Neuroscience
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Review
Neurotrophins in the ventral tegmental area: Role in social stress, mood disorders and drug abuse.
This review discusses the impact of neurotrophins and other trophic factors, including fibroblast growth factor and glial cell line-derived neurotrophic factor, on mood disorders, weight regulation and drug abuse, with an emphasis on stress- and drug-induced changes in the ventral tegmental area (VTA). Neurotrophins, comprising nerve growth factor, brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4/5 play important roles in neuronal plasticity and the development of different psychopathologies. In the VTA, most research has focused on the role of BDNF, because other neurotrophins are not found there in significant quantities. ⋯ Social defeat stress that is continuous in mice or intermittent in rats increases VTA BDNF expression, and is associated with depressive and social avoidance behaviors. Intermittent social defeat stress induces persistent VTA BDNF expression that triggers psychostimulant cross-sensitization. Understanding the cellular and molecular substrates of neurotrophin effects may lead to novel therapeutic approaches for the prevention and treatment of substance use and mood disorders.
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The midbrain dopamine (DA) neurons play a central role in developing appropriate goal-directed behaviors, including the motivation and cognition to develop appropriate actions to obtain a specific outcome. Indeed, subpopulations of DA neurons have been associated with these different functions: the mesolimbic, mesocortical, and nigrostriatal pathways. ⋯ This chapter reviews the connections of the midbrain DA cells and their role in integrating information across limbic, cognitive and motor functions. Emphasis is placed on the interface between these functional domains within the striatum through corticostriatal connections, through the striato-nigro-striatal connection, and through the lateral habenula projection to the midbrain.
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The functions of the D1- and D2-dopamine receptors in the basal ganglia have remained somewhat enigmatic, with a number of competing theories relating to the interactions of the 'direct' and 'indirect pathways'. Computational models have been good at simulating properties of the system, but are typically divorced from the underlying neural architecture. ⋯ The D2DR-expressing striatal pathways then shape and 'select' from this initial response set framework. This article is part of a Special Issue entitled: Ventral Tegmentum & Dopamine.
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Dopaminergic neurons in a range of species are responsive to sensory stimuli. In the anesthetized preparation, responses to non-noxious and noxious sensory stimuli are usually tonic in nature, although long-duration changes in activity have been reported in the awake preparation as well. However, in the awake preparation, short-latency, phasic changes in activity are most common. ⋯ At the forebrain level, sensory-related changes in the tonic activity of dopaminergic neurons may regulate the impact of the cortex on forebrain structures such as the nucleus accumbens. In contrast, the short latency of the phasic responses to sensory stimuli in dopaminergic neurons, coupled with the activation of these neurons by non-rewarding stimuli, suggests that phasic responses of dopaminergic neurons may provide a signal to the forebrain which indicates that a salient event has occurred (and possibly an estimate of how salient that event is). A stimulus-related salience signal could be used by downstream systems to reinforce behavioral choices.
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Midbrain dopamine systems play important roles in Parkinson's disease, schizophrenia, addiction, and depression. The participation of midbrain dopamine systems in diverse clinical contexts suggests these systems are highly complex. Midbrain dopamine regions contain at least three neuronal phenotypes: dopaminergic, GABAergic, and glutamatergic. ⋯ Rat VTA VGluT2 neurons exhibit intrinsic VTA projections and extrinsic projections to the accumbens and to the prefrontal cortex. Mouse VTA VGluT2 neurons project to accumbens shell, prefrontal cortex, ventral pallidum, amygdala, and lateral habenula. Given their molecular diversity and participation in circuits involved in addiction, we hypothesize that individual VGluT2 subpopulations of neurons play unique roles in addiction and other disorders.