Neuroscience
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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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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.
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Almost every physiological or behavioral process in mammals follows rhythmic patterns, which depend mainly on a master circadian clock located in the hypothalamic suprachiasmatic nucleus (SCN). The dopaminergic (DAergic) system in the brain is principally implicated in motor functions, motivation and drug intake. ⋯ Here we examine what is currently understood about the anatomical and functional central multi-oscillatory circadian system, highlighting how the main SCN clock communicates timing information with other brain clocks to regulate the DAergic system and conversely, how DAergic cues may have feedback effects on the SCN. These studies give new insights into the role of the brain circadian system in DA-related neurologic pathologies, such as Parkinson's disease, attention deficit/hyperactive disorder and drug addiction.
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Learning to associate specific objects or actions with rewards and remembering the associations are everyday tasks crucial for our flexible adaptation to the environment. These higher-order cognitive processes depend on the prefrontal cortex (PFC) and frontostriatal circuits that connect areas in the frontal lobe with the striatum in the basal ganglia. Both structures are densely innervated by dopamine (DA) afferents that originate in the midbrain. ⋯ In addition, D2 receptors may also contribute to motivation. The learning deficits correlated with reductions of neural information about the associations in PFC neurons, alterations in global excitability and spike synchronization, and exaggerated alpha and beta neural oscillations. Our findings provide new insights into how DA transmission modulates associative learning and memory processes in frontostriatal systems.
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Projection systems arising from the ventral tegmental area (VTA) and the substantia nigra (SN) have a critical role in a broad range of functions, as well as in the etiology, symptoms and treatment of neurological and psychiatric diseases. Mostly studied for its dopamine neurons, the ventral tegmentum is in fact heterogeneous at cellular and functional levels. ⋯ Recent progress also highlights the need for molecular markers of functional subpopulations within the ventral tegmentum, for deeper developmental knowledge of this region, and for a single cell level of connectomic. It also raises the question of inter-individual, sex, strain and species heterogeneity, and conversely the question of data generalization in a context of human pathology models, which warrant comparative studies and translational effort.