Heterogeneity in Slow Synaptic Transmission Diversifies Purkinje Cell Timing
- Riya Elizabeth Thomas1,2,3,4,
- Franziska Mudlaff1,2,3,4,
- Kyra Schweers1,2,3,
- William Todd Farmer5,6, and
- Aparna Suvrathan1,2,3
- 1Centre for Research in Neuroscience, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montréal, Québec H3G 1A4, Canada
- 2Departments of Neurology and Neurosurgery, McGill University, Montréal, Québec H3G 1A4, Canada
- 3Pediatrics, McGill University, Montréal, Québec H3G 1A4, Canada
- 4Integrated Program in Neuroscience, McGill University, Montréal, Québec H3A 1A1, Canada
- 5Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
- 6Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
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Author contributions: R.E.T., F.M., W.T.F., and A.S. designed research; R.E.T., F.M., K.S., W.T.F., and A.S. performed research; R.E.T., F.M., K.S., W.T.F., and A.S. analyzed data; R.E.T. and A.S. wrote the paper.
Abstract
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.
- Received March 8, 2024.
- Revision received July 19, 2024.
- Accepted July 31, 2024.
- Copyright © 2024 Thomas et al.
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