Projection-dependent heterogeneity of cerebellar granule cell calcium responses

Title
Projection-dependent heterogeneity of cerebellar granule cell calcium responses
Authors
게이코 야마모토유키오 야마모토김태곤박희연이준규
Issue Date
2021-03
Publisher
Molecular Brain
Citation
VOL 14, 63
Abstract
Cerebellar granule cells (GCs) relay mossy fber (MF) inputs to Purkinje cell dendrites via their axons, the parallel fbers (PFs), which are individually located at a given sublayer of the molecular layer (ML). Although a certain degree of heterogeneity among GCs has been recently reported, variability of GC responses to MF inputs has never been associated with their most notable structural variability, location of their projecting PFs in the ML. Here, we utilize an adenoassociated virus (AAV)-mediated labeling technique that enables us to categorize GCs according to the location of their PFs, and compare the Ca2+ responses to MF stimulations between three groups of GCs, consisting of either GCs having PFs at the deep (D-GCs), middle (M-GCs), or superfcial (S-GCs) sublayer. Our structural analysis revealed that there was no correlation between position of GC soma in the GC layer and location of its PF in the ML, confrming that our AAV-mediated labeling was important to test the projection-dependent variability of the Ca2+ responses in GCs. We then found that the Ca2+ responses of D-GCs difered from those of M-GCs. Pharmacological experiments implied that the diferent Ca2+ responses were mainly attributable to varied distributions of GABAA receptors (GABAARs) at the synaptic and extrasynaptic regions of GC dendrites. In addition to GABAAR distributions, amounts of extrasynaptic NMDA receptors appear to be also varied, because Ca2+ responses were diferent between D-GCs and M-GCs when glutamate spillover was enhanced. Whereas the Ca2+ responses of S-GCs were mostly equivalent to those of D-GCs and M-GCs, the blockade of GABA uptake resulted in larger Ca2+ responses in S-GCs compared with D-GCs and M-GCs, implying existence of mechanisms leading to more excitability in S-GCs with increased GABA release. Thus, this study reveals MF stimulation-mediated non-uniform Ca2+ responses in the cerebellar GCs associated with the lo
URI
http://pubs.kist.re.kr/handle/201004/73072
ISSN
1756-6606
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