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• W1964071191 endingPage "680" @default.
• W1964071191 startingPage "666" @default.
• W1964071191 abstract "Cerebellar Purkinje cells (PCs) encode afferent information in the rate and temporal structure of their spike trains. Both spontaneous firing in these neurons and its modulation by synaptic inputs depend on Ca2+ current carried by Cav2.1 (P/Q) type channels. Previous studies have described how loss-of-function Cav2.1 mutations affect intrinsic excitability and excitatory transmission in PCs. This study examines the effects of the leaner mutation on fast GABAergic transmission and its modulation of spontaneous firing in PCs. The leaner mutation enhances spontaneous synaptic inhibition of PCs, leading to transitory reductions in PC firing rate and increased spike rate variability. Enhanced inhibition is paralleled by an increase in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) measured under voltage clamp. These differences are abolished by tetrodotoxin, implicating effects of the mutation on spike-induced GABA release. Elevated sIPSC frequency in leaner PCs is not accompanied by increased mean firing rate in molecular layer interneurons, but IPSCs evoked in PCs by direct stimulation of these neurons exhibit larger amplitude, slower decay rate, and a higher burst probability compared to wild-type PCs. Ca2+ release from internal stores appears to be required for enhanced inhibition since differences in sIPSC frequency and amplitude in leaner and wild-type PCs are abolished by thapsigargin, an ER Ca2+ pump inhibitor. These findings represent the first account of the functional consequences of a loss-of-function P/Q channel mutation on PC firing properties through altered GABAergic transmission. Gain in synaptic inhibition shown here would compromise the fidelity of information coding in these neurons and may contribute to impaired cerebellar function resulting from loss-of function mutations in the CaV2.1 channel gene." @default.
• W1964071191 created "2016-06-24" @default.
• W1964071191 creator A5026312332 @default.
• W1964071191 creator A5036467116 @default.
• W1964071191 date "2010-09-16" @default.
• W1964071191 modified "2023-10-16" @default.
• W1964071191 title "Enhanced Synaptic Inhibition Disrupts the Efferent Code of Cerebellar Purkinje Neurons in Leaner Cav2.1 Ca2+ Channel Mutant Mice" @default.
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• W1964071191 doi "https://doi.org/10.1007/s12311-010-0210-9" @default.
• W1964071191 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3627404" @default.
• W1964071191 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20845003" @default.
• W1964071191 hasPublicationYear "2010" @default.
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