Matches in SemOpenAlex for { <https://semopenalex.org/work/W3201014779> ?p ?o ?g. }
- W3201014779 endingPage "20210454" @default.
- W3201014779 startingPage "20210454" @default.
- W3201014779 abstract "In the suprachiasmatic nucleus (SCN), γ-aminobutyric acid (GABA) is a primary neurotransmitter. GABA can signal through two types of GABAA receptor subunits, often referred to as synaptic GABAA (gamma subunit) and extra-synaptic GABAA (delta subunit). To test the functional roles of these distinct GABAA in regulating circadian rhythms, we developed a multicellular SCN model where we could separately compare the effects of manipulating GABA neurotransmitter or receptor dynamics. Our model predicted that blocking GABA signalling modestly increased synchrony among circadian cells, consistent with published SCN pharmacology. Conversely, the model predicted that lowering GABAA receptor density reduced firing rate, circadian cell fraction, amplitude and synchrony among individual neurons. When we tested these predictions, we found that the knockdown of delta GABAA reduced the amplitude and synchrony of clock gene expression among cells in SCN explants. The model further predicted that increasing gamma GABAA densities could enhance synchrony, as opposed to increasing delta GABAA densities. Overall, our model reveals how blocking GABAA receptors can modestly increase synchrony, while increasing the relative density of gamma over delta subunits can dramatically increase synchrony. We hypothesize that increased gamma GABAA density in the winter could underlie the tighter phase relationships among SCN cells." @default.
- W3201014779 created "2021-09-27" @default.
- W3201014779 creator A5011280307 @default.
- W3201014779 creator A5046196950 @default.
- W3201014779 creator A5055870546 @default.
- W3201014779 creator A5076424703 @default.
- W3201014779 creator A5085032105 @default.
- W3201014779 date "2021-09-01" @default.
- W3201014779 modified "2023-10-14" @default.
- W3201014779 title "Modelling the functional roles of synaptic and extra-synaptic γ-aminobutyric acid receptor dynamics in circadian timekeeping" @default.
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