Contribution of postsynaptic T‐type calcium channels to parallel fibre‐Purkinje cell synaptic responses
Authors: Ly Romain , Bouvier Guy , Szapiro German , Prosser Haydn M. , Randall Andrew D. , Kano Masanobu , Sakimura Kenji , Isope Philippe , Barbour Boris , Feltz Anne 
Published: December 2015

Key points

At the parallel fibre‐Purkinje cell glutamatergic synapse, little or no Ca2+ entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage‐gated Ca2+ channels therefore constitute the sole rapid postsynaptic Ca2+ 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.

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.