Biology subjects

Mieda, M.

Publications and source records attributed to Mieda, M..

3 recordsLinked to original sources

bioRxiv2025

Neuronal feedback loop in the suprachiasmatic nucleus generates robust circadian rhythms

The central circadian clock of the suprachiasmatic nucleus (SCN) is a network consisting of various types of neurons and glial cells, but its mechanism remains elusive. Here, by monitoring cellular calcium rhythms in vivo in vasoactive intestinal polypeptide (VIP)-deficient mice, we show that arginine vasopressin (AVP) neurons intrinsically oscillate with a short period and that VIP amplifies and delays the AVP neuronal rhythm to lengthen its period to [~]24 hours. Consistently, the circadian behavior period is shortened and lengthened by VIP receptor disruption and neurotransmission blockade of AVP neurons, respectively. VIP and other neurons occasionally exhibit weak, unstable, long-period calcium rhythms only when AVP neuronal oscillation is attenuated. Together with our previous finding that AVP neurons act as the primary pacesetter cells of the SCN ensemble rhythm, our results indicate that the feedback neuronal circuit of AVP cellular oscillator and VIP peptide signaling is crucial for the robust circadian rhythm.

neuroscience↗

bioRxiv2025

GABAergic network from AVP neurons to VIP neurons in the suprachiasmatic nucleus sets the activity/rest time of the circadian behavior rhythm

The central circadian clock of the suprachiasmatic nucleus (SCN) is a network composed of multiple types of {gamma}-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the precise role of GABAergic transmission in the SCN remains unclear. In this study, we investigated the GABAergic regulation from arginine vasopressin (AVP)-producing neurons in the SCN shell to vasoactive intestinal polypeptide (VIP)-producing neurons in the SCN core. Blocking GABA release from AVP neurons by a vesicular GABA transporter (Vgat) gene deletion lengthened the activity time (the interval between the onset and offset of locomotor activity) and shortened the duration of high Ca2+ activity in VIP neurons to match the behavioral rest time. Conversely, eliminating functional GABAA receptors (GABAAR) in VIP neurons by in vivo genome editing reduced locomotor activity level and the activity time, and lengthened the high Ca2+ duration in VIP neurons. Optogenetic activation of AVP neurons in vivo increased Ca2+ in VIP neurons during the night. A similar Ca2+ response of VIP neurons to AVP neuronal activation was also observed in SCN slices and was inhibited by a GABAAR antagonist, gabazine. Importantly, gabazine application alone raised the baseline Ca2+ in VIP neurons, suggesting a tonic depression of these neurons by GABA. Moreover, AVP neuronal activation decreased Ca2+ in non-AVP neurons located between AVP- and VIP-rich regions in the SCN. These results suggest that GABA from AVP neurons disinhibits VIP neurons indirectly by suppressing other intermediate GABA neurons to set the behavior activity/rest time precisely.

neuroscience↗

bioRxiv2022

AVP neurons act as the primary circadian pacesetter cells in vivo

The central circadian clock of the suprachiasmatic nucleus (SCN) is a network consisting of various neurons and glia. Individual cells have the autonomous molecular machinery of a cellular clock, but their intrinsic periods are considerably variable. Here, we show that arginine vasopressin (AVP) neurons set the ensemble period of the SCN network to control circadian behavior rhythm. Artificial lengthening of cellular periods by deleting casein kinase 1 delta (CK1{delta}) in the whole SCN lengthened the free-running period of behavior rhythm to an extent similar to CK1{delta} deletion specific to AVP neurons. In SCN slices, PER2::LUC reporter rhythms of these mice did not recapitulate the period lengthening. However, in vivo calcium rhythms of both AVP and vasoactive intestinal peptide (VIP) neurons demonstrated lengthened periods similar to the behavioral rhythm upon AVP neuron-specific CK1{delta} deletion. These results indicate that AVP neurons act as the primary determinant of the SCN ensemble period.

neuroscience↗