ReviewHeterogeneity of dopamine neuron activity across traits and states
Introduction
Midbrain dopamine neurons are essential mediators of a number of normal behaviors including voluntary movement, feeding, associative learning, and motivation. In addition, several pathologies are related to dysfunction of these neurons including Parkinson’s disease and drug addiction. Given this varied set of behaviors, it is not surprising that the search for a single function for dopamine has been elusive. Concurrent with the search for one role has been a supposition that dopamine neurons themselves form a homogeneous group with similar properties and responses to stimuli. This picture has gradually shifted during the last decade as a new appreciation for heterogeneity of dopamine neurons both within and between individuals has become accepted. In this review, we will examine this heterogeneity as it relates to several features including firing rates and patterns, neuroanatomy, anesthesia, species, development, and life events (e.g. exposure to abused drugs and stress).
Section snippets
Anatomy of the dopamine system
The anatomy of the dopamine system is described in detail in other contributions to this special issue (Walsh and Han, 2014, Yetnikoff et al., 2014); here we only present a very brief summary. The majority of dopamine neurons of the midbrain originate in the ventral tegmental area (VTA, also known as the A10 cell area) and the substantia nigra pars compacta (SNc, A9 cell area), with VTA placed ventromedial to SNc. These dopamine neurons send projections to several forebrain regions – most
Evaluating dopamine neuron activity
Dopamine neuron activity, and more broadly activity in the mesolimbic dopamine projection, can be assayed in a number of ways. These include in vivo methods in both awake and anesthetized subjects, as well as ex vivo methods in tissue slices.
‘Basal’ activity
Dopamine neurons fire with characteristic patterns of activity in basal conditions (i.e. without stimulation), and these differ across in vivo and ex vivo preparations. Most of this section will review studies made in vivo, in anesthetized rats, as these are the most abundant.
Dopamine neuron activity in response to ‘life events’
The activity of dopamine neurons is modulated by different types of life event including exposure to addictive drugs, environmental stimuli, and stress. In studies that have analyzed firing patterns, these changes can involve either non-bursting, bursting, or both.
Summary
There are multiple ways in which midbrain dopamine neurons exhibit heterogeneity. Dopamine neurons fire irregularly, with interspersed burst events. The differing patterns of activity can lead to differences in neurotransmitter output and can be altered by multiple factors. Some of these factors vary on a cell-by-cell basis within an individual (e.g. dependent on projection site, location within midbrain); some vary on a subject-to-subject basis (e.g. at different ages, or in different
Acknowledgments
This work was supported by NIH Grants DA033380 (JEM) and DA031577 (MM). We thank Dr. Michael Beckstead for providing the electrophysiology trace reported in Fig. 3.
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