Abstract
The mesolimbic and nigrostriatal dopamine (DA) systems play a key role in the physiology of reward seeking, motivation and motor control. Importantly, they are also involved in the pathophysiology of Parkinson’s and Huntington’s disease, schizophrenia and addiction. Control of DA release in the striatum is tightly linked to firing of DA neurons in the ventral tegmental area (VTA) and the substantia nigra (SN). However, local influences in the striatum affect release by exerting their action directly on axon terminals. For example, endogenous glutamatergic and cholinergic activity is sufficient to trigger striatal DA release independently of cell body firing. Recent developments involving genetic manipulation, pharmacological selectivity or selective stimulation have allowed for better characterization of these phenomena. Such termino-terminal forms of control of DA release transform considerably our understanding of the mesolimbic and nigrostriatal systems, and have strong implications as potential mechanisms to modify impaired control of DA release in the diseased brain. Here, we review these and related mechanisms and their implications in the physiology of ascending DA systems.
Highlights
ROLE OF DA IN MOTOR AND LIMBIC FUNCTION Dopamine (DA) plays a critical role in the organization of reward-seeking behavior and motor responses (Joshua et al, 2009; Schultz, 2013)
The mesolimbic system is formed by dopaminergic neurons located in the ventral tegmental area (VTA) and their projections to the nucleus accumbens (NAc), cortex, amygdala and hippocampus, which participate in the configuration of reward-seeking behaviors (Björklund and Dunnett, 2007; Stuber et al, 2012; Nieh et al, 2013)
Local control at the level of the striatum has been traditionally linked to DA reuptake and to feedback control on DA release through activation of D2 autoreceptors
Summary
The mesolimbic and nigrostriatal dopamine (DA) systems play a key role in the physiology of reward seeking, motivation and motor control They are involved in the pathophysiology of Parkinson’s and Huntington’s disease, schizophrenia and addiction. Recent developments involving genetic manipulation, pharmacological selectivity or selective stimulation have allowed for better characterization of these phenomena Such termino-terminal forms of control of DA release transform considerably our understanding of the mesolimbic and nigrostriatal systems, and have strong implications as potential mechanisms to modify impaired control of DA release in the diseased brain. We review these and related mechanisms and their implications in the physiology of ascending DA systems
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