Figure 4 - Source Data 2 Data related to M2 manipulation control (GFP in biM2) group. __________________________________________________________________________________________________________ Mean percent correct for reversing stimulus, during stable period (each row contains data from one animal) Saline CNO 88.5383597883598 90.1318027210884 80.0496031746032 89.2857142857143 86.6850649350649 88.0952380952381 81.1607142857143 83.3055555555555 84.0151338313103 88.2948908730159 84.572940287226 84.0354437229437 79.1418650793651 82.577380952381 85.0076083064805 83.7225274725275 81.1111111111111 77.6568405139834 82.321648486981 80.6607142857143 78.0418192918193 79.1904761904762 77.0627289377289 77.9092261904762 82.3060273060273 83.989417989418 ____________ Test results Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.1272 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 68 , -23 Sum of signed ranks (W) 45 Number of pairs 13 Median of differences Median 1.41 How effective was the pairing? rs (Spearman) 0.6484 P value (one tailed) 0.0097 P value summary ** Was the pairing significantly effective? Yes _____________________________________________________________________________________________________________ Mean percent correct for reversing stimulus, during switching period (each row contains data from one animal) Saline CNO 43.3996558996559 33.8624338624339 40.6123222016079 49.2724867724868 46.8456514550265 41.417044595616 44.4338151927438 43.1394993894994 45.5203823953824 45.3648589065256 39.6344627594628 46.7805177626606 53.8148148148148 52.7970779220779 49.3426832829007 53.3406084656085 49.7534013605442 51.8458393458393 51.0045129162776 50.3868384031428 47.2560783572688 50.7013125763126 51.9655257936508 53.4507275132275 47.4339402427638 55.3661616161616 ____________ Test results Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.3757 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 59 , -32 Sum of signed ranks (W) 27 Number of pairs 13 Median of differences Median 1.485 How effective was the pairing? rs (Spearman) 0.6978 P value (one tailed) 0.0051 P value summary ** Was the pairing significantly effective? Yes ________________________________________________________________________________________________________________________________________ Decision boundary distance, estimated from psychometric curves AFTER switching period(in cyc/deg, each row contains data from one animal) Saline CNO 0.0346994103993655 0.0257819548497012 0.00795994429665403 0.0271707297299647 0.0287772504668674 0.0153664477126622 0.0190739152635909 0.0200262830431753 0.0235668733534663 0.0174432568115725 0.018303743304614 0.023355838173852 0.0221099576536765 0.0146103172464363 0.0152667346491197 0.0184182491344899 0.0165252733158873 0.0147988906466988 0.0201495847359587 0.0196644000116296 0.0135442031372123 0.0119040840743969 0.0118449635493978 0.0129247504634045 0.0179065352892087 0.0270508263570704 ____________ Test results Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.8394 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 42 , -49 Sum of signed ranks (W) -7 Number of pairs 13 Median of differences Median -0.0004852 How effective was the pairing? rs (Spearman) 0.08791 P value (one tailed) 0.3892 P value summary ns Was the pairing significantly effective? No __________________________________________________________ Average block length (each row contains data from one animal) Saline CNO 99 91 86.75 77.4 78.6608391608392 72.5673076923077 86.25 74.8712121212121 76.6666666666667 78.0666666666667 80.3333333333333 74.6616161616162 66.58 70.9541666666667 69.3508771929825 65.7252747252747 64.7791666666667 72.6 67.9429723502304 64.0630952380952 70.7214285714286 72.7166666666667 68.1678321678322 73.7444444444444 68.6590909090909 66.0277777777778 ____________ Test results Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.1909 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 26 , -65 Sum of signed ranks (W) -39 Number of pairs 13 Median of differences Median -3.626 How effective was the pairing? rs (Spearman) 0.7143 P value (one tailed) 0.0040 P value summary ** Was the pairing significantly effective? Yes __________________________________________________________ Average number of switches per session (each row contains data from one animal) Saline CNO 4 3.5 2.42857142857143 2 4 4.28571428571429 3.85714285714286 3.71428571428571 6 5.42857142857143 3.28571428571429 3.71428571428571 4.69230769230769 4.44444444444445 4.07692307692308 3.88888888888889 3.30769230769231 2.77777777777778 5.38461538461539 5.44444444444445 3.15384615384615 3.33333333333333 2.61538461538462 2.44444444444444 2.84615384615385 2.55555555555556 ____________ Test results Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.0942 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 21 , -70 Sum of signed ranks (W) -49 Number of pairs 13 Median of differences Median -0.188 How effective was the pairing? rs (Spearman) 0.9366 P value (one tailed) <0.0001 P value summary **** Was the pairing significantly effective? Yes _______________________________________________________________________________________________________________ Model 1 parameters during stable period, for saline/CNO sessions(each row contains data from one animal) __________________ ¦Á1, stable period Saline CNO -0.24401 0.158842 -0.05973 -0.25032 -0.02788 0.025483 -0.01556 -0.15145 -0.07125 -0.0976 0.12154 -0.33385 0.314072 -0.23005 0.039888 -0.1851 -0.12929 -0.06167 -0.03482 -0.09362 -0.14956 -0.25984 -0.21881 -0.18169 -0.20908 -1.11014 ___________________ Test results for ¦Á1 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.0803 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 20 , -71 Sum of signed ranks (W) -51 Number of pairs 13 Median of differences Median -0.1103 How effective was the pairing? rs (Spearman) -0.1923 P value (one tailed) 0.2646 P value summary ns Was the pairing significantly effective? No Was the pairing significantly effective? No __________________ ¦Á2, stable period Saline CNO -0.28727 -0.30165 0.475548 0.343167 0.598401 0.202562 0.418745 0.388751 0.379318 0.668352 0.194705 0.326038 0.404397 0.457005 0.374353 0.90191 -0.01334 2.056323 0.950392 0.19661 0.080172 0.130602 1.00215 0.889254 0.696039 0.597233 ___________________ Test results for ¦Á2 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.9460 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 47 , -44 Sum of signed ranks (W) 3 Number of pairs 13 Median of differences Median -0.01438 How effective was the pairing? rs (Spearman) 0.1099 P value (one tailed) 0.3616 P value summary ns Was the pairing significantly effective? No __________________ ¦Â, stable period Saline CNO 0.070075 0.142579 0.045093 -0.13392 0.098507 0.097373 0.032436 0.083371 0.019267 0.062664 0.192324 0.113653 0.371243 0.174662 0.359553 0.405735 -0.11654 0.585428 0.32365 0.085319 -0.06194 -0.00992 0.415426 0.38215 0.370374 0.331073 ___________________ Test results for ¦Â Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.8926 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 43 , -48 Sum of signed ranks (W) -5 Number of pairs 13 Median of differences Median -0.001134 How effective was the pairing? rs (Spearman) 0.4505 P value (one tailed) 0.0624 P value summary ns Was the pairing significantly effective? No __________________ ¦Ã1, stable period Saline CNO 2.803763 3.235482 2.430239 2.31088 2.727233 3.324104 2.697393 2.645819 3.379784 3.833131 4.000972 3.236943 5.129633 5.066122 5.005965 5.643376 4.691407 4.353423 4.811196 4.862065 3.087583 3.337479 3.51616 3.340508 4.533134 6.015236 ___________________ Test results for ¦Ã1 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.4143 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 58 , -33 Sum of signed ranks (W) 25 Number of pairs 13 Median of differences Median 0.05087 How effective was the pairing? rs (Spearman) 0.8681 P value (one tailed) 0.0001 P value summary *** Was the pairing significantly effective? Yes __________________ ¦Ã2, stable period Saline CNO 0.516302 0.687571 0.265373 0.029288 0.375293 0.502912 0.167685 0.396642 0.236547 0.408243 0.664673 0.66854 0.981317 0.695548 1.262265 1.384809 -0.0687 1.509881 1.120276 0.499097 0.029461 0.21227 1.208682 0.938562 1.221437 2.073681 ___________________ Test results for ¦Ã2 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.6355 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 53 , -38 Sum of signed ranks (W) 15 Number of pairs 13 Median of differences Median 0.1276 How effective was the pairing? rs (Spearman) 0.533 P value (one tailed) 0.0321 P value summary * Was the pairing significantly effective? Yes _______________________________________________________________________________________________________________ Model 4 parameters during stable period, for saline/CNO sessions(each row contains data from one animal) ________________ ¦Â, stable period Saline CNO 0.195974 0.132916 0.039339 -0.06739 0.072861 0.114961 0.028441 0.091765 -0.01856 0.073594 0.152232 0.162765 0.288424 0.27181 0.349156 0.439224 -0.07901 0.504939 0.294914 0.093351 -0.00839 0.044847 0.421721 0.278634 0.384939 0.528554 __________________ Test results for ¦Â Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.6355 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 53 , -38 Sum of signed ranks (W) 15 Number of pairs 13 Median of differences Median 0.0421 How effective was the pairing? rs (Spearman) 0.5165 P value (one tailed) 0.0370 P value summary * Was the pairing significantly effective? Yes ________________ ¦Ã1, stable period Saline CNO 2.821245 3.213867 2.310652 2.216936 2.622825 3.248928 2.622618 2.672278 3.349827 3.76667 3.902506 3.287456 4.97367 4.907368 4.974607 5.549831 4.702339 4.061711 4.681791 4.838593 3.063119 3.360213 3.433262 3.292131 4.432448 5.74315 ___________________ Test results for ¦Ã1 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.3396 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 60 , -31 Sum of signed ranks (W) 29 Number of pairs 13 Median of differences Median 0.1568 How effective was the pairing? rs (Spearman) 0.8846 P value (one tailed) <0.0001 P value summary **** Was the pairing significantly effective? Yes ________________ ¦Ã2, stable period Saline CNO 0.694796 0.687188 0.258923 -0.04017 0.348609 0.607454 0.172905 0.386434 0.139149 0.45467 0.675915 0.619682 0.972678 0.864585 1.295989 1.471872 -0.06081 1.433354 1.101568 0.478003 0.081445 0.192454 1.186516 0.726935 1.220775 1.954103 ___________________ Test results for ¦Ã2 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.4973 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 56 , -35 Sum of signed ranks (W) 21 Number of pairs 13 Median of differences Median 0.111 How effective was the pairing? rs (Spearman) 0.5879 P value (one tailed) 0.0190 P value summary * Was the pairing significantly effective? Yes _______________________________________________________________________________________________________________ Model 1 parameters during switching period, for saline/CNO sessions(each row contains data from one animal) __________________ ¦Á1, switching period Switching Stable 0.060801 -0.24401 0.320751 -0.05973 0.092966 -0.02788 0.048922 -0.01556 0.240278 -0.07125 -0.15745 0.12154 -0.23369 0.314072 -0.09942 0.039888 -0.27254 -0.12929 -0.22896 -0.03482 -0.05239 -0.14956 -0.00398 -0.21881 -0.68729 -0.20908 ___________________ Test results for ¦Á1 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.2439 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 28 , -63 Sum of signed ranks (W) -35 Number of pairs 13 Median of differences Median -0.04417 How effective was the pairing? rs (Spearman) 0.5659 P value (one tailed) 0.0237 P value summary * Was the pairing significantly effective? Yes __________________ ¦Á2, switching period Switching Stable -0.17308 -0.28727 -0.2963 0.475548 -0.43921 0.598401 0.179453 0.418745 -0.29848 0.379318 -0.6067 0.194705 -0.27342 0.404397 -0.083 0.374353 -0.39487 -0.01334 -0.17077 0.950392 0.028654 0.080172 -0.18875 1.00215 -0.17297 0.696039 ___________________ Test results for ¦Á2 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.4143 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 58 , -33 Sum of signed ranks (W) 25 Number of pairs 13 Median of differences Median -0.00629 How effective was the pairing? rs (Spearman) -0.2473 P value (one tailed) 0.2075 P value summary ns Was the pairing significantly effective? No __________________ ¦Â, switching period Saline CNO 0.264016 0.044978 0.320549 0.500178 0.251594 0.123447 0.574654 0.243772 0.324991 0.346639 0.311105 0.304915 0.57955 0.303085 0.29769 0.538758 0.957561 0.512912 0.350319 0.395852 0.274172 0.237261 0.199487 0.718562 0.391692 0.737944 ___________________ Test results for ¦Â Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.9460 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 44 , -47 Sum of signed ranks (W) -3 Number of pairs 13 Median of differences Median -0.00619 How effective was the pairing? rs (Spearman) 0.2198 P value (one tailed) 0.2351 P value summary ns Was the pairing significantly effective? No __________________ ¦Ã1, switching period Saline CNO 3.067727 2.271054 1.623022 1.85135 2.882046 2.87515 2.13327 2.232428 2.97359 2.620582 3.262703 2.9692 5.132091 5.166434 4.472997 4.421966 5.479434 4.184434 4.511131 5.201114 3.260895 2.756132 3.398886 2.841062 4.01378 3.857166 ___________________ Test results for ¦Ã1 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.1272 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 23 , -68 Sum of signed ranks (W) -45 Number of pairs 13 Median of differences Median -0.1566 How effective was the pairing? rs (Spearman) 0.8901 P value (one tailed) <0.0001 P value summary **** Was the pairing significantly effective? Yes __________________ ¦Ã2, switching period Saline CNO 0.443782 0.374752 0.245092 0.190272 0.520195 0.410668 -0.27571 0.270304 0.361169 0.295599 0.525161 0.348267 0.893998 0.595198 0.457059 0.852711 0.803252 1.128707 0.552885 0.907856 0.331994 0.234094 0.440494 0.704753 0.637935 0.77286 ___________________ Test results for ¦Ã2 Column A Saline vs. vs. Column B CNO Wilcoxon matched-pairs signed rank test P value 0.3396 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 31 , -60 Sum of signed ranks (W) -29 Number of pairs 13 Median of differences Median 0.05482 How effective was the pairing? rs (Spearman) 0.7637 P value (one tailed) 0.0017 P value summary ** Was the pairing significantly effective? Yes _______________________________________________________________________________________________________________ Model 4 parameters during switching period, for saline/CNO sessions(each row contains data from one animal) __________________ ¦Â, switching period Saline CNO 0.212327 -0.02181 0.220775 0.532449 0.188453 0.041931 0.796402 0.162094 0.266019 0.439414 0.100032 0.252058 0.491673 0.252756 0.246328 0.413577 0.949242 0.531025 0.270956 0.242575 0.27358 0.236723 0.178683 0.393302 0.212156 0.752323 ___________________ Test results for ¦Â Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.9460 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 44 , -47 Sum of signed ranks (W) -3 Number of pairs 13 Median of differences Median -0.02838 How effective was the pairing? rs (Spearman) 0.02198 P value (one tailed) 0.4747 P value summary ns Was the pairing significantly effective? No __________________ ¦Ã1, switching period Saline CNO 3.08979 2.299607 1.612 1.718872 2.934945 2.684348 2.098682 2.194314 2.932697 2.692793 3.260399 3.001515 5.208405 5.214671 4.488344 4.48405 5.573378 4.356405 4.615237 5.188736 3.243664 2.770761 3.466266 2.985059 4.162446 3.880087 ___________________ Test results for ¦Ã1 Column B CNO vs. vs. Column A Saline Wilcoxon matched-pairs signed rank test P value 0.0803 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 20 , -71 Sum of signed ranks (W) -51 Number of pairs 13 Median of differences Median -0.2506 How effective was the pairing? rs (Spearman) 0.9396 P value (one tailed) <0.0001 P value summary **** Was the pairing significantly effective? Yes __________________ ¦Ã2, switching period Saline CNO 0.394004 0.320338 0.242286 0.2147 0.373837 0.347489 -0.30952 0.240123 0.310392 0.159979 0.255312 0.267366 0.700186 0.464577 0.348349 0.58525 0.787756 0.848476 0.38683 0.484062 0.313901 0.223818 0.346869 0.351421 0.334576 0.685612 ___________________ Test results for ¦Ã2 Column A Saline vs. vs. Column B CNO Wilcoxon matched-pairs signed rank test P value 0.6848 Exact or approximate P value? Exact P value summary ns Significantly different (P < 0.05)? No One- or two-tailed P value? Two-tailed Sum of positive, negative ranks 39 , -52 Sum of signed ranks (W) -13 Number of pairs 13 Median of differences Median -0.004552 How effective was the pairing? rs (Spearman) 0.6978 P value (one tailed) 0.0051 P value summary ** Was the pairing significantly effective? Yes