Preferential transduction of parvalbumin-expressing cortical neurons by AAV-mDLX5/6 vectors

Padideh Yazdan-Shahmorad; Shane Gibson; Joanne C Lee; Gregory D Horwitz

doi:10.3389/fnins.2023.1269025

Preferential transduction of parvalbumin-expressing cortical neurons by AAV-mDLX5/6 vectors

Front Neurosci. 2024 Feb 12:17:1269025. doi: 10.3389/fnins.2023.1269025. eCollection 2023.

Authors

Padideh Yazdan-Shahmorad^{1

2}, Shane Gibson^{2

3}, Joanne C Lee^{2

3}, Gregory D Horwitz^{2

3}

Affiliations

¹ Department of Electrical and Computer Engineering, University of Washington, Seattle, WA, United States.
² Washington National Primate Research Center, Seattle, WA, United States.
³ Department of Physiology and Biophysics, University of Washington, Seattle, WA, United States.

Abstract

A major goal of modern neuroscience is to understand the functions of the varied neuronal types that comprise the mammalian brain. Toward this end, some types of neurons can be targeted and manipulated with enhancer-bearing AAV vectors. These vectors hold great promise to advance basic and translational neuroscience, but to realize this potential, their selectivity must be characterized. In this study, we investigated the selectivity of AAV vectors carrying an enhancer of the murine Dlx5 and Dlx6 genes. Vectors were injected into the visual cortex of two macaque monkeys, the frontal cortex of two others, and the somatosensory/motor cortex of three rats. Post-mortem immunostaining revealed that parvalbumin-expressing neurons were transduced efficiently in all cases but calretinin-expressing neurons were not. We speculate that this specificity is a consequence of differential activity of this DLX5/6 enhancer in adult neurons of different developmental lineages.

Keywords: AAV; DLX5/6; calretinin; cell type-specificity; enhancer; macaque; parvalbumin.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by NIH grants EY030441, OD010425, and OD016240.