Dopamine and Its Actions in the Basal Ganglia System
The dopaminergic system is implicated in a broad range of neurological syndromes, including Parkinson’s disease, dementia, dystonia, stuttering, depression, and schizophrenia. It is likely that systems-level computer simulations will guide future therapeu
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Dopamine and Its Actions in the Basal Ganglia System Daniel Bullock
5.1
Introduction: Consensus Summary of Dopamine’s Actions in the Circuitry of the Basal Ganglia
There have been many recent excellent reviews of selected aspects of the dopamine (DA) system, including the range of stimuli and internal signals to which DA neurons respond (e.g., Bromberg-Martin et al. 2010; Schultz 2013), how DA release depends jointly on DA neuron firing and myriad factors present at release sites in the basal ganglia (BG) (e.g., Rice et al. 2011), the systematic effects of DA in the striatum (e.g., Gerfen and Surmeier 2011), and the role dopamine plays in various neurological disorders (e.g., Linnet 2014; Lloyd et al. 2014; Covey et al. 2014; Belujon and Grace 2015; Nutt et al. 2015) beyond its critical role in Parkinson’s disease and schizophrenia (e.g., Iversen and Iversen 2007). This chapter will reprise many of the key findings needed to understand the consensus that is emerging about the neural systems—especially the BG system—within which DA plays its most critical role. Like noradrenaline (NA), dopamine (DA) is an aminergic neurotransmitter, and Dahlström and Fuxe (1964) identified and designated 14 clusters of aminergic neurons: A1–A7 designate NA clusters, and A8–A14 designate DA clusters, most in the midbrain (see also Björklund and Dunnett 2007). In each cluster, DA cells are mixed with other cell types, but in all of these clusters, the aminergic neurons represent a large proportion of cells, and they typically project aminergic axons far beyond the nuclei in which their somas reside. Other brain structures also contain intermixed
D. Bullock, Ph.D. (*) Department of Psychological and Brain Sciences, Boston University, 677 Beacon Street, Boston, MA 02215, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 J.-J. Soghomonian (ed.), The Basal Ganglia, Innovations in Cognitive Neuroscience, DOI 10.1007/978-3-319-42743-0_5
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DA neurons—a good example is the retina—but these neurons are not a large proportion of the total, and function as interneurons, with no projections beyond the area. Recently, Fuxe and colleagues (2010) reviewed the huge literature that has developed since the A8–A14 clusters were mapped. They reprised impressive evidence that (1) a highly similar mapping applies across a wide range of mammalian species and (2) DA often works via volume transmission, which utilizes diffusion well beyond release sites (Rice and Cragg 2008; but see Ishikawa et al. 2013), hence does not require that the DA release sites be immediately adjacent to the receptors at which DA acts. Of course, all systemically delivered neuroactive drugs also work via volume transmission, after crossing the blood–brain barrier. Consistent with this mode of operation, single DA neurons exhibit remarkably widespread branching, with multiple axonal bushes, in target areas such as the striatum (e.g., Matsuda et al 2009). Thus, DA is typically regarded as a nonspecific, “broadcast” signal, highly distinct
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