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Abstract
The basal ganglia (BG) are a collection of interconnected subcortical nuclei that participate in a great variety of functions, ranging from motor programming and execution to procedural learning, cognition, and emotions. This network is also the region primarily affected by the degeneration of midbrain dopaminergic neurons localized in the substantia nigra pars compacta (SNc). This degeneration causes cellular and synaptic dysfunctions in the BG network, which are responsible for the appearance of the motor symptoms of Parkinson’s disease. Dopamine (DA) modulation and the consequences of its loss on the striatal microcircuit have been extensively studied, and because of the discrete nature of DA innervation of other BG nuclei, its action outside the striatum has been considered negligible. However, there is a growing body of evidence supporting functional extrastriatal DA modulation of both cellular excitability and synaptic transmission. In this review, the functional relevance of DA modulation outside the striatum in both normal and pathological conditions will be discussed.
Highlights
The basal ganglia (BG) participate in a great variety of functions including motor programming and execution, procedural learning, cognition, and emotions [1,2]
There is a growing body of evidences supporting the existence of discrete, functional dopaminergic innervation of extra-striatal nuclei (ESN), namely the subthalamic nucleus (STN), the internal and external segments of the globus pallidus (GPi and GPe, respectively) and the substantia nigra pars reticulata (SNr) [5]
Striato-pallidal synapses are characterized by short-term facilitation (STF) [93,94] and their strength is modulated by a plethora of G protein–coupled receptors (GPCR) [95,96,97,98,99,100,101,102] including presynaptic D2 receptors (D2Rs), which decrease the probability of GABA release [93,103]
Summary
The basal ganglia (BG) participate in a great variety of functions including motor programming and execution, procedural learning, cognition, and emotions [1,2]. There is a growing body of evidences supporting the existence of discrete, functional dopaminergic innervation of extra-striatal nuclei (ESN), namely the subthalamic nucleus (STN), the internal and external segments of the globus pallidus (GPi and GPe, respectively) and the substantia nigra pars reticulata (SNr) [5] In line with this evidence, the action exerted by DA on ESN has been investigated only recently and is the focus of the present review. As view predicted by the anatomical-functional and theofindirect been challenged by a studythat showing iSPNs and are model the BGpathways [8], it hashas been shown experimentally thesethat twoboth pathways exertdSPNs opposite co-activated initiation This coordinated activity has been interpreted as direct dSPN control over before motor movement execution [9].
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