Network Dynamics Mediate Circadian Clock Plasticity

• DOI: 10.1016/j.neuron.2016.12.022
• Publication Date: 2017-01-06T05:53:39Z
• Authors: Abdelhalim Azzi; Jennifer A. Evans; Tanya Leise; Jihwan Myung; Toru Takumi; Alec J. Davidson; Steven A. Brown
• Keywords: Male; 0301 basic medicine; Patch-Clamp Techniques; Light; 10050 Institute of Pharmacology and Toxicology; Action Potentials; 610 Medicine & health; 612; patch clamp; Mice; 03 medical and health sciences; Thalamus; thalamus; Circadian Clocks; Animals; autopatcher; Biology; gamma-Aminobutyric Acid; automation; Neurons; 2800 General Neuroscience; Period Circadian Proteins; DNA Methylation; Models, Theoretical; Circadian Rhythm; whole-cell; subcortical; in vivo; 570 Life sciences; biology; Suprachiasmatic Nucleus

A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock properties, but rather through altered networking within the suprachiasmatic nuclei (SCN), the circadian "master clock," which is DNA methylated in region-specific manner. DNA methylation is necessary to temporally reorganize circadian phasing among SCN neurons, which in turn changes the period length of the network as a whole. Interruption of neural communication by inhibiting neuronal firing or by physical cutting suppresses both SCN reorganization and period changes. Mathematical modeling suggests, and experiments confirm, that this SCN reorganization depends upon GABAergic signaling. Our results therefore show that basic circadian clock properties are governed by dynamic interactions among SCN neurons, with neuroadaptations in network function driven by the environment.