Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity.
Journal of Physiology
This is an open access article. (c) 2013 The Authors. The Journal of Physiology (c) 2013 The Physiological Society.
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.
This work was supported by the Wellcome Trust OXION initiative (M.T.C., O.P.) and a National Institute of Child Health and Human Development (NICHD) intramural award (C.J.M.). M.T.C. held a Wellcome Trust Prize Studentship, received travel funding from the British Embassy Science and Innovation Division, and is an NIH Visiting Fellow. E.W.M. is supported by the NIH MD/PhD Partnership Training programme and by the Rhodes Trust. We are grateful to Olivia Shipton for useful discussions and help with animal breeding.
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
This is the final version of the article. Available from Wiley via the DOI in this record.
Vol. 591, Iss. 4, pp. 835 - 843
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