Synaptic Integration in Motor Neurons

A typical neuron continuously processes synaptic inputs from thousands of other neurons and converts these inputs into reliable frequency-coded messages that are relayed to other neurons and effectors. Establishing how individual neurons integrate such complex input is essential for understanding how the brain processes information, yet surprisingly little is known about how this fundamental process operates. This is partly due to the difficulty of experimentally controlling the intensity of synaptic input to a neuron. Experimentalists instead rely on artificial excitation by injecting current pulses into neurons through microelectrodes. Such current-injection methods may not validly represent the actual process of synaptic integration. Furthermore, transformation of synaptic input into a firing rate response involves complex interactions among passive and active membrane properties. We propose to characterize basic features of synaptic integration by recording the firing-rate responses of human motor neurons to relatively controlled levels of synaptic input. Motor neurons are particularly attractive for these purposes because their activities can be readily recorded in human subjects, the synaptic drive to motor neurons can be easily controlled, and such activity transpires within an intact, un-anesthetized nervous system. We propose three specific aims to address the following questions: 1) what is the nature of the rate-coding response over the entire range of voluntary synaptic drive?, 2) what mechanisms underlie the leveling-off (saturation) of firing rate at low levels in response to increased intensity of synaptic drive?, and 3) can chronic alteration in motor unit activity lead to plastic changes in synaptic integration? Answering these questions will provide new insights into the fundamental process by which neurons transform synaptic input into frequency-coded responses. This information is essential for understanding how the brain operates - a prerequisite for understanding and treating a host of disorders of the nervous system.