Figure 1. Presynaptic GABA_B receptors contribute to spontaneous termination of the Up state whilst postsynaptic GABA_B receptors are necessary for layer 1 stimulus-evoked termination of the Up state.

(A), blockade of GABA_B receptors with the selective antagonist CGP55845 prolongs the Up state (evoked in response to layer 3 stimulation in medial entorhinal cortex) in wildtype mice and those lacking the GABA_B1b subunit, but not those lacking the GABA_B1a subunit, implying that presynaptic GABA_B receptors are involved in the spontaneous termination of the UP state. (B)_, electrical stimulation in layer 1 can terminate an ongoing Up state in wildtype mice and those lacking the GABA_B1a subunit, but not in those lacking the GABA_B1b subunit, demonstrating that afferent-evoked termination of the UP state is mediated by postsynaptic GABA_B receptors. (C) and (D), schematic representation of proposed model: recurrent excitatory and inhibitory (GABA_A receptor-mediated) connections sustain the Up state, with presynaptic GABA_B receptors regulating the duration of the Up state by inhibiting transmitter release. Inputs to layer 1 (perhaps from the thalamus or other cortical regions) activate neurogliaform (NGF) cells, which target dendritic GABA_B receptors to inhibit principal cell firing through reduced calcium entry, causing the network to enter a Down state. Neurogliaform cells may also regulate Up state duration by targeting GABA_B receptors on the presynaptic glutamatergic terminals of the inputs arriving in layer 1. (A) and (B) adapted from [16], with permission.