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

Cell Rep. 2020 Oct 13;33(2):108255. doi: 10.1016/j.celrep.2020.108255.

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.

Keywords: astrocytes; circadian rhythms; corticosterone; glutamate; hippocampus; learning and memory; synapses; synaptic integration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Transport System X-AG / metabolism
  • Animals
  • Astrocytes / physiology*
  • CA1 Region, Hippocampal / physiology*
  • CA1 Region, Hippocampal / ultrastructure
  • Circadian Clocks / genetics
  • Circadian Rhythm / physiology*
  • Corticosterone / metabolism
  • Darkness
  • Excitatory Postsynaptic Potentials / physiology
  • Gene Expression Regulation
  • Glutamic Acid / metabolism
  • Memory / physiology
  • Mice, Inbred C57BL
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Neuropil Threads / metabolism
  • Open Field Test
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / physiology
  • Time Factors
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism

Substances

  • Amino Acid Transport System X-AG
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Corticosterone