disruption of the apical belt and altered delamination profiles during development. Our results give insight into the role of primary cilia in human cortical development and address fundamental questions regarding the diversity and convergence of gene function in development and disease manifestation. It has the potential to uncover novel pharmacological targets, facilitate personalized medicine, and improve the lives of individuals affected by NDDs through targeted cilia-based therapies.

Contrasting developmental principles of human brain development and their relevance to neurodevelopmental disorders

Investigating activity-dependent processes during cortical neuronal assembly in development and disease

Cortical interneurons from brain development to disease

Brain-heart interactions at the edges of consciousness

Various clinical cases have provided evidence linking cardiovascular, neurological, and psychiatric disorders to changes in the brain-heart interaction. Our recent experimental evidence on patients with disorders of consciousness revealed that observing brain-heart interactions helps to detect residual consciousness, even in patients with absence of behavioral signs of consciousness. Those findings support hypotheses suggesting that visceral activity is involved in the neurobiology of consciousness and sum to the existing evidence in healthy participants in which the neural responses to heartbeats reveal perceptual and self-consciousness. Furthermore, the presence of non-linear, complex, and bidirectional communication between brain and heartbeat dynamics can provide further insights into the physiological state of the patient following severe brain injury. These developments on methodologies to analyze brain-heart interactions open new avenues for understanding neural functioning at a large-scale level, uncovering that peripheral bodily activity can influence brain homeostatic processes, cognition, and behavior.

Dyslexia, Rhythm, Language and the Developing Brain

Recent insights from auditory neuroscience provide a new perspective on how the brain encodes speech. Using these recent insights, I will provide an overview of key factors underpinning individual differences in children’s development of language and phonology, providing a context for exploring atypical reading development (dyslexia). Children with dyslexia are relatively insensitive to acoustic cues related to speech rhythm patterns. This lack of rhythmic sensitivity is related to the atypical neural encoding of rhythm patterns in speech by the brain. I will describe our recent data from infants as well as children, demonstrating developmental continuity in the key neural variables.

Of glia and macrophages, signaling hubs in development and homeostasis

We are interested in the biology of macrophages, which represent the first line of defense against pathogens. In Drosophila, the embryonic hemocytes arise from the mesoderm whereas glial cells arise from multipotent precursors in the neurogenic region. These cell types represent, respectively, the macrophages located outside and within the nervous system (similar to vertebrate microglia). Thus, despite their different origin, hemocytes and glia display common functions. In addition, both cell types express the Glide/Gcm transcription factor, which plays an evolutionarily conserved role as an anti-inflammatory factor. Moreover, embryonic hemocytes play an evolutionarily conserved and fundamental role in development. The ability to migrate and to contact different tissues/organs most likely allow macrophages to function as signaling hubs. The function of macrophages beyond the recognition of the non-self calls for revisiting the biology of these heterogeneous and plastic cells in physiological and pathological conditions across evolution.

Genomic investigation of sex-differential neurodevelopment and risk for autism

Measures and models of multisensory integration in reaction times

First, a new measure of MI for reaction times is proposed that takes the entire RT distribution into account. Second, we present some recent developments in TWIN modeling, including a new proposal for the sound-induced flash illusion (SIFI).

Cellular and genetic mechanisms of cerebral cortex folding

One of the most prominent features of the human brain is the fabulous size of the cerebral cortex and its intricate folding, both of which emerge during development. Over the last few years, work from my lab has shown that specific cellular and genetic mechanisms play central roles in cortex folding, particularly linked to neural stem and progenitor cells. Key mechanisms include high rates of neurogenesis, high abundance of basal Radial Glia Cells (bRGCs), and neuron migration, all of which are intertwined during development. We have also shown that primary cortical folds follow highly stereotyped patterns, defined by a spatial-temporal protomap of gene expression within germinal layers of the developing cortex. I will present recent findings from my laboratory revealing novel cellular and genetic mechanisms that regulate cortex expansion and folding. We have uncovered the contribution of epigenetic regulation to the establishment of the cortex folding protomap, modulating the expression levels of key transcription factors that control progenitor cell proliferation and cortex folding. At the single cell level, we have identified an unprecedented diversity of cortical progenitor cell classes in the ferret and human embryonic cortex. These are differentially enriched in gyrus versus sulcus regions and establish parallel cell lineages, not observed in mouse. Our findings show that genetic and epigenetic mechanisms in gyrencephalic species diversify cortical progenitor cell types and implement parallel cell linages, driving the expansion of neurogenesis and patterning cerebral cortex folds.

Trends in NeuroAI - Meta's MEG-to-image reconstruction

Trends in NeuroAI is a reading group hosted by the MedARC Neuroimaging & AI lab (https://medarc.ai/fmri). Title: Brain-optimized inference improves reconstructions of fMRI brain activity Abstract: The release of large datasets and developments in AI have led to dramatic improvements in decoding methods that reconstruct seen images from human brain activity. We evaluate the prospect of further improving recent decoding methods by optimizing for consistency between reconstructions and brain activity during inference. We sample seed reconstructions from a base decoding method, then iteratively refine these reconstructions using a brain-optimized encoding model that maps images to brain activity. At each iteration, we sample a small library of images from an image distribution (a diffusion model) conditioned on a seed reconstruction from the previous iteration. We select those that best approximate the measured brain activity when passed through our encoding model, and use these images for structural guidance during the generation of the small library in the next iteration. We reduce the stochasticity of the image distribution at each iteration, and stop when a criterion on the "width" of the image distribution is met. We show that when this process is applied to recent decoding methods, it outperforms the base decoding method as measured by human raters, a variety of image feature metrics, and alignment to brain activity. These results demonstrate that reconstruction quality can be significantly improved by explicitly aligning decoding distributions to brain activity distributions, even when the seed reconstruction is output from a state-of-the-art decoding algorithm. Interestingly, the rate of refinement varies systematically across visual cortex, with earlier visual areas generally converging more slowly and preferring narrower image distributions, relative to higher-level brain areas. Brain-optimized inference thus offers a succinct and novel method for improving reconstructions and exploring the diversity of representations across visual brain areas. Speaker: Reese Kneeland is a Ph.D. student at the University of Minnesota working in the Naselaris lab. Paper link: https://arxiv.org/abs/2312.07705

Astrocyte reprogramming / activation and brain homeostasis

Astrocytes are multifunctional glial cells, implicated in neurogenesis and synaptogenesis, supporting and fine-tuning neuronal activity and maintaining brain homeostasis by controlling blood-brain barrier permeability. During the last years a number of studies have shown that astrocytes can also be converted into neurons if they force-express neurogenic transcription factors or miRNAs. Direct astrocytic reprogramming to induced-neurons (iNs) is a powerful approach for manipulating cell fate, as it takes advantage of the intrinsic neural stem cell (NSC) potential of brain resident reactive astrocytes. To this end, astrocytic cell fate conversion to iNs has been well-established in vitro and in vivo using combinations of transcription factors (TFs) or chemical cocktails. Challenging the expression of lineage-specific TFs is accompanied by changes in the expression of miRNAs, that post-transcriptionally modulate high numbers of neurogenesis-promoting factors and have therefore been introduced, supplementary or alternatively to TFs, to instruct direct neuronal reprogramming. The neurogenic miRNA miR-124 has been employed in direct reprogramming protocols supplementary to neurogenic TFs and other miRNAs to enhance direct neurogenic conversion by suppressing multiple non-neuronal targets. In our group we aimed to investigate whether miR-124 is sufficient to drive direct reprogramming of astrocytes to induced-neurons (iNs) on its own both in vitro and in vivo and elucidate its independent mechanism of reprogramming action. Our in vitro data indicate that miR-124 is a potent driver of the reprogramming switch of astrocytes towards an immature neuronal fate. Elucidation of the molecular pathways being triggered by miR-124 by RNA-seq analysis revealed that miR-124 is sufficient to instruct reprogramming of cortical astrocytes to immature induced-neurons (iNs) in vitro by down-regulating genes with important regulatory roles in astrocytic function. Among these, the RNA binding protein Zfp36l1, implicated in ARE-mediated mRNA decay, was found to be a direct target of miR-124, that be its turn targets neuronal-specific proteins participating in cortical development, which get de-repressed in miR-124-iNs. Furthermore, miR-124 is potent to guide direct neuronal reprogramming of reactive astrocytes to iNs of cortical identity following cortical trauma, a novel finding confirming its robust reprogramming action within the cortical microenvironment under neuroinflammatory conditions. In parallel to their reprogramming properties, astrocytes also participate in the maintenance of blood-brain barrier integrity, which ensures the physiological functioning of the central nervous system and gets affected contributing to the pathology of several neurodegenerative diseases. To study in real time the dynamic physical interactions of astrocytes with brain vasculature under homeostatic and pathological conditions, we performed 2-photon brain intravital imaging in a mouse model of systemic neuroinflammation, known to trigger astrogliosis and microgliosis and to evoke changes in astrocytic contact with brain vasculature. Our in vivo findings indicate that following neuroinflammation the endfeet of activated perivascular astrocytes lose their close proximity and physiological cross-talk with vasculature, however this event is at compensated by the cross-talk of astrocytes with activated microglia, safeguarding blood vessel coverage and maintenance of blood-brain integrity.

Connectome-based models of neurodegenerative disease

Neurodegenerative diseases involve accumulation of aberrant proteins in the brain, leading to brain damage and progressive cognitive and behavioral dysfunction. Many gaps exist in our understanding of how these diseases initiate and how they progress through the brain. However, evidence has accumulated supporting the hypothesis that aberrant proteins can be transported using the brain’s intrinsic network architecture — in other words, using the brain’s natural communication pathways. This theory forms the basis of connectome-based computational models, which combine real human data and theoretical disease mechanisms to simulate the progression of neurodegenerative diseases through the brain. In this talk, I will first review work leading to the development of connectome-based models, and work from my lab and others that have used these models to test hypothetical modes of disease progression. Second, I will discuss the future and potential of connectome-based models to achieve clinically useful individual-level predictions, as well as to generate novel biological insights into disease progression. Along the way, I will highlight recent work by my lab and others that is already moving the needle toward these lofty goals.

DISTINCT SPECTRAL, CONNECTIVITY, AND FIRING DYNAMICS AROUND SEIZURES IN RAT MODELS OF SYNGAP1 AND GRIN2B NEURODEVELOPMENTAL DISORDERS

FENS Forum 2026

ROLE OF MENINGEAL MACROPHAGES IN DEVELOPMENTAL NEUROGENESIS AND MEMORY FUNCTION

FENS Forum 2026

REELIN SOURCES IN CORTICAL DEVELOPMENT AND NEURODEVELOPMENTAL DISORDERS

FENS Forum 2026

MATERNAL DIETARY IMBALANCE BETWEEN OMEGA-6 AND OMEGA-3 FATTY ACIDS INDUCES SHORT- AND LONG-TERM SEX-SPECIFIC NEURODEVELOPMENTAL ALTERATIONS

FENS Forum 2026

TRACKING AND PERTURBING THE DEVELOPMENT OF SINGLE NEURONS USING TARGETED OPTOGENETICS

FENS Forum 2026

ELECTROPHYSIOLOGICAL CORRELATES OF AUDITORY DEVELOPMENT AT ADOLESCENCE: ROLE OF PUBERTY AND COGNITION

FENS Forum 2026

SHAPING CORTICAL INTERNEURON MIGRATION THROUGH MECHANICAL SIGNALING DURING BRAIN DEVELOPMENT

FENS Forum 2026

ALTERED GRANULE DYNAMICS OF CDKL5 DEFICIENCY DURING DEVELOPMENT

FENS Forum 2026

SPATIOTEMPORAL DEVELOPMENT OF SPARSE EXCITATORY NEURONAL TYPES WITHIN THE DEEP MOUSE CORTEX

FENS Forum 2026

ELUCIDATING SYNGAP1 ISOFORM FUNCTIONS IN HUMAN NEURODEVELOPMENT USING CEREBRAL ORGANOIDS

FENS Forum 2026

IMPACTS OF <EM>GRIN1</EM> MUTATIONS ON NMDA RECEPTOR LOCALIZATION AND CORTICAL DEVELOPMENT

FENS Forum 2026

RATIONAL DEVELOPMENT OF PDE9A-TARGETING COMPOUNDS TO MITIGATE NEUROINFLAMMATION: A COMBINED COMPUTATIONAL AND IN VITRO STUDY

FENS Forum 2026

STARGAZING: HOW ARE ASTROCYTES MADE? ROLE OF ZEB1 IN TRANSCRIPTIONAL REGULATION OF ASTROCYTE SPECIFICATION ACROSS DEVELOPMENT AND ADULTHOOD

FENS Forum 2026

KCNQ1 REGULATES HUMAN NEURONAL DEVELOPMENT THROUGH MITOCHONDRIAL AND INSULIN SIGNALLING PATHWAYS

FENS Forum 2026

ELUCIDATING THE ROLE OF CRB2 IN VENTRICULAR SYSTEM DEVELOPMENT AND HYDROCEPHALUS PATHOGENESIS

FENS Forum 2026

DEVELOPMENT AND IMPROVEMENT OF ULTRA-THIN FLUORESCENCE ENDOSCOPE IMAGING SYSTEM (U-FEIS) AND ITS APPLICATION TO NEURAL ACTIVITY RECORDING IN BEHAVING MICE

FENS Forum 2026

DEVELOPMENTAL PLASTICITY AND SENSORY EXPERIENCE SHAPE ADULT CODING AND PERCEPTION OF SOUND INTENSITY AND ITS MODULATION

FENS Forum 2026

FNIRS AS A NEW BIOMARKER FOR RARE NEURODEVELOPMENTAL DISORDERS

FENS Forum 2026

DEVELOPMENTAL EXPRESSION PATTERNS OF NEURONAL GROWTH GENES (GAL, GAP43, SEMA3B, MAP1B) ACROSS HUMAN BRAIN STAGES USING BGEE TRANSCRIPTOMIC DATA

FENS Forum 2026

ROLE OF TYPE I INTERFERON RECEPTOR IN BRAIN DEVELOPMENT

FENS Forum 2026

ORGANIZATION, DEVELOPMENT, AND PLASTICITY OF THE SEROTONERGIC DORSAL RAPHE NUCLEUS

FENS Forum 2026

A KNOCK-IN <EM>IGFN1</EM><SUP>ICRE</SUP> TRANSGENIC LINE PROVIDES PARTIAL DEVELOPMENTAL ACCESS TO DIRECTION SELECTIVE TYPE-7 BIPOLAR CELLS

FENS Forum 2026

EARLY LIFE STRESS ALTERS AMYGDALA DEVELOPMENT IN A SEX-SPECIFIC MANNER

FENS Forum 2026

NON-IONOTROPIC NMDA RECEPTOR FUNCTIONS OF GLUN2B SHAPE EARLY CORTICAL DEVELOPMENT

FENS Forum 2026

A DEVELOPMENTAL DISSECTION IN THE AUDITORY BRAINSTEM OF MONGOLIAN GERBILS OF NEURAL DELAYS UNDERLYING SOUND LOCALIZATION

FENS Forum 2026

DEVELOPMENTAL DIFFERENCES IN NEURAL RESPONSES TO ACUTE STRESS IN RELATION TO DNA METHYLATION OF ESTROGEN-RESPONSIVE NEURONAL GENES IN FEMALES

FENS Forum 2026

PIEZO1 REGULATES MICROGLIAL MOTILITY AND RESPONSES TO EXTRACELLULAR MATRIX REMODELING DURING ZEBRAFISH BRAIN DEVELOPMENT

FENS Forum 2026

A STRATEGY FOR RESTORING CHOLESTEROL-DEPENDENT SHH SIGNALLING IN A LIPID STORAGE NEURODEVELOPMENTAL DISORDER

FENS Forum 2026

DEVELOPMENTAL EXPOSITION TO FUNGICIDES INDUCES AUTISTIC-LIKE BEHAVIOR IN MICE

FENS Forum 2026

MATERNAL SEROTONIN SHAPES HYPOTHALAMIC DEVELOPMENT TOWARD SOCIAL NECESSITY PATHWAYS IN RODENTS

FENS Forum 2026

PRENATAL STRESS REWIRES ADULT- AND DEVELOPMENTAL-BORN DENTATE GRANULE NEURONS CONNECTIVITY

FENS Forum 2026

MICRORNA-19B-MEDIATED REGULATORY MECHANISMS IN CHICK PALLIUM DEVELOPMENT

FENS Forum 2026

ROLE OF MYELOID CELLS IN REGULATING CEREBELLUM DEVELOPMENT

FENS Forum 2026

SLEEP EEG DYNAMICS REFLECT DIVERGENT NEURODEVELOPMENTAL TRAJECTORIES IN INFANTS

FENS Forum 2026

DEVELOPMENT OF A NOVEL OPEN-CHANNEL BLOCKER FOR GLUN1/GLUN2 NMDA RECEPTORS: MECHANISM AND PHARMACOLOGY

FENS Forum 2026

OREXIN/HYPOCRETIN KNOCKOUT IMPAIRS ADULT MOUSE VISUAL PERCEPTION AND PROCESSING, AND DISRUPTS DEVELOPMENT OF THE CORTICAL SUBPLATE

FENS Forum 2026

CELLULAR AND DEVELOPMENTAL ORIGINS OF LOWE SYNDROME

FENS Forum 2026

PATHOPHYSIOLOGY OF CA2 IN HCN1-G380D MICE: A MODEL OF DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY

FENS Forum 2026

BEYOND HEARING: MULTISENSORY INTEGRATION AS A BEHAVIOURAL MARKER OF DEVELOPMENTAL CORTICAL REORGANISATION IN PAEDIATRIC COCHLEAR IMPLANT USERS

FENS Forum 2026

EARLY PARVALBUMIN INHIBITION SHAPES THE DEVELOPMENT OF CORTICAL INTERHEMISPHERIC EXCITATORY CONNECTIVITY

FENS Forum 2026