Francisco Alvarez (Committee Member), Steven Berberich (Committee Chair), Timothy Cope (Advisor), Michael Hennessy (Committee Member), Mark Rich (Committee Member)
Doctor of Philosophy (PhD)
Successful regeneration of a severed peripheral nerve is insufficient to restore the stretch reflex. This deficit occurs despite successful muscle reinnervation and functional restoration of the circuit components. For example, Ia afferents encode muscle stretch, Ia-motoneuron synapses reform to the extent of restoring low frequency transmission, and activation of motoneurons results in muscle force output. However, when recording intracellularly from reinnervated rat motoneurons during ramp hold and release muscle stretch, no excitatory synaptic potentials are detected in 2/3 motoneurons (Haftel et al., 2005), a clear sign that the synapses connecting Ia afferents with motoneurons are physiologically disrupted. This thesis examines extensively the cellular properties of the presynaptic Ia afferent, postsynaptic motoneuron, and the function of their central synapse to identify where along this circuit deficits are occurring. Using intraaxonal recordings from regenerated muscle afferents, we found that not only were regenerated afferents capable of encoding stretch information, but they were, by many parameters, indistinguishable from normal. In addition, intracellular recordings from regenerated motoneurons indicated that intrinsic motoneuron properties (rheobase, input resistance, and afterhyperpolarization potential) returned to control levels with reinnervation. To study synaptic function between regenerated afferents and motoneurons, muscle stretch and electrical stimulation at group I strength were used to activate regenerated afferents. Whereas electrical stimulation at both low (1 pps) and physiologic frequencies was capable of producing synaptic responses, muscle stretch was entirely ineffective in some motoneurons. Examination of individual synapses using spike triggered averaging suggested that many regenerated afferents responding to muscle stretch in patterns typical of Ia do not make physiologic monosynaptic connections with motoneurons. In total, these data demonstrate a disconnect between peripheral reinnervation by regenerated afferents and central connectivity with motoneurons: many afferents regaining normal stretch responses are not centrally connected to motoneurons, however, many group I afferents that do not reinnervate muscle spindles maintain central synaptic connections with motoneurons. This finding may result from factors including nonspecific reinnervation, synaptic stripping of afferent input at proximal/distal sites, and electrotonic decay of afferent input at distal synapses and may explain why the stretch reflex is not restored even after successful muscle reinnervation.
Department or Program
Year Degree Awarded
Copyright 2009, all rights reserved. This open access ETD is published by Wright State University and OhioLINK.