Dr. Mathieu Letellier 
The Interdisciplinary Institute for Neuroscience (IINS), University of Bordeaux

Title: Making input-specific synaptic changes last: from synaptic tagging mechanisms to cell-adhesion codes

Abstract:
Neural circuits must remain plastic while preserving the identity and specificity of individual connections. A central question is therefore how activity-dependent changes at selected synapses are converted into molecular changes that persist over time. Beyond rapid modifications of synaptic proteins, long-term plasticity relies on gene expression, through both local translation and transcription.
I will present two studies exploring how these mechanisms support persistent, connection-specific changes across different timescales. First, I will show how activity-dependent local translation of synaptopodin, a key component of the spine apparatus, molecularly tags selected hippocampal synapses to support input-specific long-term homeostatic plasticity. I will then turn to the developing olivo-cerebellar circuit, where climbing fiber connectivity onto Purkinje Cells (PCs) is extensively refined during a critical developmental period to reach long-term stabilization of a single input. Using Patch-seq to link the functional properties of individual connections to transcriptional profiles, we find that developmental plasticity shapes gamma-protocadherins expression in PCs, suggesting that refinement leaves a persistent molecular signature. We propose that this transcriptional code contributes to the long-term stabilization and maintenance of connectivity established during development. Together, these studies illustrate how translation- and transcription-dependent mechanisms can convert plastic changes into persistent molecular states.