Synaptic plasticity in the adult spinal dorsal horn: The appearance of new functional connections following peripheral nerve regeneration

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Abstract

Peripherally regenerated fibers were impaled in the dorsal columns. Each impaled fiber's adequate stimulus was determined and the fiber was activated by passing brief (200 ms) current pulses through the microelectrode. Cord dorsum potentials (CDPs) elicited by fiber stimulation were recorded at 8 sites, and then the fiber was injected with Neurobiotin (NB). In the same preparations, dorsal horn cells were impaled and their receptive fields (RFs) mapped; areas of skin from which the most vigorous responses were elicited were noted. Needle electrodes inserted into these cutaneous “hot spots” were used to electrically activate minimal numbers of peripherally regenerated fibers while simultaneously recording the resulting CDPs and any intracellular EPSPs. This allowed determination of connectivity between regenerated fibers and dorsal horn cells with overlapping RFs. In agreement with findings in intact animals, NB revealed long-ranging collaterals which were not seen using intraaxonally injected horseradish peroxidase (HRP). Although there was no qualitative difference in their morphology compared to those seen in controls, the correlation between spatial distribution of boutons and amplitudes of the monosynaptic CDPs of peripherally regenerated fibers revealed significant shifts in the functional efficacy of many central connections. Transcutaneous electrical stimulation revealed a significantly higher incidence of connectivity between regenerated fibers and cells with overlapping RFs at 9–12 months (86%) than at 5–6 months (34%). Although there was no obvious anatomical reorganization of afferent projections in the dorsal horn, the observed functional changes with time following transection show the formation of new functional central connections.

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