Mechanisms and Regulation of Neuronal GABA_B Receptor-Dependent Signaling

γ-Aminobutyric acid B receptors (GABA_BRs) are broadly expressed throughout the central nervous system where they play an important role in regulating neuronal excitability and synaptic transmission. GABA_BRs are G protein-coupled receptors that mediate slow and sustained inhibitory actions via modulation of several downstream effector enzymes and ion channels. GABA_BRs are obligate heterodimers that associate with diverse arrays of proteins to form modular complexes that carry out distinct physiological functions. GABA_BR-dependent signaling is fine-tuned and regulated through a multitude of mechanisms that are relevant to physiological and pathophysiological states. This review summarizes the current knowledge on GABA_BR signal transduction and discusses key factors that influence the strength and sensitivity of GABA_BR-dependent signaling in neurons.