Title: Relative Location of Inhibitory Synapses and Persistent Inward Currents Determines the Magnitude and Mode of Synaptic Amplification in Motoneurons

In some motoneurons, L-type Ca channels that partly mediate persistent inward currents (PICs) have been estimated to be arranged in 50 to 200 μm long discrete regions in the dendrites, centered 100 to 400 μm from the soma. As a consequence of this non-uniform distribution, the interaction between synaptic inputs to motoneurons and these channels may vary according to the distribution of the synapses. For instance, over 93% of synapses from Renshaw cells have been observed to be located 65 to 470 μm away from the cell body of motoneurons. Our goal was to assess whether Renshaw cell synapses are distributed in a position to more effectively control the activation of the L-type Ca channels. Using compartmental models of motoneurons with L-type Ca channels distributed in 100 μm long hot spots centered 100 to 400 μm away from the soma, we compared the inhibition generated by four distributions of inhibitory synapses: proximal, distal, uniform and one based on the location of Renshaw cell synapses on motoneurons. Regardless of whether the synapses were activated tonically or transiently, in the presence of L-type Ca channels, inhibitory synapses distributed according to the Renshaw cell synapse distribution generate the largest inhibitory currents. The effectiveness of a particular distribution of inhibitory synapses in the presence of PICs depends on their ability to deactivate the channels underlying PICs, which is influenced by the superposition between synapses and channels, as well as the distance away from the somatic voltage-clamp. Page 2 of 44