Peptidergic projections from the rat paraventricular hypothalamic nucleus to the spinal cord

• The survival of the organism is dependent on keeping a balanced internal milieu in an ever-changing environment The process to achieve this balance is called homeostasis and it is accomplished by the consonant action of the endocrine system and the autonomic nervous system. Specific parts of the central nervous system (CNS) control these systems in response to various sensory inputs. One of the key sites for the coordinated action of these two homeostasis systems is the paraventricular hypothalamic nucleus (PVH). Tirrough its projections to the pituitary the PVH controls the release of different hormones. In addition, it projects heavily to brain stem and spinal cord autonomic centers. Furthermore, the PVH projects to the superficial layers of the spinal cord, where nerve fibers conveying pain and temperature modalities terminate. Thus, in addition to its motor control of the homeostasis system, the PVH may influence the processing of sensory inputs that are important for homeostatic regulation. The aim of this thesis was to investigate some aspects of the organization and function of the neuronal pathways projecting from the PVH to the spinal cord in the rat.Vasopressin, which is a peptide that is synthesized by PVH neurons, has been proposed to regulate several different processes in the spinal cord. However, the source of vasopressin fibers within the spinal cord has been a matter of some dispute. Thus, firstly, we investigated the distribution of neurons expressing vasopressin mRNA in the naive rat, thereby providing the first complete screening of the CNS for this neuropeptide at the mRNA level. The results confmn some earlier work, but also demonstrate several new sites of vasopressin mRNA synthesis. Some sites previously thought to produce vasopressin displayed no vasopressin mRNA. Our results show that the PVH is the only putative site of spinally-projecting vasopressin neurons in the naive rat Hence, all functions exerted by vasopressin in the spinal cord are likely to be controlled by the PVH.Secondly, we examined the neurochemical profile of the PVH neurons that project to the spinal cord. We show that 41% of these neurons express dynorphin mRNA, 20% express enkephalin mRNA, 38% express oxytocin mRNA, and 42% express vasopressin mRNA. This is the first time that dynorphin has been shown in PVH neurons with spinal projections, and the figures for the other peptides are substantially higher than what has been reported in previous shldies. In addition, we demonstrate that each of the spinal cord projecting subdivisions of the PVH displays distinct peptide expression patterns.Thirdly, we investigated the physiological effect of the PVH on nociceptive transmission in the spinal cord dorsal horn. However, with the present experimental approach we could not show a consistent effect of PVH stimulation on nociceptive neurons in the spinal dorsal horn. The varying results we achieved are ascribed to the functional heterogeneity of the PVH as revealed by our previous studies.The present data contribute to the nnderstanding of the complex organization of the PVH. The parcellation of peptide-expressing neurons into distinct spinal cord projecting subnuclei is likely to reflect distinct functional roles of these subnuclei, and may provide the anatomical basis for the ability of the PVH to control many different processes in the spinal cord The nnderstanding of the physiological profile of these different subnuclei will provide insight into the control of homeostasis.

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