Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys

O'Shea, D. J., Kalanithi, P., Ferenczi, E. A., Hsueh, B., Chandrasekaran, C., Goo, W., Diester, I., Ramakrishnan, C., Kaufman, M. T., Ryu, S. I., Yeom, K. W., Deisseroth, K., Shenoy, K. V. (April 2018) Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys. Sci Rep, 8 (1). p. 6775. ISSN 2045-2322

URL: https://www.ncbi.nlm.nih.gov/pubmed/29712920
DOI: 10.1038/s41598-018-24362-7

Abstract

Optogenetic tools have opened a rich experimental landscape for understanding neural function and disease. Here, we present the first validation of eight optogenetic constructs driven by recombinant adeno-associated virus (AAV) vectors and a WGA-Cre based dual injection strategy for projection targeting in a widely-used New World primate model, the common squirrel monkey Saimiri sciureus. We observed opsin expression around the local injection site and in axonal projections to downstream regions, as well as transduction to thalamic neurons, resembling expression patterns observed in macaques. Optical stimulation drove strong, reliable excitatory responses in local neural populations for two depolarizing opsins in anesthetized monkeys. Finally, we observed continued, healthy opsin expression for at least one year. These data suggest that optogenetic tools can be readily applied in squirrel monkeys, an important first step in enabling precise, targeted manipulation of neural circuits in these highly trainable, cognitively sophisticated animals. In conjunction with similar approaches in macaques and marmosets, optogenetic manipulation of neural circuits in squirrel monkeys will provide functional, comparative insights into neural circuits which subserve dextrous motor control as well as other adaptive behaviors across the primate lineage. Additionally, development of these tools in squirrel monkeys, a well-established model system for several human neurological diseases, can aid in identifying novel treatment strategies.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neuronal circuits

Investigative techniques and equipment > optogenetics
CSHL Authors:
Communities: CSHL labs > Churchland lab
Depositing User: Matt Covey
Date: 30 April 2018
Date Deposited: 22 May 2018 19:51
Last Modified: 22 May 2018 19:51
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36565

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