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

The dopaminergic (DA) neurons in the ventral tegmental area (VTA) of the
middle brain play an 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 of hard work, we begin to understand how the excitability
of VTA DA neurons is 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. Based on this, we will further study the mechanism
which underlies the alteration of excitability of VTA DA neurons in the
condition of a depression state, and still further the related depression
behaviour.