NEURAL PLASTICITY IN PELVIC VISCERAL TISSUES

有充分的理由相信充分的考虑

There is sufficient reason to believe that the full consideration of complications following injury of the nervous system should include synaptic reorganization, in addition to the loss of specific neural elements. Synaptic plasticity may occur at varied levels in the neural pathways, which for visceral tissues such as the penis, include the central nervous system, autonomic ganglia and peripheral target tissues. Stimuli for reorganization in autonomic ganglia may be especially vigorous, perhaps muting or at least influencing the course of change at other levels. By documenting specific plastic changes in pelvic autonomic pathways, the proposed studies are the first attempt to define the milieu in the pelvic plexus subsequent to injury. Specifically, the changing synaptology of penile parasympathetic neurons will be followed after their partial or total disconnection from the spinal cord. These studies model injury to the sacral portion of the spinal cord, including that represented by direct trauma to the conus medullaris and cauda equina or by conditions such as spina bifida. It is proposed to: (1) use quantitative electron microscopy to describe the synaptology of postganglionic penile neurons following interruption of preganglionic nerves, (2) employ histochemistry and immunohistochemistry for neurotransmitters/neuromodulators to determine whether penile neurons reacquire a specific subset of presynaptic fibers, (3) analyze the contribution of dendrites and axons to the emergent innervation of decentralized penile neurons by staining for microtubular associated protein (MAP-2) and growth associated protein (GAP-43), (4) analyze changes in the neural circuitry in pelvic ganglia following nerve lesions by using c-fos immunoreactivity as a metabolic marker, (5) to determine whether hypogastric nerve-induced erection, apparent after nerve lesions, is mediated by nitric oxide, (6) to determine whether the post-lesion, plastic changes in the innervation of the corpus cavernosum also occurs in the other erectile body of the penis, the corpus spongiosum. These studies should unravel the degree to which the ordered arrangement of pre- and postganglionic connections is altered by nerve injury. This knowledge is central to understanding perturbations in control of visceral organs and the application of strategies to improve function.