Endocannabinoids regulate cerebellar GABAergic transmission in a synapse type-dependent manner
Moritoshi Hirono1,2, Yuchio Yanagawa3
1Organization for Research Initiatives and Development, Doshisha University, Kyoto, Japan.
Journal of Neuroscience Research
|December 3, 2020
Summary
Endocannabinoids (eCBs) do not modulate GABA release from cerebellar Purkinje cells (PCs) to globular cells or deep cerebellar nuclei neurons. This suggests cannabinoid receptor (CBR) functions are synapse-specific in the cerebellum.
Area of Science:
- Neuroscience
- Cellular and Molecular Neuroscience
- Synaptic Plasticity
Background:
- Endocannabinoids (eCBs) are key neuromodulators acting via cannabinoid receptors (CBRs).
- Cerebellar Purkinje cells (PCs) form inhibitory synapses with deep cerebellar nuclei (DCN) neurons, globular cells, and Lugaro cells.
- The role of eCBs in modulating GABA release from PC axon terminals remains largely unexplored.
Purpose of the Study:
- To investigate the functional role of CBRs in modulating GABAergic transmission at PC-globular cell and PC-large DCN neuron synapses.
- To determine if eCBs affect spontaneous and miniature inhibitory postsynaptic currents (IPSCs) at these specific cerebellar synapses.
Main Methods:
- Electrophysiological recordings were performed on mouse cerebellar slices.
- The effects of CBR agonists (WIN55212, HU308) and a Gi/o protein-coupled receptor agonist (baclofen) on IPSCs were analyzed.
- Depolarization-induced suppression of inhibition was assessed in PC target neurons.
Main Results:
- WIN55212 did not alter spontaneous or miniature IPSCs in globular cells or large DCN neurons.
- Baclofen significantly reduced miniature IPSC frequency in globular cells, indicating Gi/o-coupled receptor involvement.
- HU308 and depolarization-induced suppression of inhibition were ineffective at these synapses.
- These findings indicate a lack of functional CBRs at PC axon terminals.
Conclusions:
- Cannabinoid receptors (CBRs) do not play a significant role in modulating GABA release from Purkinje cell (PC) axon terminals onto globular cells and large deep cerebellar nuclei (DCN) neurons.
- The absence of CBR modulation at these specific synapses contrasts with eCB-mediated modulation at other cerebellar inputs.
- These results highlight the synapse-specific actions of endocannabinoids (eCBs) in the cerebellum, potentially fine-tuning information processing and signal transmission.
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