Cerebellar granule cells (GrCs) are usually regarded as a uniform cell type that collectively expands the coding space of the cerebellum by integrating diverse combinations of mossy fiber inputs. Accordingly, stable molecularly or physiologically defined GrC subtypes within a single cerebellar region have not been reported. The only known cellular property that distinguishes otherwise homogeneous GrCs is the correspondence between GrC birth timing and the depth of the molecular layer to which their axons project. To determine the role birth timing plays in GrC wiring and function, we developed genetic strategies to access early- and late-born GrCs. We initiated retrograde monosynaptic rabies virus tracing from control (birth timing unrestricted), early-born, and late-born GrCs, revealing the different patterns of mossy fiber input to GrCs in vermis lobule 6 and simplex, as well as to early- and late-born GrCs of vermis lobule 6: sensory and motor nuclei provide more input to early-born GrCs, while basal pontine and cerebellar nuclei provide more input to late-born GrCs. In vivo multidepth two-photon Ca 2+ imaging of axons of early- and late-born GrCs revealed representations of diverse task variables and stimuli by both populations, with modest differences in the proportions encoding movement, reward anticipation, and reward consumption. Our results suggest neither organized parallel processing nor completely random organization of mossy fiber→GrC circuitry but instead a moderate influence of birth timing on GrC wiring and encoding. Our imaging data also provide evidence that GrCs can represent generalized responses to aversive stimuli, in addition to recently described reward representations.
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Shared Cortex-Cerebellum Dynamics in the Execution and Learning of a Motor Task.
Throughout mammalian neocortex, layer 5 pyramidal (L5) cells project via the pons to a vast number of cerebellar granule cells (GrCs), forming a fundamental
pathway. Yet, it is unknown how neuronal dynamics are transformed through the L5/GrC pathway. Here, by directly comparing premotor L5 and GrC activity during a forelimb movement task usingdual-site two-photon Ca2+ imaging, we found that in expert mice, L5 and GrC dynamics were highly similar. L5 cells and GrCs shared a common set of task-encoding activity patterns, possessed similar diversity of responses, and exhibited high correlations comparable to local correlations among L5 cells. Chronic imaging revealed that these dynamics co-emerged in cortex and cerebellum over learning: as behavioral performance improved, initially dissimilar L5 cells and GrCs converged onto a shared, low dimensional, task-encoding set of neural activity patterns. Thus, a key function of cortico-cerebellar communication is the propagation of shared dynamics that emerge during learning.
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- Award ID(s):
- 1707261
- NSF-PAR ID:
- 10100523
- Date Published:
- Journal Name:
- Cell
- ISSN:
- 1097-4172
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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