Viral vector-based reversible neuronal inactivation and behavioral manipulation in the macaque monkey
- 1Systems Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
- 2National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Viral vectors are promising tools for the dissection of neural circuits. In principle, they can manipulate neurons at a level of specificity not otherwise achievable. While many studies have used viral vector-based approaches in the rodent brain, only a few have employed this technique in the non-human primate, despite the importance of this animal model for neuroscience research. Here, we report evidence that a viral vector-based approach can be used to manipulate a monkey's behavior in a task. For this purpose, we used the allatostatin receptor/allatostatin (AlstR/AL) system, which has previously been shown to allow inactivation of neurons in vivo. The AlstR was expressed in neurons in monkey V1 by injection of an adeno-associated virus 1 (AAV1) vector. Two monkeys were trained in a detection task, in which they had to make a saccade to a faint peripheral target. Injection of AL caused a retinotopic deficit in the detection task in one monkey. Specifically, the monkey showed marked impairment for detection targets placed at the visual field location represented at the virus injection site, but not for targets shown elsewhere. We confirmed that these deficits indeed were due to the interaction of AlstR and AL by injecting saline, or AL at a V1 location without AlstR expression. Post-mortem histology confirmed AlstR expression in this monkey. We failed to replicate the behavioral results in a second monkey, as AL injection did not impair the second monkey's performance in the detection task. However, post-mortem histology revealed a very low level of AlstR expression in this monkey. Our results demonstrate that viral vector-based approaches can produce effects strong enough to influence a monkey's performance in a behavioral task, supporting the further development of this approach for studying how neuronal circuits control complex behaviors in non-human primates.
Keywords: monkey, V1, viral vector, inactivation, visual detection
Citation: Nielsen KJ, Callaway EM and Krauzlis RJ (2012) Viral vector-based reversible neuronal inactivation and behavioral manipulation in the macaque monkey. Front. Syst. Neurosci. 6:48. doi:10.3389/fnsys.2012.00048
Received: 28 February 2012; Accepted: 26 May 2012;
Published online: 19 June 2012.
, Cold Spring Harbor Laboratory, USA Xue Han
, Boston University, USA Ilka Diester
, Ernst Struengmann Institute in Cooperation with Max Planck Society, Germany
Copyright: © 2012 Nielsen, Callaway and Krauzlis. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Kristina J. Nielsen, Systems Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA. e-mail: firstname.lastname@example.org
†Present address: Zanvyl Krieger Mind/Brain Institute and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21218, USA.