Subcellular distribution of 5‐HT<sub>1b</sub> and 5‐HT<sub>7</sub> receptors in the mouse suprachiasmatic nucleus

Belenky, Michael; Pickard, Gary E.

doi:10.1002/cne.1109

Cited by 98 publications

(64 citation statements)

References 62 publications

(80 reference statements)

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“…5-HT on the other hand has little effect on the phase of the clock at night (MeyerBernstein et al 1997). Anatomical and functional data indicate that 5-HT modulates light signalling to the clock via 5-HT 1B receptors located on RHT terminals (Pickard et al 1996(Pickard et al , 1999Pickard and Rea 1997;Belenky and Pickard 2001). These findings are supported by studies in mice lacking the 5-HT 1B receptor; these mice have an increased sensitivity to light compared with wild-type mice (Pickard et al 1999).…”

Section: Pacap Interacts With Glutamate Signalling During Light-inducmentioning

confidence: 85%

Neurotransmitters of the retino-hypothalamic tract

2002

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The brain's biological clock, which, in mammals, is located in the suprachiasmatic nucleus (SCN), generates circadian rhythms in behaviour and physiology. These biological rhythms are adjusted daily (entrained) to the environmental light/dark cycle via a monosynaptic retinofugal pathway, the retinohypothalamic tract (RHT). In this review, the anatomical and physiological evidence for glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) as principal transmitters of the RHT will be considered. A combination of immunohistochemistry at both the light- and electron-microscopic levels and tract-tracing studies have revealed that these two transmitters are co-stored in a subpopulation of retinal ganglion cells projecting to the retino-recipient zone of the ventral SCN. The PACAP/glutamate-containing cells, which constitute the RHT, also contain a recently identified photoreceptor protein, melanopsin, which may function as a "circadian photopigment". In vivo and in vitro studies have shown that glutamate and glutamate agonists such as N-methyl- D-aspartate mimic light-induced phase shifts and that application of glutamate antagonists blocks light-induced phase shifts at subjective night indicating that glutamate mediates light signalling to the clock. PACAP in nanomolar concentrations has similar phase-shifting capacity as light and glutamate, whereas PACAP in micromolar concentrations modulates glutamate-induced phase shifts. Possible targets for PACAP and glutamate are the recently identified clock genes Per1 and Per2, which are induced in the SCN by light, glutamate and PACAP at night.

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Section: Pacap Interacts With Glutamate Signalling During Light-inducmentioning

confidence: 85%

Neurotransmitters of the retino-hypothalamic tract

2002

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“…The SCN are densely innervated by 5-HT neurons in the midbrain raphe nuclei in rodents (Cagampang et al, 1993;Cagampang and Inouye, 1994;Meyer-Bernstein and Morin, 1996). Systemic or local injections of 8-hydroxydipropylaminotetralin (8-OH-DPAT), an agonist for 5-HT 1A and 5-HT 7 receptors, suppress the light-induced phase shifts of hamster activity rhythms Mintz et al, 1997;Weber et al, 1998;Belenky and Pickard 2001;Smith et al, 2001), light-induced c-fos expression in the hamster SCN (Selim et al, 1993;Glass et al, 1994 Picard et al, 1997), and the firing rates of light responsive cells in the hamster SCN (Ying and Rusak, 1994, 1997). In in vitro studies, Liou et al (1986) and Rea et al (1994) reported that 5-HT suppressed the optic nerve stimulation-evoked field potentials in the rat SCN and hamster SCN, respectively.…”

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confidence: 99%

Extended action of MKC‐242, a selective 5‐HT_1A receptor agonist, on light‐induced Per gene expression in the suprachiasmatic nucleus in mice

Takahashi

Yoshinobu

Aida

et al. 2002

J of Neuroscience Research

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We reported previously that (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole hydrochloride (MKC-242) (3 mg kg(-1), i.p.), a selective 5-HT(1A) receptor agonist, accelerated the re-entrainment of hamster wheel-running rhythms to a new 8 hr delayed or advanced light-dark cycle, and also potentiated the phase advance of the wheel-running rhythm produced by light pulses. The molecular mechanism underlying MKC-242-induced potentiation of this phase shift, however, has not yet been elucidated. We examined the effects of MKC-242 on light-induced mPer1 and mPer2 mRNA expression in the suprachiasmatic nucleus (SCN) of mice. MKC-242 (5 mg kg(-1), i.p.) potentiated light-induced mPer1 and mPer2 expression in the SCN of mice housed in constant darkness for 2 days, when mRNA levels were observed 3 hr after light-exposure. More potentiating action of MKC-242 on mPer2 expression in the SCN was observed in mice housed in constant darkness for 9-10 days. This facilitatory action of MKC-242 on mPer1 expression was antagonized by WAY100635, a selective 5-HT(1A) receptor blocker, indicating that MKC-242 activated 5-HT(1A) receptors. Other drugs such as 8-hydroxy-dipropylaminotetralin (10 mg kg(-1), i.p.), paroxetine (10 mg kg(-1), i.p.), buspirone (10 mg kg(-1), i.p.), and diazepam (10 mg kg(-1), i.p.) did not display a potentiating action on light-induced mPer1 and mPer2 expression in the SCN. In the behavioral experiments, we found that MKC-242 (5 mg kg(-1), i.p.) potentiated light-induced phase delays of free-running rhythm in mice. The present results suggest that prolonged increase of mPer1 or mPer2 expression in the SCN by MKC-242 may be involved in the potentiation of photic entrainment by MKC-242 in mice.

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“…Several serotonin (5-HT) receptor subtypes are found in the SCN (Belenky and Pickard, 2001). Bilateral enucleation reduces 5-HT 1B binding sites in the SCN by 35% (Pickard et al, 1996;Manrique et al, 1999), and the 5-HT 1B receptor is located on RHT terminals (Pickard et al, 1999).…”

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confidence: 99%

Photic Entrainment Is Altered in the 5-HT_1B Receptor Knockout Mouse

et al. 2006

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The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that receives glutamatergic afferents from the retina and serotonergic afferents from the midbrain. Activation of presynaptic serotonin 1B (5-HT1B) receptors on retinal terminals in the SCN inhibits retinohypothalamic neurotransmission and light-induced behavioral phase shifts. To assess the role of 5-HT1B receptors in photic entrainment, 5-HT1B receptor knockout (5-HT1B KO) and wild-type (WT) mice were maintained in non-24 h L:D cycles (T cycles). WT mice entrained to T = 21 h and T = 22 h cycles, whereas 5-HT1B KO animals did not. 5-HT1B KO animals did entrain to T = 23 h and T = 26 h cycles, although their phase angle of entrainment was altered compared to WT animals. 5-HT1BKO mice were significantly more phase delayed under T = 23 h conditions and significantly more phase advanced under T = 26 h conditions compared to WT mice. When 5-HT1B KO mice were housed in a T = 23 h short-day photoperiod (9.5L:13.5D), the delayed phase angle of entrainment was more pronounced. Light-induced phase shifts were reduced in 5-HT1B KO mice, consistent with their behavior in T cycles, suggesting an attenuated response to light. Based on previous work, this attenuated response to light might not have been predicted but can be explained by consideration of GABAergic mechanisms within the SCN. Phase-delayed circadian rhythms during the short days of winter are characteristic of patients suffering from seasonal affective disorder, and 5-HT has been implicated in its pathophysiology. The 5-HT1B KO mouse may be useful for investigating the altered entrainment evident during this serious mood disorder.

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Subcellular distribution of 5‐HT_1b and 5‐HT₇ receptors in the mouse suprachiasmatic nucleus

Cited by 98 publications

References 62 publications

Neurotransmitters of the retino-hypothalamic tract

Neurotransmitters of the retino-hypothalamic tract

Extended action of MKC‐242, a selective 5‐HT_1A receptor agonist, on light‐induced Per gene expression in the suprachiasmatic nucleus in mice

Photic Entrainment Is Altered in the 5-HT_1B Receptor Knockout Mouse

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Subcellular distribution of 5‐HT1b and 5‐HT7 receptors in the mouse suprachiasmatic nucleus

Cited by 98 publications

References 62 publications

Neurotransmitters of the retino-hypothalamic tract

Neurotransmitters of the retino-hypothalamic tract

Extended action of MKC‐242, a selective 5‐HT1A receptor agonist, on light‐induced Per gene expression in the suprachiasmatic nucleus in mice

Photic Entrainment Is Altered in the 5-HT1B Receptor Knockout Mouse

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Subcellular distribution of 5‐HT_1b and 5‐HT₇ receptors in the mouse suprachiasmatic nucleus

Extended action of MKC‐242, a selective 5‐HT_1A receptor agonist, on light‐induced Per gene expression in the suprachiasmatic nucleus in mice

Photic Entrainment Is Altered in the 5-HT_1B Receptor Knockout Mouse