Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby 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.

Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity

“…In the crab stomatogastric ganglion, perturbation of neuromodulatory input, independent of spiking activity, appears to be critical to the homeostatic regulation of ionic conductances (26). At the neuromuscular junction, transmitter blockade has been shown to trigger retrograde changes in motoneuron cellular excitability (27,28), and this was independent of cellular spiking activity (29). Reduced neurotransmission triggering synaptic scaling has been proposed previously (17,30).…”

Swimming against the tide: investigations of the C-bouton synapse

“…These specific changes may account for some, but not all, of the physiological changes that have been observed (Kuno et al, 1974a,b; Cope et al, 1986; Bichler et al, 2007a,b; Bullinger et al, 2011; Prather et al, 2011), including altered post-spike AHP duration and repetitive firing properties (Kuno et al, 1974a; Gustafsson and Pinter, 1984). …”

Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons

“…All these animals were compared with a control group (n ϭ 4) that received similar tracer injections without nerve surgeries. Finally, a third category of experiments included two types of terminal electrophysiological studies performed with an in vivo whole animal rat spinal cord preparation described in detail in our earlier reports (Bichler et al 2007;Haftel et al 2004Haftel et al , 2005 and in the companion paper (Bullinger et al 2011). Electrophysiological experiments were performed from 6 to 16 mo after the nerve injury.…”