Drive and Reinforcement Circuitry in the Brain: Origins, Neurotransmitters, and Projection Fields

Abstract

Brain stimulation has identified two central subsets of stimulation sites with motivational relevance. First, there is a large and disperse set of sites where stimulation is reinforcing, increasing the frequency of the responses it follows, and second, a much more restricted set of sites where-along with reinforcement-stimulation also has drive-like effects, instigating feeding, copulation, predation, and other motivated acts in otherwise sated or peaceful animals. From this work a dispersed but synaptically interconnected network of reinforcement circuitry is emerging: it includes afferents to the ventral tegmental area and substantia nigra; the dopamine systems themselves; glutamatergic afferents to the striatum; and one of two dopamine-receptor-expressing efferent pathways of the striatum. Stimulation of a limited subset of these sites, including descending inhibitory medial forebrain bundle fibers, induces both feeding and reinforcement, and suggests the possibility of a subset of fibers where stimulation has both drive-like and reinforcing effects. This review stresses the common findings of sites and connectivity between electrical and optogenetic studies of core drive and reinforcement sites. By doing so, it suggests the biological importance of optogenetic follow-up of less-publicized electrical stimulation findings. Such studies promise not only information about origins, neurotransmitters, and connectivity of related networks, by covering more sensory and at least one putative motor component they also promote a much deeper understanding of the breadth of motivational function.

Figure 1

Reinforcing and drive-like input pathways to the ventral tegmental area (a) and striatum (b), confirmed by optogenetic studies. Amyg: amygdala; BST: bed nucleus of the stria terminalis; DR: dorsal raphe; DS: dorsal striatum; LDTg: latero-dorsal tegmental nucleus; LHA: lateral hypothalamic area; mPFC: medial prefrontal cortex; mPOA: medial preoptic area; PPTg: pedunculopontine tegmental area; SNc: substantia nigra, zona compacta; vHippo: ventral hippocampus; VS: ventral striatum; VTA: ventral tegmental area.

Figure 2

A variety of reinforcement-related regions identified in electrical stimulation studies but not yet tested in optogenetic studies.