Segregation of the intra- and extrahypothalamic neuropeptide Y and catecholaminergic inputs on paraventricular neurons, including those producing thyrotropin-releasing hormone.

In fasting, declining circulating thyroid hormone levels coincide with suppressed thyrotropin-releasing hormone (TRH) mRNA and peptide levels and elevated NPY release and binding in the parvicellular paraventricular nucleus (PVN). It is suggested that NPY, in parallel with triggering feeding behavior, interrupts normal thyroid feedback in food deprivation. To gain further insights into the involvement of NPY in the regulation of TRH cells, this study sought to elucidate the source of the NPY innervation of TRH neurons. The median forebrain bundle (MFB) that carries the ascending NPY fibers from the brain stem catecholaminergic nuclei was unilaterally transected. Animals were sacrificed 2 and 5 days after surgery and double immunocytochemistry for NPY and TRH or tyrosine hydroxylase (TH) and TRH was performed on sections from the PVN. Two days after the surgery, light microscopic examination revealed no changes in the numbers of NPY boutons making putative contacts with TRH cell bodies and proximal dendrites. On the other hand, under the electron microscope, NPY- and TH-immunoreactive fibers containing autophagous cytolysosomes, an early sign of catecholaminergic fiber degeneration, were found to establish asymmetric synapses on distal dendrites and dendritic spines of TRH-immunoreactive cells. However, the same electron microscopic analysis did not reveal any degenerating NPY-immunolabeled fibers in synaptic contact with TRH cell bodies and proximal dendrites. Five days after the surgery, when NPY and TH immunoreactivities were no longer detected in the ipsilateral MFB, no decrease in the numbers of NPY and TH boutons on TRH cell bodies and proximal dendrites could be detected, when compared to the contralateral side. Electron microscopy revealed fibers with Wallerian degeneration establishing asymmetric synapses exclusively on the distal dendrites and spines of TRH neurons. In conclusion, this study demonstrated that the NPY and catecholaminergic input on PVN TRH cells are of mixed origin. The cell bodies and proximal dendrites of TRH neurons receive a robust, putative inhibitory NPY input from the hypothalamus. The distal dendrites and dendritic spines of the TRH cells also receive a putative stimulatory NPY input from the brain stem catecholaminergic neurons. It is suggested that because of its proximal location and abundance, NPY of hypothalamic origin exerts a tonic inhibition on PVN TRH cells that interrupts negative thyroid feedback during food deprivation. Furthermore, it is likely that a general inhibition and not stimulation of parvicellular PVN activity may underlie the triggering of feeding behavior by hypothalamic NPY.