Investigating the role of substance P in photic responses of the circadian system: Individual and combined actions with gastrin-releasing peptide

The suprachiasmatic nucleus (SCN) contains the master mammalian circadian pacemaker. It is comprised of several phenotypically distinct cell groups, some of which are situated in the weakly rhythmic retinoresponsive ventrolateral region while others are found in the rhythmic, non-retinoresponsive dorsomedial region. The mechanism by which retinorecipient cells convey photic information to the dorsomedial clock cells is unclear. The ventrolateral SCN core contains a variety of cell phenotypes. Two neuropeptides, namely substance P (SP) and gastrin-releasing peptide (GRP) extensively colocalize with calbindin D28K, a marker for SCN cells that are strongly light-responsive. Previous studies have implicated these neuropeptides in photic phase shifting of the circadian system. The present study examines how these peptides interact to regulate photic responses of the circadian system. It was observed that 55.5 ± 9.1% of SP cells colocalized GRP. SP did not enhance GRP-induced phase shifts in the early-subjective night, while it significantly attenuated GRP-induced phase shifts during the late-subjective night. SP induced significant phase shifts that did not resemble light in the early-subjective night, but was not necessary for light-induced phase shifts and Fos expression at this time. SP induced significant Fos expression only in the late subjective night. SP may not be a necessary component in the pathway(s) involved in photic phase shifting during the early-subjective night, but may modulate phase shifts during the late-subjective night. Distinct biochemical mechanisms that underlie behavioral phase shifts may account for the differences observed in the early- vs. late-subjective night.