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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

(A) Stimulus sequences in the two trial types (see text for a description of the task). (B) Receptive fields and target locations for the two monkeys. Black ellipses: Receptive field locations recorded at the V1 site selected for virus injection, computed from single unit and multiunit activity (see Materials and Methods). The red and green circles indicate the two target locations. Red circle: AlstR location; green circle: contralateral location.
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Figure 1: (A) Stimulus sequences in the two trial types (see text for a description of the task). (B) Receptive fields and target locations for the two monkeys. Black ellipses: Receptive field locations recorded at the V1 site selected for virus injection, computed from single unit and multiunit activity (see Materials and Methods). The red and green circles indicate the two target locations. Red circle: AlstR location; green circle: contralateral location.

Mentions: The detection task consisted of two types of trials, distinguished by whether or not a peripheral target was presented (see Figure 1). Eighty percent of the trials in a session were target-present trials. All trials began with the presentation of a central white fixation square (size: 0.16 × 0.16°) on a trial-unique, noise-textured background (size: 10 × 10°). The rest of the screen, outside of the texture, was set to a uniform gray (luminance: 45 cd m−2). The noise texture was constructed by assigning each of its pixels a gray scale value independently drawn from a Gaussian distribution. The mean of the Gaussian distribution was chosen to match the luminance of the rest of the screen, and the standard deviation σtexture was fixed at 5.5 cd/m−2. Pixel values outside of the range from 0 to 255 were set to either 0 or 255, respectively. In the target-absent trials, the central fixation square was presented for a variable time between 800 and 1400 ms before its color changed to red. After another 300–1000 ms, the fixation square and texture were removed, and the entire screen turned gray. In these target-absent trials, monkeys were rewarded if they maintained fixation of the central square as long as it was visible, irrespective of its color. In the target-present trials, the initial presentation of fixation square and texture was followed after 500–800 ms by the additional appearance of a small peripheral target. Targets measured 0.16 × 0.16° (3 × 3 pixels at our screen resolution and viewing distance), and were generated by adding a luminance increment to the gray scale values of the texture pixels at the target location. Luminance increments were expressed in terms of σtexture. Four different luminance increments were chosen for monkey W (1, 1.5, 2, 3, and 4 × σtexture). For monkey V, we added a fifth luminance increment (5 × σtexture) to decrease the overall task difficulty. Four target locations were used, chosen based on which injection site was visited. After an additional 300–600 ms, the fixation square turned red. The monkeys were required to maintain fixation within a window centered on the fixation square until this time. After the fixation spot changed color, they were trained to make a saccade directly to the location of the target: within 600 ms after the color change, their center of gaze had to leave the fixation window; after another 100 ms, it had to fall within a second window centered on the target's location. After an additional fixation period of 300 ms, the entire screen turned gray to indicate the end of the trial.


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

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

(A) Stimulus sequences in the two trial types (see text for a description of the task). (B) Receptive fields and target locations for the two monkeys. Black ellipses: Receptive field locations recorded at the V1 site selected for virus injection, computed from single unit and multiunit activity (see Materials and Methods). The red and green circles indicate the two target locations. Red circle: AlstR location; green circle: contralateral location.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: (A) Stimulus sequences in the two trial types (see text for a description of the task). (B) Receptive fields and target locations for the two monkeys. Black ellipses: Receptive field locations recorded at the V1 site selected for virus injection, computed from single unit and multiunit activity (see Materials and Methods). The red and green circles indicate the two target locations. Red circle: AlstR location; green circle: contralateral location.
Mentions: The detection task consisted of two types of trials, distinguished by whether or not a peripheral target was presented (see Figure 1). Eighty percent of the trials in a session were target-present trials. All trials began with the presentation of a central white fixation square (size: 0.16 × 0.16°) on a trial-unique, noise-textured background (size: 10 × 10°). The rest of the screen, outside of the texture, was set to a uniform gray (luminance: 45 cd m−2). The noise texture was constructed by assigning each of its pixels a gray scale value independently drawn from a Gaussian distribution. The mean of the Gaussian distribution was chosen to match the luminance of the rest of the screen, and the standard deviation σtexture was fixed at 5.5 cd/m−2. Pixel values outside of the range from 0 to 255 were set to either 0 or 255, respectively. In the target-absent trials, the central fixation square was presented for a variable time between 800 and 1400 ms before its color changed to red. After another 300–1000 ms, the fixation square and texture were removed, and the entire screen turned gray. In these target-absent trials, monkeys were rewarded if they maintained fixation of the central square as long as it was visible, irrespective of its color. In the target-present trials, the initial presentation of fixation square and texture was followed after 500–800 ms by the additional appearance of a small peripheral target. Targets measured 0.16 × 0.16° (3 × 3 pixels at our screen resolution and viewing distance), and were generated by adding a luminance increment to the gray scale values of the texture pixels at the target location. Luminance increments were expressed in terms of σtexture. Four different luminance increments were chosen for monkey W (1, 1.5, 2, 3, and 4 × σtexture). For monkey V, we added a fifth luminance increment (5 × σtexture) to decrease the overall task difficulty. Four target locations were used, chosen based on which injection site was visited. After an additional 300–600 ms, the fixation square turned red. The monkeys were required to maintain fixation within a window centered on the fixation square until this time. After the fixation spot changed color, they were trained to make a saccade directly to the location of the target: within 600 ms after the color change, their center of gaze had to leave the fixation window; after another 100 ms, it had to fall within a second window centered on the target's location. After an additional fixation period of 300 ms, the entire screen turned gray to indicate the end of the trial.

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