Review
Dissecting the diversity of midbrain dopamine neurons

https://doi.org/10.1016/j.tins.2013.03.003Get rights and content

Highlights

  • There are distinct phenotypes of midbrain dopamine neurons with segregated axonal projections.

  • The differential inputome for midbrain dopamine subpopulations is defined.

  • Optogenetic analyses of the behavioral roles of distinct midbrain dopamine neurons are discussed.

Midbrain dopamine (DA) neurons are essential for controlling key functions of the brain, such as voluntary movement, reward processing, and working memory. The largest populations of midbrain DA neurons are localized in two neighboring nuclei, the substantia nigra (SN) and the ventral tegmental area (VTA). Regardless of their different axonal projections to subcortical and cortical targets, midbrain DA neurons have traditionally been regarded as a relatively homogeneous group of neurons, with a stereotypical set of intrinsic electrophysiological properties and in vivo pattern of activity. In this review, I highlight recent data supporting an unexpected degree of diversity among these midbrain DA neurons in the mammalian brain, ranging from their developmental lineages and different synaptic connectivity to their electrophysiological properties and behavioral functions.

Section snippets

Identifying DA neurons in the midbrain

This short, noncomprehensive, review focuses on recent developments in understanding the diversity of midbrain DA neurons. Thus, it does not discuss many important contributions to the general physiology of these neurons. When single midbrain DA neurons were first systematically characterized in vivo by the pioneering studies of Grace and Bunney 1, 2, 3, a robust set of features emerged from their observations, including broad action potential waveforms, inhibition by DA D2 autoreceptor

Creating diversity in midbrain DA neurons

The diversity of midbrain DA neurons can be described on many levels, ranging from classical anatomical and histological categories to gene expression profiles, functional neurophysiological properties, and connectivity (for a general discussion of the taxonomy of neuronal types, see [44]). The initial diversity of the midbrain DA system is created by a controlled ontogenetic process of their specification, migration, and differentiation, as well as by axonal path finding to create specific

Wiring midbrain DA diversity

Most current knowledge regarding the connectivity of midbrain DA neurons is derived from classical anatomical tracer studies [47], but novel molecular labeling tools have recently enabled the selective targeting of DA neurons as well as the reconstruction of the entire axonal trees of individual cells [61] and the mapping of synaptic inputs of selected SN and VTA populations [41]. Matsuda and colleagues achieved the expression of palmitoylated GFP driven by Sindbis virus transduction in

Functional diversity in midbrain DA neurons

Development and connectivity set the stage for the functional aspects of midbrain DA diversity. Unbiased sampling of electrophysiological phenotypes of tyrosine hydroxylase (TH)-positive DA neurons in the postnatal midbrain had suggested the presence of topographically organized functional diversity 21, 22. Lammel and colleagues described the intrinsic in vitro properties of TH-positive DA neurons in the adult midbrain, which were differentiated by their axonal projection areas [38]. Whereas

Optogenetic dissection of functional diversity among midbrain DA neurons

As in many other fields of neuroscience, the explosion of optogenetic approaches has provided a powerful tool to move from correlations of electrical activity and behaviors to investigation of direct causal connections. Almost ironically, the reinforcing properties of intracranial self-stimulation of the reward pathway, believed to be a classical showcase of causality in the DA field 75, 76, were not reproducible by intracranial optogenetic self-stimulation of selectively labeled DA neurons in

Concluding remarks

This review illustrates how the midbrain DA system is not homogeneous, but, rather that different DA subpopulations in the VTA and SN, each with discrete axonal projections, might be endowed with different electrophysiological properties and behavioral functions (Table 1). This diverse midbrain dopaminergic system might be captured as an intrinsic taste system of the brain providing a low-dimensional description of sensory cues and actions with parallel competing lines for good and bad, and old

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