Cerebellar connectivity maps embody individual adaptive behavior in mice

Ludovic Spaeth,Demian Battaglia,Kevin Dorgans,Theo Gagneux,Izumi Sugihara,Philippe Isope,Jyotika Bahuguna,Bernard Poulain

doi:10.1038/s41467-022-27984-8

Abstract

The cerebellar cortex encodes sensorimotor adaptation during skilled locomotor behaviors, however the precise relationship between synaptic connectivity and behavior is unclear. We studied synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs) in murine acute cerebellar slices using photostimulation of caged glutamate combined with patch-clamp in developing or after mice adapted to different locomotor contexts. By translating individual maps into graph network entities, we found that synaptic maps in juvenile animals undergo critical period characterized by dissolution of their structure followed by the re-establishment of a patchy functional organization in adults. Although, in adapted mice, subdivisions in anatomical microzones do not fully account for the observed spatial map organization in relation to behavior, we can discriminate locomotor contexts with high accuracy. We also demonstrate that the variability observed in connectivity maps directly accounts for motor behavior traits at the individual level. Our findings suggest that, beyond general motor contexts, GC-PC networks also encode internal models underlying individual-specific motor adaptation.

Highlights

The cerebellar cortex encodes sensorimotor adaptation during skilled locomotor behaviors, the precise relationship between synaptic connectivity and behavior is unclear
We investigated whether functional synaptic maps between granule cells (GC) and Purkinje cells (PC) in the anterior cerebellar vermis, an area involved in adaptation of locomotion[26,27,28,29,30], are modified in different locomotor contexts and during development
These markers, which are highly conserved between individuals, delimit zebrin positive (e.g. P1+ and P2+) and negative (e.g., P1− and P2−) bands of PCs matching with the topographical arrangement of the climbing fibers (CF) inputs[43,44], outlining cerebellar microzones in the cortex (Supplementary Fig. 1)

Summary

Introduction

The cerebellar cortex encodes sensorimotor adaptation during skilled locomotor behaviors, the precise relationship between synaptic connectivity and behavior is unclear. Population dynamics in cortical networks encoding stimulus features route information to different parts of the brain dedicated to motor planning and motor control If these neuronal dynamics eventually succeed in producing an adapted behavior, they are stabilized through synaptic plasticity yielding to a mutual structuring of circuit connectivity and activity patterns across the brain[8,9,10,11]. Connectivity maps would represent individual-specific engrams of adaptive behaviors established throughout motor learning and such feature-based maps would be animal and context specific[20,21] To address this hypothesis, we investigated whether functional synaptic maps between granule cells (GC) and Purkinje cells (PC) in the anterior cerebellar vermis, an area involved in adaptation of locomotion[26,27,28,29,30], are modified in different locomotor contexts (after training in a wheel or following impairment of locomotion) and during development. We found that while connectivity maps are correlated to behavioral conditions, each mouse developed a specific individual combination of connectivity traits linked to its individual and highly specific locomotor activity, suggesting that behavior may causally shape the spatial (re)organization of functional connectivity maps, biased but not fully determined by somatotopic hardwiring

Methods

Results

Conclusion