Distinct roles of GABAA and GABAB receptors in balancing and terminating persistent cortical activity

Mann, E. O., Kohl, M. M. and Paulsen, O. (2009) Distinct roles of GABAA and GABAB receptors in balancing and terminating persistent cortical activity. Journal of Neuroscience, 29(23), pp. 7513-7518. (doi: 10.1523/JNEUROSCI.6162-08.2009) (PMID:19515919) (PMCID:PMC4326656)

Abstract

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 GABAA and GABAB 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 GABAA receptor antagonist, gabazine (50–500 nm), concentration-dependently decreased Up state duration, eventually leading to epileptiform bursts. In contrast, the GABAB 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 GABAA receptor-mediated inhibition is necessary for balancing persistent activity, activation of GABAB receptors contributes to terminating Up states.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kohl, Dr Michael
• Authors: Mann, E. O., Kohl, M. M., and Paulsen, O.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Journal of Neuroscience
• Publisher: Society for Neuroscience
• ISSN: 0270-6474
• ISSN (Online): 1529-2401