The ion channel mechanisms of the subthreshold inward depolarizing currents in the VTA dopaminergic neurons and their roles in the depression-like behavior

The dopaminergic (DA) neurons in the ventral tegmental area (VTA) of middle brain play important role in emotion related behaviour, and the alteration of excitability of VTA DA neurons are believed to be the key determinants in behaviours of depression and drug addictions. The excitability of VTA DA neurons controls the release of DA in the projection fiber terminals thus controls the function of VTA DA neurons. After many years hard work, we begin to understand how the excitability of VTA DA neurons are regulated, but these achievements are far from satisfactory. Furthermore, with recent progress and realization that property of VTA DA neurons, against the classical view that VTA DA neurons are homogeneous population, are distinctly different, thus the accumulated limited knowledge on the mechanism of excitability modulation of VTA DA neurons is especially short of expectation. The most outstanding indications of the heterogeneity of VTA DA neurons are represented by the distinctly different electrophysiological properties among VTA DA neurons projecting to different brain regions. However the underlying mechanism is not clear. In this application we plan to investigate the underlying mechanism determining the distinct excitability of VTA DA neurons projecting to the cortical and the limbic regions of the brain by single cell RNA sequencing (scRNA-seq). The main focus of the study will be on the intrinsic ion channels and the related modulation mechanism of VTA DA neuron excitability. On the basis of this we will further study the mechanism which underlie alteration of excitability of VTA DA neurons in condition of depression state, and still further the related depression behaviour.