RUI: Circadian Rhythms in NPY and Y5 Receptor Deficient Mice

Smith College, Northampton MA

Investigators

Abstract

Mary E. Harrington, 0234203, RUI: Circadian rhythms in NPY and Y5 receptor deficient mice. Biological rhythms are reset each day by external signals to maintain a 24 hour internal cycle. The light:dark cycle is one very important cue for synchronizing these circadian rhythms. Responses to light are mediated through a direct retinal input to the circadian clock, an input that can be modified by other neural inputs. One important modulating neurochemical is neuropeptide Y (NPY). Interactions between NPY and light resetting provide a point of flexibility for adjustments of light entrainment relative to ecological or internal factors. The present research will examine the role of NPY in circadian clock phase resetting by light, making use of mice with deletion of either the NPY gene or the gene for an important NPY receptor, the NPY Y5 receptor. Wheel-running activity rhythms of these mice will be studied and it is expected that NPY- and NPY Y5 receptor-deficient mice will show decreased stability and reliability of entrainment to a light:dark cycle. Mice studied under constant darkness will reveal effects these neurochemicals have on circadian rhythm generation and expression. The mammalian circadian pacemaker is located in the hypothalamic suprachiasmatic nuclei (SCN). Suprachiasmatic nucleus cells maintain a self-sustained oscillation in culture, allowing measures of phase-shifting behavior from an isolated clock. To determine if the Y5 receptor mediates the effects of NPY on light phase shifts, mice with gene deletions will be compared with controls for the effect of NPY applied to the circadian clock in the SCN after a phase shift. It is expected that the Y5 receptor deficient mouse will not show evidence for NPY blocking light-induced phase shifts, providing definitive proof of the importance of this receptor in mediating the effect of NPY on circadian clock resetting. This work relates to the everyday situation of maintaining synchronization with the external 24 h light:dark cycle. Expanding our understanding of the role of NPY in the circadian system will allow better knowledge of the neural basis of flexibility as we adapt to changing environmental cycles. This research will be conducted at an undergraduate college for women, with promising undergraduate women and minorities taking leadership roles in conducting the studies.