Roles of Suprachiasmatic Nuclei and Intergeniculate Leaflets in Mediating the Phase-Shifting Effects of a Serotonergic Agonist and Their Photic Modulation during Subjective Day

Oct 23, 1998Journal of biological rhythms

How brain's internal clock regions respond to a serotonin drug and light to shift daily rhythms during the day

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Abstract

Bilateral injections of the 5-HT1A/7 receptor agonist 8-OH-DPAT into the SCN or IGL resulted in significant phase advances of circadian activity (p < .001).

The suprachiasmatic nucleus (SCN) and intergeniculate leaflet (IGL) are influenced by serotonin projections from the median and dorsal raphe nuclei.
Phase advances occurred following microinjections of 8-OH-DPAT into either the SCN or IGL during the mid-subjective day.
The phase advances from IGL injections were dependent on the dosage of 8-OH-DPAT.
Light exposure during the subjective day can affect the phase-resetting effects of serotonergic stimulation, particularly blocking the response in the IGL.
Activation of serotonergic receptors in the SCN still caused phase advances even when followed by a light pulse.

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Serotonin (5-HT) has been implicated in the phase adjustment of the circadian system during the subjective day in response to nonphotic stimuli. Two components of the circadian system, the suprachiasmatic nucleus (SCN) (site of the circadian clock) and the intergeniculate leaflet (IGL), receive serotonergic projections from the median raphe nucleus and the dorsal raphe nucleus, respectively. Experiment 1, performed in golden hamsters housed in constant darkness, compared the effects of bilateral microinjections of the 5-HT1A/7 receptor agonist, 8-hydroxydipropylaminotetralin (8-OH-DPAT; 0.5 microgram in 0.2 microliter saline per side), into the IGL or the SCN during the mid-subjective day. Bilateral 8-OH-DPAT injections into either the SCN or the IGL led to significant phase advances of the circadian rhythm of wheel-running activity (p < .001). The phase advances following 8-OH-DPAT injections in the IGL were dose department (p < .001). Because a light pulse administered during the middle of the subjective day can attenuate the phase-resetting effect of a systemic injection of 8-OH-DPAT, Experiment 2 was designed to determine whether light could modulate 5-HT agonist activity at the level of the SCN and/or the IGL. Serotonergic receptor activation within the SCN, followed by a pulse of light (300 lux of white light lasting 30 min), still induced phase advances. In contrast, the effect of serotonergic stimulation within the IGL was blocked by a light pulse. These results indicate that the respective 5-HT projections to the SCN and IGL subserve different functions in the circadian responses to photic and nonphotic stimuli.

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Roles of Suprachiasmatic Nuclei and Intergeniculate Leaflets in Mediating the Phase-Shifting Effects of a Serotonergic Agonist and Their Photic Modulation during Subjective Day

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