The viruses used in this article from BrainVTA are in the table below

The precise contributions of ventral tegmental area (VTA) dopaminergic (DAergic) neurons to reward-related behaviors are a longstanding hot topic of debate. Whether the activity of VTA DAergic neurons directly modulates rewarding behaviors remains uncertain. In the present study, we investigated the fundamental role of VTA DAergic neurons in reward-related movement and reinforcement by employing dopamine transporter (DAT)-Cre transgenic mice expressing hM3Dq, hM4Di or channelrhodopsin 2 (ChR2) in VTA DAergic neurons through Cre-inducible adeno-associated viral vector transfection. On the one hand, locomotion was tested in an open field to examine motor activity when VTA DAergic neurons were stimulated or inhibited by injection of the hM3Dq or hM4Di ligand clozapine-N-oxide (CNO), respectively. CNO injection to selectively activate or inhibit VTA DAergic neurons significantly increased or decreased locomotor activity, respectively, compared with vehicle injection, indicating that VTA DAergic neuron stimulation is directly involved in the regulation of motor activity. On the other hand, we used the optical intracranial self-stimulation (oICSS) model to investigate the causal link between reinforcement and VTA DAergic neurons. Active poking behavior but not inactive poking behavior was significantly escalated in a frequency- and pulse duration-dependent manner. In addition, microdialysis revealed that the concentration of dopamine (DA) in the nucleus accumbens (NAc) was enhanced by selective optogenetic activation of VTA DAergic neurons. Furthermore, systemic administration of a DA D1 receptor antagonist significantly decreased oICSS reinforcement. Our research profoundly demonstrates a direct regulatory role of VTA DAergic neurons in movement and reinforcement and provides meaningful guidance for the development of novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.

 

Fig. 1 Motor activity was modulated by VTA DAergic neuron activity.

To specifically address the role of VTA DAergic neurons in reward-related motor activity and reinforcement, the authors employed a chemogenetic approach and optogenetic stimulation (From BrainVTA)  to achieve temporally precise manipulation of VTA DAergic neurons in a cell-type specific manner. The results profoundly demonstrate a direct regulatory role of VTA DAergic neurons in movement and reinforcement and provides meaningful guidance for the development of novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.
 
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