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

doi:10.1016/j.neuron.2017.06.029

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

Neuron. 2017 Aug 2;95(3):531-549.e9. doi: 10.1016/j.neuron.2017.06.029. Epub 2017 Jul 14.

Authors

Affiliations

¹ Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
² Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
³ Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
⁴ Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
⁵ UCLA Cardiac Arrhythmia Center, Neurocardiology Research Center for Excellence, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
⁶ Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
⁷ Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
⁸ Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA. Electronic address: [email protected].

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.

Keywords: Aldh1l1; Cre/ERT2; GCaMP; RNA-seq; astrocyte; calcium; diversity; hippocampus; proteomics; striatum.

MeSH terms

Animals
Astrocytes / metabolism*
Calcium / metabolism*
Calcium Signaling / physiology*
Corpus Striatum / metabolism
Glutamic Acid / metabolism
Hippocampus / physiology*
Mice
Neostriatum / metabolism
Proteomics* / methods
Synapses / metabolism*
Transcriptome*

Substances

Glutamic Acid
Calcium

Abstract

MeSH terms

Substances

Grants and funding