In the decades since the suprachiasmatic nucleus (SON) was first discovered as the brain clock, its function, cellular elements, and network organization have set the standard for understanding brain function at behavioral, physiological and molecular levels through analysis of cells, tissue and organisms. It was initially thought that the SCN was constituted of a uniform population of oscillators, sending out a coherent signal to the body. It is now clear that the brain clock is constituted of a functionally heterogeneous "circadian clock cells" that can be organized into distinct oscillating networks. Furthermore, there are oscillators and oscillating tissues in numerous organs. The hamster is the subject of choice as it has very precise daily rhythms, significant photoperiodic responses and a wealth of background studies indicating a) clock gene and protein expression in distinct SCN cells reveal the presence of "non-oscillating "gate" cells as well as oscillator cells (based on clock gene expression and electrical rhythmicity), b) on evidence that some intra-SCN cells are "slave oscillators" dependent on the eye, and c) on afferent and efferent connections of neurons of SCN sub-regions to each known brain target sites. The proposed research will characterize SCN activity to assess the consequence of network plasticity on central and peripheral oscillator responses. The first aim focuses on the SCN, characterizing network plasticity. The experiments entail examination of the phase of oscillating and non-oscillating cells of the SCN, under various experimental photic conditions, using molecular markers of circadian phase (clock genes) and neural activation (FOS) (Aim 1). The next focus is on rhythmic extra-SCN sites, examining rhythmicity induced in brain and peripheral target tissues (Aims 2 and 3). (Aim 4) proposes to use mathematical modeling to provide testable hypotheses and to conceptualize the results of the physiological studies. The hypothesis is that we will be able to delineate the relationship between activity of specific intra-SCN networks and brain target sites thereby addressing the long-sought explanation for SCN heterogeneity.
NIH ExPorter
NIH ExPorter