Specific targeting of ganglion cell sprouts provides an additional mechanism for restoring peripheral motor circuits in pelvic ganglia after spinal nerve damage

Abstract

The pelvic ganglia contain both sympathetic and parasympathetic neurons and provide an interesting model in which to study the effects of a distributed spinal nerve lesion. Previous animal studies have suggested that after either lumbar or sacral nerve injury, some functional connections are restored between preganglionic and postganglionic neurons. It has been proposed that this is because of intact preganglionic axons sprouting collaterals to supply denervated ganglion cells. However, this has never been demonstrated, and our study has investigated whether the ganglion cells themselves contribute to axogenesis and restoration of peripheral circuitry. We have monitored the growth of axons from pelvic ganglion cells after lumbar or sacral nerve injury (partial decentralization), or a combination of the two (total decentralization). These new processes were distinguished from intact preganglionic terminals by their immunoreactivity for substances present only in pelvic ganglion neurons (vasoactive intestinal peptide, neuropeptide Y, and tyrosine hydroxylase). The proportion of pelvic neurons surrounded by these immunostained fibers was then assessed. Complete removal of preganglionic terminals provides the biggest stimulus for growth of new axon processes (sprouts), which grow profusely within just a few days. These arise from each of the main chemical classes of pelvic neurons but grow at different rates and have different distributions. Importantly, some chemical classes of sprouts preferentially supply neurons of dissimilar histochemistry, suggesting the presence of very specific targeting mechanisms rather than random growth. These sprouts are transient, however, those formed after partial decentralization appear to be maintained. Moreover, after lesion of either lumbar or sacral spinal nerves, many sprouts arise from neurons with intact spinal connections and innervate neurons that have lost their preganglionic inputs. This provides a very different alternative mechanism to reestablish communication between preganglionic and postganglionic neurons. In conclusion, we have demonstrated a rapid and selective axogenesis within the pelvic ganglion after spinal nerve injury. This may allow the development of novel strategies by which autonomic nerve pathways can be experimentally manipulated, to facilitate more rapid return of appropriate peripheral reflex control.