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Review
. 2024 Mar 30;25(7):3875.
doi: 10.3390/ijms25073875.

The Formation and Function of the VTA Dopamine System

Guoqiang Hou  1   2 , Mei Hao  1   2 , Jiawen Duan  1   2 , Ming-Hu Han  1   2
Affiliations
Review

The Formation and Function of the VTA Dopamine System

Guoqiang Hou et al. Int J Mol Sci. .

Abstract

The midbrain dopamine system is a sophisticated hub that integrates diverse inputs to control multiple physiological functions, including locomotion, motivation, cognition, reward, as well as maternal and reproductive behaviors. Dopamine is a neurotransmitter that binds to G-protein-coupled receptors. Dopamine also works together with other neurotransmitters and various neuropeptides to maintain the balance of synaptic functions. The dysfunction of the dopamine system leads to several conditions, including Parkinson's disease, Huntington's disease, major depression, schizophrenia, and drug addiction. The ventral tegmental area (VTA) has been identified as an important relay nucleus that modulates homeostatic plasticity in the midbrain dopamine system. Due to the complexity of synaptic transmissions and input-output connections in the VTA, the structure and function of this crucial brain region are still not fully understood. In this review article, we mainly focus on the cell types, neurotransmitters, neuropeptides, ion channels, receptors, and neural circuits of the VTA dopamine system, with the hope of obtaining new insight into the formation and function of this vital brain region.

Keywords: dopamine; ion channels; neuropeptides; neurotransmitters; receptors; ventral tegmental area.

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Conflict of interest statement

The authors G.H., M.H., J.D., and M-H.H. declare no competing financial and/or non-financial interests.

Figures

Figure 1
Figure 1
Mechanism of behavioral adaptation induced by chronic social defeat stress. Chronic social defeat stress (CSDS) triggers homeostatic plasticity in the VTA mediated by a balance between excitatory Ih and inhibitory K+ currents. In susceptible mice, CSDS increases the activity of VTA NAc-projecting dopaminergic neurons via the enhancement of Ih, which promotes social avoidance. In resilient mice, CSDS enhances the NE release from the nucleus LC, which leads to an increase in K+ currents and greater enhancement of Ih in the VTA. This adaptive plasticity maintains the control-like activity of the VTA NAc-projecting dopaminergic neurons in resilient mice [54,68,97]. Thus, the LC-VTA-NAc circuit emerges as pivotal for social resilience and anti-depression. NE, norepinephrine; DA, dopamine.
Figure 2
Figure 2
Schematic representation of VTA’s connections with the NAc, PFC, CeA, and LHb. CeA, central nucleus of the amygdala; DA, dopamine; PFC, prefrontal cortex; LHb, lateral habenula; NAc, nucleus accumbens; PN, pyramidal neuron; PV+, parvalbumin-positive; RMTg, rostral medial tegmental nucleus; VTA, ventral tegmental area.
See this image and copyright information in PMC

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Grants and funding

This work is supported by the National Key Research and Development Program of China (Grant: 2021ZD0202902 and 2021ZD0202900), Research Fund for International Scientists of National Natural Science Foundation of China (Grant: T2250710685), Shenzhen Key Basic Research Project (Grant: JCYJ20220818101600001), Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression (Grant: ZDSYS20220606100606014), Shenzhen Medical Research Fund (SMRF B2303012), and Science and Technology Research and Development Foundation of Shenzhen (High-level Talent Innovation and Entrepreneurship Plan of Shenzhen Team Funding, KQTD20221101093608028).

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