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Peripheral optogenetic stimulation induces whisker movement and sensory perception in head-fixed mice

View Article: PubMed Central - PubMed

ABSTRACT

We discovered that optical stimulation of the mystacial pad in Emx1-Cre;Ai27D transgenic mice induces whisker movements due to activation of ChR2 expressed in muscles controlling retraction and protraction. Using high-speed videography in anesthetized mice, we characterize the amplitude of whisker protractions evoked by varying the intensity, duration, and frequency of optogenetic stimulation. Recordings from primary somatosensory cortex (S1) in anesthetized mice indicated that optogenetic whisker pad stimulation evokes robust yet longer latency responses than mechanical whisker stimulation. In head-fixed mice trained to report optogenetic whisker pad stimulation, psychometric curves showed similar dependence on stimulus duration as evoked whisker movements and S1 activity. Furthermore, optogenetic stimulation of S1 in expert mice was sufficient to substitute for peripheral stimulation. We conclude that whisker protractions evoked by optogenetic activation of whisker pad muscles results in cortical activity and sensory perception, consistent with the coding of evoked whisker movements by reafferent sensory input.

Doi:: http://dx.doi.org/10.7554/eLife.14140.001

No MeSH data available.


Related in: MedlinePlus

Behavioral performance in mice trained to detect optogenetic stimulation of the whisker pad.(A) Illustration of the behavioral task. Water deprived, head-fixed mice were rewarded with water for licking within a 2 s response window (gray boxes) after optical stimulation (460 nm) of the rostral whisker pad (Hit trials). Licking in the absence of stimulation resulted in a False Alarm (FA) and punishment (tone and/or 2M salt water). (B) Changes in behavioral performance with training. A maintained Hit rate (blue) and reduced FA rate (red) accounted for the increase in performance (d’; black) over sessions (mean ± SEM, n = 4 mice). Note that learning curves for 2 of 4 mice are shown from the time of introduction of salt water punishment for FA and are aligned to first learning session (d’>1). (C) Dependence of Hit rate (left axis) and reaction time (right axis) on stimulation duration. In expert mice, optical whisker pad stimuli of various durations were included randomly on 10% of trials during behavioral sessions (mean ± SEM; n = 4 mice). (D) A second optical fiber delivered either visual stimulation (left) or S1 optogenetic stimulation (right) on a random 10% of trials (100 ms duration for all stimuli). Lick probability was reduced for visual stimuli (left), but not S1 stimulation (right). *p<0.05; N.S., not significant.DOI:http://dx.doi.org/10.7554/eLife.14140.01210.7554/eLife.14140.013Figure 4—source data 1.Data for Figure 4B.DOI:http://dx.doi.org/10.7554/eLife.14140.013Data for Figure 4C.DOI:http://dx.doi.org/10.7554/eLife.14140.014
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fig4: Behavioral performance in mice trained to detect optogenetic stimulation of the whisker pad.(A) Illustration of the behavioral task. Water deprived, head-fixed mice were rewarded with water for licking within a 2 s response window (gray boxes) after optical stimulation (460 nm) of the rostral whisker pad (Hit trials). Licking in the absence of stimulation resulted in a False Alarm (FA) and punishment (tone and/or 2M salt water). (B) Changes in behavioral performance with training. A maintained Hit rate (blue) and reduced FA rate (red) accounted for the increase in performance (d’; black) over sessions (mean ± SEM, n = 4 mice). Note that learning curves for 2 of 4 mice are shown from the time of introduction of salt water punishment for FA and are aligned to first learning session (d’>1). (C) Dependence of Hit rate (left axis) and reaction time (right axis) on stimulation duration. In expert mice, optical whisker pad stimuli of various durations were included randomly on 10% of trials during behavioral sessions (mean ± SEM; n = 4 mice). (D) A second optical fiber delivered either visual stimulation (left) or S1 optogenetic stimulation (right) on a random 10% of trials (100 ms duration for all stimuli). Lick probability was reduced for visual stimuli (left), but not S1 stimulation (right). *p<0.05; N.S., not significant.DOI:http://dx.doi.org/10.7554/eLife.14140.01210.7554/eLife.14140.013Figure 4—source data 1.Data for Figure 4B.DOI:http://dx.doi.org/10.7554/eLife.14140.013Data for Figure 4C.DOI:http://dx.doi.org/10.7554/eLife.14140.014

Mentions: In order to determine whether Emx1-Cre;Ai27D mice can perceive peripheral optogenetic stimulation, we established a modified head-fixed sensory detection task inspired by recent studies (O'Connor et al., 2013; Sachidhanandam et al., 2013) (Figure 4A). We trained mice to report the presence of 100 ms (9.94 mW) peripheral optogenetic stimulation by licking for water reward. In each Hit trial, mice received a water drop for licking within a 2 s time window after a stimulus. False Alarm (FA) trials occurred if the mouse licked when no light was delivered during the stimulus time window and resulted in presentation of a 2 s, 5 kHz tone and 5–10 s time out before the next trial. Inter-trial time randomly varied from 5–10 s. Two of four mice learned the task (d’>1) within 4 sessions (2 sessions per day, 125 trials per session), showing maintained Hit rate with relatively low FA rate (FA rate < 0.3). The other two mice learned only after introducing 2 M salt water solution as additional punishment for licking during FA trials. We aligned learning curves for all mice relative to the start of learning (d’>1) (Figure 4B), which was after the introduction of salt water punishment in 2/4 mice. Overall, behavioral performance improved via a maintained high Hit rate and a decrease in FA rate, resulting in an increase in d’ from 0.7 ± 0.1 to 2.3 ± 0.4 (mean ± SEM; p = 0.017, paired t-test; n = 4 mice) over the course of training (Figure 4B).10.7554/eLife.14140.012Figure 4.Behavioral performance in mice trained to detect optogenetic stimulation of the whisker pad.


Peripheral optogenetic stimulation induces whisker movement and sensory perception in head-fixed mice
Behavioral performance in mice trained to detect optogenetic stimulation of the whisker pad.(A) Illustration of the behavioral task. Water deprived, head-fixed mice were rewarded with water for licking within a 2 s response window (gray boxes) after optical stimulation (460 nm) of the rostral whisker pad (Hit trials). Licking in the absence of stimulation resulted in a False Alarm (FA) and punishment (tone and/or 2M salt water). (B) Changes in behavioral performance with training. A maintained Hit rate (blue) and reduced FA rate (red) accounted for the increase in performance (d’; black) over sessions (mean ± SEM, n = 4 mice). Note that learning curves for 2 of 4 mice are shown from the time of introduction of salt water punishment for FA and are aligned to first learning session (d’>1). (C) Dependence of Hit rate (left axis) and reaction time (right axis) on stimulation duration. In expert mice, optical whisker pad stimuli of various durations were included randomly on 10% of trials during behavioral sessions (mean ± SEM; n = 4 mice). (D) A second optical fiber delivered either visual stimulation (left) or S1 optogenetic stimulation (right) on a random 10% of trials (100 ms duration for all stimuli). Lick probability was reduced for visual stimuli (left), but not S1 stimulation (right). *p<0.05; N.S., not significant.DOI:http://dx.doi.org/10.7554/eLife.14140.01210.7554/eLife.14140.013Figure 4—source data 1.Data for Figure 4B.DOI:http://dx.doi.org/10.7554/eLife.14140.013Data for Figure 4C.DOI:http://dx.doi.org/10.7554/eLife.14140.014
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fig4: Behavioral performance in mice trained to detect optogenetic stimulation of the whisker pad.(A) Illustration of the behavioral task. Water deprived, head-fixed mice were rewarded with water for licking within a 2 s response window (gray boxes) after optical stimulation (460 nm) of the rostral whisker pad (Hit trials). Licking in the absence of stimulation resulted in a False Alarm (FA) and punishment (tone and/or 2M salt water). (B) Changes in behavioral performance with training. A maintained Hit rate (blue) and reduced FA rate (red) accounted for the increase in performance (d’; black) over sessions (mean ± SEM, n = 4 mice). Note that learning curves for 2 of 4 mice are shown from the time of introduction of salt water punishment for FA and are aligned to first learning session (d’>1). (C) Dependence of Hit rate (left axis) and reaction time (right axis) on stimulation duration. In expert mice, optical whisker pad stimuli of various durations were included randomly on 10% of trials during behavioral sessions (mean ± SEM; n = 4 mice). (D) A second optical fiber delivered either visual stimulation (left) or S1 optogenetic stimulation (right) on a random 10% of trials (100 ms duration for all stimuli). Lick probability was reduced for visual stimuli (left), but not S1 stimulation (right). *p<0.05; N.S., not significant.DOI:http://dx.doi.org/10.7554/eLife.14140.01210.7554/eLife.14140.013Figure 4—source data 1.Data for Figure 4B.DOI:http://dx.doi.org/10.7554/eLife.14140.013Data for Figure 4C.DOI:http://dx.doi.org/10.7554/eLife.14140.014
Mentions: In order to determine whether Emx1-Cre;Ai27D mice can perceive peripheral optogenetic stimulation, we established a modified head-fixed sensory detection task inspired by recent studies (O'Connor et al., 2013; Sachidhanandam et al., 2013) (Figure 4A). We trained mice to report the presence of 100 ms (9.94 mW) peripheral optogenetic stimulation by licking for water reward. In each Hit trial, mice received a water drop for licking within a 2 s time window after a stimulus. False Alarm (FA) trials occurred if the mouse licked when no light was delivered during the stimulus time window and resulted in presentation of a 2 s, 5 kHz tone and 5–10 s time out before the next trial. Inter-trial time randomly varied from 5–10 s. Two of four mice learned the task (d’>1) within 4 sessions (2 sessions per day, 125 trials per session), showing maintained Hit rate with relatively low FA rate (FA rate < 0.3). The other two mice learned only after introducing 2 M salt water solution as additional punishment for licking during FA trials. We aligned learning curves for all mice relative to the start of learning (d’>1) (Figure 4B), which was after the introduction of salt water punishment in 2/4 mice. Overall, behavioral performance improved via a maintained high Hit rate and a decrease in FA rate, resulting in an increase in d’ from 0.7 ± 0.1 to 2.3 ± 0.4 (mean ± SEM; p = 0.017, paired t-test; n = 4 mice) over the course of training (Figure 4B).10.7554/eLife.14140.012Figure 4.Behavioral performance in mice trained to detect optogenetic stimulation of the whisker pad.

View Article: PubMed Central - PubMed

ABSTRACT

We discovered that optical stimulation of the mystacial pad in Emx1-Cre;Ai27D transgenic mice induces whisker movements due to activation of ChR2 expressed in muscles controlling retraction and protraction. Using high-speed videography in anesthetized mice, we characterize the amplitude of whisker protractions evoked by varying the intensity, duration, and frequency of optogenetic stimulation. Recordings from primary somatosensory cortex (S1) in anesthetized mice indicated that optogenetic whisker pad stimulation evokes robust yet longer latency responses than mechanical whisker stimulation. In head-fixed mice trained to report optogenetic whisker pad stimulation, psychometric curves showed similar dependence on stimulus duration as evoked whisker movements and S1 activity. Furthermore, optogenetic stimulation of S1 in expert mice was sufficient to substitute for peripheral stimulation. We conclude that whisker protractions evoked by optogenetic activation of whisker pad muscles results in cortical activity and sensory perception, consistent with the coding of evoked whisker movements by reafferent sensory input.

Doi:: http://dx.doi.org/10.7554/eLife.14140.001

No MeSH data available.


Related in: MedlinePlus