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Viral vector-based reversible neuronal inactivation and behavioral manipulation in the macaque monkey.

Nielsen KJ, Callaway EM, Krauzlis RJ - Front Syst Neurosci (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Systems Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla CA, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Performance of monkey V in the detection task for control and injection experiments, for targets shown at the contralateral and AlstR location. Black circles and line: Average behavior and psychometric function in control experiments (error bars: SEM). Red triangles and lines: Performance (raw data and fit) in individual AL injection experiments.
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Figure 4: Performance of monkey V in the detection task for control and injection experiments, for targets shown at the contralateral and AlstR location. Black circles and line: Average behavior and psychometric function in control experiments (error bars: SEM). Red triangles and lines: Performance (raw data and fit) in individual AL injection experiments.

Mentions: We repeated the experiments in monkey V, and injected virus into V1, followed by AL injections at the same location. All experimental procedures were nearly identical for the two animals. Figure 4 shows monkey V's performance in the detection task for control experiments (black line, contralateral location: N = 41 for, AlstR location: N = 43) and during AL injection (red lines, N = 3 for both locations). In this monkey, AL injection failed to produce the same results as in monkey W, as performance was not noticeably changed by AL injection at the AlstR location. A comparison of the parameters of the psychometric functions showed no significant differences between control and injection data at either target location (p > 0.01 for all parameters and target locations). Performance in the target-absent trials was also unaffected by AL injection (U = 74, p = 1).


Viral vector-based reversible neuronal inactivation and behavioral manipulation in the macaque monkey.

Nielsen KJ, Callaway EM, Krauzlis RJ - Front Syst Neurosci (2012)

Performance of monkey V in the detection task for control and injection experiments, for targets shown at the contralateral and AlstR location. Black circles and line: Average behavior and psychometric function in control experiments (error bars: SEM). Red triangles and lines: Performance (raw data and fit) in individual AL injection experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378014&req=5

Figure 4: Performance of monkey V in the detection task for control and injection experiments, for targets shown at the contralateral and AlstR location. Black circles and line: Average behavior and psychometric function in control experiments (error bars: SEM). Red triangles and lines: Performance (raw data and fit) in individual AL injection experiments.
Mentions: We repeated the experiments in monkey V, and injected virus into V1, followed by AL injections at the same location. All experimental procedures were nearly identical for the two animals. Figure 4 shows monkey V's performance in the detection task for control experiments (black line, contralateral location: N = 41 for, AlstR location: N = 43) and during AL injection (red lines, N = 3 for both locations). In this monkey, AL injection failed to produce the same results as in monkey W, as performance was not noticeably changed by AL injection at the AlstR location. A comparison of the parameters of the psychometric functions showed no significant differences between control and injection data at either target location (p > 0.01 for all parameters and target locations). Performance in the target-absent trials was also unaffected by AL injection (U = 74, p = 1).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Systems Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla CA, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus