Brain researchSep 15, 2000

Resetting the daily rhythm of hormone-releasing brain cells by a signaling molecule in the body’s internal clock

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 19, 2026

Abstract

The lowest concentration of vasoactive intestinal peptide (VIP) required to induce phase-shifts in vasopressin release is 30 nM.

Vasopressin release from cultured neurons exhibits a circadian rhythm, peaking in the middle of the subjective day.
VIP can induce phase-shifts of the vasopressin rhythm, with the direction and magnitude of the shift depending on the timing of its application.
Applying VIP 6-12 hours before the peak of the vasopressin rhythm leads to advances, while application 4-8 hours after the peak causes delays.
Glutamate does not affect the phase of the vasopressin rhythm but can transiently stimulate vasopressin release at high concentrations.
Vasopressinergic cells in the suprachiasmatic nucleus are suggested to contain synchronized circadian oscillators.

Simplified

Mammalian circadian pacemaker is located in suprachiasmatic nuclei (SCN) of the hypothalamus. The pacemaker is entrained by light-dark cycle; the photic information is transmitted primarily via the retino-hypothalamic tract (RHT). The main neurotransmitter of the tract is glutamate. RHT fibers end on the ventrolateral part of the nucleus, where vasoactive intestinal peptide (VIP)-immunopositive neurons are localized. They send their axons into dorsomedial SCN, where most of the vasopressinergic (AVP) neurones are located. The AVP neurons retain the clock-like properties in vitro. Vasopressin release from the cultured neurons shows circadian rhythm peaking in the middle of subjective day. VIP induces phase-shifts of the rhythm, magnitude and direction of the shift depending on timing of the application. VIP applied 6-12 h before the peak of vasopressin rhythm induces advances, application 4-8 h after the peak induces delays. The lowest concentration required to induce the phase-shift is 30 nM, further increase of the concentration does not affect the magnitude of the shift. In contrast, glutamate has no effect on the phase of vasopressin rhythm, although in high concentrations it transiently stimulates vasopressin release. The data indicate that the vasopressinergic cells in the SCN contain circadian oscillators, whose rhythms run mutually synchronized in our cultures. VIP acts directly on the vasopressinergic cells to shift the phase of their pacemakers; glutamate has no such effect presumably because in vivo it acts through the VIP-ergic cells but the neuronal network is altered after the dissociation of the cells.

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Resetting the daily rhythm of hormone-releasing brain cells by a signaling molecule in the body’s internal clock

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