TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses

Tatjana Lalic (), Aiste Steponenaite, Liting Wei, Sridhar R. Vasudevan, Alistair Mathie, Stuart N. Peirson, Gurprit S. Lall () and M. Zameel Cader ()
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Tatjana Lalic: University of Oxford
Aiste Steponenaite: University of Kent and University of Greenwich
Liting Wei: University of Oxford
Sridhar R. Vasudevan: University of Oxford
Alistair Mathie: University of Kent and University of Greenwich
Stuart N. Peirson: University of Oxford
Gurprit S. Lall: University of Kent and University of Greenwich
M. Zameel Cader: University of Oxford

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract The suprachiasmatic nucleus (SCN) is a complex structure dependent upon multiple mechanisms to ensure rhythmic electrical activity that varies between day and night, to determine circadian adaptation and behaviours. SCN neurons are exposed to glutamate from multiple sources including from the retino-hypothalamic tract and from astrocytes. However, the mechanism preventing inappropriate post-synaptic glutamatergic effects is unexplored and unknown. Unexpectedly we discovered that TRESK, a calcium regulated two-pore potassium channel, plays a crucial role in this system. We propose that glutamate activates TRESK through NMDA and AMPA mediated calcium influx and calcineurin activation to then oppose further membrane depolarisation and rising intracellular calcium. Hence, in the absence of TRESK, glutamatergic activity is unregulated leading to membrane depolarisation, increased nocturnal SCN firing, inverted basal calcium levels and impaired sensitivity in light induced phase delays. Our data reveals TRESK plays an essential part in SCN regulatory mechanisms and light induced adaptive behaviours.

Date: 2020
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DOI: 10.1038/s41467-020-17978-9

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