The Department of Neuroscience at Washington University School of Medicine is currently recruiting investigators with the passion to create knowledge, pursue bold visions, and challenge canonical thinking as we expand into our new 600,000 sq ft purpose-built neurosciences research building. We are now seeking a tenure-track investigator at the level of Assistant Professor to develop an innovative research program in Theoretical/Computational Neuroscience. The successful candidates will join a thriving theoretical/computational neuroscience community at Washington University, including the new Center for Theoretical and Computational Neuroscience. In addition, the Department also has world-class research strengths in systems, circuits and behavior, cellular and molecular neuroscience using a variety of animal models including worms, flies, zebrafish, rodents and non-human primates. We are particularly interested in outstanding researchers who are both creative and collaborative.

Bilkent University invites applications for multiple open-rank faculty positions in the Department of Neuroscience. The department plans to expand research activities in certain focus areas and accordingly seeks applications from promising or established scholars who have worked in the following or related fields: Cellular/molecular/developmental neuroscience with a strong emphasis on research involving animal models. Systems/cognitive/computational neuroscience with a strong emphasis on research involving emerging data-driven approaches, including artificial intelligence, robotics, brain-machine interfaces, virtual reality, computational imaging, and theoretical modeling. Candidates with a research focus in those areas whose research has a neuroimaging component are particularly encouraged to apply. The Department’s interdisciplinary Graduate Program in Neuroscience that offers Master's and PhD degrees was established in 2014. The department is affiliated with Bilkent’s Aysel Sabuncu Brain Research Center (ASBAM) and the National Magnetic Resonance Research Center (UMRAM). Faculty affiliated with the department has the privilege to access state-of-the-art research facilities in these centers, including animal facilities, cellular/molecular laboratory infrastructure, psychophysics laboratories, eyetracking laboratories, EEG laboratories, a human-robot interaction laboratory, and two MRI scanners (3T and 1.5T).

The Carney Institute for Brain Science at Brown University is seeking Postdoctoral Fellows to join the NIMH funded T32 Training Program in Computational Psychiatry. The program’s goal is to train research fellows with expertise in computational cognitive and systems neuroscience, capable of collaborating with clinical researchers to advance knowledge of psychiatric disorders and treatments. Eligible research topics include brain and cognitive modeling over multiple scales and levels of analysis (ranging from biophysics to artificial intelligence), and the use of these models to understand mechanisms of psychiatric disorders with the ultimate goal of improving treatments. The program applies an apprenticeship model in which fellows work with a primary research trainer in a computational field and a secondary research mentor in clinical psychiatry. In this apprenticeship model, the trainer works closely with the fellow and a secondary clinical psychiatry mentor, who is conducting research in areas such as neuroimaging, neurostimulation, digital phenotyping, and/or animal models. The list of eligible faculty trainers can be found on the Training Program in Computational Psychiatry’s website.

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.

Emotions and social interactions color our lives and shape our behaviors. Using animal models and engineered manipulations, we aim to understand how social and emotional behaviors are encoded in the brain, focusing on the neural circuits underlying dominance hierarchy and depression. This lecture will highlight our recent discoveries on how downward social mobility leads to depression; how ketamine tames depression by blocking burst firing in the brain’s antireward center; and, how glia-neuron interaction plays a surprising role in this process. I will also present our recent work on the mechanism underlying the sustained antidepressant activity of ketamine and its brain region specificity. With these results, we hope to illuminate on a more unified theory on ketamine’s mode of action and inspire new treatment strategies for depression.

Emotions and social interactions color our lives and shape our behaviors. Using animal models and engineered manipulations, we aim to understand how social and emotional behaviors are encoded in the brain, focusing on the neural circuits underlying dominance hierarchy and depression. This lecture will highlight our recent discoveries on how downward social mobility leads to depression; how ketamine tames depression by blocking burst firing in the brain’s antireward center; and, how glia-neuron interaction plays a surprising role in this process. I will also present our recent work on the mechanism underlying the sustained antidepressant activity of ketamine and its brain region specificity. With these results, we hope to illuminate on a more unified theory on ketamine’s mode of action and inspire new treatment strategies for depression.

The ability to organise one's body for action without having to think about it is taken for granted, whether it is handwriting, typing on a smartphone or computer keyboard, tying a shoelace or playing the piano. When compromised, e.g. in stroke, neurodegenerative and developmental disorders, the individuals’ study, work and day-to-day living are impacted with high societal costs. Until recently, indirect methods such as invasive recordings in animal models, computer simulations, and behavioural markers during sequence execution have been used to study covert motor sequence planning in humans. In this talk, I will demonstrate how multivariate pattern analyses of non-invasive neurophysiological recordings (MEG/EEG), fMRI, and muscular recordings, combined with a new behavioural paradigm, can help us investigate the structure and dynamics of motor sequence control before and after movement execution. Across paradigms, participants learned to retrieve and produce sequences of finger presses from long-term memory. Our findings suggest that sequence planning involves parallel pre-ordering of serial elements of the upcoming sequence, rather than a preparation of a serial trajectory of activation states. Additionally, we observed that the human neocortex automatically reorganizes the order and timing of well-trained movement sequences retrieved from memory into lower and higher-level representations on a trial-by-trial basis. This echoes behavioural transfer across task contexts and flexibility in the final hundreds of milliseconds before movement execution. These findings strongly support a hierarchical and dynamic model of skilled sequence control across the peri-movement phase, which may have implications for clinical interventions.

Programmed axon death is a widespread and completely preventable mechanism in injury and disease. Mouse and Drosophila studies define a molecular pathway involving activation of SARM1 NA Dase and its prevention by NAD synthesising enzyme NMNAT2 . Loss of axonal NMNAT2 causes its substrate, NMN , to accumulate and activate SARM1 , driving loss of NAD and changes in ATP , ROS and calcium. Animal models caused by genetic mutation, toxins, viruses or metabolic defects can be alleviated by blocking programmed axon death, for example models of CMT1B , chemotherapy-induced peripheral neuropathy (CIPN), rabies and diabetic peripheral neuropathy (DPN). The perinatal lethality of NMNAT2 null mice is completely rescued, restoring a normal, healthy lifespan. Animal models lack the genetic and environmental diversity present in human populations and this is problematic for modelling gene-environment combinations, for example in CIPN and DPN , and identifying rare, pathogenic mutations. Instead, by testing human gene variants in WGS datasets for loss- and gain-of-function, we identified enrichment of rare SARM1 gain-of-function variants in sporadic ALS , despite previous negative findings in SOD1 transgenic mice. We have shown in mice that heterozygous SARM1 loss-of-function is protective from a range of axonal stresses and that naturally-occurring SARM1 loss-of-function alleles are present in human populations. This enables new approaches to identify disorders where blocking SARM1 may be therapeutically useful, and the existence of two dominant negative human variants in healthy adults is some of the best evidence available that drugs blocking SARM1 are likely to be safe. Further loss- and gain-of-function variants in SARM1 and NMNAT2 are being identified and used to extend and strengthen the evidence of association with neurological disorders. We aim to identify diseases, and specific patients, in whom SARM1 -blocking drugs are most likely to be effective.

Parkinson’s Disease (PD), the most common neurodegenerative movement disorder, is based on a complex interplay between genetic predispositions, aging processes, and environmental influences. In order to better understand the gene-environment axis in PD, we pursue a multi-omics approach to comprehensively interrogate genome-wide changes in histone modifications, DNA methylation, and hydroxymethylation, accompanied by transcriptomic profiling in cell and animal models of PD as well as large patient cohorts. Furthermore, we assess the plasticity of epigenomic modifications under influence of environmental factors using longitudinal cohorts of sporadic PD cases as well as mouse models exposed to specific environmental factors. Here, we present gene expression changes in PD mouse models in context of aging as well as environmental enrichment and high-fat diet.

Habitual consumption of a “Western diet”, containing higher than recommended levels of simple sugars and saturated fatty acids, is associated with cognitive impairments in humans and in various experimental animal models. Emerging findings reveal that the specific mnemonic processes that are disrupted by Western diet consumption are those that rely on the hippocampus, a brain region classically linked with memory control and more recently with the higher-order control of food intake. Our laboratory has established rat models in which excessive consumption of different components of a Western diet during the juvenile and adolescent periods of development yields long-term impairments in hippocampal-dependent memory function without concomitant increases in total caloric intake, body weight, or adiposity. Our ongoing work is investigating alterations in the gut microbiome as a potential underlying neurobiological mechanism linking early life unhealthy dietary factors to adverse neurocognitive outcomes.

WEBINAR 1 Breaking the barrier: Using focused ultrasound for the development of targeted therapies for brain tumours presented by Dr Ekaterina (Caty) Salimova, Monash Biomedical Imaging Glioblastoma multiforme (GBM) - brain cancer - is aggressive and difficult to treat as systemic therapies are hindered by the blood-brain barrier (BBB). Focused ultrasound (FUS) - a non-invasive technique that can induce targeted temporary disruption of the BBB – is a promising tool to improve GBM treatments. In this webinar, Dr Ekaterina Salimova will discuss the MRI-guided FUS modality at MBI and her research to develop novel targeted therapies for brain tumours. Dr Ekaterina (Caty) Salimova is a Research Fellow in the Preclinical Team at Monash Biomedical Imaging. Her research interests include imaging cardiovascular disease and MRI-guided focused ultrasound for investigating new therapeutic targets in neuro-oncology. - WEBINAR 2 Disposition of the Kv1.3 inhibitory peptide HsTX1[R14A], a novel attenuator of neuroinflammation presented by Sanjeevini Babu Reddiar, Monash Institute of Pharmaceutical Sciences The voltage-gated potassium channel (Kv1.3) in microglia regulates membrane potential and pro-inflammatory functions, and non-selective blockade of Kv1.3 has shown anti-inflammatory and disease improvement in animal models of Alzheimer’s and Parkinson’s diseases. Therefore, specific inhibitors of pro-inflammatory microglial processes with CNS bioavailability are urgently needed, as disease-modifying treatments for neurodegenerative disorders are lacking. In this webinar, PhD candidate Ms Sanju Reddiar will discuss the synthesis and biodistribution of a Kv1.3-inhibitory peptide using a [64Cu]Cu-DOTA labelled conjugate. Sanjeevini Babu Reddiar is a PhD student at the Monash Institute of Pharmaceutical Sciences. She is working on a project identifying the factors governing the brain disposition and blood-brain barrier permeability of a Kv1.3-blocking peptide.

Developmental epileptic encephalopathies are early-onset epilepsies, often refractory to therapy, with developmental delay or regression. These disorders carry poor neurodevelopmental prognosis, with long-term refractory epilepsy and persistent cognitive, behavioral and motor deficits. Mutations in the CACNA1A gene, encoding the pore-forming α1 subunit of CaV2.1 voltage-gated calcium channels, result in a spectrum of neurological disorders, including severe, early-onset epileptic encephalopathies. Recent work from the Rossignol lab helped characterize the phenotypic spectrum of CACNA1A-related epilepsies in humans. Using conditional genetics and novel animal models, the Rossignol lab unveiled some of the underlying pathophysiological mechanisms, including critical deficits in cortical inhibition, resulting in seizures and a range of cognitive-behavioral deficits. Importantly, Dr. Rossignol’s team demonstrated that the targeted activation of specific GABAergic interneuron populations in selected cortical regions prevents motor seizures and reverts attention deficits and cognitive rigidity in mouse models of the disorder. These recent findings open novel avenues for the treatment of these severe CACNA1A-associated neurodevelopmental disorders.

The human gut microbiome has emerged as a key player in the bidirectional communication of the gut-brain axis, affecting various aspects of homeostasis and pathophysiology. Until recently, the majority of studies that seek to explore the mechanisms underlying the microbiome-gut-brain axis cross-talk relied almost exclusively on animal models, and particularly gnotobiotic mice. Despite the great progress made with these models, various limitations, including ethical considerations and interspecies differences that limit the translatability of data to human systems, pushed researchers to seek for alternatives. Over the past decades, the field of in vitro modelling of tissues has experienced tremendous growth, thanks to advances in 3D cell biology, materials, science and bioengineering, pushing further the borders of our ability to more faithfully emulate the in vivo situation. Organ-on-chip technology and bioengineered tissues have emerged as highly promising alternatives to animal models for a wide range of applications. In this talk I’ll discuss our progress towards generating a complete platform of the human microbiota-gut-brain axis with integrated monitoring and sensing capabilities. Bringing together principles of materials science, tissue engineering, 3D cell biology and bioelectronics, we are building advanced models of the GI and the BBB /NVU, with real-time and label-free monitoring units adapted in the model architecture, towards a robust and more physiologically relevant human in vitro model, aiming to i) elucidate the role of microbiota in the gut-brain axis communication, ii) to study how diet and impaired microbiota profiles affect various (patho-)physiologies, and iii) to test personalised medicine approaches for disease modelling and drug testing.

Real-time rendering of closed-loop visual environments is important for next-generation understanding of brain function and behaviour, but is often prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. BonVision has been tested on humans and mice, and is capable of supporting new experimental designs in other animal models of vision. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks, and communication with behavioural and physiological measurement and manipulation devices.

Electro- and magneto-encephalography (EEG/MEG) are the leading methods to non-invasively record human neural dynamics with millisecond temporal resolution. However, it can be extremely difficult to infer the underlying cellular and circuit level origins of these macro-scale signals without simultaneous invasive recordings. This limits the translation of E/MEG into novel principles of information processing, or into new treatment modalities for neural pathologies. To address this need, we developed the Human Neocortical Neurosolver (HNN: https://hnn.brown/edu ), a new user-friendly neural modeling tool designed to help researchers and clinicians interpret human imaging data. A unique feature of HNN’s model is that it accounts for the biophysics generating the primary electric currents underlying such data, so simulation results are directly comparable to source localized data. HNN is being constructed with workflows of use to study some of the most commonly measured E/MEG signals including event related potentials, and low frequency brain rhythms. In this talk, I will give an overview of this new tool and describe an application to study the origin and meaning of 15-29Hz beta frequency oscillations, known to be important for sensory and motor function. Our data showed that in primary somatosensory cortex these oscillations emerge as transient high power ‘events’. Functionally relevant differences in averaged power reflected a difference in the number of high-power beta events per trial (“rate”), as opposed to changes in event amplitude or duration. These findings were consistent across detection and attention tasks in human MEG, and in local field potentials from mice performing a detection task. HNN modeling led to a new theory on the circuit origin of such beta events and suggested beta causally impacts perception through layer specific recruitment of cortical inhibition, with support from invasive recordings in animal models and high-resolution MEG in humans. In total, HNN provides an unpresented biophysically principled tool to link mechanism to meaning of human E/MEG signals.

My laboratory studies how the retina processes visual scenes and transmits this information to the brain. We use multi-electrode arrays to record the activity of hundreds of retina neurons simultaneously in conjunction with transgenic mouse lines and chemogenetics to manipulate neural circuit function. We are interested in three major areas. First, we work to understand how neurons in the retina are functionally connected. Second we are studying how light-adaptation and circadian rhythms alter visual processing in the retina. Finally, we are working to understand the mechanisms of retinal degenerative conditions and we are investigating potential treatments in animal models.

Uncertainty regarding which psychological mechanisms are fundamental in mediating SSRI treatment outcomes and wide-ranging variability in their efficacy has raised more questions than it has solved. Since subjective mood states are an abstract scientific construct, only available through self-report in humans, and likely involving input from multiple top-down and bottom-up signals, it has been difficult to model at what level SSRIs interact with this process. Converging translational evidence indicates a role for serotonin in modulating context-dependent parameters of action selection, affect, and social cognition; and concurrently supporting learning mechanisms, which promote adaptability and behavioural flexibility. We examine the theoretical basis, ecological validity, and interaction of these constructs and how they may or may not exert a clinical benefit. Specifically, we bridge crucial gaps between disparate lines of research, particularly findings from animal models and human clinical trials, which often seem to present irreconcilable differences. In determining how SSRIs exert their effects, our approach examines the endogenous functions of 5-HT neurons, how 5-HT manipulations affect behaviour in different contexts, and how their therapeutic effects may be exerted in humans – which may illuminate issues of translational models, hierarchical mechanisms, idiographic variables, and social cognition.

TheVirtualBrain (TVB; thevirtualbrain.org) is a software platform for simulating whole-brain network dynamics. TVB models link biophysical parameters at the cellular level with systems-level functional neuroimaging signals. Data available from animal models can provide vital constraints for the linkage across spatial and temporal scales. I will describe the construction of a macaque cortical connectome as an initial step towards a comprehensive multi-scale macaque TVB model. I will also describe our process of validating the connectome and show an example simulation of macaque resting-state dynamics using TVB. This connectome opens the opportunity for the addition of other available data from the macaque, such as electrophysiological recordings and receptor distributions, to inform multi-scale models of brain dynamics. Future work will include extensions to neurological conditions and other nonhuman primate species.

Psychotic disorders are devastating conditions without any mechanistic treatment available. One major hurdle in the biological study of psychosis is the challenge of rigorously probing this condition in pre-clinical animal models. The goal of our research is to develop and exploit innovative frameworks for the study of psychosis in mice. In our present work, where we developed a cross-species computational psychiatry approach to probe hallucination-like perception. This enabled us to directly relate human and mouse behavior, and to demonstrate and dissect the causal role of striatal dopamine in hallucination-like perception. Our results suggest a neural circuit mechanism for the long-standing dopamine hypothesis of psychosis, and provide a new translational framework for the biological study of psychosis. This opens up exciting possibilities for advancing the biological understanding of psychosis and to identify mechanistic treatment targets.

Genetic mutations of the SCN1A gene, the voltage gated sodium channel NaV1.1, cause well-defined epilepsies, including the severe developmental and epileptic encephalopathy Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+), as well as a severe form of migraine with aura, familial hemiplegic migraine (FHM). More recently, they have been identified in an extremely severe early infantile encephalopathy. Functional studies and animal models have contributed to disclose pathological mechanisms, which can be often linked to a straightforward loss- vs gain- of channel function. However, although this simple dichotomy is pertinent and useful, detailed pathological mechanisms in neuronal circuits can be more complex, sometimes because of unexpected homeostatic or pathologic responses. I will compare pathological mechanisms of epilepsy and migraine mutations studied with cellular, animal and computational models, highlighting a novel homeostatic response implemented by CCK-positive GABAergic neurons in a mouse model of Dravet syndrome, which may be boosted in therapeutic approaches.

Interpretation of interval timing data generated from animal models is complicated by ostensible motivational effects which arise from the delay-to-reward imposed by interval timing tasks, as well as overlap between timed and non-timed responses. These factors become increasingly prevalent at longer intervals. To address these concerns, two adjustments to long interval timing tasks are proposed. First, subjects should be afforded with reinforced non-timing behaviors concurrent with timing. Second, subjects should initiate the onset of timed stimuli. Under these conditions, interference by extraneous behavior would be detected in the rate of concurrent non- timing behaviors, and changes in motivation would be detected in the rate at which timed stimuli are initiated. In a task with these characteristics, rats initiated a concurrent fixed-interval (FI) random-ratio (RR) schedule of reinforcement. This design facilitated response-initiated timing behavior, even at increasingly long delays. Pre-feeding manipulations revealed an effect on the number of initiated trials, but not on the timing peak function.

An emerging hypothesis in the field of Alzheimer’s disease (AD) is that neuronal hyperexcitability and other forms of aberrant network activity play an important role in shaping the clinical course of AD. In this talk, Dr. Lam will highlight the close and bi-directional relationships between epilepsy and AD, noting recent advances in our understanding of this topic spanning from animal models to humans. She will describe recent intracranial electrode recordings in humans that have revealed silent hippocampal epileptiform activity occurring in early stages of AD. Finally, she will discuss machine learning approaches that her laboratory has been developing to non-invasively diagnose and quantify silent hippocampal epileptiform activity from scalp EEG recordings.

The microbiota-gut-brain axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of brain development and behaviour during early life, adolescence & ageing. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or by way of microbial metabolites such as short chain fatty acids. Studies in animal models have shown that the development of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of factors can impact the microbiota in early life including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress as well as host genetics. Recently, the gut microbiota has been implicated in regulating the stress response, and social behaviour. Moreover, fundamental brain processes from adult hippocampal neurogenesis to myelination to microglia activation have been shown to be regulated by the microbiome. Further studies will focus on understanding the mechanisms underlying such brain effects and how they can be exploited by microbiota-targeted interventions including ‘psychobiotics’ and diet

One of the major roadblocks to medical progress in the field of neurodegeneration is the absence of animal models that fully recapitulate features of the human diseases. Unprecedented opportunities to tackle this challenge are emerging e.g. from genome engineering and stem cell technologies, and there are intense efforts to develop models with a high translational value. Simultaneously, single-cell, multi-omics and optogenetics technologies now allow longitudinal, molecular and functional analysis of human disease processes in these models at high resolution. During this workshop, 12 experts will present recent progress in the field and discuss: - What are the most advanced disease models available to date? - Which aspects of the human disease do these accurately models, which ones do they fail to replicate? - How should models be validated? Against which reference, which standards? - What are currently the best methods to analyse these models? - What is the field still missing in terms of modelling, and of technologies to analyse disease models? CURE-ND stands for 'Catalysing a United Response in Europe to Neurodegenerative Diseases'. It is a new alliance between the German Center for Neurodegenerative Diseases (DZNE), the Paris Brain Institute (ICM), Mission Lucidity (ML, a partnership between imec, KU Leuven, UZ Leuven and VIB in Belgium) and the UK Dementia Research Institute (UK DRI). Together, these partners embrace a joint effort to accelerate the pace of scientific discovery and nurture breakthroughs in the field of neurodegenerative diseases. This Neurotechnology Workshop is the first in a series of joint events aiming at exchanging expertise, promoting scientific collaboration and building a strong community of neurodegeneration researchers in Europe and beyond.

Major depressive disorder (MDD) is a sexually dimorphic disease. This sexual dimorphism is believed to result from sex-specific molecular alterations affecting functional pathways regulating the capacity of men and women to cope with daily life stress differently. Transcriptional changes associated with epigenetic alterations have been observed in the brain of men and women with depression and similar changes have been reported in different animal models of stress-induced depressive-like behaviors. In fact, most of our knowledge of the biological basis of MDD is derived from studies of chronic stress models in rodents. However, while these models capture certain aspects of the features of MDD, the extent to which they reproduce the molecular pathology of the human syndrome remains unknown and the functional consequences of these changes on the neuronal networks controlling stress responses are poorly understood. During this presentation, we will first address the extent by which transcriptional signatures associated with MDD compares in men and women. We will then transition to the capacity of different mouse models of chronic stress to recapitulate some of the transcriptional alterations associated with the expression of MDD in both sexes. Finally, we will briefly elaborate on the functional consequences of these changes at the neuronal level and conclude with an integrative perspective on the contribution of sex-specific transcriptional profiles on the expression of stress responses and MDD in men and women.

For social animals, successfully communicating with others is essential for interactions and survival. My research aims to answer a central question on the neuronal basis of this ability, from the perspective of the listener: how do our brains enable us to communicate with each other? My work develops nonhuman animal models to study the behavioural and neuronal mechanisms underlying the perception of vocal patterns. I will start by providing an overview of my past research characterizing the neuronal-level substrates of voice processing along the primate temporal lobe. I will then focus on my current work on vocal perception in mice, in which I utilize natural male-female courtship behaviour to evaluate the acoustic dimensions extracted by listeners from ultrasonic sequences. I will then talk about ongoing work investigating the neuronal substrates supporting the perception of behaviourally relevant acoustic cues from mouse vocal sequences.

Birdsong emerges when a set of highly interconnected brain areas manage to generate a complex output. The similarities between birdsong production and human speech have positioned songbirds as unique animal models for studying learning and production of this complex motor skill. In this work, we developed a low dimensional model for a neural network in which the variables were the average activities of different neural populations within the nuclei of the song system. This neural network is active during production, perception and learning of birdsong. We performed electrophysiological experiments to record neural activity from one of these nuclei and found that the low dimensional model could reproduce the neural dynamics observed during the experiments. Also, this model could reproduce the respiratory motor patterns used to generate song. We showed that sparse activity in one of the neural nuclei could drive a more complex activity downstream in the neural network. This interdisciplinary work shows how low dimensional neural models can be a valuable tool for studying the emergence of complex motor tasks

Marmosets (Callithrix jacchus) are small South American monkeys which are being increasingly becoming adopted as animal models in neuroscience. Knowledge about the marmoset visual system has developed rapidly over the last decade. But what are the comparative advantages, and disadvantages involved in adopting this emerging model, as opposed to the more traditionally used macaque monkey? In this talk I will present case studies where the simpler brain morphology and short developmental cycle of the marmoset have been key factors in facilitating discoveries about the anatomy and physiology of the visual system. Although no single species provides the “ideal” animal model for invasive studies of the neural bases of visual processing, I argue that the development of robust methodologies for the study of the marmoset brain provides exciting opportunities to address long-standing problems in neuroscience.

Investigations of the neurophysiological processes underlying animal behaviors are almost exclusively done inside the laboratory, typically using few animal models born and reared under artificially stabilized conditions. Yet, animals living in the wild have to cope with much complex and variable environments. Thus, while the laboratory provides the technical possibilities for physiological research, the field offers a more realistic perspective about the animal´s behavioral abilities. We study neural circuits underlying the visually guided prey and predator behaviors in a semiterrestrial crab. By combining lab and field experiments we have, for example, found that the level of predation risk experienced by the animals in the wild affects the responsiveness of identified neurons involved in the animal escape response. Using this and other results from my lab I will illustrate and discuss the importance of complementing lab with field studies in wild animals for understanding the neural mechanisms subserving behavior.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting up to 1% of the population. Over the past few years, large-scale genomic studies have identified hundreds of genetic loci associated with liability to ASD. It is now time to translate these genetic discoveries into functional studies that can help us understand convergences and divergences across risk genes, and build pre-clinical cell and animal models. In this seminar, I will discuss some of the most recent findings on the genetic risk architecture of ASD. I will then expand on our work on biomarkers discovery and neurodevelopmental analyses in two rare genetic conditions associated with ASD: ADNP and DDX3X syndrome.

Neurodevelopmental disorders are a group of very heterogeneous diseases in which the development of the central nervous system is defective. In neurodevelopmental disorders defective brain development translates into aberrant brain function, which can manifest for example as impaired learning, motor function, or social interaction. Despites years of investigation in animal models and clinical research on neurodevelopmental disorders, there are currently no approved pharmacological treatments for core symptoms of the vast majority of them. Here, I will share some recent work (but also some apprehensions) of our laboratory on the development of strategies for the treatment of neurodevelopmental disorders, with a focus on Down syndrome.

Africa is blessed with a rich diversity and abundance in rodent and avian populations. This natural endowment on the continent portends research opportunities to study unique anatomical profiles and investigate animal models that may confer better neural architecture to study neurodegenerative diseases, adult neurogenesis, stroke and stem cell therapies. To this end, African researchers are beginning to pay closer attention to some of her indigenous rodents and birds in an attempt to develop spontaneous laboratory models for homegrown neuroscience-based research. For this presentation, I will be showing studies in our lab, involving cellular neuroanatomy of two rodents, the African giant rat (AGR) and Greater cane rat (GCR), Eidolon Bats (EB) and also the Striped Owl (SO). Using histological stains (Cresyl violet and Rapid Golgi) and immunohistochemical biomarkers (GFAP, NeuN, CNPase, Iba-1, Collagen 2, Doublecortin, Ki67, Calbindin, etc), and Electron Microscopy, morphology and functional organizations of neuronal and glial populations of the AGR , GCR, EB and SO brains have been described, with our work ongoing. In addition, the developmental profiles of the prenatal GCR brains have been chronicled across its entire gestational period. Brains of embryos/foetuses were harvested for gross morphological descriptions and then processed using immunofluorescence biomarkers to determine the pattern, onset, duration and peak of neurogenesis (Pax6, Tbr1, Tbr2, NF, HuCD, MAP2) and the onset and peak of glial cell expressions and myelination in the prenatal GCR. The outcome of these research efforts has shown unique neuroanatomical expressions and networks amongst Africa’s rich biodiversity. It is hopeful that continuous effort in this regard will provide sufficient basic research data on neural developments and cellular neuroanatomy with subsequent translational consequences.

Malformations of the human cerebral cortex represent a major cause of developmental disabilities. To date, animal models carrying mutations of genes so far identified in human patients with brain malformations only partially recapitulate the expected phenotypes and therefore do not provide reliable models to entirely understand the molecular and cellular mechanisms responsible for these disorders. Hence, we combine the in vivo mouse model and the human brain organoids in order to better comprehend the mechanisms involved in the migration of neurons during human development and tackle the causes of neurodevelopmental disorders. Our results show that we can model human brain development and disorders using human brain organoids and contribute to open new avenues to bridge the gap of knowledge between human brain malformations and existing animal models.

The dynamic nature of sleep in most animals suggests distinct stages which serve different functions. Genetic sleep induction methods in animal models provide a powerful way to disambiguate these stages and functions, although behavioural methods alone are insufficient to accurately identify what kind of sleep is being engaged. In Drosophila, activation of the dorsal fan-shaped body (dFB) promotes sleep, but it remains unclear what kind of sleep this is, how the rest of the fly brain is behaving, or if any specific sleep functions are being achieved. Here, we developed a method to record calcium activity from thousands of neurons across a volume of the fly brain during dFB-induced sleep, and we compared this to the effects of a sleep-promoting drug. We found that drug-induced spontaneous sleep decreased brain activity and connectivity, whereas dFB sleep was not different from wakefulness. Paradoxically, dFB-induced sleep was found to be even deeper than drug- induced sleep. When we probed the sleeping fly brain with salient visual stimuli, we found that the activity of visually-responsive neurons was blocked by dFB activation, confirming a disconnect from the external environment. Prolonged optogenetic dFB activation nevertheless achieved a significant sleep function, by correcting visual attention defects brought on by sleep deprivation. These results suggest that dFB activation promotes a distinct form of sleep in Drosophila, where brain activity and connectivity remain similar to wakefulness, but responsiveness to external sensory stimuli is profoundly suppressed.