VIP receptors control excitability of suprachiasmatic nuclei neurones

Abstract

The role of vasoactive intestinal polypeptide (VIP) receptors on excitable properties of neurones in slices acutely prepared from the suprachiasmatic nuclei (SCN) of wild-type (WT) and VPAC(2)-receptor-deficient (Vipr2 ( -/- )) mice was studied under voltage clamp with the use of patch-clamp recording in the whole-cell configuration. The resting membrane potential in Vipr2 ( -/- ) neurones was significantly hyperpolarised as compared to WT cells (-60+/-7 vs -72+/-6 mV, p<0.01). Bath application of 100 nM VIP or the VPAC(2) receptor agonist RO 25-1553 triggered a slow inward current in a subpopulation of WT SCN neurones; the VIP-induced current was not affected by slice incubation with 25 microM of bicuculline but disappeared completely when the cells were dialysed with CsCl-containing/K(+)-free solution. Application of VIP or RO 25-1553 to neurones from Vipr2 ( -/- ) mice did not induce currents in all cells tested. Incubation of WT slices with 100 nM VIP or RO 25-1553 resulted in inhibition of fast tetrodotoxin-sensitive sodium currents and delayed rectifier K(+) currents in most of the cells tested. This effect was completely absent in cells from Vipr2 ( -/- ) mice. We postulate that VIP receptors control excitability of SCN neurones at the postsynaptic level by direct modulation of membrane potential via inhibition of K(+) channels and by tonic inhibition of sodium and potassium voltage-gated currents.

Depolarization and Neurotransmitter Regulation of Vasopressin Gene Expression in the Rat Suprachiasmatic NucleusIn Vitro

“…The effect of potassium depolarization to increase VP gene transcription in TTX that was blocked by inhibitors of calcium ion influx through voltage-gated calcium channels (Fig. 9, Cd, nimodipine) is consistent with this hypothesis and with reports describing voltage-gated calcium channels as an important factor in the regulation of circadian rhythms in the SCN (Pennartz et al, 2002;Lundkvist et al, 2005;Pakhotin et al, 2006). Inhibition by the CaM general protein kinase inhibitor (KN62) but not by a specific CaM protein kinase II inhibitor (KN93) suggests that this signal transduction pathway might use CaM IV (Obrietan et al, 2002).…”

“…This suggested that there might also be a depolarization-evoked, presumably calcium iondependent, pathway that could increase VP gene transcription in TTX. It should be noted here that the extent and synchrony of spike activity in the SCN are highly regulated by the VPAC2 receptor and are dysregulated in the Vipr2 Ϫ/Ϫ SCN (Reed et al, 2002;Cutler et al, 2003;Piggins and Cutler, 2003;Pakhotin et al, 2006). Therefore, these two mechanisms are not entirely independent.…”

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

“…2A). This prediction is in agreement with data showing that VIP is excitatory (Pakhotin et al, 2006) and that increasing GABA always generated greater IPSC in the core of the SCN (Albus et al, 2005). GABA depletion increased firing rates in agreement with experimental studies (Gribkoff et al, 2003; Shirakawa et al, 2000).…”

The Mammalian Circadian Timing System: Organization and Coordination of Central and Peripheral Clocks

“…In particular, Per1 transcription positively correlates with firing rate in a linear fashion in Per1:GFP (green fluorescent protein) mice (113). In vasoactive intestinal peptide receptor 2 (VPAC2) receptor-deficient mice, Per1, Per2, and Cry1 gene expression is attenuated in the SCN (114), and similar blunted rhythms are observed in the cellular excitability in these animals (115)(116)(117). However, it is unclear whether all extra-SCN brain regions translate clock gene expression cycles into physiologically relevant firing rate rhythms.…”