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The Journal of Neuroscience, June 10, 2009, 29(23):7513-7518; doi:10.1523/JNEUROSCI.6162-08.2009

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Brief Communications
Distinct Roles of GABA_A and GABA_B Receptors in Balancing and Terminating Persistent Cortical Activity

Edward O. Mann, ^* Michael M. Kohl, ^* and Ole Paulsen

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom

Correspondence should be addressed to Dr. Ole Paulsen at the above address. Email: ole.paulsen{at}dpag.ox.ac.uk

Cortical networks spontaneously fluctuate between persistently active Up states and quiescent Down states. The Up states are maintained by recurrent excitation within local circuits, and can be turned on and off by synaptic input. GABAergic inhibition is believed to be important for stabilizing such persistent activity by balancing the excitation, and could have an additional role in terminating the Up state. Here, we report that GABA_A and GABA_B receptor-mediated inhibition have distinct and complementary roles in balancing and terminating persistent activity. In a model of Up–Down states expressed in slices of rat entorhinal cortex, the GABA_A receptor antagonist, gabazine (50–500 nM), concentration-dependently decreased Up state duration, eventually leading to epileptiform bursts. In contrast, the GABA_B receptor antagonist, CGP55845 (50 nM to 1 µM), increased the duration of persistent network activity, and prevented stimulus-induced Down state transitions. These results suggest that while GABA_A receptor-mediated inhibition is necessary for balancing persistent activity, activation of GABA_B receptors contributes to terminating Up states.

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Received Dec. 26, 2008; revised April 4, 2009; accepted April 27, 2009.

Correspondence should be addressed to Dr. Ole Paulsen at the above address. Email: ole.paulsen{at}dpag.ox.ac.uk

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