TY - JOUR T1 - T-type calcium channels contribute to burst firing in a subpopulation of medial habenula neurons JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0201-20.2020 SP - ENEURO.0201-20.2020 AU - Casey R. Vickstrom AU - Xiaojie Liu AU - Yuqi Zhang AU - Lianwei Mu AU - Thomas J. Kelly AU - Xudong Yan AU - Meng-ming Hu AU - Shana T. Snarrenberg AU - Qing-song Liu Y1 - 2020/07/27 UR - http://www.eneuro.org/content/early/2020/07/27/ENEURO.0201-20.2020.abstract N2 - Action potential (AP) burst firing caused by the activation of low-voltage-activated T-type Ca2+ channels is a unique mode of neuronal firing. T-type channels have been implicated in diverse physiological and pathophysiological processes, including epilepsy, autism, and mood regulation, but the brain structures involved remain incompletely understood. The medial habenula (MHb) is an epithalamic structure implicated in anxiety-like and withdrawal behavior. Previous studies have shown that MHb neurons fire tonic APs at a frequency of ∼2-10 Hz or display depolarized low amplitude membrane oscillations. Here, we report in C57BL/6J mice that a subpopulation of MHb neurons are capable of firing transient, high frequency AP bursts mediated by T-type channels. Burst firing was observed following rebounding from hyperpolarizing current injections or during depolarization from hyperpolarized membrane potentials in ∼20% of MHb neurons. It was rarely observed at baseline but could be evoked in MHb neurons displaying different initial activity states. Further, we show that T-type channel mRNA, in particular Cav3.1, is expressed in the MHb in both cholinergic and substance P-ergic neurons. Pharmacological Cav3 antagonism blocked both burst firing and evoked Ca2+ currents in MHb neurons. Additionally, we observed high frequency AP doublet firing at sustained depolarized membrane potentials that was independent of T-type channels. Thus, there is a greater diversity of AP firing patterns in MHb neurons than previously identified, including T-type channel-mediated burst firing, which may uniquely contribute to behaviors with relevance to neuropsychiatric disease.Significance statement Previous studies have reported that medial habenula neurons solely fire tonic action potentials at ∼2-10 Hz or display depolarized low amplitude membrane oscillations. In contrast, we found that a subpopulation of medial habenula neurons fire high frequency action potential bursts that share the characteristics of T-type Ca2+ channel-mediated low threshold spikes and were blocked by pharmacological antagonism of T-type Ca2+ channels. T-type Ca2+ channel mRNA, especially Cav3.1, is expressed in the medial habenula in both cholinergic and substance P-ergic neurons. T-type channel-independent action potential doublets were also observed in medial habenula neurons at sustained depolarized membrane potentials. Thus, there is a greater diversity of AP firing patterns in MHb neurons than previously recognized, including T-type Ca2+ channel-mediated burst firing. ER -