Recovery of tail-elicited siphon-withdrawal reflex following unilateral axonal injury is associated with ipsi- and contralateral changes in gene expression in Aplysia californica

Abstract

Behavioral, cellular and molecular changes were examined following axonal injury in the marine mollusc Aplysia californica. Unilateral nerve injury was performed by crushing the pleural-pedal connective and the peripheral pedal nerves innervating one side of the posterior body wall and the tail. The injury procedure severs the axons of the pleural sensory neurons resulting in the blockade of the tail-elicited siphon- withdrawal reflex. Partial reflex recovery is observed within 3 d and reaches 50% of the pretest value by six weeks postinjury. Retrograde staining of injured nerves combined with electrophysiological recordings from siphon motor neurons show that axons can regenerate through the crushed site and reconnect with the tail by three weeks postinjury. Moreover, the behavioral and electrophysiological measurements suggest that the contralateral sensory neurons may contribute to the early recovery of the siphon-withdrawal reflex. The levels of mRNAs coding for actin and calreticulin are elevated while the mRNAs coding for intermediate filament protein, sensorin A, FMRFamide are reduced in the ipsilateral pleural ganglia as detected by Northern blots. In the contralateral pleural ganglia, the levels of mRNAs coding for actin, sensorin A and FMRFamide are elevated. These molecular changes in both the ipsi- and contralateral sides are consistent with the hypothesis that both sides are participating in the behavioral recovery following unilateral axonal injury.

Sequestration of cAMP response element-binding proteins by transcription factor decoys causes collateral elaboration of regenerating Aplysia motor neuron axons

“…A few short collaterals can be seen emerging from the tip of the regenerating axon. The regenerating axon has not yet crossed the crush site, consistent with our previous studies in intact animals that showed no recovery of the tail-elicited tail-siphon withdrawal reflex at this time point (10). Fig.…”

“…Collateral elaboration is thought to be a key event in the navigation of axons to the proper target during axonal regeneration as well as during the development of the CNS (3,4). This process appears to involve alterations in gene expression and protein synthesis (5)(6)(7)(8)(9)(10)(11). However, the genomic programs that mediate collateral formation are yet to be identified.…”

“…Approximately 15 min after the microinjection of plasmid DNA, the p9 pedal nerves for both the experimental and its paired control were crushed under a dissection microscope by using fine forceps (10). The crush transected the axons but not the surrounding sheath.…”

Unilateral nerve injury produces bilateral loss of distal innervation

“…15 Nerve injury reduces cutaneous innervation in the appropriate distal cutaneous territory ipsilaterally 16 and causes later collateral sprouting from adjacent uninjured nerves into hypoinnervated areas. 17 To investigate its contralesional effects, we initiated Wallerian degeneration without infection by performing unilateral axotomies and evaluating the effects on innervation within skin samples from contralateral as well as ipsilesional paw.…”

Regeneration as an application of gastropod neural plasticity

“…On the other hand, behavioral recovery can proceed in the absence of regeneration in relevant neurons, as was documented following branchial nerve crush in Aplysia (Hamilton and Fredman, 1998). Similarly, when partial recovery of the siphon withdrawal reflex was found 3 days after the pleural-pedal connective and pedal nerves were crushed unilaterally, the compensatory growth of contralateral sensory neurons was found to be responsible, because the injured neurons regenerate over a period of 6 weeks (Noel et al, 1995). It would be interesting to know if the projections of sensory neurons into the denervated area disappear after the regenerated projections arrive.…”