Title

Permanent Central Synaptic Disconnection of Proprioceptors After Nerve Injury and Regeneration. II. Loss of Functional Connectivity with Motoneurons

Document Type

Article

Publication Date

11-2011

Abstract

Regeneration of a cut muscle nerve fails to restore the stretch reflex, and the companion paper to this article [Alvarez FJ, Titus-Mitchell HE, Bullinger KL, Kraszpulski M, Nardelli P, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01095.2010] suggests an important central contribution from substantial and persistent disassembly of synapses between regenerated primary afferents and motoneurons. In the present study we tested for physiological correlates of synaptic disruption. Anesthetized adult rats were studied 6 mo or more after a muscle nerve was severed and surgically rejoined. We recorded action potentials (spikes) from individual muscle afferents classified as IA like (*IA) by several criteria and tested for their capacity to produce excitatory postsynaptic potentials (EPSPs) in homonymous motoneurons, using spike-triggered averaging (STA). Nearly every paired recording from a *IA afferent and homonymous motoneuron (93%) produced a STA EPSP in normal rats, but that percentage was only 17% in rats with regenerated nerves. In addition, the number of motoneurons that produced aggregate excitatory stretch synaptic potentials (eSSPs) in response to stretch of the reinnervated muscle was reduced from 100% normally to 60% after nerve regeneration. The decline in functional connectivity was not attributable to synaptic depression, which returned to its normally low level after regeneration. From these findings and those in the companion paper, we put forward a model in which synaptic excitation of motoneurons by muscle stretch is reduced not only by misguided axon regeneration that reconnects afferents to the wrong receptor type but also by retraction of synapses with motoneurons by spindle afferents that successfully reconnect with spindle receptors in the periphery.

DOI

10.​1152/​jn.​01097.​2010