Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity

During slow-wave sleep, cortical neurons display synchronous fluctuations between periods of persistent activity (UP states') and periods of relative quiescence (DOWN states'). Such UP and DOWN states are also seen in isolated cortical slices. Recently, we reported that both spontaneous and evoked termination of UP states in slices from the rat medial entorhinal cortex (mEC) involves GABAB receptors. Here, in order to dissociate the roles of GABAB1a- and GABAB1b-containing receptors in terminating UP states, we used mEC slices from mice in which either the GABAB1a or the GABAB1b subunit had been genetically ablated. Pharmacological blockade of GABAB receptors using the antagonist CGP55845 prolonged the UP state duration in both wild-type mice and those lacking the GABAB1b subunit, but not in those lacking the GABAB1a subunit. Conversely, electrical stimulation of layer 1 could terminate an ongoing UP state in both wild-type mice and those lacking the GABAB1a subunit, but not in those lacking the GABAB1b subunit. Together with previous reports, indicating a preferential presynaptic location of GABAB1a- and postsynaptic location of GABAB1b-containing receptors, these results suggest that presynaptic GABAB receptors contribute to spontaneous DOWN state transitions, whilst postsynaptic GABAB receptors are essential for the afferent termination of the UP state. Inputs to layer 1 from other brain regions could thus provide a powerful mechanism for synchronizing DOWN state transitions across cortical areas via activation of GABAergic interneurons targeting postsynaptic GABAB receptors.