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http://purl.uniprot.org/citations/26627919http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Key points

At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca(2+) entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid postsynaptic Ca(2+) signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics. This component can amount up to 20% of the EPSC, and this fraction is maintained even at the high frequencies sometimes encountered in sensory processing. Modelling based on our biophysical characterization of T-type calcium channels in Purkinje cells suggests that the brief spine EPSCs cause the activated T-type channels to deactivate rather than inactivate, enabling repetitive activation.

Abstract

In the cerebellum, sensory information is conveyed to Purkinje cells (PC) via the granule cell/parallel fibre (PF) pathway. Plasticity at the PF-PC synapse is considered to be a mechanism of information storage in motor learning. The induction of synaptic plasticity in the cerebellum and elsewhere usually involves intracellular Ca(2+) signals. Unusually, postsynaptic Ca(2+) signalling in PF-PC spines does not involve ionotropic glutamatergic receptors because postsynaptic NMDA receptors are absent and the AMPA receptors are Ca(2+) -impermeable; postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid Ca(2+) signalling mechanism. Low-threshold activated T-type calcium channels are present at the synapse, although their contribution to PF-PC synaptic responses is unknown. Taking advantage of 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide, a selective T-type channel antagonist, we show in the mouse that inhibition of these channels reduces PF-PC excitatory postsynaptic currents and excitatory postsynaptic potentials by 15-20%. This contribution was preserved during sparse input and repetitive activity. We characterized the biophysical properties of native T-type channels in young animals and modelled their activation during simulated dendritic excitatory postsynaptic potential waveforms. The comparison of modelled and observed synaptic responses suggests that T-type channels only activate in spines that are strongly depolarized by their synaptic input, a process requiring a high spine neck resistance. This brief and local activation ensures that T-type channels rapidly deactivate, thereby limiting inactivation during repetitive synaptic activity. T-type channels are therefore ideally situated to provide synaptic Ca(2+) entry at PF-PC spines."xsd:string
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http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Isope P."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Kano M."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Sakimura K."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Randall A.D."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Feltz A."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Prosser H.M."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Bouvier G."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Barbour B."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Szapiro G."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/author"Ly R."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/name"J Physiol"xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/pages"915-936"xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/title"Contribution of postsynaptic T-type calcium channels to parallel fibre-Purkinje cell synaptic responses."xsd:string
http://purl.uniprot.org/citations/26627919http://purl.uniprot.org/core/volume"594"xsd:string
http://purl.uniprot.org/citations/26627919http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26627919
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