title: Enhanced transmission at a spinal synapse triggered in vivo by an injury signal independent of altered synaptic activity.
abstract: Peripheral nerve crush initiates a robust increase in transmission strength at spinal synapses made by axotomized group IA primary sensory neurons. To study the injury signal that initiates synaptic enhancement in vivo, we designed experiments to manipulate the enlargement of EPSPs produced in spinal motoneurons (MNs) by IA afferents 3 d after nerve crush in anesthetized adult rats. If nerve crush initiates IA EPSP enlargement as proposed by reducing impulse-evoked transmission in crushed IA afferents, then restoring synaptic activity should eliminate enlargement. Daily electrical stimulation of the nerve proximal to the crush site did, in fact, eliminate enlargement but was, surprisingly, just as effective when the action potentials evoked in crushed afferents were prevented from propagating into the spinal cord. Consistent with its independence from altered synaptic activity, we found that IA EPSP enlargement was also eliminated by colchicine blockade of axon transport in the crushed nerve. Together with the observation that colchicine treatment of intact nerves had no short-term effect on IA EPSPs, we conclude that enhancement of IA-MN transmission is initiated by some yet to be identified positive injury signal generated independent of altered synaptic activity. The results establish a new set of criteria that constrain candidate signaling molecules in vivo to ones that develop quickly at the peripheral injury site, move centrally by axon transport, and initiate enhanced transmission at the central synapses of crushed primary sensory afferents through a mechanism that can be modulated by action potential activity restricted to the axons of crushed afferents.
authors.affiliation: Department of Physiology, Emory University, Atlanta, Georgia 30345, USA.
authors.forename: Edyta K
authors.initials: EK
authors.lastname: Bichler
authors.forename: Stan T
authors.initials: ST
authors.lastname: Nakanishi
authors.forename: Qing-Bo
authors.initials: QB
authors.lastname: Wang
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Pinter
authors.forename: Mark M
authors.initials: MM
authors.lastname: Rich
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Cope
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D009046:Motor Neurons / Q000502:physiology*; D009409:Nerve Crush; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013979:Tibial Nerve / Q000293:injuries* / Q000502:physiology*