Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence

Hua Chai, Blanca Diaz-Castro, Eiji Shigetomi, Emma Monte, J. Christopher Octeau, Xinzhu Yu, Whitaker Cohn, Pradeep S. Rajendran, Thomas M. Vondriska, Julian P. Whitelegge, Giovanni Coppola, Baljit S. Khakh

Research output: Contribution to journalArticlepeer-review

Abstract

Astrocytes are ubiquitous in the brain and are widely held to be largely identical. However, this view has not been fully tested, and the possibility that astrocytes are neural circuit specialized remains largely unexplored. Here, we used multiple integrated approaches, including RNA sequencing (RNA-seq), mass spectrometry, electrophysiology, immunohistochemistry, serial block-face-scanning electron microscopy, morphological reconstructions, pharmacogenetics, and diffusible dye, calcium, and glutamate imaging, to directly compare adult striatal and hippocampal astrocytes under identical conditions. We found significant differences in electrophysiological properties, Ca2+ signaling, morphology, and astrocyte-synapse proximity between striatal and hippocampal astrocytes. Unbiased evaluation of actively translated RNA and proteomic data confirmed significant astrocyte diversity between hippocampal and striatal circuits. We thus report core astrocyte properties, reveal evidence for specialized astrocytes within neural circuits, and provide new, integrated database resources and approaches to explore astrocyte diversity and function throughout the adult brain. Video Abstract [Formula presented]

Original languageEnglish (US)
Pages (from-to)531-549.e9
JournalNeuron
Volume95
Issue number3
DOIs
StatePublished - Aug 2 2017
Externally publishedYes

Keywords

  • Aldh1l1
  • astrocyte
  • calcium
  • Cre/ERT2
  • diversity
  • GCaMP
  • hippocampus
  • proteomics
  • RNA-seq
  • striatum

ASJC Scopus subject areas

  • Neuroscience(all)

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