Circadian modulation of neurons and astrocytes controls synaptic plasticity in hippocampal area CA1

Author:

McCauley John P.ORCID,Petroccione Maurice A.ORCID,D’Brant Lianna Y.ORCID,Todd Gabrielle C.ORCID,Affinnih NuratORCID,Wisnoski Justin J.ORCID,Zahid ShergilORCID,Shree SwastiORCID,Sousa Alioscka A.ORCID,De Guzman Rose M.,Migliore Rosanna,Brazhe AlexeyORCID,Leapman Richard D.ORCID,Khmaladze AlexanderORCID,Semyanov AlexeyORCID,Zuloaga Damian G.,Migliore MicheleORCID,Scimemi AnnalisaORCID

Abstract

SummaryMost animal species operate according to a 24-hour period set by the suprachiasmatic nucleus (SCN) of the hypothalamus. The rhythmic activity of the SCN is known to modulate hippocampal-dependent memory processes, but the molecular and cellular mechanisms that account for this effect remain largely unknown. Here, we show that there are 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, whereas 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 learningin vivo. We identify corticosterone as a key contributor to changes in synaptic strength. These findings identify 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.

Publisher

Cold Spring Harbor Laboratory

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