Date of Award

6-12-2006

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Patrick A. Carr

Abstract

There is an abundance of electrophysiological and pharmacological data describing Renshaw cells (RC), however comparatively little is known about their distribution, metabolism, ionic regulation, modulation or exact role in motor behaviors. In this dissertation enzyme histochemistry and immunohistochemistry in conjunction with light, fluorescent and confocal microscopic methodologies were used to address the hypothesis that "the distribution of RC is contingent on their functional role in specific α motoneuronal pools and their unique electrophysiological and functional characteristics are reflected by their neurochemistry and synaptic inputs." The highest concentration of RC (number of RC per mm2) was found in the thoracic region of the spinal cord with the concentrations decreasing through the lumbar, cervical and sacral regions respectively. Neurochemical studies demonstrated low to moderate levels of acid phosphatase, cytochrome oxidase and NADPH diaphorase (NADPHd) in all RC analyzed. NADPHd labeled boutons were also observed in close contact with RC. Analysis of the distribution of Na+/K+ ATPase α subunits suggests that most RC display the α3 subunit, to the almost complete exclusion of the widely distributed α1 subunit. RC were also observed in close contact with presynaptic terminals containing calcitonin gene relate peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and glutamic acid decarboxylase 65 (GAD65). No primary afferent nociceptive terminals containing these neurochemicals were observed making close contacts with RC. This work provides numerous novel insights into RC function. The enzyme histochemical studies suggest that RC do not routinely discharge at high frequencies. The Na+/K + ATPase results demonstrate a concentrated expression of the α3 subunit, the kinetically fastest α subunit. This profile would support the capability of RC to discharge at high frequencies. The distribution, and synaptic input from CGRP and NADPHd suggest that RC are involved in rhythmic motor circuitry in the spinal cord with GAD65, NPY and SP providing additional modulatory influences. Overall, the results support the hypothesis and suggest that RC operate as variable gain generators within the rhythmic motor circuitry of the spinal cord, and receive a diverse array of input from both the surrounding neurons and supraspinal control systems.

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