Possible Effects of Depolarizing GABAA Conductance on the Neuronal Input-Output Relationship: A Modeling Study

1 Department of Complexity Science and Engineering, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa; 2 Exploratory Research for Advanced Technology Aihara Complexity Modelling Project, Japan Science and Technology Agency, Tokyo; and 3 Institute of Industrial Science, The University of Tokyo, Tokyo, Japan Submitted 21 September 2004; accepted in final form 27 January 2005 Recent in vitro experiments revealed that the GABA A reversal potential is about 10 mV higher than the resting potential in mature mammalian neocortical pyramidal cells; thus GABAergic inputs could have facilitatory, rather than inhibitory, effects on action potential generation under certain conditions. However, how the relationship between excitatory input conductances and the output firing rate is modulated by such depolarizing GABAergic inputs under in vivo circumstances has not yet been understood. We examine herewith the input–output relationship in a simple conductance-based model of cortical neurons with the depolarized GABA A reversal potential, and show that a tonic depolarizing GABAergic conductance up to a certain amount does not change the relationship between a tonic glutamatergic driving conductance and the output firing rate, whereas a higher GABAergic conductance prevents spike generation. When the tonic glutamatergic and GABAergic conductances are replaced by in vivo–like highly fluctuating inputs, on the other hand, the effect of depolarizing GABAergic inputs on the input–output relationship critically depends on the degree of coincidence between glutamatergic input events and GABAergic ones. Although a wide range of depolarizing GABAergic inputs hardly changes the firing rate of a neuron driven by noncoincident glutamatergic inputs, a certain range of these inputs considerably decreases the firing rate if a large number of driving glutamatergic inputs are coincident with them. These results raise the possibility that the depolarized GABA A reversal potential is not a paradoxical mystery, but is instead a sophisticated device for discriminative firing rate modulation. Address for reprint requests and other correspondence: K. Morita, Institute of Industrial Science, The University of Tokyo, Ce601, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan (E-mail: morita{at}sat.t.u-tokyo.ac.jp )