Circadian Modulation of Neurons and Astrocytes Controls Synaptic Plasticity in Hippocampal Area CA1
John P. McCauley, Maurice A. Petroccione, Lianna Y. D’Brant, Gabrielle C. Todd, Nurat Affinnih, Justin J. Wisnoski, Shergil Zahid, Swasti Shree, Alioscka A. Sousa, Rose M. De Guzman, Rosanna Migliore, Alexey Brazhe, Richard D. Leapman, Alexander Khmaladze, Alexey Semyanov, Damian G. Zuloaga, Michele Migliore, Annalisa Scimemi
Abstract
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.