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Dissecting striato-pallidal circuit for motor control using in vivo optical approaches
16 May : Guillaume Dorothée, INSERM UMRS 938, Hôpital Saint Antoine
11 may 10h : Flavio Kapczinski, Université McMaster, Canada
The interplay of recurrent mood disorders and dementia
Salle du conseil de l'UFR de Biologie
11 april : Jean-Baptiste Penigault, Société Nanostring
Spatial transcritomic and proteomic solutions on slides
28 march: Maya Medalla
Prefrontal cortico-limbic networks in cognition: cellular and circuit diversity
Abstract: The goal my research is to develop an understanding of the synaptic and cellular diversity across distinct prefrontal pathways associated with high-order cognitive and emotional processes, and how this diversity relates to selective circuit vulnerability in disease in primates. To this effect I have employed multi-faceted anatomical and electrophysiological approaches at the systems, cellular and synaptic levels, combining whole-cell patch-clamp recording and intracellular labeling techniques in in vitro brain slices, with tract-tracing and multiple-immunolabeling techniques for confocal microscopy and 3D serial electron microscopy. The main question in my laboratory is to understand what differentiates excitatory, inhibitory and neuromodulatory circuits in the primate prefrontal cortex, and related sensory, motor and limbic cortices, that endow the capacity for complex high-order processing and underlie selective vulnerability in disease.
Title: Life without brain serotonin: Cognitive and social characterization of TPH2-ko rats in classical tests vs. automated home cage environment.
Abstract: Central serotonin is one major molecular target for treatment of several mental disorders. As such it appears a promising transdiagnostic biological marker of mental illness. A better understanding of the specific role of serotonin in the modulation of co-morbid impairments will be instrumental for the development of more efficient and personalized treatment for patients.
In this study, beyond a categorical view of mental disorders and in line with the search for endophenotypes, we aimed to expose the consequences of complete central serotonin deficiency on cognitive, social and everyday behaviors, using recently generated TPH2 knockout rats. We used a combination of state of the art semi-automated home-cage and stand-alone classical testing, a multidimensional profiling approach and unsupervised machine learning.
Although surprisingly, no cognitive function evaluated in classical tests were altered by the absence of brain serotonin, in the day-to-day context of the home-cage, the same TPH2-ko animals presented drastic changes in multiple aspects of their daily life with significant social disorganization (hierarchy and social networks). While developmental neurological compensations may have occurred these results challenge the concept of an essential role of serotonin for expressing cognitive abilities when tested in classical tests. Central serotonin appeared to be a key modulator of essential social and naturalistic home-cage behaviors when living in more complex environments. In the home-cage, TPH2-ko animals presented a profile reminiscent of the symptomatology of impulse control and anxiety disorders.
Our novel methodological framework to analyze an animal model under complex environmental conditions highlighted the importance to complement the use of classical behavioral tests with ethologically valid paradigms where the complexity of the animals’ natural behavior can be evaluated. This may in fact for some cases be the only way to discover subtle dysfunctions in animal models and which could effectively translate to human pathological conditions.
The general goal of my research is to map and dissect the neural circuits and to decipher the neuronal codes underlying the formation of internal representations of the external space within hippocampal-neocortical networks. In my talk, I will address two scientific directions. First,what are the neuronal ensemble mechanisms underlying the large capacity of the brain to rapidly encode and remember multiple sequential experiences? We recently uncovered the existence of internal generative predictive codes for the statistical regularities of the external space in the hippocampus that rely on the functional connectivity within and between high-repeat short motifs of sequential neurons called ‘tuplets’. This organization into neuronal tuplets segments extended temporal sequences into shorter modules, analogous to segmentation of words into syllables. This segmentation can vastly expand the generative encoding capacity of the network by rapidly combining neuronal tuplets into multiple independent extended sequences. Second, when and how do internally generated representations supporting memory formation and spatial/mental navigation emerge during brain development? I will discuss our work describing three distinct stages and timepoints in the postnatal development of time-compressed neuronal sequences of firing in the rat hippocampus area CA1 thought to be ethologically relevant for the emergence of memory encoding and consolidation.separation
Dr Tim Sargeant started his career in neuroscience with a PhD at Victoria University of Wellington, New Zealand. Tim went on to two postdoctoral positions at the Department of Medicine and the Department of Pathology at the University of Cambridge (UK) where he researched the cell’s recycling machinery (called the lysosomal system) and obtained training in molecular and cell biology. Tim was appointed to head of Lysosomal Health in Ageing in the Hopwood Centre for Neurobiology (formally the Lysosomal Diseases Research Unit) at SAHMRI in 2015. His current research focuses on the role of lysosomal recycling in common age-related disease such as Alzheimer’s disease. The lysosomal system is important for slowing cell ageing, as it removes damaged and unwanted material from the cell. This process is critically important for healthy brain function. Work from Lysosomal Health in Ageing has shown that this system is damaged in Alzheimer’s disease, and that changes in genes that are involved in the lysosomal system are associated with Alzheimer’s disease. Our current research focuses on development of methods for measurement of lysosomal system activity (through a process called autophagy) in humans. We are also developing interventions that improve the lysosomal system with the goal of delaying Alzheimer’s disease.
11 October: Aniko Korosi:
Aniko Korosi was a postdoc at UCI in the lab of dr. Baram (2006-2010) where she studied how enriched early life experience rewires the hypothalamus. At the end of 2010 she started her team and she is currently an Associate Professor at the University of Amsterdam. Her research is funded by several national and international programs (e.g. NWO Food Cognition and Behavior, NWO Meervoud, JPI- Nutri-Cog and ISAO). Her team includes several PhD students and postdocs and her research focuses on the programming of cognitive functions by early-life stress and aging and on the role of metabolic signals, nutrients and epigenetic mechanisms in this context. Her work encompasses pre-clinical work using an established mouse model of chronic early-life stress and clinical work and she is interested in developing peripheral (e.g. nutritional) intervention to prevent and/or reverse the lasting consequences of early-life stress as well as human studies investigating the effects of stress on breastmilk composition.
Early-life stress induced cognitive decline: a synergistic role for stress, nutrition and inflammation.
Abstract: Early-life stress (ES) is associated with increased vulnerability to cognitive impairments as well as metabolic disorders like obesity later in life. We investigate the role of a synergistic effect of stress, metabolic factors, nutrition and the neuroimmune system in this early-life induced programming.
We use an established model of chronic ES and expose mice to limited nesting and bedding material during first postnatal week and study the central and peripheral systems under basal and challenged conditions (i.e. LPS, amyloid accumulation, western style diet (WSD) and exercise) to gain further insight in the functionality of brain plasticity, neurogenesis microglia and adipose tissue. In addition, given the high nutritional demand during development, we propose that early nutrition is critical for programming of brain and body. We focus on essential micronutrients and fatty acids and propose that an early dietary intervention with a diet enriched with these nutrients might protect against ES-induced functional deficits.
We show that ES leads to cognitive impairments associated with reduced hippocampal neurogenesis at basal conditions as well as in response to exercise, primed microglia with exaggerated response to LPS or amyloid accumulation. Metabolically, ES mice exhibit a leaner phenotype but they accumulate more fat in response to WSD. Finally, with an early dietary intervention with micronutrient or fatty acid we were able to (at least partly) prevent ES-induced cognitive decline, likely mediated by modulation of microglia, without however affecting the ES-induced metabolic profile. These studies give new insights for the development of targeted dietary interventions for vulnerable populations.
Andrea Rau is a research scientist and biostatistician with strong expertise in omics data analysis and methods development. She currently holds a joint appointment at INRAE in the Animal Genetics and Integrative Biology (GABI) research unit and the BioEcoAgro joint cross-border research unit. Her research centers on “useable and useful” methodological developments for high-dimensional single- and multi-omics data analyses, including differential expression analyses, co-expression analyses, network inference, and integrative multi-omic analyses. As a strong proponent for the implementation and dissemination of methods in open-source software packages, she is an active user and developer of the R programming language, and has developed or co-developed several R packages and Shiny web applications. Over the past decade, she has successfully worked in close collaboration with biologists in animal, plant, and human genomics on interdisciplinary problems at the interface of statistics and biology.
Leveraging multi-comic data for integrative exploratory, predictive, and network analyses
Abstract: The increased availability and affordability of high-throughput sequencing technologies in recent years have facilitated the use of multi-omic studies, expanding and enriching our understanding of complex systems across hierarchical biological levels. Integrative methods for these heterogeneous and multi-faceted omics data have shown promise for enhancing the interpretability of exploratory analyses, improving predictive power, and contributing to a holistic understanding of systems biology. However, such integrative analyses are accompanied by several major obstacles, including the potentially ambiguous relationships among omic levels, high dimensionality coupled with small sample sizes, technical artefacts due to batch effects, potentially incomplete or missing data… and the occasional difficulty in posing well-defined and answerable research questions of such data. In light of these challenges, in this talk I will discuss a few of our recent methodological contributions to integrate multi-omic data for (1) exploratory analyses, (2) genomic prediction, and (3) network inference, all with a focus on enhanced interpretability and user-friendly software implementations.