Multiple Modes of Amplification of Synaptic Inhibition to Motoneurons by Persistent Inward Currents

Canadian Institutes of Health Research Group in Sensory-Motor Systems, Department of Physiology, Centre for Neuroscience Studies, Queen's University, Kingston, Canada Submitted 27 June 2007; accepted in final form 27 November 2007 The ability of inhibitory synaptic inputs to dampen the excitability of motoneurons is augmented when persistent inward currents (PICs) are activated. This amplification could be due to an increase in the driving potential of inhibitory synapses or the deactivation of the channels underlying PICs. Our goal was to determine which mechanism leads to the amplification of inhibitory inputs by PICs. To reach this goal, we measured inhibitory postsynaptic currents (IPSCs) in decerebrate cats during somatic voltage-clamp steps. These IPSCs were generated by tonic activation of Renshaw cells. The IPSCs exhibited a rapid rise and a slower decay to a plateau level. Activation of PICs always led to an increase in the peak of the IPSC, but the amount of decay after the peak of the IPSC was inversely related to the size of the IPSC. These results were replicated in simulations based on compartmental models of motoneurons incorporating distributions of Renshaw cell synapses based on anatomical observations, and L-type calcium channels distributed as 100-µm-long hot spots centered 100 to 400 µm away from the soma. For smaller IPSCs, amplification by PICs was due to an increase in the driving force of the inhibitory synaptic current. For larger IPSCs, amplification was caused by deactivation of the channels underlying PICs leading to a lesser decay of the IPSCs. As a result of this change in the time course of the IPSC, deactivation of the channels underlying PICs leads to a greater amplification of the total inhibitory synaptic current. Address for reprint requests and other correspondence: K. Rose, Department of Physiology, Botterell Hall, Queen's University, Kingston, Canada, K7L 3N6 (E-mail: ken{at}biomed.queensu.ca )