UCLA

Astrocytes are one of the major types of glia ubiquitously found 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. We deployed integrated optical, anatomical, electrophysiological, transcriptomic and proteomic approaches to explore astrocyte similarities and differences in two adult neural circuits under identical conditions. To overcome the paucity of tools permitting astrocyte selective genetic manipulations, we generated Aldh1l1-Cre/ERT2 transgenic mice and adeno-associated viruses to selectively target astrocytes in vivo. Crosses with RiboTag mice allowed sequencing of actively translated mRNAs and determination of the adult cortical, striatal, and hippocaompal astrocyte transcriptomes. Unbiased evaluation of actively translated RNA and proteomic data found significant astrocyte diversity between hippocampal and striatal circuits. Significant differences between striatal and hippocampal astrocytes were also found in electrophysiological properties, Ca2+ signaling, morphology and astrocyte-synapse proximity. Our data provide strong, direct evidence for neural circuit-specialized astrocytes in the adult brain and provide new, integrated database resources and approaches to explore astrocyte diversity and function throughout the adult brain.