Neuronal specification and differentiation require precise spatiotemporal regulation of gene expression programs. How these programs are transcriptionally coordinated in progenitors and postmitotic neurons during development is poorly understood. Chromatin regulation may provide a mechanism to orchestrate transcriptional programs since environmental stimuli and neuronal activity can induce chromatin epigenetic changes. This symposium will focus on epigenetic and transcriptional regulation of neuronal development. D. Jabaudon will present single-cell RNA sequencing data to trace the lineage of mouse cortical apical progenitors (APs) and their daughter neurons. Moreover, he will discuss how the Polycomb chromatin repressor complex epigenetically regulates AP temporal progression into distinct postmitotic progenies of cortical neurons. A. Riccio will discuss the role of chromatin remodelling complex NuRD in mouse cortical development and how neurotrophins and nitric oxide regulate chromatin remodelling complex activity. S-nitrosylation of epigenetic factors will be also discussed. F. Rijli will discuss the recent identification of distinct Polycomb chromatin signatures regulating activity-dependent transcription in developing somatosensory neurons during whisker-related barrelette map formation. B. Treutlein will present single-cell genomics tools to study human brain development and discuss comparative transcriptomics between human, chimpanzee and macaque using brain organoids.

Neuroscientists use a broad range of organisms (from worms, flies and zebrafish to rodents and primates, and now to organoids) to study brain function and behavior. This Brain Debate aims at illustrating why different scientists study different systems and what can be achieved with different approaches. Animal preparations are frequently presented as ‘model organisms’. Does this suggest that the ultimate goal of animal work should be to understand and treat the human brain? Translating animal brain research to clinical implications is certainly a key goal of a large part of the research carried out. The neuroscientific community may, however, have diverse views on the purpose of studying many systems, on what can be achieved with different brain ‘models’, and on what the ultimate goals of each research field and envisioned applications may be. In this Brain Debate, we will discuss the merits of focused and comparative approaches and reflect on our scientific mission and on our vision for the field.Speakers and discussants:Gilles Laurent - Frankfurt, GermanyEmre Yaksi - Trondheim, NorwayChristian Lüscher - Geneva, SwitzerlandGuo-li Ming - Pennsylvania, USAAngela Roberts - Cambridge, UKPeter Dayan - Tübingen, GermanyTracy Bale - Maryland, USA Irene Tracey - Oxford, UK Moderator: Trevor Robbins - Cambridge, UK

The notion of synaptome has recently emerged as the diverse ensemble of synapses established within a circuit of interest. Yet our current knowledge of the molecular synapse diversity within neuronal networks is very poor. Indeed, monitoring the cellular and molecular mechanisms that establish the precise patterns of connectivity and the functional characteristics of synapses has long remained challenging. Recent technological advances provide a very promising entry into the era of synaptomics. Here, we will present our latest contribution and discuss the perspectives in the definition of more precise synaptomes. Dr Anne-Sophie Hafner (Max Planck Institute for Brain Research) will present how local translation at synapses allows for local alterations of the synaptic proteome and neurotransmission in axons and dendrites. Pr Csaba Foldy (University of Zurich) will show how single cell RNA sequencing reveals the mechanisms of adhesion coding through splicing of neurexin proteins. Dr Poulopoulos (University of Maryland) will present how subcellular multi-omic approaches unravel projection specific features. Finally, Dr Fekrije Selimi (Collège de France) will present current knowledge on excitatory synapse differentiation at the different inputs to cerebellar Purkinje cells. Altogether, our symposium will update the community on how molecular approaches of synapse biology contribute to our understanding of network development and function.

Blindness can result either from the loss of photoreceptors in retinal dystrophies or from retinal ganglion cell degeneration in glaucoma or diabetic retinopathy. Gene therapy is just emerging for rare diseases targeting either photoreceptor or retinal ganglion cell degeneration. In the absence of large-scale treatments, the aging of the population is drastically increasing the percentage of affected patients. Recent advances in molecular genetics, cell biology and nanobiotechnologies are elucidating the pathophysiological mechanisms underlying these disorders and aim at identifying new effective therapeutic strategies. Among the most promising approaches, cell reprogramming, optogenetics, neuro-electronic and opto-neural interfaces (retinal prostheses and visual cortex stimulation) are exponentially expanding. The four speakers, who are recognized experts in the specific fields, will report the most recent and fascinating advances in visual restoration in the following topics: cell reprogramming and retina regeneration (M.P. Cosma), optogenetics and infrared-sensitive wireless photovoltaic prosthetics (S. Picaud), polymeric light-sensitive interfaces for retinal prosthetics (F. Benfenati) and electrical stimulation of the visual cortex (X. Chen). The speakers come from 4 distinct European countries and are gender-balanced (2 males and two females) and one speaker is an early career researcher (X. Chen, from the Roelfsema Research Group Vision & Cognition).

Recent advances in optogenetic and viral strategies as well as sophisticated imaging techniques have yielded unprecedented insight into the molecular underpinnings of memory. Converging evidence suggest that memories are stored in part as specific populations of ‘engram’ cells. In this symposium, leading early career memory researchers will share their continuously developing insights on how engram cells contribute to information encoding and storage, across diverse brain regions, species, and behavioral modalities. Emphasis will be given to engram accessibility across development, during sleep deprivation, and following stress. Altogether, this symposium will foster our understanding of how engram connectivity relates to memory fidelity and endurance, which in turn may edify strategies to improve memory precision under environmentally challenging conditions and in central nervous system disorders. Upon attending this symposium, participants should be able to: 1) Understand how sleep deprivation impact cognitive processes at the level of memory engrams in the hippocampus. 2) Describe how the hippocampus segregates fear and reward engrams at the population and projection-specific level. 3) Recapitulate how memory engrams are modulated by postnatal brain development, and how they relate to innate instinctual drives. 4) Integrate knowledge about hippocampal memory mechanisms with network-level accounts of memory processes in the human brain.

Tanycytes, specialized glial cells lining the third ventricle of hypothalamus mediate the dialogue between the brain and the periphery. These highly plastic and heterogenous cells regulate the secretion of neuropeptides from hypothalamic neurons into the pituitary portal system as well control blood-brain and blood-cerebrospinal fluid exchanges. They also sense and shuttle circulating metabolic signals to hypothalamic neurons involved in regulation of food intake. Tanycytes, thus potentially represent a missing link connecting behavior, hormonal changes, signal transduction and activation of central neurons. Disruptions in these pathways predispose an organism to a number of age-related disorders, including metabolic diseases such as obesity and type 2 diabetes. In order to come up with therapeutic strategies to combat these metabolic and cognitive diseases, it is extremely important to study the heterogeneity of tanycytes as well as to study the molecular basis of their interaction with hypothalamic neurons and the periphery. This symposium brings together 3 basic scientists, who have been awarded an ERC Synergy grant in 2018, and a brilliant young female PI, each working towards deciphering the biology of tanycytes using a unique rationale. The focus of this symposium would be to highlight cutting-edge genetic approaches, systems neuroscience and pharmacological approaches designed to explore the role of tanycytes in health and well-aging.

Immune function is closely related to the progression of neurodegenerative diseases. Studies have shown that a reduced adaptive immune response, functional changes in innate immunocytes, and other factors can cause chronic inflammation, which accelerates the pathology of neurological diseases. Recent research has addressed the question of how changes in the body’s immune response affect the central nervous system specifically. Moreover, organ function is empirically known to be influenced by neuronal activity and an individual’s mental state. Many studies have shown that organ function is improved in a comfortable environment and worsened by psychological stress. Information can also travel ‘backwards’ via afferent signaling, from organs to neurons, meaning that changes in organ function can result in changes in neural activity elsewhere in the body. In recent years, there has been renewed interest in and a rapid expansion of research on how various organs interact with the nervous system. The speakers will address, on a cellular and molecular level, the interaction of immune system and nervous system thereby highlighting the function of organ system interactions in neural degeneration processes and during development. Based on mechanistic findings about the linkage between the nervous system and immune system, they will further describe about the possibility of development for treatment of the intractable neurological diseases.

Neuromodulators, the master switches of the brain, enable a fixed configuration of neurons to shape myriad behavioral patterns. But, how this is achieved is largely unknown. The organizing principles of neuromodulatory logic across cells, synapses, dendrites and microcircuits in health and disease has not been comprehensively covered in recent FENS symposia. Therefore, this propitious symposium will bring together a distinguished panel of junior and senior scientists unifying in vivo, in vitro and in silico approaches developed in global brain initiatives to unravel the functional logic of neuromodulatory circuits in shaping behavioral states. The multidisciplinary panel will deliver insight on how multiple neuromodulatory mechanisms regulate behavioral states in health and disease, foster dialogue, and aim to identify common organizing principles of their engagement across different brain regions and species. Catherine Dulac will present insights on the molecular, cellular and circuit-level modulation of social behaviors. Liqun Luo will highlight the input-output organization of norepinephrine, dopamine, and serotonin systems in the mouse brain. Srikanth Ramaswamy will present a computational framework to predict how cholinergic signaling breaks down during epileptic behavior in cortex. Stephen Williams will highlight the neuromodulatory mechanisms that control active dendritic integration during behaviorally related circuit computations in neocortical pyramidal neurons.

Our thinking on the rules of synaptic plasticity is strongly influenced by Hebb, focusing on the coincidence of electrical activity between pre- and postsynaptic neurons. However new developments have expanded our view: High-resolution imaging and molecular biology techniques have uncovered multiscale biochemical signalling within and between individual synapses. Advances in computational modelling have allowed us to capture this complexity in multi-scale simulations. Results from these studies show that classic Hebbian models are no longer fit for purpose: we need new guiding theories for how synapses perform computations across multiple timescales, and how they communicate at various spatial scales. This symposium brings together experimentalists and computational modellers leading this effort: Kim Blackwell’s team have pioneered efforts to apply computational techniques from systems biology to complex biochemical signalling at synapses. Suhita Nadkarni’s team lead work on biophysical computational modelling of calcium signalling at synapses during plasticity. Thomas Oertner’s team develop genetic tools for all-optical induction and monitoring of plasticity induction at single synapses. Ryohei Yasuda’s team develop genetic probes for FRET/FLIM imaging of temporal activation of proteins at single synapses during plasticity induction. The aim is to offer an update on current work in this field, and spark a dialogue about new multiscale theories of synaptic plasticity.

Optogenetics is a highly active and interdisciplinary field of research with major relevance to the broad neuroscience community. Optogenetics enables cell-type- and brain area-specific, spatially confined and graded stimulation and inhibition of neurons. Optogenetics ranges from tool making to applications in clinical neurosciences. Insight into new optogenetic tools: tailored opsins and vectors (Boyden, Dalkara, Gradinaru, Moser) and light delivery approaches: structured illumination by spatial light modulators and implantable micro-LED arrays (Emiliani, Moser). Understanding neural circuitry using optogenetic manipulation (Boyden, Gradinaru, Emiliani). Restoring the function of neural circuitry by optogenetic stimulation (Boyden, Gradinaru, Dalkara, Moser). Selection of speakers covers leading experts with balanced representation of gender (50% female), age, and European nations, two transatlantic speakers

This symposium will present the latest advances in the study of neural circuits for somatosensation at both spinal and supraspinal levels. This topic is particularly timely, as we are just starting to dissect these circuits. Our speakers comprise a multinational group of researchers. Notably, this symposium will present results from different subfields of somatosensation (e.g. pain, itch, touch) and a range of techniques (electrophysiology, optogenetics, molecular genetics), in order to present the audience with state-of-the-art approaches to defining functional circuitry. We will report the study of spinal neural circuits underlying touch, and how local inhibitory neurons gate sensory feedback to the spinal motor system during walking (Bourane et al., Cell, 2015; Koch et al., Neuron, 2017). The functional diversity of the spinal neural circuits is complemented by the study of gating mechanisms for itch sensation (Bourane et al., Science, 2015; Ralvenius et al., Nat Commun. 2018; Pagani et al., Neuron, In press). We will also present functional studies on ascending pathways for itch and pain (Han et al., Cell, 2015; Mu et al., Science 2017). In addition, we will show the circuit mechanism underlying descending modulation of the spinal itch circuit (Gao et al., Neuron, 2019). These studies have dissected circuit mechanisms of both the sensory and emotional components of somatosensation, and will be of great interest to a broad scientific audience.

The workshop will highlight the measurement capabilities of key technologies for large-scale monitoring of neural activity, in particular fully integrated Neuropixels silicon probes and wide-field 2-photon imaging. We have selected leading experts in the field as speakers to share recent data and protocols related to all technical aspects; from building setups, to data processing (spike sorting and image processing), storage and analysis. The workshop also aims at stimulating discussions about major challenges, in particular the analysis of large datasets and the scientific interpretation of brain-wide signals in the context of behavior. Finally, we will discuss current technical limitations and possible improvements in next generation technologies. The purpose of the workshop is to bring together the rapidly growing user community and to establish best-practices in order to ensure data quality is maintained at the larger scale of measurement. The workshop further aims at facilitating the adoption of new technologies by lowering the threshold to become first-time users. Taken together, it will advance the technical capabilities of the circuit neuroscience community and it will foster scientific exchange related to a major question in neuroscience – how the coordinated neural activity across brain regions gives rise to mental function and behavior.

Understanding the molecular mechanisms that underlie the organization and functions of axons has provided fundamental insights into the function and pathology of neurons. Emerging data implicates myosin II based contractility in the regulation of actin rings, and potentially of other actin-based structures, and thereby multiple aspects of axon biology. Thus, myosin II-actin interactions are providing new insights into the mechanisms by which neurons establish their polarity, how they regulate the initiation of the action potentials, and broadly how they maintain axonal organization and function. Individually obtained findings of the symposium speakers extend and challenge current paradigms. Therefore, we propose to present these new ideas at a FENS Forum 2020 by the leaders of the field. Our goal is to generate new models of how acto-myosin contractility regulates axons. In particular, we will address the following series of questions: What kind of actin structures contract and when? How does contractility affect the functions of neurons? How do actin rings widen to get big cargoes through axons? James Salzer has already published their first article on this topic (Berger et al., Neuron 2018), and the other three speakers have recently submitted their new results for publication. All speakers are experienced presenting their results to a broad multidisciplinary audience and in linking the basic cell biology studies to neuron functionality and animal behavior.

The past 4 decades highlighted the importance of glia, shifting the neurocentric vision of structure, function and pathology of nervous system to a more holistic perspective. In this view, the demand of technologies targeting the selective monitoring and control of glia is emerging as a challenge across Neuroscience, Engineering and Material Science. This workshop aims to present the most promising advances in unconventional tools & methods, that enabled to reach unprecedented insights into the 4 dimensional (4D) nature of spatio-temporal neuron-glial interactions, in the healthy and pathological brain. Specifically, we will show how 1)(bio)materials as silicon nanowire, graphene or hydrogels can provide transition from 2D to 3D models, mimicking in-vivo structure, where to study healthy or reactive glial cells in vitro 2)the use of nanostructured device allows stimulation and recording of astrocytes and neurons at different spatiotemporal scale 3)computational approaches and control theory can reverse-engineer neuron-glial interactions 4)combination of opto/chemogenetics, CLARITY and two-photon imaging reveals clues on significance of astrocytic domains in memory consolidation 5)photonic and spectroscopic methods uncover the signature of microglial cells in pain. The forum, presented by scientists from 5 different countries, will provide a multidisciplinary perspective on tools, potentially enabling to extend our knowledge on cognitive functions, pain and Alzheimer diseases

Mitochondria (Mt) play a central role in the brain by regulating energy metabolism and cell signalling, contribute to cell plasticity, growth, maturation and communication systems, and are possibly involved in disease pathogenesis and progression. Recent advances have revealed that not only neurons, but also astrocytes require a network of functional Mt in order to produce energy, regulate intracellular homeostasis (including calcium levels), and respond to stress. However, very little is known about how they behave in neurons or astrocytes under particular physiological and pathological conditions, or what influences them biochemically and physically. This applies to various aspects of Mt behavior, including their motility, morphology/distribution and buffering capacity. The aim of this Symposium is to bring together researchers who will highlight recent advances in the functional significance of Mt functions in astrocytes and neurons and will stimulate the scientific community to discuss the role of Mt in brain physiology and pathology. Amit Agarwal and Nicolas Toni will talk about the role of Mt in regulating calcium homeostasis in astrocytes and in the genesis of neurodegenerative diseases, and Franck Polleux and Paola Bezzi will talk about the role of Mt distribution and function in regulating neuronal physiology and in the onset of neuropsychiatric disorders.

People who plan electron microscopy connectomics tend to underestimate the sheer amount of work required after serial section images are obtained. Here technical challenges and solutions for the fly connectome projects with transmission and focused ion beam scanning EM will be reported and shared with the people working on diverse organisms. Timing is ideal, because a series of FIB-SEM connectome papers will be published just before the Forum. To promote communication we provide ten minute discussion for each talk. S. Plaza established a computational platform for analyzing EM section images and visualizing/annotating the traced data. M. Januszewski developed the first automated neuron segmentation algorithm that works with reliable precision, which was a breakthrough for FIB-SEM analysis. A. Cardona established a platform for cooperative manual segmentation/annotation and organized a large collaborative project. R. Parekh trained and coordinated a team of tens of technicians who segment, proofread, and annotate data of both TEM and FIB-SEM with high throughput. H. Otsuna developed systems for finding homologous neurons between EM and light microscopy images, making it possible to switch EM and LM analyses freely. (The proposal might conflict with the FENS policy in that 3 speakers come from a single institute. It is inevitable given that all the large-scale fly EM connectomics are done at Janelia. We appreciate your flexible evaluation in this regard for this rare occasion.)

This symposium will highlight novel research on the role of sex in determining the neurobiological basis, as well as cognitive and emotional aspects of certain neuropsychiatric disorders. Dr. Bangasser will discuss sex differences in stress responses and will focus on the role of CRF in arousal and attention. Dr. Dalla will present sex differences in animal models of depression with a focus on neuroestrogens and neuroplasticity. Dr. Srivastava will show how estradiol induces long-lasting changes in synaptic plasticity via the rapid regulation of local protein translation in the hippocampus. Dr. Milad will present neuroimaging data on the effect of estradiol on neural nodes, as well as computational modelling, in relation to fear and anxiety. Speakers are two women and two men, from four different countries/states, experts on sex differences with complementary, pioneer work on acute brain slices (Srivastava), rodents (Dalla and Bangasser) and humans (Milad) with a wide range of approaches, such as behavioral, molecular, neurochemical, neuroimaging, computational and -omics. The chairperson, Dr. Dalla, is one of the few neuroscientists in Europe promoting sex-oriented research worldwide, has recently led a Special Issue on Sex Differences at Eur. J. of Neuroscience and this symposium will further contribute to this aim. Moreover, it will enhance our understanding of the etiology of disorders, such as depression, anxiety and PTSD, as well as their sex-specific treatment.