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Arginine vasopressin neurons in the suprachiasmatic nucleus determine the circadian rhythm period of other suprachiasmatic nucleus neurons.
Yusuke Tsuno (Michihiro Mieda)

We are active during the day and sleep at night based on the light/dark cycle of the external environment. Even without external light/dark cycles, the body has internal mechanisms that regulate activity and sleep, called circadian rhythms. In mammals, the circadian rhythm is controlled by the suprachiasmatic nucleus in the hypothalamus, and its destruction results in the loss of the circadian rhythm.
Genetically modified mice to have lengthened circadian rhythms in the arginine vasopressin neurons of the suprachiasmatic nucleus displayed longer behavioral circadian rhythms. However, because the suprachiasmatic nucleus also contains other cell types besides arginine vasopressin neurons, the details of these other cell types' circadian rhythms in the mice were unknown.
In this study, we established a fiber photometry technique to measure the calcium activity of arginine vasopressin neurons and other suprachiasmatic nucleus neurons in living mice for two consecutive weeks. We found that arginine vasopressin neurons in the genetically modified mice exhibited calcium activity with a period longer than 24 hours. In addition, the period of other neurons in the suprachiasmatic nucleus also showed the period longer than 24 hours, consistent with the period of arginine vasopressin neurons. This suggests that the arginine vasopressin neurons affect the circadian period of other neurons in the suprachiasmatic nucleus and ultimately determine the behavioral period of the mice.

In vivo recording of suprachiasmatic nucleus dynamics reveals a dominant role of arginine vasopressin neurons in circadian pacesetting. Tsuno Y, Peng Y, Horike S, Wang M, Matsui A, Yamagata K, Sugiyama M, Nakamura TJ, Daikoku T, Maejima T, Mieda M. (2023) PLOS Biology 21: e3002281 (https://doi.org/10.1371/journal.pbio.3002281)


<Figure Legends>
The circadian periods of the entire suprachiasmatic nucleus and spontaneous locomotor activity are determined by arginine vasopressin neurons in the suprachiasmatic nucleus. (Top) Simultaneous recordings of spontaneous locomotor activity (black) and calcium activity (red) of arginine vasopressin (AVP)-positive neurons of the suprachiasmatic nucleus (SCN) in mice kept in a light/dark environment for 5 days followed by 10-12 days of constant darkness. A gray background is displayed when the room light is off, while a white background indicates the light is on. Because mice are nocturnal, they are active when the room light is off, and this timing of activity is maintained even in a constant-dark environment. In a constant-dark environment, mice lacking CK1δ (casein kinase 1 delta) in AVP neurons (right) display a longer circadian period of spontaneous behavior in comparison to control mice (left). Also, the circadian period of calcium activity in AVP neurons was prolonged in the gene-deficient mice (right).
(Bottom) Simultaneous recordings of spontaneous behavior (black) and calcium activity of vasoactive intestinal peptide (VIP)-positive neurons (green) in the suprachiasmatic nucleus of mice. The circadian period of VIP neuron calcium activity was also prolonged in mice lacking CK1δ in AVP neurons (right).


Department of Integrative Neurophysiology, Graduate School of Medical Sciences, Kanazawa University, Japan.