Elsevier

Neuroscience

Volume 282, 12 December 2014, Pages 176-197
Neuroscience

Review
Heterogeneity of dopamine neuron activity across traits and states

https://doi.org/10.1016/j.neuroscience.2014.07.034Get rights and content

Highlights

  • Midbrain dopamine neuron activity varies with respect to firing rates and patterns across individuals and across states.

  • Heterogeneity in dopamine cell activity is seen over development, stressful events, drug exposure, and behavioral stimuli.

  • We review heterogeneity in firing and provide insight into how it may facilitate development of psychiatric conditions.

Abstract

Midbrain dopamine neurons fire irregularly, with interspersed clusters of high-frequency spikes, commonly called ‘bursts’. In this review we examine such heterogeneity in activity, and provide insight into how it can participate in psychiatric conditions such as drug addiction. We first describe several techniques used to evaluate dopamine neuron activity, and comment on the different measures that each provides. We next describe the activity of dopamine neurons in ‘basal’ conditions. Specifically, we discuss how the use of anesthesia and reduced preparations may alter aspects of dopamine cell activity, and how there is heterogeneity across species and regions. We also describe how dopamine cell firing changes throughout the peri-adolescent period and how dopamine neuron activity differs across the population. In the final section, we discuss how dopamine neuron activity changes in response to life events. First, we focus attention on drugs of abuse. Drugs themselves change firing activity through a variety of mechanisms, with effects on firing while drug is present differing from those seen after drug discontinuation. We then review how stimuli that are rewarding, aversive, or salient can evoke changes in firing rate and discharge pattern of dopamine neurons, and provide behavioral relevance of dopamine signaling. Finally, we discuss how stress can modulate dopamine neuron firing and how this may contribute to the role that stressful experiences play in psychiatric disorders such as addiction and depression.

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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