The long-term objective of the proposed research is to determine the role of neurotransmitter receptors in the mammalian circadian system. Receptors undergo up- and down-regulation, which may contribute to cyclic patterns of synaptic activity generated in the supreachiasmatic nucleus (SCN). The SCN contains several neurotransmitters and exhibits the two fundamental properties of a circadian clock: pacemaking and entrainment to the day-night cycle. Quantitative autoradiography of in vitro labeled brain sections will be used to characterize the distribution and circadian variation of a number of neurotransmitter receptors in the SCN and associated hypothalamic nuclei. Since light is the strongest entrainment cue, influences of the retinohypothalamic tract on SCN receptor levels will be examined. While daily variation in metabolic rate is already evident in the fetal and neonatal rat SCN, many endocrine and behavioral rhythms do not appear until 1-4 weeks after birth. Developmental patterns of neurotransmitter receptor distribution will be examined and considered in relation to anatomical development of the hypothalamus and the ontogeny of various endocrine and behavioral rhythms. The proposed research is essential for understanding the functional organization of developing and mature mammalian circadian systems. Furthermore, application of the information and techniques from this research will be valuable in testing the effectiveness and site of action of antidepressant drugs which alter the circadian characteristics of neurotransmitter receptor rhythms.
