Time-restricted feeding entrains long-term behavioral changes through the IGF2-KCC2 pathway.

Authors
Zhai, Qiaocheng 
Zeng, Yizhun 
Gu, Yue 
Li, Zhihao 
Zhang, Tao 

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Article
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Abstract

The suprachiasmatic nucleus (SCN) integrates light and systemic signals from peripheral tissues to coordinate physiology and behavior daily rhythms. However, the contribution that nutrients and feeding patterns provide to the SCN network regulation remains controversial. Here, we found that time-restricted feeding (TRF) in ZT0-4 (Zeitgeber Time) generates a robust and long-term shift in locomotor behavior and increased wakefulness. Intracellular Ca2+ signals in SCN GABAergic neurons of freely moving mice showed significant activation after ZT0-4 TRF treatment. Furthermore, RNA-seq profiling of SCN showed that TRF during ZT0-4 increased Insulin-like Growth Factor 2 (Igf2) expression and dysregulated ion transporters, including the downregulation of Kcc2. SCN neuron-specific loss of function of Kcc2 amplified ZT0-4 TRF induced aftereffect. Moreover, overexpression of IGF2 in SCN GABAergic neurons extended the locomotion range, mirroring the TRF aftereffect. In summary, our study showed that the IGF2-KCC2 pathway plays an important role for TRF induced behavior changes.

Publication Date
2022-05-20
Online Publication Date
2022-04-18
Acceptance Date
2022-04-13
Keywords
Behavioral neuroscience, Molecular neuroscience, Neuroscience
Journal Title
iScience
Journal ISSN
2589-0042
2589-0042
Volume Title
25
Publisher
Elsevier BV
Sponsorship
Medical Research Council (G0802051)
Medical Research Council (G0400192)
Medical Research Council (MC_UU_12012/2)
Medical Research Council (MC_UU_12012/5)
MRC (MC_UU_00014/2)
MRC (MC_UU_00014/5)