MOLECULAR MECHANISMS OF SIGNAL INTEGRATION IN HYPOTHALAMIC NEURONS

The purpose of this paper is to describe our studies focused on the me chanisms by which hypothalamic neurons process multiple signals and pr oduce an integrated response. We illustrate our research strategy by r eviewing our work on two separate neural systems: the hypothalamic par aventricular nucleus (PVN) and the suprachiasmatic nucleus (SCN). We h ave focused on different peptidergic subpopulations within these nucle i to address two issues. In the PVN, we concentrate on the population of neurons containing thyrotropin-releasing hormone (TRH). These neuro ns are inhibited by thyroid hormones, but activated by cold exposure. Using a molecular approach, we have demonstrated that these conflictin g signals simultaneously act on the same population of TRH neurons. Th is system will continue to be a productive model to study the mechanis ms by which neurons process multiple signals. In the SCN, we concentra te on the population of neurons containing vasoactive intestinal pepti de (VIP), peptide histidine isoleucine (PHI) and gastrin releasing pep tide (GRP). We have demonstrated that injection of all three peptides into the SCN of hamsters mimics the phase-delaying effects of light on circadian wheel running behavior. In addition, the genes encoding the se peptides exhibit different 24-hour profiles of changes in neurons o f the SCN. These data support the hypothesis that one mechanism by whi ch these neurons produce an integrated response is by changing the con centration ratio of co-released peptides.