| Neuronal phenotype in the adult is not fixed but can be altered by its environment. Experiments in this proposal test the hypothesis that sympathetic nerves regulate transmitter phenotype of co-projecting parasympathetic neurons. Experiments utilized a tractable model system consisting of the rat pterygopalatine parasympathetic ganglion, which innervates cranial targets. Chronic sympathetic denervation was accomplished by unilaterally excising the superior cervical ganglion, leaving the intact contralateral ganglion as a control.; Chapter 1 describes changes in parasympathetic neuronal nitrergic phenotype. Following sympathectomy for 1 month, numbers of pterygopalatine ganglion neurons intensely stained for nitric oxide synthase were decreased significantly, while unstained cells were increased. Similarly, cells staining intensely for the nitrergic marker nicotinamide adenine dinucleotide phosphate-diaphorase were decreased while unstained cells increased after sympathectomy. In addition to reduced somatic staining, numbers of nitric oxide synthase-immunoreactive axons were also reduced, indicating generalized neuronal downregulation of parasympathetic nitrergic phenotype after sympathectomy.; Chapter 2 reports changes in cholinergic phenotype after sympathectomy. Neuronal immunoreactivities for both choline acetyltransferase (ChAT), which synthesizes acetylcholine, and vesicular acetylcholine transporter (VAChT), which is responsible for storage, were decreased significantly in pterygopalatine ganglion neurons after long-term sympathectomy. Within tarsal smooth muscle and meibomiam gland targets, axonal immunoreactivity for ChAT and VAChT were both reduced. Thus post-sympathectomy downregulation involves multiple transmitter systems.; In Chapter 3, the target specificity of altered cholinergic phenotype was examined in target-projecting neurons identified by retrograde tracing. After sympathectomy, parasympathetic neurons projecting to superior tarsal muscle, where sympathetic-parasympathetic axonal interactions are abundant, showed a robust decrease in VAChT. In ocular choroid, where autonomic interactions are more limited, only modest reductions occurred. No change occurred in the lacrimal gland, which receives only parasympathetic innervation.; Together, these experiments show that the presence of sympathetic nerves is a strong determinant of many aspects of parasympathetic neuronal transmitter phenotype. This influence varies in a target-specific manner, in relation to the degree of axonal interaction. These studies show that sympathetic nerve damage not only leads to target deficits due to axonal degeneration, but can also lead to secondary changes as a result of altered parasympathetic phenotype. |
