The study finding that burst firings of 35–80 Hz appeared in the culturing SCN slice of fetal mice; and obscured the circadian firing rhythm when GABA signaling was genetically or pharmacologically disrupted. Calcium spikes, which synchronizing with burst firings; were also observing in GABA-deficient SCN. Researchers discover role of GABA neurons in the central circadian clock.
Physiology and behavior such as sleep/wakefulness, body temperature; and endocrine functions, exhibit 24-hour oscillations called circadian rhythms. The temporal order of physiology and behavior is regulating by the central circadian clock located in the SCN. Our findings can be developing to understand how the SCN regulates physiological phenomena.
Furthermore, it might aid the development of new clinical approaches for a variety of diseases related to the circadian clock. The temporal order of physiology and behavior in mammals is controlled by the master circadian clock locating in the SCN. The SCN generates an endogenous circadian oscillation that entrains a day-night alternation.
Slice of fetal mice
The SCN is composing of heterogeneous neurons with various neurotransmitters. Of these, an inhibitory neurotransmitter, γ-Amino-Butyric-Acid (GABA) is expressing in almost all SCN neurons; however, its role in circadian physiology is still unclear. In the present study, we examining GABA signaling in the SCN using mice lacking vesicular GABA transporter (VGAT-/-) or a GABA synthesizing enzyme, glutamate decarboxylase.
We simultaneously measured circadian rhythms with a bioluminescence reporter for the clock gene product PER2 (PER2::LUC), spontaneous firing, and intracellular calcium (Ca2+) levels for several circadian cycles in cultured SCN slices of perinatal mice. The burst firing was associating with an abrupt increase in intracellular Ca2+; which was synchronous throughout the entire SCN slice. By contrast, the circadian PER2 rhythm was essentially keeping intact.
Output signals clear
Study also finding that SCN-specific VGAT depletion in adult mice deteriorating the circadian behavioral rhythms. Mice with deleted VGAT specifically in the SCN showed damped circadian behavioral rhythms without changes in the free-running period. From these findings, we conclude that GABA refines the circadian firing rhythm in the fetal SCN to make output signals clear.
In conclusion, 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. The GABA network may refine the circadian firing rhythm to ensure noiseless communications with neurons outside the SCN. Therefore it is a matter of discussion whether the synchronous burst firings; throughout the SCN are specific for the neonates or not.