Cerebellar connectivity maps embody individual adaptive behavior in mice

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.

Excitation and inhibition delays within a feedforward inhibitory pathway modulate cerebellar Purkinje cell output in mice

“…Therefore, we suggest that similar rules may apply in the cerebellar GC-MLI-PC FFI pathway and individual GC clusters might be selected by PCs to ensure proper E/I balance in PCs. These findings are in agreement with the spatial organization of the GC-PC connectivity maps that correlate with specific locomotor context at the level of individuals (Spaeth et al, 2022). FFI circuits similar to the GC-MLI-PC with synapses that show STD are ubiquitous in the brain.…”

“…Indeed, this behavior mimics physiological properties as incoming action potentials from the pre-cerebellar nuclei likely invade all the MF collaterals in the cerebellum. Anatomical reconstructions showed that a single MF gives rise to many distant rosettes in a cerebellar lobule (Shinoda et al, 2000;Sultan, 2001;Quy et al, 2011;Na et al, 2019), activating discrete and distinct GC clusters that may target the same PCs as shown previously (Valera et al, 2016;Spaeth et al, 2022). This latter configuration is also mimicked by the surface illumination used in our experiments which showed similar results than single rosette excitation but with a wider range of ΔLat.…”

“…Spikelet propagation in the MLI network ensure synchronization, while chemical synapses curtail integration time window (Hoehne et al, 2020). Altogether, selecting groups of GCs targeting specifically MLIs or PCs or both in combination (Valera et al, 2016; Spaeth et al, 2022) with specific short term dynamics (Chabrol et al, 2015; Dorgans et al, 2019) can enhance both the dynamic range and the resolution for temporal encoding in the MF-GC-PC pathway. Furthermore, we and others demonstrated that long term plasticity (LTP and LTD) at the GC-PC synapses is gated by MLIs (Binda et al, 2016; Rowan et al, 2018).…”

“…This arrangement leads to temporally dispersed GC activation as observed in lobule IX and X of the cerebellar cortex (Chabrol et al, 2015). Furthermore, clusters of GCs make active synaptic connections with specific groups of PC and MLIs independently as a result of activity-dependent processes (Barbour, 1993; Isope and Barbour, 2002; Valera et al, 2016; Spaeth et al, 2022). Indeed, PCs and MLIs located in the same cerebellar module have specific GC input connectivity maps, suggesting that GCs may contact either MLIs or PCs at a given location.…”

What Can We Learn from Synaptic Connectivity Maps about Cerebellar Internal Models?

“…Furthermore, many pre-cerebellar nuclei carrying distinct modalities project MFs to the GC layer of the same microzone 27, 11. In the anterior lobe, for example, lobule IV and V receive MFs from the spinocerebellar tract (e.g., DSCT, dorsal spinocerebellar tract) and the external cuneate conveying proprioceptive information from the hindlimbs and the forelimbs, respectively, as well [24] as from the pontine nuclei, which carry information from the cerebral cortex such as motor plans and motor commands [28]. Therefore, individual GCs can integrate multimodal information [26,29] but see [30] that combine both motor plans or commands and sensory feedback.…”