Regulation of the NMDA component of EPSPs by different components of postsynaptic GABAergic inhibition: A computer simulation analysis in piriform cortex. A. Kapur, W.W. Lytton, K.L. Ketchum, L.B. Haberly. Department of Anatomy, University of Wisconsin, 1300 University Ave., Madison, WI 53706.
APStracts 4:139N, 1997.
ABSTRACT
Physiological analysis in the companion paper demonstrated that GABAA-mediated inhibition in piriform cortex is generated by circuits that are largely independent in apical dendritic and somatic regions of pyramidal cells, and that GABAA-mediated IPSCs in distal dendrites have a slower timecourse than those in the somatic region. This study used modeling methods to explore these characteristics of GABAA-mediated inhibition with respect to regulation of the NMDA component of EPSPs. Such regulation is relevant to understanding NMDA- dependent LTP and the integration of repetitive synaptic inputs that can activate the NMDA component, as well as pathological processes that can be activated by over-expression of the NMDA component. A working hypothesis was that the independence and differing properties of IPSCs in apical dendritic and somatic regions provide a means whereby the NMDA component and other dendritic processes can be controlled by way of GABAergic tone without substantially altering system excitability. The analysis was performed on a branched compartmental model of a pyramidal cell in piriform cortex constructed with physiological and anatomical data derived by whole-cell patch recording. Simulations with the model revealed that NMDA expression is more effectively blocked by the slow GABAA component than the fast. Since the slow component is present in greater proportion in apical dendritic than somatic regions, this characteristic would increase the capacity of dendritic IPSCs to regulate NMDA mediated processes. The simulations further revealed that somatic-region GABAergic inhibition can regulate the generation of action potentials with little effect on the NMDA component generated by afferent fibers in apical dendrites. As a result, if expression of the NMDA component or other dendritic processes were enabled by selective block of dendritic inhibition, for example by centrifugal fiber systems that may regulate learning and memory, the somatic-region IPSC could preserve system stability through feedback regulation of firing, without counteracting the effect of the dendritic-region block. Simulations with paired inputs revealed that the dendritic GABAA-mediated IPSC can regulate the extent to which a strong excitatory input facilitates the NMDA component of a concurrent weak input, providing a possible mechanism for control of "associative LTP" that has been demonstrated in this system. Postsynaptic GABAB-mediated inhibition had less effect on the NMDA component than either the fast or slow GABAA components. Depolarization from a concomitant AMPA component was also found to have comparatively little effect on current through the NMDA channel because of its brief timecourse. 

Received 19 March 1997; accepted in final form 3 July 1997.
APS Manuscript Number J234-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997