Abstract
The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here, we report that the EPAC-PKCε module has a critical role in a presynaptic form of long-term potentiation in the cerebellum and motor behavior in mice. Presynaptic cAMP-EPAC-PKCε signaling cascade induces a previously unidentified threonine phosphorylation of RIM1α, and thereby initiates the assembly of the Rab3A-RIM1α-Munc13-1 tripartite complex that facilitates docking and release of synaptic vesicles. Granule cell-specific blocking of EPAC-PKCε signaling abolishes presynaptic long-term potentiation at the parallel fiber to Purkinje cell synapses and impairs basic performance and learning of cerebellar motor behavior. These results unveil a functional relevance of presynaptic plasticity that is regulated through a novel signaling cascade, thereby enriching the spectrum of cerebellar learning mechanisms.
Original language | English |
---|---|
Article number | e80875 |
Journal | eLife |
Volume | 12 |
DOIs | |
Publication status | Published - 26 Apr 2023 |
Keywords
- Animals
- Mice
- Cerebellum/physiology
- Long-Term Potentiation/physiology
- Neurons
- Purkinje Cells
- Synapses/physiology
- Guanine Nucleotide Exchange Factors