bims-climfi 2023-05-14 papers

Issue of 2023‒05‒14
two papers selected by
Jun Maruta
Mount Sinai Health System

Elife. 2023 Apr 26. pii: e80875. [Epub ahead of print]12

cAMP-EPAC-PKCε-RIM1α signaling regulates presynaptic long-term potentiation and motor learning.

Xin-Tai Wang, Lin Zhou, Bin-Bin Dong, Fang-Xiao Xu, De-Juan Wang, En-Wei Shen, Xin-Yu Cai, Yin Wang, Na Wang, Sheng-Jian Ji, Wei Chen, Martijn Schonewille, J Julius Zhu, Chris I De Zeeuw, Ying Shen.

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.

Keywords: Purkinje cell; cerebellum; mouse; neuroscience; plasticity; protein kinase A

DOI: https://doi.org/10.7554/eLife.80875

Exp Neurobiol. 2023 Apr 30. 32(2): 83-90

mGluR1 Regulates the Interspike Interval Threshold for Dendritic Ca2+ Transients in the Cerebellar Purkinje Cells.

Dong Cheol Jang, Changhyeon Ryu, Geehoon Chung, Sun Kwang Kim, Sang Jeong Kim.

Ca2++ transients can be observed in the distal dendrites of Purkinje cells (PCs) despite their lack of action potential backpropagation. These Ca2++ events in distal dendrites require specific patterns of PC firing, such as complex spikes (CS) or simple spikes (SS) of burst mode. Unlike CS, which can act directly on voltage-gated calcium channels in the dendrites through climbing fiber inputs, the condition that can produce the Ca2++ events in distal dendrites with burst mode SS is poorly understood. Here, we propose the interspike interval threshold (ISIT) for Ca2++ transients in the distal dendrites of PC. We found that to induce the Ca2++ transients in distal dendrites the frequency of spike firing of PC should reach 250 Hz (3 ms ISI). Metabotropic glutamate receptor 1 (mGluR1) activation significantly relieved the ISIT and established cellular conditions in which spike firing with 50 Hz (19 ms ISI) could induce Ca2++ transients in the distal dendrites. In contrast, blocking T-type Ca2++ channels or depleting the endoplasmic reticulum Ca2++ store resulted in a stricter condition in which spike firing with 333 Hz (2 ms ISI) was required. Our findings demonstrate that the PC has strict ISIT for dendritic Ca2++ transients, and this ISIT can be relieved by mGluR1 activation. This strict restriction of ISIT could contribute to the reduction of the signal-to-noise ratio in terms of collecting information by preventing excessive dendritic Ca2++ transients through the spontaneous activity of PC.

Keywords: Calcium signaling; Cerebellum; Dendrites; Purkinje cells

DOI: https://doi.org/10.5607/en22040