Circadian Modulation of Neurons and Astrocytes Controls Synaptic Plasticity in Hippocampal Area CA1

Most animal species operate according to a 24-h period set by the suprachiasmatic nucleus (SCN) of the hypothalamus. The rhythmic activity of the SCN modulates hippocampal-dependent memory, but the molecular and cellular mechanisms that account for this effect remain largely unknown. Here, we identify cell-type-specific structural and functional changes that occur with circadian rhythmicity in neurons and astrocytes in hippocampal area CA1. Pyramidal neurons change the surface expression of NMDA receptors. Astrocytes change their proximity to synapses. Together, these phenomena alter glutamate clearance, receptor activation, and integration of temporally clustered excitatory synaptic inputs, ultimately shaping hippocampal-dependent learning in vivo. We identify corticosterone as a key contributor to changes in synaptic strength. These findings highlight important mechanisms through which neurons and astrocytes modify the molecular composition and structure of the synaptic environment, contribute to the local storage of information in the hippocampus, and alter the temporal dynamics of cognitive processing. [Display omitted] •Hippocampal plasticity varies with circadian rhythmicity•Neurons reduce the surface expression of NMDA receptors during the dark phase•Astrocytes retract their processes from synapses during the dark phase•These effects alter synaptic integration and hippocampal-dependent learning McCauley et al. shed light on the molecular and cellular mechanisms that allow hippocampal neurons and astrocytes to shape circadian changes in synaptic plasticity and hippocampal-dependent behaviors. They identify corticosterone as a key molecule mediating these effects, capable of tuning the temporal dynamics of cognitive processing in mice.