J Neurosci. 2024 Aug 15. pii: e0455242024. [Epub ahead of print]
The cerebellum plays an important role in diverse brain functions, ranging from motor learning to cognition. Recent studies have suggested that molecular and cellular heterogeneity within cerebellar lobules contributes to functional differences across the cerebellum. However, the specific relationship between molecular and cellular heterogeneity and diverse functional outputs of different regions of the cerebellum remains unclear. Here, we describe a previously unappreciated form of synaptic heterogeneity at parallel fiber synapses to Purkinje cells in the mouse cerebellum (both sexes). In contrast to uniform fast synaptic transmission, we found that the properties of slow synaptic transmission varied by up to three-fold across different lobules of the mouse cerebellum, resulting in surprising heterogeneity. Depending on the location of a Purkinje cell, the time of peak of slow synaptic currents varied by hundreds of milliseconds. The duration and decay-time of these currents also spanned hundreds of milliseconds, based on lobule. We found that, as a consequence of the heterogeneous synaptic dynamics, the same brief input stimulus was transformed into prolonged firing patterns over a range of timescales that depended on Purkinje cell location.Significance statement The cerebellum is separated into functionally distinguished lobules, yet the lobules have a repeated and similar pattern of connectivity. Thus, it remains unclear how cells and circuits manage to perform the diverse functions that the cerebellum supports. Our results demonstrate that cerebellar Purkinje cells have synapses with strikingly different properties across lobules. This synaptic diversity drives heterogeneously timed output responses to the same input. Our results lay the framework for elucidating heterogeneity in the intracellular signaling pathways of these synapses. Overall, we demonstrate a heterogeneity of synaptic timing properties that can serve to diversify information processing across functionally different regions of the cerebellum.