Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities

Neuron. 2020 Jun 17;106(6):992-1008.e9. doi: 10.1016/j.neuron.2020.03.025. Epub 2020 Apr 21.


Astrocytes play essential roles in brain function by supporting synaptic connectivity and associated circuits. How these roles are regulated by transcription factors is unknown. Moreover, there is emerging evidence that astrocytes exhibit regional heterogeneity, and the mechanisms controlling this diversity remain nascent. Here, we show that conditional deletion of the transcription factor nuclear factor I-A (NFIA) in astrocytes in the adult brain results in region-specific alterations in morphology and physiology that are mediated by selective DNA binding. Disruptions in astrocyte function following loss of NFIA are most pronounced in the hippocampus, manifested by impaired interactions with neurons, coupled with diminution of learning and memory behaviors. These changes in hippocampal astrocytes did not affect basal neuronal properties but specifically inhibited synaptic plasticity, which is regulated by NFIA in astrocytes through calcium-dependent mechanisms. Together, our studies reveal region-specific transcriptional dependencies for astrocytes and identify astrocytic NFIA as a key transcriptional regulator of hippocampal circuits.

Keywords: Astrocyte; Hippocampal Circuits; NFIA; Regional Diversity; Transcription Factor.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / physiology
  • Brain / cytology
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Stem / cytology
  • Brain Stem / metabolism
  • Brain Stem / physiopathology
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / physiopathology
  • Calcium / metabolism*
  • Gene Expression Regulation*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Learning / physiology*
  • Long-Term Potentiation / physiology
  • Memory / physiology
  • Mice
  • Mice, Knockout
  • NFI Transcription Factors / genetics*
  • Neural Pathways
  • Neuronal Plasticity
  • Neurons
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / physiopathology
  • Patch-Clamp Techniques
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • Spatial Memory / physiology


  • NFI Transcription Factors
  • Nfia protein, mouse
  • Calcium