Elsevier

Neuroscience

Volume 282, 12 December 2014, Pages 248-257
Neuroscience

Review
The place of dopamine in the cortico-basal ganglia circuit

https://doi.org/10.1016/j.neuroscience.2014.10.008Get rights and content

Highlights

  • There are key areas within the striatum that receive convergent terminals from different functional cortical regions.

  • Subpopulations of dopamine neurons are involved in different functions including reward, cognition and motor control.

  • The striato-nigra system is a key factor in integrating information across functional domains.

Abstract

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. The mesolimbic and nigrostriatal pathways are an integral part of the basal ganglia through its reciprocal connections to the ventral and dorsal striatum respectively. 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.

Introduction

A key component in developing appropriate goal-directed behaviors is the ability to first correctly evaluate different aspects of reward, including value versus risk and predictability, and inhibit maladaptive choices, based on previous experience. These calculations rely on integration of different aspects of motivation and cognition to develop and execute appropriate action plans. The midbrain dopamine (DA) neurons play a central role in these behaviors including reward, cognition, and motor control. Indeed, subpopulations of DA neurons have been associated with these different functions: the mesolimbic, mesocortical, and nigrostriatal pathways, respectively (Wullner et al., 1994, Sawaguchi, 1995, Goldman-Rakic, 1998, Wise, 2004). Recently, all DA cell groups have been associated with the development of reward-based learning, leading to goal-directed behaviors (Schultz, 2002).

The substantia nigra (SN) was first recognized in 1786 with the description of brain neuromelanin distribution (Vicq D’Azyr, 1786). The link to the motor system came much later with its association with Parkinson’s disease (PD) (Brissaud, 1895, Bremer, 1920, Hassler, 1939). Collectively the work of several investigators then demonstrated that the cells contained DA, that DA was a neurotransmitter, and that these cells were depleted in PD (Ehringer and Hornykiewicz, 1960, Hornykiewicz, 1966, Bazelton et al., 1967). Around the same time DA was also linked to psychoses and subsequently addiction, and behavioral disorders, see (Baldessarini, 1985). With the visualization of DA neurons and the advances in connectivity and lesion methods in the 1960s, the subpopulations of DA neurons were associated with reward, cognition, or motor control: the mesolimbic (ventral tegmental area-VTA), mesocortical (VTA-retrorubral), and nigrostriatal (substantia nigra, pars compacta-SNc) pathways, respectively. Collectively these discoveries demonstrated that the DA cells are an integral part of the basal ganglia (BG). The VTA and SNc send a massive output to the striatum, the main input structure of the BG. Moreover, this is a bidirectional pathway, with the DA cells receiving a major input from the striatum.

Overall, the BG was best known for its relevance to motor functions, due to its role in movement control diseases. This concept dramatically changed in the last 35+ years to a more complex set of functions that mediate the full range of goal-directed behaviors, including emotions, motivation, and cognition. In the late 1970s, Heimer discovered that the nucleus accumbens (NAcc), (a basal forebrain region associated with limbic function), and the surrounding area were actually part of the striatum and termed this the ventral striatum (VS). Moreover, he identified the cells that were located ventral to the anterior commissure as pallidal in nature and showed that they received inputs from the VS. These cells are referred to as the ventral pallidum (VP) (Heimer, 1978). Subsequently he and others showed that the VP projected to the medial dorsal (MD) thalamus and back to non-motor cortex, thus identifying a separate functional loop of the BG (Young III et al., 1984, Haber et al., 1985). The concept of several functional, yet separate cortical loops through BG was then expanded in primates (Alexander et al., 1990). While the notion that these circuits are anatomically segregated remains prominent in the field, the idea of a motivation-to-movement interface, rather than separate loops through BG circuits was developed soon after the discovery of the VS/VP circuit. Researchers interested in how motivation impacts learning and the development of habits, recognized that integration between functional circuits was necessary to carry out goal-directed behaviors (Mogenson et al., 1980, Percheron and Filion, 1991, Dickinson and Balleine, 1994, Haber et al., 2000, Belin and Everitt, 2008, Leung and Balleine, 2013). Thus, the BG is now recognized to mediate the full range of behaviors leading to the development and execution of action plans, including the emotions, motivation, and cognition that drive them.

Section snippets

Overview of the BG circuitry

The striatum is the main input structure of the BG. Its afferent projections are derived from three major sources: (1) it receives a massive and topographic input from all of the cerebral cortex; (2) the second largest input is derived from the thalamus; and (3) the third main input is from the brainstem, the largest from the midbrain DA cells. Striatal functional domains are derived from the topography of its cortical inputs. Thus, we briefly review the topography of those inputs here. In

Organization of the midbrain DA cells in primates

The SNc has been divided into three groups: a dorsal (α) group, also referred to as the pars dorsalis; a main, densocellular (β) group; and a ventral (γ) group, or the cell columns (Olszewski and Baxter, 1982, Poirier et al., 1983, Francois et al., 1985, Halliday and Tork, 1986, Haber et al., 1995b). The dorsal group is composed of loosely arranged cells that extend dorsolaterally and circumvent the ventral and lateral superior cerebellar peduncle and the red nucleus. They are oriented

Connections

The main efferent projections of the midbrain DA system are to the striatum and cortex. Other projections include those to the thalamus, amygdala and hippocampus, and globus pallidus. The main afferent projections to the DA cells arise from the striatum and the brainstem pedunculopontine nucleus. Other key afferent projections include those from the lateral habenula (LHb) via the rostromedial tegmental nucleus (RMTg), the globus pallidus, and the superior colliculus. Each of these plays a key

Striato-midbrain-striato connections: the spiral

As indicated above, each functional region differs in its proportional projections that significantly alter their relationship to each other. The VS receives inputs from the areas involved in emotional processing, reward, and motivation. This includes the OFC, ACC, amygdala, and hippocampus. The VS receives a limited midbrain input, primarily from the VTA and dorsal tier. Yet, projections from this limbic area terminate widely in the midbrain, including the dorsal tier and the dorsal part of

Functional considerations

The ability to maintain focus in the execution of specific behaviors and the ability to adapt appropriately to external and internal cues are key deficits in BG diseases that affect these aspects of motor control, cognition, and motivation. Thus, a system that contains separate circuits to mediate various functions to maintain focus in coordinating actions maybe important. However, to have a system that was designed only with parallel and segregated circuits, without interaction between those

Acknowledgment

This work was supported by the NIMH grant MH045573-24.

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