Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors.

Dopamine release in striatal circuits, including the nucleus accumbens (NAc), tracks separable features of reward such as motivation and reinforcement. However, the cellular and circuit mechanisms by which dopamine receptors transform dopamine release into distinct constructs of reward remain unclear. Here, we show that dopamine D3 receptor (D3R) signaling in the NAc drives motivated behavior by regulating local NAc microcircuits. Furthermore, D3Rs co-express with dopamine D1 receptors (D1Rs), which regulate reinforcement, but not motivation. Paralleling dissociable roles in reward function, we report non-overlapping physiological actions of D3R and D1R signaling in NAc neurons. Our results establish a novel cellular framework wherein dopamine signaling within the same NAc cell type is physiologically compartmentalized via actions on distinct dopamine receptors. This structural and functional organization provides neurons in a limbic circuit with the unique ability to orchestrate dissociable aspects of reward-related behaviors that are relevant to the etiology of neuropsychiatric disorders.

Prefrontal Interneurons: Populations, Pathways, and Plasticity Supporting Typical and Disordered Cognition in Rodent Models.

Prefrontal cortex (PFC) inhibitory microcircuits regulate the gain and timing of pyramidal neuron firing, coordinate neural ensemble interactions, and gate local and long-range neural communication to support adaptive cognition and contextually tuned behavior. Accordingly, perturbations of PFC inhibitory microcircuits are thought to underlie dysregulated cognition and behavior in numerous psychiatric diseases and relevant animal models. This review, based on a Mini-Symposium presented at the 2022 Society for Neuroscience Meeting, highlights recent studies providing novel insights into: (1) discrete medial PFC (mPFC) interneuron populations in the mouse brain; (2) mPFC interneuron connections with, and regulation of, long-range mPFC afferents; and (3) circuit-specific plasticity of mPFC interneurons. The contributions of such populations, pathways, and plasticity to rodent cognition are discussed in the context of stress, reward, motivational conflict, and genetic mutations relevant to psychiatric disease.

Daily changes in light influence mood via inhibitory networks within the thalamic perihabenular nucleus.

Exposure to irregular lighting schedules leads to deficits in affective behaviors. The retino-recipient perihabenular nucleus (PHb) of the dorsal thalamus has been shown to mediate these effects in mice. However, the mechanisms of how light information is processed within the PHb remains unknown. Here, we show that the PHb contains a distinct cluster of GABAergic neurons that receive direct retinal input. These neurons are part of a larger inhibitory network composed of the thalamic reticular nucleus and zona incerta, known to modulate thalamocortical communication. In addition, PHbGABA neurons locally modulate excitatory-relay neurons, which project to limbic centers. Chronic exposure to irregular light-dark cycles alters photo-responsiveness and synaptic output of PHbGABA neurons, disrupting daily oscillations of genes associated with inhibitory and excitatory PHb signaling. Consequently, selective and chronic PHbGABA manipulation results in mood alterations that mimic those caused by irregular light exposure. Together, light-mediated disruption of PHb inhibitory networks underlies mood deficits.