Séminaire départemental Dr. Owen Randlett

vendredi 15 Septembre 11h00 , en Amphithéâtre CAUCHY

Department of Cell and Developmental Biology,
Perelman School of Medicine, University of Pennsylvania
Department of Molecular and Cellular Biology, Harvard University

Understanding how plasticity in neural circuits creates long-lived memories remains a fundamental question in neuroscience. It is clear that synaptic plasticity underlies memory formation. But, how such processes are distributed across neural circuits, and how this leads to specific behavioural alterations remains poorly understood. The larval zebrafish is a vertebrate with a relatively simple brain that is small enough to be studied at the whole-brain scale and is appropriate for high-throughput analyses. We have developed a robust, high-throughput (600 fish/experiment) assay based on the “simplest” form of memory: habituation. Habituation occurs in response to repetitive stimuli, where the animal adapts and reduces its responsiveness over time. In our assay, habituation memories are made in nearly all individual fish and last over 8 hours. Interestingly, habituation manifests in multiple independent aspects of the response, indicating that multiple learning pathways operate in parallel. To gain insights into these process, we screened a library of over 2000 compounds with annotated targets, which identified >25 compounds that either block or potentiate aspects of habituation. To build on this pharmacological data and to understand how habituation memories manifest in the brain, it would be ideal to assay neural activity comprehensively across the entire brain. For such purposes, we developed a method based on the phosphorylation of ERK and automated image volume registration. This method rapidly creates whole-brain activity maps at near-cellular resolution from freely behaving animals. Additionally, we created the Z-Brain neuroanatomical atlas (www.zbra.in), which automatically contextualizes activity maps and can identify candidate cell types underling behaviour. I will describe how we are beginning to use these tools to understand how drugs identified in our behavioural screen act upon habituation. By studying the molecular, cellular and circuit mechanisms of simple memory paradigms in a simple vertebrate brain, my proposed research program aims to make fundamental insights into the mechanisms used by vertebrate circuits to build and store memories.

Lieu(x) : Ecole Polytechnique, Amphithéâtre MONGE