Distinct cell populations of ventral tegmental area process motivated behavior

Abstract

It is well known that dopamine transmission from the ventral tegmental area (VTA) modulates motivated behavior and reinforcement learning. Although dopaminergic neurons are the major type of VTA neurons, recent studies show that a significant proportion of the VTA contains GABAergic and type 2 vesicular glutamate transporter (VGLUT2)-positive neurons. The non-dopaminergic neurons are also critically involved in regulating motivated behaviors. Some VTA neurons appear to co-release two different types of neurotransmitters. They are VGLUT2-DA neurons, VGLUT2-GABA neurons and GABA-DA neurons. These co-releasing neurons show distinct features compared to the neurons that release a single neurotransmitter. Here, we review how VTA cell populations wire to the other brain regions and how these projections differentially contribute to motivated behavior through the distinct molecular mechanism. We summarize the activities, projections and functions of VTA neurons concerning motivated behavior. This review article discriminates VTA cell populations related to the motivated behavior based on the neurotransmitters they release and extends the classical view of the dopamine-mediated reward system.

Distinct neuromodulatory effects of endogenous orexin and dynorphin corelease on projection-defined ventral tegmental dopamine neurons.

“…However, the functional consequences of this diversity on behavior remains poorly elucidated. DA projections from the VTA to the NAc, play an important role in motivated behaviors, reinforcement learning, and reward processing (Hamid et al, 2016;Kim and Kaang, 2022). Recent studies have shown the contribution of VTA projections to the amygdala in encoding state-specific motivational salience (Lutas et al, 2019), regulating approach/avoidance behavior toward threats (Miller et al, 2019), and have established the role of VTA projections in modulating BLA activity during aversive conditioning (Tang et al, 2020).…”

Stress-induced anxiety-related behavior in mice is driven by enhanced excitability of ventral tegmental area GABA neurons

“…In support of this contention, we found that uFS did not increase the percentage of VTA GABA neurons exhibiting spontaneous activity, but it did increase the rate of VTA GABA neurons that did exhibit spontaneous activity. The VTA is host to GABA neuron subtypes that can be differentiated based on molecular and neurochemical markers, as well as afferent and efferent connections ( Paul et al, 2018 ; Bouarab et al, 2019 ; Kim and Kaang, 2022 ). Our electrophysiological assessments and chemogenetic manipulations of VTA GABA neurons did not discriminate among VTA GABA neuron subtypes.…”

Heterogeneity of mesencephalic dopaminergic neurons: From molecular classifications, electrophysiological properties to functional connectivity

“…Motivation is the process by which thoughts influence behavior and may incorporate the current state and pertinent cues in the context of reward-based training. 72 The functional significance of DA in the realm of rewardbased behaviors has been debated for quite a while. To explain the role of DA in motivation, two primary theories have been proposed.…”