Modulation of parasympathetic neuron phenotype and function by sympathetic innervation

Selective sympathetic nerve dysfunction occurs during aging and in certain disease states. Here, we review findings concerning the effects of chronic sympathetic denervation on parasympathetic innervation to orbital target tissues in the adult rat. Long-term sympathetic denervation was induced by excising the ipsilateral superior cervical ganglion for 5-6 weeks prior to analyses. Following sympathectomy, pterygopalatine ganglion parasympathetic neurons show reduced nitric oxide synthase protein in their somata and projections to vascular targets. Laser Doppler measurements of ocular blood flow indicate that sympathectomy is also accompanied by reduced nitrergic vasodilatation. In the superior tarsal muscle of the eyelid, parasympathetic varicosities, normally, are distant to smooth muscle cells but make axo-axonal contacts with sympathetic nerves, consistent with physiological evidence showing only prejunctional inhibitory effects on sympathetically mediated smooth muscle contraction. Following sympathectomy, parasympathetic varicosities proliferate and closely appose smooth muscle cells, and this is accompanied by establishment of parasympathetic-smooth muscle excitatory neurotransmission. Many pterygopalatine parasympathetic neurons normally contain nerve growth factor (NGF) protein and express NGF mRNA. However, following chronic sympathectomy or elimination of sympathetic impulse activity, NGF mRNA and protein are markedly reduced, indicating that sympathetic neurotransmission enhances NGF expression in parasympathetic neurons. Together, these findings portray a striking dependency of parasympathetic neurons on sympathetic nerves to maintain normal phenotype and function. Sympathetic influences on parasympathetic neurons may be mediated, in part, through axo-axonal synapses. NGF synthesis and release by parasympathetic neurons may represent a molecular basis underlying the formation of these synapses, and up-regulation of NGF synthesis by sympathetic nerve activity may act to reinforce these associations.