摘要：SummaryThe 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 ofKcc2. SCN neuron-specific loss of function ofKcc2amplified 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.Graphical abstractDisplay OmittedHighlights•Time-restricted feeding near light-on induces long-term behavioral changes•The suprachiasmatic nucleus (SCN) neurons can be activated by TRF stimulation•The IGF2-KCC2 pathway is associated with behavioral response to TRF entrainmentBehavioral neuroscience; Molecular neuroscience; Neuroscience
