Role of Active Synaptic Integration in Motoneuron Output

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DESCRIPTION (provided by applicant): Motoneurons appear to have the ability to strongly amplify their own inputs based on neuromodulatory input from the brainstem. This amplification appears to preferentially effect fluctuating, rather than steady, synaptic input. In some input situations this effect results in what we refer to as "direct" mode firing. The objective of this project is to examine this amplification and to understand the role that a "fast" persistent inward current (PIC) plays in generating this amplification. The specific aims for this project are: 1) to quantify "fast" dendritic amplification of synaptic inputs; 2) to characterize direct mode firing; 3) to evaluate possible mechanisms for direct mode firing. In regards to the health relatedness of this project, this amplification may explain the profound weakness that occurs in cases of descending brainstem input disruption due to injury or disease. Overall, motoneuron research has been in a state of flux for several years as the effect of neuromodulators on motoneuron behavior has become increasingly apparent. The significance of this project is that it represents the culmination of this revolutionary period of change, bringing together much of the recent data along with the results anticipated from the work proposed here. In order to form this new view of motoneuron input processing based on steady inputs as well as input dynamics and neuromodulatory influences, the intended experimental approach utilizes a novel means of separating ionic currents based on their kinetics of activation. This approach permits instantaneous switching between measuring motoneuron firing and measuring ionic currents in intracellular in vivo experiments. Furthermore, voltage-clamp recording of currents generated by dynamic synaptic events can be examined for amplification and re-injected during current-clamp to determine their effect on the timing of individual spikes and firing rate in general.