Abstract
Light is a powerful external cue modulating the biological rhythm of internal clock neurons in the suprachiasmatic nucleus (SCN). GABA signaling in SCN is critically involved in this process. Both phasic and tonic modes of GABA signaling exist in SCN. Of the two modes, the tonic mode of GABA signaling has been implicated in light-mediated synchrony of SCN neurons. However, modulatory effects of external light on tonic GABA signalling are yet to be explored. Here, we systematically characterized electrophysiological properties of the clock neurons and determined the spatio-temporal profiles of tonic GABA current. Based on the whole-cell patch-clamp recordings from 76 SCN neurons, the cells with large tonic GABA current (>15 pA) were more frequently found in dorsal SCN. Moreover, tonic GABA current in SCN was highly correlated with the frequency of spontaneous inhibitory postsynaptic current (sIPSC), raising a possibility that tonic GABA current is due to spill-over from synaptic release. Interestingly, tonic GABA current was inversely correlated with slice-to-patch time interval, suggesting a critical role of retinal light exposure in intact brain for an induction of tonic GABA current in SCN. To test this possibility, we obtained meticulously prepared retina-attached SCN slices and successfully recorded tonic and phasic GABA signaling in SCN neurons. For the first time, we observed an early-onset, long-lasting tonic GABA current, followed by a slow-onset, short-lasting increase in the phasic GABA frequency, upon direct light-illumination of the attached retina. This result provides the first evidence that external light cue can directly trigger both tonic and phasic GABA signaling in SCN cell. In conclusion, we propose tonic GABA as the key mediator of external light in SCN.
Highlights
Light is a strong external cue which can powerfully modulate circadian rhythm in mammalian animals
Spatio‐temporal profiling of tonic γ-aminobutyric acid (GABA) in suprachiasmatic nucleus (SCN) The previous computational modeling predicted that the heterogeneity of spatial and temporal diversity in SCN might have differential effect on GABA signaling [7]
In terms of relationship between tonic and phasic GABA, we found a positive correlation on tonic current with spontaneous inhibitory postsynaptic current (sIPSC) frequency and amplitude (Pearson’s Coeff. of sIPSC Frequency, r = 0.73, p
Summary
Light is a strong external cue which can powerfully modulate circadian rhythm in mammalian animals. Light input received from the retina is transmitted as electrical signals to SCN through the retinohypothalamic tract (RHT) [1]. Despite the general consensus on the importance of GABA in SCN, the role of GABA has been controversial over the question of whether it synchronizes or desynchronizes SCN neurons [6]. This discrepancy is the result of a variety of confounding factors including different activity pattern across the circadian period, heterogeneity of cell types across the regions, different modes (phasic and tonic) of GABAergic actions, switching of inhibitory to excitatory action of GABA and so on [6].
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