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To study the injury signal that initiates synaptic enhancement<jats:italic>in vivo<\/jats:italic>, 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<jats:italic>in vivo<\/jats:italic>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.<\/jats:p>","DOI":"10.1523\/jneurosci.1997-07.2007","type":"journal-article","created":{"date-parts":[[2007,11,21]],"date-time":"2007-11-21T18:29:04Z","timestamp":1195669744000},"page":"12851-12859","source":"Crossref","is-referenced-by-count":18,"title":["Enhanced Transmission at a Spinal Synapse Triggered<i>In Vivo<\/i>by an Injury Signal Independent of Altered Synaptic Activity"],"prefix":"10.1523","volume":"27","author":[{"given":"Edyta K.","family":"Bichler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stan 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