5-HT1B receptor knockout mice exhibit an enhanced response to constant light

Patricia J Sollars, Malcolm D. Ogilvie, Michael A. Rea, Gary E Pickard

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Serotonin (5-HT) can act presynaptically at 5-HT1B receptors on retinal terminals in the suprachiasmatic nucleus (SCN) to inhibit glutamate release, thereby modulating the effects of light on circadian behavior. 5-HT1B receptor agonists (1) inhibit light-induced phase shifts of circadian activity rhythms, (2) attenuate light-induced Fos expression in the SCN, and (3) reduce the amplitude of optic nerve-evoked excitatory postsynaptic currents in SCN neurons in vitro. To determine whether functional disruption of the 5-HT1B presynaptic receptors would result in an amplified response of the SCN to light, the period (τ) of the circadian rhythm of wheel-running activity was estimated under several different conditions in 5-HT1B receptor knockout (KO) mice and genetically matched wild-type animals. Under constant light (LL) conditions, the τ of 5-HT1B receptor KO mice was significantly greater than the τ of wild-type mice. A quantitative analysis of the wheel-running activity revealed no differences between wild-type and KO mice in either total activity or the temporal distribution of activity under LL conditions, suggesting that the observed increase in τ was not a function of reduced activity. Under constant dark conditions, the period of the circadian rhythm of wheel-running activity of wild-type and 5-HT1B receptor KO mice was similar. In addition, no differences were noted between wild-type and 5-HT1B receptor KO mice in the rate of reentrainment to a 6 h phase advance in the 12:12 light:dark cycle or in phase shifts in response to a 10 min light pulse presented at circadian time 16. The enhanced response of the SCN circadian clock of the 5-HT1B receptor KO mice to LL conditions is consistent with the hypothesis that the endogenous activation of 5-HT1B presynaptic receptors modulates circadian behavior by attenuating photic input to the SCN.

Original languageEnglish (US)
Pages (from-to)428-437
Number of pages10
JournalJournal of Biological Rhythms
Volume17
Issue number5
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

Fingerprint

Receptor, Serotonin, 5-HT1B
Knockout Mice
Suprachiasmatic Nucleus
Light
Circadian Rhythm
Running
Presynaptic Receptors
Serotonin
Serotonin 5-HT1 Receptor Agonists
Circadian Clocks
Wild Animals
Excitatory Postsynaptic Potentials
Photoperiod
Optic Nerve
Glutamic Acid
Neurons

Keywords

  • 5-HT receptor knockout
  • 5-HT receptors
  • Circadian rhythms
  • Retinohypothalamic tract
  • Serotonin
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

5-HT1B receptor knockout mice exhibit an enhanced response to constant light. / Sollars, Patricia J; Ogilvie, Malcolm D.; Rea, Michael A.; Pickard, Gary E.

In: Journal of Biological Rhythms, Vol. 17, No. 5, 01.10.2002, p. 428-437.

Research output: Contribution to journalArticle

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AB - Serotonin (5-HT) can act presynaptically at 5-HT1B receptors on retinal terminals in the suprachiasmatic nucleus (SCN) to inhibit glutamate release, thereby modulating the effects of light on circadian behavior. 5-HT1B receptor agonists (1) inhibit light-induced phase shifts of circadian activity rhythms, (2) attenuate light-induced Fos expression in the SCN, and (3) reduce the amplitude of optic nerve-evoked excitatory postsynaptic currents in SCN neurons in vitro. To determine whether functional disruption of the 5-HT1B presynaptic receptors would result in an amplified response of the SCN to light, the period (τ) of the circadian rhythm of wheel-running activity was estimated under several different conditions in 5-HT1B receptor knockout (KO) mice and genetically matched wild-type animals. Under constant light (LL) conditions, the τ of 5-HT1B receptor KO mice was significantly greater than the τ of wild-type mice. A quantitative analysis of the wheel-running activity revealed no differences between wild-type and KO mice in either total activity or the temporal distribution of activity under LL conditions, suggesting that the observed increase in τ was not a function of reduced activity. Under constant dark conditions, the period of the circadian rhythm of wheel-running activity of wild-type and 5-HT1B receptor KO mice was similar. In addition, no differences were noted between wild-type and 5-HT1B receptor KO mice in the rate of reentrainment to a 6 h phase advance in the 12:12 light:dark cycle or in phase shifts in response to a 10 min light pulse presented at circadian time 16. The enhanced response of the SCN circadian clock of the 5-HT1B receptor KO mice to LL conditions is consistent with the hypothesis that the endogenous activation of 5-HT1B presynaptic receptors modulates circadian behavior by attenuating photic input to the SCN.

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