Cellular Clocks in AVP Neurons of the SCN Are Critical for Interneuronal Coupling Regulating Circadian Behavior Rhythm

• Published in: Neuron (Cambridge, Mass.) Mass.), 2015-03, Vol.85 (5), p.1103-1116
• Main Authors: Mieda, Michihiro, Ono, Daisuke, Hasegawa, Emi, Okamoto, Hitoshi, Honma, Ken-ichi, Honma, Sato, Sakurai, Takeshi
• Format: Article
• Language: English
• Subjects: Animals; Arginine Vasopressin - metabolism; ARNTL Transcription Factors - deficiency; ARNTL Transcription Factors - genetics; Artificial chromosomes; Behavior; Bioluminescence; Circadian Clocks - physiology; Circadian Rhythm - physiology; Interneurons - physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neurons - physiology; Rodents; Statistical analysis; Studies; Suprachiasmatic Nucleus - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.02.005

The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, is a network structure composed of multiple types of neurons. Here, we report that mice with a Bmal1 deletion specific to arginine vasopressin (AVP)-producing neurons showed marked lengthening in the free-running period and activity time of behavior rhythms. When exposed to an abrupt 8-hr advance of the light/dark cycle, these mice reentrained faster than control mice did. In these mice, the circadian expression of genes involved in intercellular communications, including Avp, Prokineticin 2, and Rgs16, was drastically reduced in the dorsal SCN, where AVP neurons predominate. In slices, dorsal SCN cells showed attenuated PER2::LUC oscillation with highly variable and lengthened periods. Thus, Bmal1-dependent oscillators of AVP neurons may modulate the coupling of the SCN network, eventually coupling morning and evening behavioral rhythms, by regulating expression of multiple factors important for the network property of these neurons. •Bmal1 deficiency in AVP neurons lengthens the free-running period and activity time•Bmal1 deficiency in AVP neurons weakens coupling among SCN neurons•Bmal1 coordinates expression of multiple key factors in AVP neurons•Cellular oscillators in AVP neurons stabilize SCN network circadian oscillations The primary circadian pacemaker SCN is a network structure composed of multiple types of neurons. Mieda et al. find that Bmal1-dependent oscillators of AVP neurons modulate the coupling of SCN neurons to determine free-running period and activity time.