T-Type Calcium Channels Contribute to Burst Firing in a Subpopulation of Medial Habenula Neurons.

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.

SurfaceGenie: a web-based application for prioritizing cell-type-specific marker candidates.

MOTIVATION: Cell-type-specific surface proteins can be exploited as valuable markers for a range of applications including immunophenotyping live cells, targeted drug delivery and in vivo imaging. Despite their utility and relevance, the unique combination of molecules present at the cell surface are not yet described for most cell types. A significant challenge in analyzing 'omic' discovery datasets is the selection of candidate markers that are most applicable for downstream applications. RESULTS: Here, we developed GenieScore, a prioritization metric that integrates a consensus-based prediction of cell surface localization with user-input data to rank-order candidate cell-type-specific surface markers. In this report, we demonstrate the utility of GenieScore for analyzing human and rodent data from proteomic and transcriptomic experiments in the areas of cancer, stem cell and islet biology. We also demonstrate that permutations of GenieScore, termed IsoGenieScore and OmniGenieScore, can efficiently prioritize co-expressed and intracellular cell-type-specific markers, respectively. AVAILABILITY AND IMPLEMENTATION: Calculation of GenieScores and lookup of SPC scores is made freely accessible via the SurfaceGenie web application: www.cellsurfer.net/surfacegenie. CONTACT: Rebekah.gundry@unmc.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.