Brain Research 958 (2002) 261–271 www.elsevier.com / locate / brainres Research report Per and neuropeptide expression in the rat suprachiasmatic nuclei: compartmentalization and differential cellular induction by light * ´ ´ Hugues Dardente, Vincent-Joseph Poirel, Paul Klosen, Paul Pevet, Mireille Masson-Pevet ´ Neurobiologie des Rythmes, UMR 7518 CNRS / ULP , IFR 37, 12 Rue de l’ Universite, 67000 Strasbourg, France Accepted 30 August 2002 Abstract Per1 and Per2, two clock genes rhythmically expressed in the suprachiasmatic nucleus (SCN), are implicated in the molecular mechanism of the circadian pacemaker and play a major role in its entrainment by light. To date, it is not known if every cell of the SCN, a heterogeneous structure in respect of neuropeptide content, expresses clock genes equally. The aim of this study was to identify, by single and double non-radioactive and/or radioactive hybridizations, the cell types (AVP, VIP and GRP) expressing Per1 or Per2 in the SCN of rats, (1) when Per are highly expressed during the daytime, and (2) after induction of Per expression by a light pulse at night. Our results indicate that, during the daytime, Per1 and Per2 genes are both mainly expressed in the AVP cells of the dorso-median part of the SCN, whereas only a few VIP cells in the ventral part of the SCN exhibit Per gene expression. In contrast, following a light pulse at night, there is differential induction of the two Per genes. Per1 expression essentially occurs in the ventro-lateral GRP cells, while Per2 expression is not restricted to the retinorecipient part of the SCN as it also occurs in AVP cells. Altogether, our results suggest that Per1 and Per2 are mainly expressed in AVP cells during the daytime and suggest that GRP cells play an important role in resetting of the clock by light.  2002 Elsevier Science B.V. All rights reserved. Theme: Neural basis of behavior Topic: Biological rhythms and sleep Keywords: Circadian; AVP; VIP; GRP; Clock gene 1. Introduction [36]. Per1 and Per2 have been demonstrated to be light- inducible in a phase-dependent manner in different rodent In mammals, circadian rhythms are generated by a species [61,48,38]. Thus, Per1 and Per2, as well as being circadian pacemaker located in the suprachiasmatic nu- part of the core molecular clock, constitute light responsive cleus (SCN) of the hypothalamus [37,51]. Since identifica- elements of the clock, promoting phase-shifts and thus tion of the first mammalian clock gene ( Clk; [57,26]), great permitting adjustment to the external environment progress has been made in understanding the molecular [48,38,2]. Per1 and Per2 induction by light seems to be mechanisms underlying circadian rhythmicity. The core restricted to the retinorecipient, ventral part of the SCN, mechanism of the clock appears to be based on two whereas peak levels of their expression seem to be found interlocking transcriptional / translational feedback loops throughout the SCN [61,48]. involving different sets of clock genes including Per1 and The ventro-lateral part of the SCN, which receives Per2 [47]. In order to keep the organism in phase with its synaptic inputs from the retina, is known to contain environment, the SCN is reset every day by light to adjust neuropeptides such as VIP and GRP, whereas the dorso- to the 24-h light / dark cycle. Photic information is carried median part, mediating part of the outputs of the SCN, is from the retina to the SCN by the retinohypothalamic tract mainly characterized by expression of AVP [9]. While the clock seems to function as a synchronized structure, individual SCN cells appear to be the smallest unit of *Corresponding author. Fax: 133-3-9024-0528. ´ E-mail address: mpevet@neurochem.u-strasbg.fr (M. Masson-Pevet). rhythmicity in the circadian clock [59]. Overall SCN 0006-8993 / 02 / $ – see front matter  2002 Elsevier Science B.V. All rights reserved. PII: S0006-8993(02)03563-1