Researchers in Japan believe that their findings can be used to understand how the suprachiasmatic nucleus (SCN) regulates physiological phenomena and aid the development of new clinical approaches for of diseases related to the circadian clock.
The team of researchers from Nagoya University, Hokkaido University, and Gunma University, found that GABAergic neurons of the central circadian clock in the SCN refine circadian output rhythms, according to results published recently in Communications Biology.
In the study, researchers examined GABA signaling in the SCN using mice lacking vesicular GABA transporter or a GABA synthesizing enzyme, glutamate decarboxylase. They simultaneously measured circadian rhythms with a bioluminescence reporter for the clock gene product PER2, spontaneous firing, and intracellular calcium levels for several circadian cycles in cultured SCN slices of perinatal mice.
SCN lacking GABA exhibited burst firing throughout a day. The burst firing was associated with an abrupt increase in intracellular Ca2+, which was synchronous throughout the entire SCN slice. By contrast, the circadian PER2 rhythm was essentially kept intact. We also found that SCN-specific VGAT depletion in adult mice deteriorated the circadian behavioral rhythms.
The researchers concluded that GABA is necessary for suppressing the burst firing of neuronal activity and abrupt increases of intracellular Ca2+ levels, but not for the generation and stability of the molecular circadian oscillation in the SCN.
