Transgenic approach reveals expression of the VPAC2 receptor in phenotypically defined neurons in the mouse suprachiasmatic nucleus and in its efferent target sites

Apr 20, 2004The European journal of neuroscience

VPAC2 receptor presence in specific brain clock cells and their connected areas in mice revealed by genetic labeling

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Abstract

In the mouse suprachiasmatic nucleus (SCN), 32% of vasoactive intestinal peptide (VIP) neurons express the VPAC2 receptor.

VPAC2 expression is required for circadian rhythmicity in the SCN.
Coexpression of VPAC2 and beta-galactosidase was observed in SCN neurons.
31% of calretinin neurons in the SCN core also express beta-galactosidase.
Among arginine-vasopressin neurons in the SCN shell, 45% exhibit beta-galactosidase expression.
VPAC2 expression is detected in cell bodies at multiple sites receiving VIP-containing projections from the SCN.

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Circadian rhythms in mammals depend on the properties of cells in the suprachiasmatic nucleus (SCN). The retino-recipient core of the mouse SCN is characterized by vasoactive intestinal peptide (VIP) neurons. Expression within the SCN of VPAC2, a VIP receptor, is required for circadian rhythmicity. Using transgenic mice with beta-galactosidase as a marker for VPAC2, we have phenotyped VPAC2-expressing cells within the SCN and investigated expression of the VPAC2 marker at sites previously shown to receive VIP-containing SCN efferents. In situ hybridization and immunohistochemistry demonstrated identical distributions for VPAC2 mRNA and beta-galactosidase and coexpression of the two signals in the SCN. Double-label confocal immunofluorescence identified beta-galactosidase in 32% of the VIP and 31% of the calretinin neurons in the SCN core. Of the arginine-vasopressin neurons that characterize the SCN shell, 45% expressed beta-galactosidase. In contrast, this marker was not apparent in astrocytes within the SCN core or shell. Cell bodies containing beta-galactosidase were detected at sites reportedly receiving VIP-containing SCN efferents, including the subparaventricular zone and lateral septum and the anteroventral periventricular, preoptic suprachiasmatic, medial preoptic and paraventricular hypothalamic nuclei. The detection of a marker for VPAC2 expression in the SCN in almost one-third of the VIP and calretinin core neurons and nearly half of the arginine-vasopressin shell neurons and also in cell bodies at sites receiving VIP-immunoreactive projections from the SCN indicates that VPAC2 may contribute to autoregulation and/or coupling within the SCN core and to the control of the SCN shell and sites distal to this nucleus.

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Transgenic approach reveals expression of the VPAC2 receptor in phenotypically defined neurons in the mouse suprachiasmatic nucleus and in its efferent target sites

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