» Articles » PMID: 31263776

GABA in the Suprachiasmatic Nucleus Refines Circadian Output Rhythms in Mice

Overview
Journal Commun Biol
Specialty Biology
Date 2019 Jul 3
PMID 31263776
Citations 33
Authors
Affiliations
Soon will be listed here.
Abstract

In mammals, the circadian rhythms are regulated by the central clock located in the hypothalamic suprachiasmatic nucleus (SCN), which is composed of heterogeneous neurons with various neurotransmitters. Among them an inhibitory neurotransmitter, γ-Amino-Butyric-Acid (GABA), is expressed in almost all SCN neurons, however, its role in the circadian physiology is still unclear. Here, we show that the SCN of fetal mice lacking vesicular GABA transporter (VGAT) or GABA synthesizing enzyme, glutamate decarboxylase (GAD65/67), shows burst firings associated with large Ca spikes throughout 24 hours, which spread over the entire SCN slice in synchrony. By contrast, circadian PER2 rhythms in VGAT and GAD65/67 SCN remain intact. SCN-specific VGAT deletion in adult mice dampens circadian behavior rhythm. These findings indicate that GABA in the fetal SCN is necessary for refinement of the circadian firing rhythm and, possibly, for stabilizing the output signals, but not for circadian integration of multiple cellular oscillations.

Citing Articles

Rhythmic astrocytic GABA production synchronizes neuronal circadian timekeeping in the suprachiasmatic nucleus.

Ness N, Diaz-Clavero S, Hoekstra M, Brancaccio M EMBO J. 2024; 44(2):356-381.

PMID: 39623138 PMC: 11731042. DOI: 10.1038/s44318-024-00324-w.


GABAergic signalling in the suprachiasmatic nucleus is required for coherent circadian rhythmicity.

Klett N, Gompf H, Allen C, Cravetchi O, Hablitz L, Gunesch A Eur J Neurosci. 2024; 60(11):6652-6667.

PMID: 39558544 PMC: 11612841. DOI: 10.1111/ejn.16582.


GABA receptor subunit composition regulates circadian rhythms in rest-wake and synchrony among cells in the suprachiasmatic nucleus.

Granados-Fuentes D, Lambert P, Simon T, Mennerick S, Herzog E Proc Natl Acad Sci U S A. 2024; 121(31):e2400339121.

PMID: 39047036 PMC: 11295074. DOI: 10.1073/pnas.2400339121.


Neuron-Astrocyte Interactions and Circadian Timekeeping in Mammals.

Smyllie N, Hastings M, Patton A Neuroscientist. 2024; 31(1):65-79.

PMID: 38602223 PMC: 7616557. DOI: 10.1177/10738584241245307.


The Suprachiasmatic Nucleus at 50: Looking Back, Then Looking Forward.

Ono D, Weaver D, Hastings M, Honma K, Honma S, Silver R J Biol Rhythms. 2024; 39(2):135-165.

PMID: 38366616 PMC: 7615910. DOI: 10.1177/07487304231225706.


References
1.
Liu C, Reppert S . GABA synchronizes clock cells within the suprachiasmatic circadian clock. Neuron. 2000; 25(1):123-8. DOI: 10.1016/s0896-6273(00)80876-4. View

2.
Sangoram A, Saez L, Antoch M, Gekakis N, Staknis D, Whiteley A . Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. Neuron. 1998; 21(5):1101-13. DOI: 10.1016/s0896-6273(00)80627-3. View

3.
Schwartz W, Gross R, Morton M . The suprachiasmatic nuclei contain a tetrodotoxin-resistant circadian pacemaker. Proc Natl Acad Sci U S A. 1987; 84(6):1694-8. PMC: 304503. DOI: 10.1073/pnas.84.6.1694. View

4.
Ikeda M, Ikeda M . Bmal1 is an essential regulator for circadian cytosolic Ca²⁺ rhythms in suprachiasmatic nucleus neurons. J Neurosci. 2014; 34(36):12029-38. PMC: 6608459. DOI: 10.1523/JNEUROSCI.5158-13.2014. View

5.
Speh J, Moore R . Retinohypothalamic tract development in the hamster and rat. Brain Res Dev Brain Res. 1993; 76(2):171-81. DOI: 10.1016/0165-3806(93)90205-o. View