An AAV capsid proposed as microglia-targeting directs genetic expression in forebrain excitatory neurons

Wenhao Cao; Zhiqun Tan; Bereket T Berackey; Jason K Nguyen; Sara R Brown; Shiyang Du; Bin Lin; Qiao Ye; Magdalene Seiler; Todd C Holmes; Xiangmin Xu

doi:10.1016/j.crmeth.2025.101054

An AAV capsid proposed as microglia-targeting directs genetic expression in forebrain excitatory neurons

Cell Rep Methods. 2025 Jun 16;5(6):101054. doi: 10.1016/j.crmeth.2025.101054. Epub 2025 May 21.

Authors

Affiliations

¹ Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
² Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; Center for Neural Circuit Mapping, University of California, Irvine, Irvine, CA 92697, USA.
³ Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; Department of Physical Medicine & Rehabilitation, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
⁴ Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; Center for Neural Circuit Mapping, University of California, Irvine, Irvine, CA 92697, USA.
⁵ Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; Center for Neural Circuit Mapping, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: xiangmix@uci.edu.

Abstract

A newly developed capsid AAV-MG1.2 was reported to mediate specific microglial transduction. However, we find that AAV-MG1.2 actually enables specific genetic access to excitatory neurons in forebrain regions including hippocampal formation and visual cortex but does not confer expression in microglia or astrocytes in vivo. Furthermore, we find that AAV-MG1.2 specifically labels the deep layer of the CA1 pyramidal layer in a titer-dependent manner. We show that AAV-MG1.2-Cre can be used to genetically target excitatory neurons for cell-type-specific neural circuit mapping studies. We also find that AAV-MG1.2 conserves specificity for excitatory neurons in rat hippocampus. Thus, the AAV-MG1.2 presents a useful viral-genetic tool for targeting excitatory neurons in the forebrain across different species.

Keywords: AAV toolbox; AAV-MG1.2; CP: neuroscience; cross-species; excitatory neurons; hippocampus; neocortex; neural circuit tracing; tool development.

MeSH terms

Animals
Capsid* / metabolism
Dependovirus* / genetics
Dependovirus* / metabolism
Gene Expression
Genetic Vectors / genetics
Hippocampus / cytology
Hippocampus / metabolism
Male
Mice
Microglia* / metabolism
Neurons* / metabolism
Prosencephalon* / cytology
Prosencephalon* / metabolism
Rats
Transduction, Genetic

Abstract

MeSH terms

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