Contribution of postsynaptic T-type calcium channels to parallel fibre-Purkinje cell synaptic responses

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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 Ca2+ signals. Unusually, postsynaptic Ca2+ signalling in PF-PC spines does not involve ionotropic glutamatergic receptors because postsynaptic NMDA receptors are absent and the AMPA receptors are Ca2+-impermeable; postsynaptic voltage-gated Ca2+ channels therefore constitute the sole rapid Ca2+ 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 Ca2+ entry at PF-PC spines.

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