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

神经元和星形胶质细胞的昼夜节律调节控制海马 CA1 区突触可塑性

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作者: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

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.

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