The emerging role of GABAB receptors as regulators of network dynamics: fast actions from a 'slow' receptor?

•Metabotropic GABAB receptors can, unexpectedly, mediate rapid termination of persistent network activity in the cortex.•Layer 1 interneurons modulate network activity by targeting GABAB receptors on principal cells.•Dendritic GABAB receptors can inhibit the firing of principal cells by acting on voltage-gated calcium channels.

Convention holds that ionotropic receptors mediate fast neurotransmission and that 'slow' G-protein coupled metabotropic receptors have a secondary, modulatory role in the control of neuronal networks. Here, we discuss recent evidence showing that activation of metabotropic GABAB receptors in cortical layer 1 can powerfully inhibit principal cell activity and that their activation can rapidly halt ongoing network activity. Inputs from both within and outwith the cortex converge upon layer 1 where they target various populations of interneurons, including neurogliaform cells. We argue that neurogliaform cells are the main effector of a powerful inhibitory circuit that, acting through GABAB receptors, can be differentially recruited by long-range connections to serve in roles as diverse as conscious perception and memory consolidation.