SEGREGATION OF THE INTRAHYPOTHALAMIC 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 level s and elevated NPY release and binding in the parvicellular paraventri cular nucleus (PVN). It is suggested that NPY, in parallel with trigge ring feeding behavior, interrupts normal thyroid feedback in food depr ivation. To gain further insights into the involvement of NPY in the r egulation of TRH cells, this study sought to elucidate the source of t he NPY innervation of TRH neurons. The median forebrain bundle (MFB) t hat carries the ascending NPY fibers from the brain stem catecholamine rgic nuclei was unilaterally transected. Animals were sacrificed 2 and 5 days after surgery and double immunocytochemistry for NPY and TRH o r tyrosine hydroxylase (TH) and TRH was performed on sections from the PVN. Two days after the surgery, light microscopic examination reveal ed no changes in the numbers of NPY boutons making putative contacts w ith TRH cell bodies and proximal dendrites. On the other hand, under t he electron microscope, NPY- and TH-immunoreactive fibers containing a utophagous cytolysosomes, an early sign of catecholaminergic fiber deg eneration, were found to establish asymmetric synapses on distal dendr ites and dendritic spines of TRH-immunoreactive cells. However, the sa me electron microscopic analysis did not reveal any degenerating NPY-i mmunolabeled fibers in synaptic contact with TRH cell bodies and proxi mal dendrites. Five days after the surgery, when NPY and TH immunoreac tivities were no longer detected in the ipsilateral MFB, no decrease i n the numbers of NPY and TH boutons on TRH cell bodies and proximal de ndrites could be detected, when compared to the contralateral side. El ectron microscopy revealed fibers with Wallerian degeneration establis hing asymmetric synapses exclusively on the distal dendrites and spine s 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, pu tative inhibitory NPY input from the hypothalamus. The distal dendrite s and dendritic spines of the TRH cells also receive a putative stimul atory NPY input from the brain stem catecholaminergic neurons. It is s uggested that because of its proximal location and abundance, NPY of h ypothalamic origin exerts a tonic inhibition on PVN TRH cells that int errupts negative thyroid feedback during food deprivation. Furthermore , it is likely that a general inhibition and not stimulation of parvic ellular PVN activity may underlie the triggering of feeding behavior b y hypothalamic NPY. (C) 1998 Elsevier Science Ireland B.V. All rights reserved.