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Neuron, Published: April 21, 2020 106, 1-17, June 17, 2020 | https://doi.org/10.1016/j.neuron.2020.03.025 Region-specific transcriptional control of astrocyte function oversees local circuit activities

Anna Yu-Szu Huang^1,2,7, Junsung Woo^1,7, Debosmita Sardar¹, Brittney Lozzi¹, Navish A. Bosquez Huerta^1,2, Chia-Ching John Lin¹, Daniela Felice³, Antrix Jain⁴, Adriana Paulucci-Holthauzen⁵, Benjamin Deneen^1,2,3,6,8,*

¹Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
²Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
³Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
⁴Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX 77030, USA
⁵Department of Genetics, MD Anderson Cancer Center, Houston, TX 77030, USA
⁶Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA
⁷These authors contributed equally.
⁸Lead Contact

^*Corresponding author

Abstract

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.

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형식Research article
게재일2020년 04월 (BRIC 등록일 2020-04-27)
연구진국외 연구진
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