title: Circadian integration of glutamatergic signals by little SAAS in novel suprachiasmatic circuits.
abstract: BACKGROUND
  Neuropeptides are critical integrative elements within the central circadian clock in the suprachiasmatic nucleus (SCN), where they mediate both cell-to-cell synchronization and phase adjustments that cause light entrainment. Forward peptidomics identified little SAAS, derived from the proSAAS prohormone, among novel SCN peptides, but its role in the SCN is poorly understood.
  
  
  RESULTS
  Little SAAS localization and co-expression with established SCN neuropeptides were evaluated by immunohistochemistry using highly specific antisera and stereological analysis. Functional context was assessed relative to c-FOS induction in light-stimulated animals and on neuronal circadian rhythms in glutamate-stimulated brain slices. We found that little SAAS-expressing neurons comprise the third most abundant neuropeptidergic class (16.4%) with unusual functional circuit contexts. Little SAAS is localized within the densely retinorecipient central SCN of both rat and mouse, but not the retinohypothalamic tract (RHT). Some little SAAS colocalizes with vasoactive intestinal polypeptide (VIP) or gastrin-releasing peptide (GRP), known mediators of light signals, but not arginine vasopressin (AVP). Nearly 50% of little SAAS neurons express c-FOS in response to light exposure in early night. Blockade of signals that relay light information, via NMDA receptors or VIP- and GRP-cognate receptors, has no effect on phase delays of circadian rhythms induced by little SAAS.
  
  
  CONCLUSIONS
  Little SAAS relays signals downstream of light/glutamatergic signaling from eye to SCN, and independent of VIP and GRP action. These findings suggest that little SAAS forms a third SCN neuropeptidergic system, processing light information and activating phase-shifts within novel circuits of the central circadian clock.
authors.affiliation: Neuroscience Program, University of Illinois, Urbana, Illinois, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Atkins
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Mitchell
authors.forename: Elena V
authors.initials: EV
authors.lastname: Romanova
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Morgan
authors.forename: Tara P
authors.initials: TP
authors.lastname: Cominski
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Ecker
authors.forename: John E
authors.initials: JE
authors.lastname: Pintar
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
authors.forename: Martha U
authors.initials: MU
authors.lastname: Gillette
mesh_terms: D000818:Animals; D002940:Circadian Rhythm; D018683:Excitatory Amino Acid Agents / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D018683:Excitatory Amino Acid Agents; D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D019886:Gastrin-Releasing Peptide