Astrocytic signaling supports hippocampal-prefrontal theta synchronization and cognitive function

Glia. 2017 Dec;65(12):1944-1960. doi: 10.1002/glia.23205. Epub 2017 Sep 8.

Abstract

Astrocytes interact with neurons at the cellular level through modulation of synaptic formation, maturation, and function, but the impact of such interaction into behavior remains unclear. Here, we studied the dominant negative SNARE (dnSNARE) mouse model to dissect the role of astrocyte-derived signaling in corticolimbic circuits, with implications for cognitive processing. We found that the blockade of gliotransmitter release in astrocytes triggers a critical desynchronization of neural theta oscillations between dorsal hippocampus and prefrontal cortex. Moreover, we found a strong cognitive impairment in tasks depending on this network. Importantly, the supplementation with d-serine completely restores hippocampal-prefrontal theta synchronization and rescues the spatial memory and long-term memory of dnSNARE mice. We provide here novel evidence of long distance network modulation by astrocytes, with direct implications to cognitive function.

Keywords: astrocyte; behavior; local field potential; neuronal morphology; oscillations.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Astrocytes / ultrastructure
  • Cognition / physiology*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / genetics
  • Doxycycline / pharmacology
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / metabolism
  • Hippocampus / cytology*
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Maze Learning / physiology
  • Mice
  • Mice, Transgenic
  • Models, Neurological
  • Neurons / ultrastructure
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Recognition, Psychology / physiology
  • S100 Calcium Binding Protein beta Subunit / metabolism
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism
  • Serine / pharmacology
  • Signal Transduction / physiology*
  • Spatial Behavior / physiology
  • Theta Rhythm / drug effects
  • Theta Rhythm / genetics

Substances

  • Glial Fibrillary Acidic Protein
  • S100 Calcium Binding Protein beta Subunit
  • SNARE Proteins
  • Glutamic Acid
  • Serine
  • Doxycycline