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

First Author  Craig MT Year  2013
Journal  J Physiol Volume  591
Issue  4 Pages  835-43
PubMed ID  23266934 Mgi Jnum  J:205971
Mgi Id  MGI:5547483 Doi  10.1113/jphysiol.2012.248088
Citation  Craig MT, et al. (2013) Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity. J Physiol 591(Pt 4):835-43
abstractText  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 GABA(B) receptors. Here, in order to dissociate the roles of GABA(B1a)- and GABA(B1b)-containing receptors in terminating UP states, we used mEC slices from mice in which either the GABA(B1a) or the GABA(B1b) subunit had been genetically ablated. Pharmacological blockade of GABA(B) receptors using the antagonist CGP55845 prolonged the UP state duration in both wild-type mice and those lacking the GABA(B1b) subunit, but not in those lacking the GABA(B1a) subunit. Conversely, electrical stimulation of layer 1 could terminate an ongoing UP state in both wild-type mice and those lacking the GABA(B1a) subunit, but not in those lacking the GABA(B1b) subunit. Together with previous reports, indicating a preferential presynaptic location of GABA(B1a)- and postsynaptic location of GABA(B1b)-containing receptors, these results suggest that presynaptic GABA(B) receptors contribute to spontaneous DOWN state transitions, whilst postsynaptic GABA(B) 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 GABA(B) receptors.
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