The cerebellar cortex encodes sensorimotor adaptation during skilled locomotor behaviors, however the precise relationship between synaptic connectivity and behavior is unclear. In our recent Nature Communications paper (in collaboration with Philippe Isope’s group at INCI, Strasbourg), 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.
This is connectivity of GCs to just one PC, so conventional structural connectivity description would provide trivial graphs (a star, with many GCs connected to a common central PC). However, in cerebellum inactive connections (missing edges) are as important as present connections and, furthermore, the anatomical location of the connected GCs also matters. Therefore we designed a novel mapping between individual synaptic maps and graph entities, in which the abstract graph linking describes the geometry of the concrete spatial embedding of the structural connectivity rather than the connectivity itself. Once the mapping is made (through a covariance-based approach capturing the organization of localized patches in the connectivity map), standard graph-theoretical metrics can be used to describe the “shape” of these abstract graphs, and paremeterize thus indirectly the geometry of synaptic maps, standing between order and disorder and, therefore, complex.
Through our graph-based mapping, 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. Furthermore we can also discriminate locomotor contexts with high accuracy, which we couldn’t do with descriptions of connectivity more firmly rooted on detailed cerebellar anatomy. Indeed the features allowing to predict motor adaptations occurring in different contexts (e.g. lesioned sciatic nerve or hypertrained mice vs control) are neither related to purely local or purely global aspects of the synaptic maps but to intermediate multi-scale organization aspects that our graph mapping properly renders.
Las but not least, we also demonstrate that the variability observed in connectivity maps directly accounts for the variability of motor behavior traits at the individual level. Our findings suggest that, beyond general motor contexts, the fine spatial organization of GC-PC connectivity, only very partially accounted for by conventional anatomical subdivisions, also encode internal models underlying individual- specific motor adaptation.
To know more:
- Spaeth, L., Bahuguna, J., Gagneux, T., Dorgans, K., Sugihara, I., Poulain, B., Battaglia, D.*, Isope, P.* (2022). Cerebellar connectivity maps embody individual adaptive behavior. Nature Communications 13, 580 [*shared last authorship].