GABA_A receptor activation suppresses Period 1 mRNA and Period 2 mRNA in the suprachiasmatic nucleus during the mid‐subjective day

Abstract

The mammalian circadian clock can be entrained by photic and nonphotic environmental time cues. gamma-aminobutyric acid (GABA) is a nonphotic stimulus that induces phase advances in the circadian clock during the middle of the subjective day. Several nonphotic stimuli suppress Period 1- and Period 2 mRNA expression in the suprachiasmatic nucleus (SCN); however, the effect of GABA on Period mRNA is unknown. In the present study we demonstrate that microinjection of the GABA(A) receptor agonist muscimol into the SCN region suppresses the expression of Period 1 mRNA in the hamster. A significant suppression of Period 2 mRNA following microinjection of muscimol was not observed in free-running conditions. However, Period 2 mRNA was significantly reduced following muscimol treatment when animals were maintained under a light cycle and transferred to constant darkness 42 h prior to treatment. An additional study investigated the maximum behavioural phase advance inducible by GABA(A) receptor activation.Together, these data indicate that, like other nonphotic stimuli, GABA suppresses Period 1- and Period 2 mRNA in the SCN.

Inhibitory and excitatory networks balance cell coupling in the suprachiasmatic nucleus: A modeling approach

“…We also expected that GABA would reduce amplitude because it reduced firing rates and in turn reduced the release of VIP, and indeed GABA affected amplitude analogously to its influence on peak firing rate. These results generally are in agreement with experimental data showing that GABA can control the amplitude of circadian rhythms (Aton et al, 2006) and that GABA can counterbalance VIP through Per mRNA suppression (Ehlen et al, 2006). Meanwhile, VIP and GABA also coordinated to control period length (Fig.…”

Regulation of light's action in the mammalian circadian clock: role of the extrasynaptic GABAA receptor

“…These methods have been described previously (13,39). A fragment of hamster Per1 cDNA (donated by Dr. Joseph Takahashi, Northwestern University, Evanston, IL) or mouse Per2 cDNA (donated by Dr. Steven M. Reppert, University of Massachusetts Medical School, Worcester, MA), was linearized and used as a template to synthesize […”

The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus

“…In nocturnal animals, muscimol activation of GABA A receptors within the SCN during the subjective day produces large phase advances whether administered in vivo (Smith et al, 1989, 1990; Huhman et al, 1995, 1997; Mintz et al, 2002; Biello, 2009; Ehlen et al, 2006, 2008; Gamble et al, 2003) or in vitro (Bergeron et al, 1999; Tominaga et al, 1994). In contrast, administration of muscimol during the late subjective night consistently produces small phase delays in vivo , whereas muscimol administered in vitro does not.…”

“…In nocturnal hamsters, injection of muscimol into the SCN during the middle of the subjective day produces phase advances and consistently suppresses Per1 mRNA, and can under certain circumstances suppress Per2 mRNA as well (Ehlen et al, 2006, 2008). The systemically administered BDZ brotizolam also induces phase advances during the subjective day and suppresses both Per1 and Per2 mRNA levels in the hamster SCN (Yokota et al, 2000).…”