ePoster

Unravelling the functional diversity of granule cells in the cerebellar cortex

Christopher Small, Theo Rossi, Jerome Wandhammer, Alice Basile, Fred Doussau, Philippe Isope
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Christopher Small, Theo Rossi, Jerome Wandhammer, Alice Basile, Fred Doussau, Philippe Isope

Abstract

The cerebellum is an area of the brain involved in sensory-motor adaptation, movement coordination and higher cognitive processes. Within the cerebellar cortex, mossy fibres (MFs) convey sensorimotor input to a dense layer of granule cells (GrCs). GrCs relay this information through parallel fibre (PF) projections that synapse with Purkinje cells (PCs), the sole output of the cerebellar cortex, and molecular layer interneurons (MLI), which provide feedforward inhibition of PCs. Accordingly, PCs compute incoming sensorimotor patterns and send inhibitory outputs that rapidly adjust motor movements. Despite this seemingly uniform circuitry, GrCs possess a high degree of biological and functional heterogeneity that enhances cerebellar computation. Importantly, GrCs exhibit varied responses to different MF frequencies. Similarly, diverse modes of short-term plasticity (STP) at GrC-MLI synapses control the timing of PC discharge. However, similar STP dynamics at glutamatergic GrC-PC synapses have not been characterised. Therefore, we monitored the patterns of glutamate release from PF boutons following GrC stimulation in acute cerebellar slices. To achieve this, we applied two-photon microscopy following AAV-mediated delivery of a fluorescent glutamate sensor (iGluSnFR) in adult mice. PF boutons exhibited distinct, heterogeneous patterns of glutamatergic release during STP that occurred independently of target PCs. Hence, it is not clear how GrCs acquire functional properties as the cerebellar circuitry is established. Currently, we are characterising the evolution glutamate release during cerebellar maturation, across different GrC lineages (C1QL1). Our goal is to establish whether GrC molecular composition, or different forms of MF input, shape PF synaptic plasticity during cerebellar computation.

Unique ID: fens-24/unravelling-functional-diversity-granule-76e16530