T-type calcium channels in synaptic plasticity

Abstract

The role of T-type calcium currents is rarely considered in the extensive literature covering the mechanisms of long-term synaptic plasticity. This situation reflects the lack of suitable T-type channel antagonists that till recently has hampered investigations of the functional roles of these channels. However, with the development of new pharmacological and genetic tools, a clear involvement of T-type channels in synaptic plasticity is starting to emerge. Here, we review a number of studies showing that T-type channels participate to numerous homo-and heterosynaptic plasticity mechanisms that involve different molecular partners and both pre-and postsynaptic modifications. The existence of T-channel dependent and independent plasticity at the same synapse strongly suggests a subcellular localization of these channels and their partners that allows specific interactions. Moreover, we illustrate the functional importance of T-channel dependent synaptic plasticity in neocortex and thalamus.

Calcium channel-dependent induction of long-term synaptic plasticity at excitatory Golgi cell synapses of cerebellum

“…It is therefore possible that the intracellular calcium-dependent machinery respects the Lisman paradigm [low calcium for LTD, high calcium for LTP (Lisman, 1989;Shouval et al, 2002)] with a voltage-dependent induction mechanism enhancing calcium influx from hyperpolarized membrane potential. Similar (but probably not identical) LTP and LTD induction mechanisms engaging combinations of NMDA and voltage-gated T-type and L-type Ca 2+ channels have also been reported at synapses in thalamic nuclei, deep cerebellar nuclei, cerebral cortex, hippocampus and striatum (Leresche and Lambert, 2017).…”

“…It is therefore conceivable that modulation of Golgi cell membrane potential would profoundly affect calcium influx through these membrane channels thereby affecting the induction of long-term synaptic plasticity. We have actually tested the effect of T-type and L-type Ca 2+ channels that are reported to play key roles in LTP and LTD induction (Leresche and Lambert, 2017). Neither T-type Ca 2+ channel blockade (with mibefradil) nor L-type Ca 2+ channel blockade (with nifedipine) significantly affected basal neurotransmission, suggesting that their action was primarily postsynaptic in our experiments.…”

“…Nifedipine is a potent inhibitor of L-type Ca 2+ (Cav1.x) currents (Nguemo et al, 2013;Striessnig et al, 2015) and their involvement in long-term synaptic plasticity has been reported (Leresche and Lambert, 2017). Bath application of 20 μM nifedipine did not cause any significant changes in basal synaptic transmission (m-EPSC, -0.1 ± 4.1%, n=5; Student's paired t test, p=0.7 and d-EPSC, -16.8 ± 1.36%, n=5; Student's paired t test, p=0.7; Fig.…”

“…Golgi cells are low-frequency pacemakers (Dieudonne, 1998;Forti et al, 2006) and they have recently been shown to express Ca 2+ channels in the dendrites (Rudolph et al, 2015). The Ca 2+ channels, along with postsynaptic NMDA receptors, may actually enable the induction of long-term synaptic plasticity, as observed at other synapses (Lisman, 1989;Shouval et al, 2002;Volianskis et al, 2015;Leresche and Lambert, 2017). In this work we have combined patch-clamp recordings and calcium imaging techniques to show, for the first time, the existence of bidirectional long-term plasticity at the excitatory Golgi cell synapses activated by patterned mossy fiber stimulation.…”

mPFC Spindle Cycles Organize Sparse Thalamic Activation and Recently Active CA1 cells During non-REM Sleep

“…Thalamic cells fire in two modes, burst and tonic, depending on the activation state of a transient conductance that relies on T-type calcium channels 40,41 . Bursts correlate with thalamic hyperpolarization, which is a pre-requisite for Tchannel activation, and they can enhance transmission in thalamocortical synapses and induce synaptic plasticity 42,43 . Therefore, analyzing burst firing can provide clues on the mechanism behind the decrease in firing rate in sleep.…”