GABAB receptors: synaptic functions and mechanisms of diversity

GABAB receptors are the G-protein-coupled receptors for GABA, the main inhibitory neurotransmitter in the mammalian central nervous system. They are implicated in a variety of neurological and psychiatric disorders. With the cloning of GABAB receptors ten years ago, substantial progress was made in our understanding of this receptor system. Here, we review current concepts of synaptic GABAB functions and present the evidence that points to specific roles for receptor subtypes. We discuss ultrastructural studies revealing that most GABAB receptors are located remote from GABAergic terminals, which raises questions as to when such receptors become activated. Finally, we provide possible explanations for the perplexing situation that GABAB receptor subtypes that have indistinguishable properties in vitro generate distinct GABAB responses in vivo.