The role of T‐type calcium channels in the subiculum: to burst or not to burst?

Abstract

Several studies suggest that voltage-gated calcium currents are involved in generating high frequency burst firing in the subiculum, but the exact nature of these currents remains unknown. Here, we used selective pharmacology, molecular and genetic approaches to implicate Cav3.1-containing T-channels in subicular burst firing, in contrast to several previous reports discounting T-channels as major contributors to subicular neuron physiology. Furthermore, pharmacological antagonism of T-channels, as well as global deletion of CaV3.1 isoform, completely suppressed development of long-term potentiation (LTP) in the CA1-subiculum, but not in the CA3-CA1 pathway. Our results indicate that excitability and synaptic plasticity of subicular neurons relies heavily on T-channels. Hence, T-channels may be a promising new drug target for different cognitive deficits.

A neurosteroid analogue with T-type calcium channel blocking properties is an effective hypnotic, but is not harmful to neonatal rat brain

“…These data confirm that Tchannels play a crucial role in regulating neuronal excitability of the immature rat subiculum. 25 3b-OH decreases evoked AMPA-mediated, but not NMDA-mediated excitatory synaptic currents acting presynaptically Next, we recorded evoked inhibitory postsynaptic currents (eIPSCs) and evoked excitatory postsynaptic currents (eEPSCs) in subicular neurones using a paired-pulse protocol (Fig. 5).…”

Sweet T‐bursting is the subiculum's true badge

“…The afterdepolarizing potential (ADP) that drives burst discharge in subicular cells has been shown to be influenced by different factors that include voltage-gated calcium, sodium and potassium channels. The findings of Joksimovic et al (2017) now place Cav3 calcium channels at the centre of understanding the factors that control subicular cell firing and thus hippocampal output. Joksimovic et al (2017) use in vitro slice recordings from rats and mice to conduct a biophysical analysis of the expression pattern and role for Cav3 calcium channel isoforms in different firing patterns of pyramidal cells, as well as GABAergic interneurons.…”

“…The findings of Joksimovic et al . () now place Cav3 calcium channels at the centre of understanding the factors that control subicular cell firing and thus hippocampal output.…”

“…Joksimovic et al . () use in vitro slice recordings from rats and mice to conduct a biophysical analysis of the expression pattern and role for Cav3 calcium channel isoforms in different firing patterns of pyramidal cells, as well as GABAergic interneurons. While voltage clamp recordings from intact neurons can be subject to space clamp issues, the authors carefully assessed calcium channel properties in younger animals with the advantage of relatively new selective T‐type channel blockers and extensive past research into the physiology of low voltage‐activated calcium channels.…”

“…excitability in neurons steadily reveals that cell output can be governed by voltage-gated ion channels that are expressed on a cell-or region-specific basis. In this issue of The Journal of Physiology, Joksimovic et al (2017) identify a key contribution by T-type calcium channels to spike output of pyramidal cells in the subiculum, a region responsible for a large component of the output of hippocampus. Past work has shown that pyramidal cells in the subiculum exhibit different forms of spike output that range from regular spiking to weak or strong bursting (Jung et al 2001).…”