Venue : Centre Broca
Defense in English
Elena Baz
Team : Mechanisms of Adaptive Processes in brain circuits (MAP)
IINS
Title
Role of γ-Protocadherins in the molecular encoding of olivo-cerebellar connections
Abstract
During development, millions of neurons in the brain must choose their synaptic partners and undergo deep functional and molecular changes to stabilize specific connections. The olivo-cerebellar circuit presents a highly stereotyped development, with synapse selection happening during strict critical periods, making it a perfect model to study these phenomena. Early after birth, multiple climbing fibers (CF) emerging from the inferior olivary nucleus innervate each Purkinje cell (PC) in the cerebellum cortex. Over the three first postnatal weeks, supernumerary CF are pruned until each PC is mono-innervated by a single CF. Beyond the established role of activity in afferent selection, the molecular mechanisms underlying cell-cell interaction and recognition in this circuit remain unknown. The highly diverse family of gamma Protocadherins (γPCDH) has been recurrently proposed as part of a “molecular code of connectivity” in the cerebellum, although experimental evidence remains scarce. Here, using PatchSeq we show that during CF elimination, the diversity of γPCDH isoforms expressed by individual PC gradually decreases. In addition, overexpressing single isoforms to mimic a premature decrease in γPCDH diversity in single PCs significantly accelerates CF selection in a hindbrain explant model. Furthermore, we detected a higher similarity in γPCDH repertoire expressed by PCs connected by the same CF, suggesting that γPCDH expression in PCs is determined by the presynaptic neuron identity. Overall, our results support the role of γPCDH as part of the cerebellar molecular code of connectivity with a direct effect in CF-to-PC synapse specificity, and a not random γPCDH isoform expression.
Keywords
Cerebellum – Protocadherins – Development
Jury
- Fekrije Selimi (Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France).
- Peter Scheiffele (Biozentrum, University of Basel).
- Emilie Pacary (Neurocentre Magendie).
- Thesis supervisor: Mathieu Letellier.
- Invited member of jury: Alexandre Favereaux.