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J Neurophysiol. 2016 Jul 1;116(1):122-34. doi: 10.1152/jn.00087.2016. Epub 2016 Apr 6.

Strategies for targeting primate neural circuits with viral vectors.

Author information

1
Department of Physiology and Biophysics and Washington National Primate Research Center, University of Washington, Seattle, Washington; and.
2
Department of Neuroscience and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania.
3
Department of Physiology and Biophysics and Washington National Primate Research Center, University of Washington, Seattle, Washington; and ghorwitz@u.washington.edu.

Abstract

Understanding how the brain works requires understanding how different types of neurons contribute to circuit function and organism behavior. Progress on this front has been accelerated by optogenetics and chemogenetics, which provide an unprecedented level of control over distinct neuronal types in small animals. In primates, however, targeting specific types of neurons with these tools remains challenging. In this review, we discuss existing and emerging strategies for directing genetic manipulations to targeted neurons in the adult primate central nervous system. We review the literature on viral vectors for gene delivery to neurons, focusing on adeno-associated viral vectors and lentiviral vectors, their tropism for different cell types, and prospects for new variants with improved efficacy and selectivity. We discuss two projection targeting approaches for probing neural circuits: anterograde projection targeting and retrograde transport of viral vectors. We conclude with an analysis of cell type-specific promoters and other nucleotide sequences that can be used in viral vectors to target neuronal types at the transcriptional level.

KEYWORDS:

gene therapy; optogenetics; primate; targeting; viral vector

PMID:
27052579
PMCID:
PMC4961743
DOI:
10.1152/jn.00087.2016
[Indexed for MEDLINE]
Free PMC Article

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