title: Central suppression of regenerated proprioceptive afferents.
abstract: Long after a cut peripheral nerve reinnervates muscle and restores force production in adult cats, the muscle does not respond reflexively to stretch. Motivated by the likelihood that stretch areflexia is related to problems with sensing and controlling limb position after peripheral neuropathies, we sought to determine the underlying mechanism. Electrophysiological and morphological measurements were made in anesthetized rats having one of the nerves to the triceps surae muscles either untreated or cut and immediately rejoined surgically many months earlier. First, it was established that reinnervated muscles failed to generate stretch reflexes, extending observations of areflexia to a second species. Next, multiple elements in the sensorimotor circuit of the stretch reflex were examined in both the PNS and CNS. Encoding of muscle stretch by regenerated proprioceptive afferents was remarkably similar to normal, although we observed some expected abnormalities, e.g., increased length threshold. However, the robust stretch-evoked sensory response that arrived concurrently at the CNS in multiple proprioceptive afferents produced synaptic responses that were either smaller than normal or undetectable. Muscle stretch failed to evoke detectable synaptic responses in 13 of 22 motoneurons, although electrical stimulation generated monosynaptic excitatory postsynaptic potentials that were indistinguishable from normal. The ineffectiveness of muscle stretch was not attributable therefore to dysfunction at synapses made between regenerated Ia afferents and motoneurons. Among multiple candidate mechanisms, we suggest that centrally controlled neural circuits may actively suppress the sensory information encoded by regenerated proprioceptive afferents to prevent recovery of the stretch reflex.
authors.affiliation: Department of Physiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Valerie K
authors.initials: VK
authors.lastname: Haftel
authors.forename: Edyta K
authors.initials: EK
authors.lastname: Bichler
authors.forename: Qing-Bo
authors.initials: QB
authors.lastname: Wang
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Prather
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Pinter
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Cope
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D004576:Electromyography / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D005260:Female; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D009046:Motor Neurons / Q000502:physiology*; D009470:Muscle Spindles / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D011434:Proprioception / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D012026:Reflex, Stretch / Q000502:physiology; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase