Heterogeneity in Slow Synaptic Transmission Diversifies Purkinje Cell Timing

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The content discusses the discovery of heterogeneity in slow synaptic transmission at parallel fiber synapses to Purkinje cells in the mouse cerebellum. Unlike uniform fast synaptic transmission, the properties of slow synaptic transmission varied significantly across different lobules, leading to surprising heterogeneity in the timing of Purkinje cell firing patterns. Depending on the location of the Purkinje cell, the time of peak and duration of slow synaptic currents varied by hundreds of milliseconds. This finding sheds light on the relationship between molecular and cellular heterogeneity and the functional outputs of different regions of the cerebellum.

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 threefold 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.

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