Enhanced hippocampal type II theta activity AND altered theta architecture in mice lacking the Cav3.2 T-type voltage-gated calcium channel

Abstract

T-type Ca 2+ channels are assumed to contribute to hippocampal theta oscillations. We used implantable video-EEG radiotelemetry and qPCR to unravel the role of Ca v 3.2 Ca 2+ channels in hippocampal theta genesis. Frequency analysis of spontaneous long-term recordings in controls and Ca v 3.2 −/− mice revealed robust increase in relative power in the theta (4–8\xa0Hz) and theta-alpha (4–12\xa0Hz) ranges, which was most prominent during the inactive stages of the dark cycles. Urethane injection experiments also showed enhanced type II theta activity and altered theta architecture following Ca v 3.2 ablation. Next, gene candidates from hippocampal transcriptome analysis of control and Ca v 3.2 −/− mice were evaluated using qPCR. Dynein light chain Tctex-Type 1 (Dynlt1b) was significantly reduced in Ca v 3.2 −/− mice. Furthermore, a significant reduction of GABA A receptor δ subunits and GABA B1 receptor subunits was observed in the septohippocampal GABAergic system. Our results demonstrate that ablation of Ca v 3.2 significantly alters type II theta activity and theta architecture. Transcriptional changes in synaptic transporter proteins and GABA receptors might be functionally linked to the electrophysiological phenotype.