Diurnal Regulation of Hippocampal Synaptic Plasticity in Aged Rats and the Role of the Circadian Clock Gene Per1

Period circadian regulator 1 (PER1) regulates circadian gene expression and is critical for spatial memory. However, its role in regulating synaptic plasticity between diurnal phases remains largely unknown. Here, we examined long-term potentiation (LTP) and long-term synaptic depression (LTD) in hippocampal slices prepared from aged male Per1 knockout (Per1 KO) rats and their wildtype (WT) littermates during the light/inactive and dark/active phases. In WT rats, theta-burst stimulation (TBS) consistently induced stable LTP that was greater during the dark relative to the light phase. In contrast, in Per1 KO rats, TBS resulted in synaptic potentiation that decayed to baseline levels within ~90 min in both phases. Notably, WT rats readily expressed LTD following 1 Hz low-frequency stimulation (LFS) during the dark phase but not the light phase. By comparison, in Per1 KO rats, LTD was inducible by LFS during both the dark and light phases. LTD in both WT and Per1 KO rats was dependent on the activation of N-methyl-d-aspartate receptors. Basal synaptic transmission was reduced and GluA1 S845 phosphorylation was increased during the dark phase in both WT and Per1 KO rats. Together, our findings identify PER1 as a key regulator of synaptic plasticity between diurnal phases in aged rats.