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matlab function kstest2  (MathWorks Inc)


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    MathWorks Inc matlab function kstest2
    Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( <t>kstest2</t> , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.
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    Images

    1) Product Images from "Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding"

    Article Title: Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding

    Journal: Pain

    doi: 10.1097/j.pain.0000000000003493

    Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.
    Figure Legend Snippet: Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.

    Techniques Used: Inhibition, Expressing, Injection, Transfection, Activity Assay, Comparison, Control, Virus

    Effects of optogenetic light delivery in normalized LHb mean activity during the DNMS delay phase. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the DNMS delay phase. Normalized mean LHb activity during the DNMS delay phase (left panels), preceding correct (B) and wrong trials (C). Each experimental group exhibited distinct activity profiles under cognitive demand across the light delivery stimulation protocols. The most notable differences were observed during trials associated with wrong responses. Right heatmaps representing the task-related averaged activity of all recorded units with respect to behavioral contingency. Each row represents individual units (sham: n = 61 units; SNI: n = 77 units). Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by ** when P < 0.01 and *** when P < 0.001. Data regarding sample lever press is provided in supplementary Fig. S1 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; SNI, spared nerve injury.
    Figure Legend Snippet: Effects of optogenetic light delivery in normalized LHb mean activity during the DNMS delay phase. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the DNMS delay phase. Normalized mean LHb activity during the DNMS delay phase (left panels), preceding correct (B) and wrong trials (C). Each experimental group exhibited distinct activity profiles under cognitive demand across the light delivery stimulation protocols. The most notable differences were observed during trials associated with wrong responses. Right heatmaps representing the task-related averaged activity of all recorded units with respect to behavioral contingency. Each row represents individual units (sham: n = 61 units; SNI: n = 77 units). Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by ** when P < 0.01 and *** when P < 0.001. Data regarding sample lever press is provided in supplementary Fig. S1 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; SNI, spared nerve injury.

    Techniques Used: Activity Assay, Comparison

    Correct trials were preceded by enhanced intra-LHb activity. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the nonmatch-to-sample lever press of correct rewarded trials. Example of PETHs of 2 LHb neurons recorded during (B) a 5-second and (C) a 10-second delay-phase challenge without and with optical neuromodulation. The trial sequence is shown in ascending order from bottom to top. The orange underline background indicates the period of optical stimulation that was captured, while green dots indicate lever exposure and the blue vertical line denotes the lever press. All neurons depicted exhibited enhanced activity that was depressed after the lever press. Normalized mean LHb activity during (D) 5-second and (E) 10-second delay-phase challenge trials conducted without prior optogenetic modulation. Normalized mean LHb activity traces during (F) 5-second and (G) 10-second delay-phase trials following prior optogenetic modulation. Right heatmaps representing the task-related activity of all recorded units with respect to behavioral contingency (sham: n = 61 units; SNI: n = 77 units). Each row represents individual units. Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by *** when P < 0.001. LHb, lateral habenula; SNI, spared nerve injury.
    Figure Legend Snippet: Correct trials were preceded by enhanced intra-LHb activity. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the nonmatch-to-sample lever press of correct rewarded trials. Example of PETHs of 2 LHb neurons recorded during (B) a 5-second and (C) a 10-second delay-phase challenge without and with optical neuromodulation. The trial sequence is shown in ascending order from bottom to top. The orange underline background indicates the period of optical stimulation that was captured, while green dots indicate lever exposure and the blue vertical line denotes the lever press. All neurons depicted exhibited enhanced activity that was depressed after the lever press. Normalized mean LHb activity during (D) 5-second and (E) 10-second delay-phase challenge trials conducted without prior optogenetic modulation. Normalized mean LHb activity traces during (F) 5-second and (G) 10-second delay-phase trials following prior optogenetic modulation. Right heatmaps representing the task-related activity of all recorded units with respect to behavioral contingency (sham: n = 61 units; SNI: n = 77 units). Each row represents individual units. Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by *** when P < 0.001. LHb, lateral habenula; SNI, spared nerve injury.

    Techniques Used: Activity Assay, Sequencing, Comparison

    Wrong trials were accompanied by enhanced intra-LHb activity. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the nonmatch-to-sample lever press of wrong nonrewarded trials. Example of PETHs of 2 LHb neurons recorded during (B) a 5-second and (C) a 10-second delay-phase challenge without and with optical neuromodulation. The trial sequence is shown in ascending order from bottom to top. The orange underline background indicates the period of optical stimulation that was captured, while red dots indicate lever exposure and the blue vertical line denotes the lever press. All neurons depicted exhibited enhanced activity after the lever press. The exception was the SNI unit that revealed a peak of activity centered on the response during a 10-second delay-phase challenge. Normalized mean LHb activity during (D) 5-second and (E) 10-second delay-phase challenge trials conducted without prior optogenetic modulation. Normalized mean LHb activity traces during (F) 5-second and (G) 10-second delay-phase trials following prior optogenetic modulation. Right heatmaps representing the task-related activity of all recorded units with respect to behavioral contingency (sham: n = 61 units; SNI: n = 77 units). Each row represents individual units. Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by *** when P < 0.001. LHb, lateral habenula; SNI, spared nerve injury.
    Figure Legend Snippet: Wrong trials were accompanied by enhanced intra-LHb activity. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the nonmatch-to-sample lever press of wrong nonrewarded trials. Example of PETHs of 2 LHb neurons recorded during (B) a 5-second and (C) a 10-second delay-phase challenge without and with optical neuromodulation. The trial sequence is shown in ascending order from bottom to top. The orange underline background indicates the period of optical stimulation that was captured, while red dots indicate lever exposure and the blue vertical line denotes the lever press. All neurons depicted exhibited enhanced activity after the lever press. The exception was the SNI unit that revealed a peak of activity centered on the response during a 10-second delay-phase challenge. Normalized mean LHb activity during (D) 5-second and (E) 10-second delay-phase challenge trials conducted without prior optogenetic modulation. Normalized mean LHb activity traces during (F) 5-second and (G) 10-second delay-phase trials following prior optogenetic modulation. Right heatmaps representing the task-related activity of all recorded units with respect to behavioral contingency (sham: n = 61 units; SNI: n = 77 units). Each row represents individual units. Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by *** when P < 0.001. LHb, lateral habenula; SNI, spared nerve injury.

    Techniques Used: Activity Assay, Sequencing, Comparison



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    MathWorks Inc matlab function kstest2
    Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( <t>kstest2</t> , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.
    Matlab Function Kstest2, supplied by MathWorks Inc, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( <t>kstest2</t> , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.
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    Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( <t>kstest2</t> , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.
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    Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( <t>kstest2</t> , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.
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    Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.

    Journal: Pain

    Article Title: Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding

    doi: 10.1097/j.pain.0000000000003493

    Figure Lengend Snippet: Optogenetic inhibition of LHb CaMKIIα-expressing neurons attenuates pain-related working memory deficits and peripheral pain responses. (A) Illustration of the experimental setup applied to selectivity neuromodulate LHb CaMKIIα-expressing neurons during the DNMS task delay phase. (B) DNMS task probe sessions accuracy rate (% of correct trials − rewarded trials) using a delay-phase challenge of 5 seconds (left panel) and 10 seconds (right panel). The inhibition of contralateral LHb of rats injected with AAV1-CaMKIIa-eNpHR3.0-eYFP induced an important recovery of SNI-treated rats’ accuracy rate at the higher complexity challenges. (C) Mean number of omissions for all rats across 5-second (left panel) and 10-second (right panel) delay-phase challenges. Rats did not display significant differences in the number of omissions performed during behavioral contingencies. (D) Nonmatch phase lever press response latency related to correct trials and wrong trials. Rats did not display significant differences in their response latency profile during correct trials during behavioral contingencies. In turn, wrong trials were characterized by higher response latency values, particularly at the higher complexity challenge. (E) The level of mechanical sensitivity was measured 24 days after the lesion by withdrawal response to von Frey filaments stimulation. As expected, a large decrease was observed in the threshold required to induce a paw response in SNI-treated rats when compared with sham-treated rats without neuromodulation, which was reversed by inhibiting LHb-transfected neurons. (F) PETHs representing the normalized mean firing activity recorded in the LHb during the von Frey test (heatmaps, left panels). Each row corresponds to the averaged firing activity of a single recorded rat. Black vertical traces indicate the timing of the response evoked by the von Frey filament on the hindpaw. Vertical right values represent the pressure exerted by the von Frey filament as measured. The right panels display the normalized mean firing activity of all recorded rats per contingency. Firing distributions were compared using the activity within the time window around the response (−1, +3 seconds), and a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Comparison between experimental groups and light protocols was performed using a nonparametric Kruskal-Wallis test followed by a Dunn post hoc test. Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by * when P < 0.05, ** when P < 0.01, and *** when P < 0.001. Supplementary data regarding rats transfected with control virus AAV1-CaMKIIα-mCherry are provided in supplementary Fig. S4 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; PETH, perievent time histogram; SNI, spared nerve injury.

    Article Snippet: To determine whether the independent behavioral neuronal activity traces during different behavioral conditions exhibited distinct distribution functions, we employed the 2-sample Kolmogorov-Smirnov goodness-of-fit hypothesis test ( kstest2 , P < 0.05) applying the native MatLab function “ kstest2 .” For the recorded activity during mechanical sensitivity testing, we calculated the average PETH of LHb activity for the final selected response filament, centering the calculation on the response timestamp.

    Techniques: Inhibition, Expressing, Injection, Transfection, Activity Assay, Comparison, Control, Virus

    Effects of optogenetic light delivery in normalized LHb mean activity during the DNMS delay phase. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the DNMS delay phase. Normalized mean LHb activity during the DNMS delay phase (left panels), preceding correct (B) and wrong trials (C). Each experimental group exhibited distinct activity profiles under cognitive demand across the light delivery stimulation protocols. The most notable differences were observed during trials associated with wrong responses. Right heatmaps representing the task-related averaged activity of all recorded units with respect to behavioral contingency. Each row represents individual units (sham: n = 61 units; SNI: n = 77 units). Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by ** when P < 0.01 and *** when P < 0.001. Data regarding sample lever press is provided in supplementary Fig. S1 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; SNI, spared nerve injury.

    Journal: Pain

    Article Title: Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding

    doi: 10.1097/j.pain.0000000000003493

    Figure Lengend Snippet: Effects of optogenetic light delivery in normalized LHb mean activity during the DNMS delay phase. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the DNMS delay phase. Normalized mean LHb activity during the DNMS delay phase (left panels), preceding correct (B) and wrong trials (C). Each experimental group exhibited distinct activity profiles under cognitive demand across the light delivery stimulation protocols. The most notable differences were observed during trials associated with wrong responses. Right heatmaps representing the task-related averaged activity of all recorded units with respect to behavioral contingency. Each row represents individual units (sham: n = 61 units; SNI: n = 77 units). Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by ** when P < 0.01 and *** when P < 0.001. Data regarding sample lever press is provided in supplementary Fig. S1 (Appendix A, http://links.lww.com/PAIN/C184 ). DNMS, delayed nonmatch to sample; LHb, lateral habenula; SNI, spared nerve injury.

    Article Snippet: To determine whether the independent behavioral neuronal activity traces during different behavioral conditions exhibited distinct distribution functions, we employed the 2-sample Kolmogorov-Smirnov goodness-of-fit hypothesis test ( kstest2 , P < 0.05) applying the native MatLab function “ kstest2 .” For the recorded activity during mechanical sensitivity testing, we calculated the average PETH of LHb activity for the final selected response filament, centering the calculation on the response timestamp.

    Techniques: Activity Assay, Comparison

    Correct trials were preceded by enhanced intra-LHb activity. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the nonmatch-to-sample lever press of correct rewarded trials. Example of PETHs of 2 LHb neurons recorded during (B) a 5-second and (C) a 10-second delay-phase challenge without and with optical neuromodulation. The trial sequence is shown in ascending order from bottom to top. The orange underline background indicates the period of optical stimulation that was captured, while green dots indicate lever exposure and the blue vertical line denotes the lever press. All neurons depicted exhibited enhanced activity that was depressed after the lever press. Normalized mean LHb activity during (D) 5-second and (E) 10-second delay-phase challenge trials conducted without prior optogenetic modulation. Normalized mean LHb activity traces during (F) 5-second and (G) 10-second delay-phase trials following prior optogenetic modulation. Right heatmaps representing the task-related activity of all recorded units with respect to behavioral contingency (sham: n = 61 units; SNI: n = 77 units). Each row represents individual units. Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by *** when P < 0.001. LHb, lateral habenula; SNI, spared nerve injury.

    Journal: Pain

    Article Title: Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding

    doi: 10.1097/j.pain.0000000000003493

    Figure Lengend Snippet: Correct trials were preceded by enhanced intra-LHb activity. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the nonmatch-to-sample lever press of correct rewarded trials. Example of PETHs of 2 LHb neurons recorded during (B) a 5-second and (C) a 10-second delay-phase challenge without and with optical neuromodulation. The trial sequence is shown in ascending order from bottom to top. The orange underline background indicates the period of optical stimulation that was captured, while green dots indicate lever exposure and the blue vertical line denotes the lever press. All neurons depicted exhibited enhanced activity that was depressed after the lever press. Normalized mean LHb activity during (D) 5-second and (E) 10-second delay-phase challenge trials conducted without prior optogenetic modulation. Normalized mean LHb activity traces during (F) 5-second and (G) 10-second delay-phase trials following prior optogenetic modulation. Right heatmaps representing the task-related activity of all recorded units with respect to behavioral contingency (sham: n = 61 units; SNI: n = 77 units). Each row represents individual units. Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by *** when P < 0.001. LHb, lateral habenula; SNI, spared nerve injury.

    Article Snippet: To determine whether the independent behavioral neuronal activity traces during different behavioral conditions exhibited distinct distribution functions, we employed the 2-sample Kolmogorov-Smirnov goodness-of-fit hypothesis test ( kstest2 , P < 0.05) applying the native MatLab function “ kstest2 .” For the recorded activity during mechanical sensitivity testing, we calculated the average PETH of LHb activity for the final selected response filament, centering the calculation on the response timestamp.

    Techniques: Activity Assay, Sequencing, Comparison

    Wrong trials were accompanied by enhanced intra-LHb activity. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the nonmatch-to-sample lever press of wrong nonrewarded trials. Example of PETHs of 2 LHb neurons recorded during (B) a 5-second and (C) a 10-second delay-phase challenge without and with optical neuromodulation. The trial sequence is shown in ascending order from bottom to top. The orange underline background indicates the period of optical stimulation that was captured, while red dots indicate lever exposure and the blue vertical line denotes the lever press. All neurons depicted exhibited enhanced activity after the lever press. The exception was the SNI unit that revealed a peak of activity centered on the response during a 10-second delay-phase challenge. Normalized mean LHb activity during (D) 5-second and (E) 10-second delay-phase challenge trials conducted without prior optogenetic modulation. Normalized mean LHb activity traces during (F) 5-second and (G) 10-second delay-phase trials following prior optogenetic modulation. Right heatmaps representing the task-related activity of all recorded units with respect to behavioral contingency (sham: n = 61 units; SNI: n = 77 units). Each row represents individual units. Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by *** when P < 0.001. LHb, lateral habenula; SNI, spared nerve injury.

    Journal: Pain

    Article Title: Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding

    doi: 10.1097/j.pain.0000000000003493

    Figure Lengend Snippet: Wrong trials were accompanied by enhanced intra-LHb activity. (A) Illustration of the time window considered to compute the perievent time histograms (PETHs) during the nonmatch-to-sample lever press of wrong nonrewarded trials. Example of PETHs of 2 LHb neurons recorded during (B) a 5-second and (C) a 10-second delay-phase challenge without and with optical neuromodulation. The trial sequence is shown in ascending order from bottom to top. The orange underline background indicates the period of optical stimulation that was captured, while red dots indicate lever exposure and the blue vertical line denotes the lever press. All neurons depicted exhibited enhanced activity after the lever press. The exception was the SNI unit that revealed a peak of activity centered on the response during a 10-second delay-phase challenge. Normalized mean LHb activity during (D) 5-second and (E) 10-second delay-phase challenge trials conducted without prior optogenetic modulation. Normalized mean LHb activity traces during (F) 5-second and (G) 10-second delay-phase trials following prior optogenetic modulation. Right heatmaps representing the task-related activity of all recorded units with respect to behavioral contingency (sham: n = 61 units; SNI: n = 77 units). Each row represents individual units. Color code represents normalized firing activity (cyan, low; red, high activity). Comparison of populational mean firing distributions between experimental groups was performed using a 2-sample Kolmogorov-Smirnov test ( kstest2 , P < 0.05). Experimental groups: sham (n = 5 rats) and SNI (n = 6 rats). Significant results are indicated by *** when P < 0.001. LHb, lateral habenula; SNI, spared nerve injury.

    Article Snippet: To determine whether the independent behavioral neuronal activity traces during different behavioral conditions exhibited distinct distribution functions, we employed the 2-sample Kolmogorov-Smirnov goodness-of-fit hypothesis test ( kstest2 , P < 0.05) applying the native MatLab function “ kstest2 .” For the recorded activity during mechanical sensitivity testing, we calculated the average PETH of LHb activity for the final selected response filament, centering the calculation on the response timestamp.

    Techniques: Activity Assay, Sequencing, Comparison