Modulation of Neuron and Astrocyte Dopamine Receptors via Receptor–Receptor Interactions

Abstract

Dopamine neurotransmission plays critical roles in regulating complex cognitive and behavioral processes including reward, motivation, reinforcement learning, and movement. Dopamine receptors are classified into five subtypes, widely distributed across the brain, including regions responsible for motor functions and specific areas related to cognitive and emotional functions. Dopamine also acts on astrocytes, which express dopamine receptors as well. The discovery of direct receptor–receptor interactions, leading to the formation of multimeric receptor complexes at the cell membrane and providing the cell decoding apparatus with flexible dynamics in terms of recognition and signal transduction, has expanded the knowledge of the G-protein-coupled receptor-mediated signaling processes. The purpose of this review article is to provide an overview of currently identified receptor complexes containing dopamine receptors and of their modulatory action on dopamine-mediated signaling between neurons and between neurons and astrocytes. Pharmacological possibilities offered by targeting receptor complexes in terms of addressing neuropsychiatric disorders associated with altered dopamine signaling will also be briefly discussed.

Cholinergic Transmission in an Inducible Transgenic Mouse Model of Paroxysmal Dystonia

“…In functional heteromers, the downstream signaling dynamically switches based on the activity level and also the dynamics (i.e. the order in which GPCRs are activated) of participating neurotransmitters, resulting in disparate consequences on cellular physiology and function [34][35][36][37][38][39] . Together these observations challenge the idea of D2R excitatory signaling as "paradoxical" and point toward a new interpretation in which D2R signaling is dynamically regulated by complex receptor-receptor interactions.…”