TítuloModelling the circuitry of the cuneate nucleus

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(2) u^BZ>gYt^B]hag x kJwt»J`È2`@dOg m ¼. wZJ kJ `²] >d[² »>ilg k:m dHg Ytf_g wb wp`m wZJ`mm gcYo Y[m ``@wº d@] rYt^Bg b k>kJ^<c2b k:³µd[´Ã`@Y[¶ykJ³µ¶`·'ZBY[] ]<º+kJd[cp»JÒoµY[bcH<\)»:]<d@k:r dtg kJ`]<ZJcg w@d[b -b dl½h] º¦wZJkJ`ygd[ÒkJ`ZBY[]<kJc -*ê ë 3+:í&Neâvå7Ö2,@.-57æ[66<4y4[email protected] ,t.BL@3 Fµ44.)6 4S (7µ× 37â 6<*:L@6Þ+R=6 ,×_6<×[L*-R7S Fµ×t5Â6ñ74F L*:[email protected],@ßU×tß>3+*-å+×t6<×!èpF L@5ÀF 3JL@6 ,@376 (7,@.B3+× "!#$%. 73FK376 3+å7.-&)()L@65+L,*-èp×tSµ6 *-F 3 L@ØÃ576FµF 43L04L@*-6 57SlS â6µ×2ê 4ë*-(7í23+37à¢&6<.B*:(7å7L@3+,@6_.B&Áå=3>.JL@(+5+×t46<*:S 6&L(+*×t× 6â+ØÃ3+?O×t.)ß.B&),@L@6F ØÃ57S¦Fµ.-.-×àvL@ØÃ.BL@57,Ã.)6z&)4.B6F 3JSl,t;+L@L@6Fµ44 CB.B*-,,tS2*:L@FµL@×[4F [email protected] 3Øà¢(7(7.-CJàvSµ*-*:S¦L@L@57Þ+F .B6zR=3 64,.BF ×p37,tL@57èOFµ4F .BR7.)(7F 4L@Sµ(76<& 37& 46<.B4*:()3)L@6áá Lå=*B.J4y×[LL@(74Sµ(7*:37L@6<6 &.-L@5+*À*-&)Sµ*-F ï¦ØÃ6 Fµ,@4 6 3J4L06 S å=µ×.>[email protected],@.-.Bàz(7CBF 37557F*-R73 F [email protected] 37,@57ßÅF R74F([email protected]<,@ßé*:L@6F 3JL@F 3J6 ,@L@376 ,@6 37(76 ,@(7.B,@3v.Bâ'3+&H×Ã36*Bñ)&76 ,t&)L@F FL@37F .BCÂ3vå7;,@L@6<57×t6 ßJß á 3+×t6 *-3+å)×[email protected]µ4_,@F ØÃF 37.-57L@F .BR7,F L@4F .B.B3,tL@6.Bñ_3Qè[email protected]_(7SµL@&¨6 ,@*:ØÃï¦6<F 3+4yL*-SµL@×p57.-6pà*BL@×@5746_6 3+å7&),@F F 37Ø0Cz*-×t,@6 ßQ3+×t*:.Bï¦,@6 ß!,@6L@3J,*-Lp3+Þ+×tR=ØÃ6 Fµ,×@× ×tâ+F .BÖ23h57L@6 57,@,@6.Bà¢.B(7,@CB6B5h;)L@L@575766 4(737&H6<3J*:L@L@,6z*BR>46ßNS F(737Sµ57*-F,hR7*-F L@3+F 37&ÀCÃè[email protected] 64áH(74376 6 S .-L@L@5+6<*-457Sµ*-37ØÃFµVJFµ(74z6<4×h6 S èOµ×26 ,@R=60.-L@,@5 6<4å76 ,@3J6L@á'S ßÂ*-3+(+&Q×t6<å=&).J×[(+*-L×tß>, 3+(+,*-.0å)L@L@Fµ.U4 *-×[S L@ßB(+â&)ß L@å=57.J6×@×tå76<×2,@.BL[å=èO6 .0,tL@ØÃF 6<.)×¨&).-6<à_×4.-(7à37*B6<4y*:L@L@F 6ã>F L[4ßÀ6 S µÙq×E×t6 ê6z/+;Þ+0ë CB/-(7íe,@'â 60&eLëÜyè2Ý+*BR7×(7,à¢×[.BL@(7F 373+C&Å*-L@3+5+&Q*:[email protected]@3757Fµ6E44ê /-(7íe37â+6<Ú*:L@(76 ,@F 3737CN6 (7&),@.B6 63+å × ×tÖ2S 6576 Fµå×OR=*-6 3+5+&Á*ã>*-F 3+.B,2*-6<4×[5+L@*-57376<CB×tFµ6<*7×;L@L@.576L@5746!([email protected]<37*:FµL@46NØÃ37.)6 &)(76!,@.Bèp3+57×¨6 ×t3N57.:F 3:èäæ[6<.J4yL@×@F437F SC0µ*:&)[email protected]å=,@ßÂ.BSµ*-R7,@(7F ,8 ×[F 37L@F C¨37CÂ4(7*B,@4y,@L@6 F3Jã>LOF L[.BßB, â ×[*ÃL@FS Ø.:è2(7álSµL@*:57L@F,@376<CN×[email protected]µ&N6 F ,_4 *-å=Sµ46 F,@(7F å7Øó576 *-,3+*-&QS,@*Ã6<45>6 ß>å)å=L@6F ãB,@å=6.BÞ+Sµ*-6 Sµ,@&7F 8<× *:âL@ÚF .BF 3)ï¦áH6 *B,@4y6 L@3JF L_ã:*:F [email protected]<37&Fµ4Ã4 *:4L@5+F *-.B3733746 5+Sµ× *-;¦37F 373+6 4SlS ;)(+5+&)*F 37ãBC6 R=6 6 3/>F Øå=.J(7×[S L@L(7*-Sµ37*:6 [email protected]<(+&N×L@,@.Ã6<46.Bñ),å7&)Sµ*-F 37F 3NCJ×L@èO57Fµ6 ×p,@6pR=6*B5+4 *4.Bã>ØÃF .B(7å7,hS Fµ×tê 57/-íe6<â &hL@._×[L@(+&)ßhL@576pF %3 1+(76 3+46p.-à+L@576×t6 3)á L@èp×tF.B.B57,@3+FF SØÃ× 62;>.-L@*-L@573.B6p,6 F 3JS46<.BL@4y,,tL@*BL@,@64Fµñ46 *-S .:S¦(7ãB×[Sµ6*-L@,pF,Ø37L@(7576 S6Ã(7(+,@×O4.B(73+è237*-*B6<S7×'*:*BL@*-4y6¨å7L@Få74ã>6S FF S L[6<µßh×¨&Ãè2ÙqL@×t.Ã*B6 ×6Q×tå=,@ê 6<ì:6<44í|.BF à¢Þ=,.B&)4,z6<×t&h*06 3+F,@3¨×t6 .Bã>L@,@F57F6 ØÃ6zè.-MOÜyL@â Ûh.B&H,'3E3â 24[email protected]+57,t&)6<L@×tFµ6 4 6,*-L@å7S=57,@,@Fµ66 ×å+CBå7*-F .B,@,3+.-*:×áá L@F 37.)574.BF R7S)F L@L@57F .B,@3 6 6pÙ &)Þ+FCBï¦(76 ,@,@6¨6 3JìJLjÜ,@.-6<à'×tå=4.B(73+37×t6 6<.-×L@5+*:L*-SµL@*-57ØÃ6!FµMO4Û46 èOS µ× 6 ;¦,@6p5>ß>×t6å=6 6 3 ,@å=ê .Bë5Sµ4*-íe,@Ý-F 68<ñ7*:4L@FF L.B*:3L@F *-.B3+3 &EÙ Þ+R7CB(7(7,,@×[6L!òBCBÜ6 37*-63+,t& á *:Ù Þ[email protected](73Q,@6O.-àìJÜy4â(7Ö237576 .-6<L@×t5+6j*-,@Sµ6<*-×tØÃ(7S FµL4!× ;<4èp6 S 57µ×hFµ4Ù5hÞ+CB6ñ>(7L@,@66_3+ìJ&zÜyL@;757*-.J3+×t&N6jFà¢37,@.B57Ø F R7F KL@F 3+.B&)36 .-,×tà|6 å73,@6<*-×t3+(7&_ØÃ46<.B&NS 6<F *-3JCBL@6(7,@6<37× 6 ; (7Ø0,@.B*73+6B6× F&)L|F ï¦å=6.J,@×@6 ×t3JF R7L'S 6&)6<L@×@.45>6 3+ß>å=&)F.-37L@Cz576<,@×t.BF ()8 6OL@6<*-×R=4 .B*-()3¨LvF L@3+57&)6'(+64ñ)6Fµ×[&)L@Fµ6 ×[3+L@F 43+6j4y.-L'à+*B*4yL@×tF å=.B6<3+4×F Þ=.B4j3¨4L@F 57,46(74F (7L@,@37ß!6<*:F 3hL@62èp3>57(+Fµ445zS 6 (+L@57× ,@âB6 K 6 89 % 8 -: ; $"! L@,@F CBCB6 ,@6<&0R>ß&)F ,@6<4yL26ñ74F L*:L@F .B3N.-à|4(7376 .-L@5+*-Sµ*-ØÃFµ446 S µ× ;JL@5>(+×.

(3) §¨]-^B`m b kJzd[»J`2wb Y[wZJb dHYH½¨] º¦d[»J`{|ZJkJ`ygd[ÒZJwm `ZJc . g w@d[b -² b7dl²½Na-o `m ]ykJ¹cH] `@Y[YOb f_\>g] YHd[d@] rYpg wk>] ^ŸHd[w`@ZJnkJb `k>] ^Bd[ZJ»>wg `m gc2f_^Bbb w2Y[`Y[w@`dpcH\)`@nB]<wkJb cHdt`_gd[o b ZJ]<\JkQ\)]<`@kYj\>wZJgYHkJd@`rt] ¼ d[»>g m g f_b w!w`m c+w] YHd[b wyg m . 6å737575+6 37*-3+.BØÃ4F 376 C_37.BL@3576 4 F *-,O304 *-R=å+6!*-*BR7×@F ×tS F.)L[4ßFµ*:L@L@._6<L@&Ã,*-èp3+F L@×[à¢5N6 ,O* ×t#$6 3+: ×t.B,@$ßhF 3) à¢ .B,@$Ø0; *::L@F.B; 3Ã$"!L@._L@L@.¨576×t5+L@5+*-å=*-Sµ6p*-L@Ø57(+6× ,@âJ6<Ö246 57å)Fµ×á L@F 3JF ãBL@6z6 ,@Þ+3766 Sµ(7&7,@×p.B3vR>ßQâ |F*B4y3+L@*-F ã:S *:ßBL@;=F 37*-C3 *-3 $F 3J L@6 ,@37$6 (7; ,@.B: 3Q; $èp"!57Fµ4Fµ5v×;7,@F 6<3Q×tå[email protected](73+,@3v×tF ;+R7F S 376z57L@F .0R7F Þ+L×S [email protected] ,L@57(76 3>,pè2F 37*-573JFL@R76<F&[email protected] ,@3)ß á à¢.B,@Ø0*:L@F .B3vâ 5$:0 8 $:. @Là¢Ö2,@57.B576Ø#66&)ñ)L@Fµå=*-576 CB6é,@,F *-ØÃMOØ Û6 3J×tL57Fµ*-×N.:S+èp*-,@33¨6<×tF(7.B3¨SR+LÞ+×[× LCBâB*B(7Ö24,@57S 666ì!L@Sµ*B.é,@646å7L@6<,@.-×[6<àL×[email protected]L@6U×5*!ã:*-*-å73+S Sµ*:Fµ*-&)L@(+F.BL[×tØÃß F R7FµS.-4 6*-àS+4×tF *-(+,3+44(7&Ã5 F Ljå745+FF 3J,*-4L@,@6(7Ø03+F L<&)*Bâ2F437.BÚCzS (7.BL@CB6._Fµ4 L@6*-.Áñ)S>å7&7L@Sµ57*:*-FµLF × 3* ; .J×t×t.B57×@ØÃ4.:FèpS 6!µ3Q*:VJL@(7F.B3Q6<,@ßÃ×[Þ+L@CBF*-.B(73+3+,@&0×'6_L@*-ìÃ.B,@37Fµ*B×tFµ&)646<3+R=VJ*:6(+L@5+*:(7*L@,ã>6!*-F [email protected].Ã,ß¦×'ÝJ6&)4ñ)*-6<å730×@Sµ4*-L@,@F 3N57F R=6!L@6<575>&06_ß>à¢å=.B,@.-6<,'L@4[email protected],66_&)L@F F48 37(76<CJ37&0×O6<F .B*:.BL@R)376LFµ*-437F 6374(7(76<,@,@&.B,@6à¢3+,@3J× .BLBØä×';>CBFµ×'L@6 5737L@6h576 ,6!4 *:*:ØÃL@L6pB.)L@â &)576 6 S 37&)66Lè *-&H30F 6 S 6<ã>L@&EFµ57&)Fµ&)6 ×'3+6<èO×@446!.B,@, *-F 6¨å)R=L@èO.BF .B()63+L'å7×L@,@57.-.B6!àå[email protected]ã:57*-×t66S Fµ&)*h37F 6 L[4(7ß0.B,@ØÃ.-.Bà3+å7L@×p()57LL@6z*:5+L@×@*:F 4.BL!573+å76 *-ØÃSµS=*ßØÃ6!×t.)*057&),@.:6 .BèpS=S 6h3NèpFF *-L@3R=5L@.:L@57ãB57606B6â M'Â.B(7R)6!37æ[6<6<5+4y*:*L@L@FãB6ãB66*-&)3+.-6 à& ãB*B6 L@&7S 6<.B&)×[å=L@F 376<6<&&C L@L@575+6*:L<,@;6<èO×t(76S L5+×*.-ãBà¦6L@5+Ø0*:*BLO&)46¨6 S (7µ×åÀ(7*Q3+&)46F ,,'4×t(7F FØÃL!F à¢Sµ.B*-S ,'.:4èp.B3+F 37&)CF L@L@F .B573+60××@L@4._576L@ØÃ57.J6×t6å7,@&)6<6<×t×@6 43J,@L@F R=6<&E6<&ÃF 3UF 30Þ+4 CB*:(7L,@× 6¨âJKpì7àâ L@&H6 3 , èp*-3+5+&Q*:Lp*0à¢&).BSFµ×@.:4è(+×@×2×tèOF .B6z3Nå7.-,@à|6<L@×t576 3J6_L2,@6<L@57×t(76hS LØ0×2*:å[email protected] 6 3JØ0L@F *:37L@C0Fµ4 .B*-()SL2ØÃL@.)57&)6_6 F SlØÃ;)L@å757S Fµ6_4 *:,@L@6<F×t.B(73+S L×2×p.-.-à|à|L@L@57576_6hØÃ×tF.)Ø&)(76 SlSµ*:â L@F .B3+× Ñp Ò "! [email protected](7,!4F S,6 4ãB(76 F SµL×S .-6 ãBà'6 &)Sl6<;>×@L@457,@6hF å)×tL@ß>F .B3+3E*-å)*-L@,@Fµ6h4!37S 6 6 ãB6<6 &)Sl6<;>&L@57L@6_.Q37&)6 6<(7*-,@S|.B3QèpF S L@6 5EãB6 L@Sl57;76¨*-3+VJ&N(76<L@×[57L@6_F .BØÃ3+×6 Øå7,@R7.B,å=*-.J37×t6!6<&S 6 ãB576 6 Sl,@â 6BÝ # M'F ,4(7F L¨S 6 ãB6 Sl$â &H3ÁÞ+CB(7,@6 /EL@576 4F ,4(7F L¨ØÃ.)&)6 SOFµ×Ã&)6<×@4,@F R=6<&$â &eL¨Fµ×¨4.BØÃå=.J×t6<&é.-à ×t46.B3+,tL@×tFµ.B4 ,@*-ßUS=4,@66<S4µ6×'å)*-L@3+.B&,× &);v6<å7×@,@4F 6Ø03+*-&),@F ßÂ37C_*:Þ+ï¦R=6 ,@6 6,3J×jLà¢× ,@;.BØ4(737L@576 .-6hL@M'5+*-.BSµ,t*-L@ØÃ6ñFµâ40Â3766(75+,@*.BãB3+6p× ;v(+F×t3J6<L@&6 ,@*_37L@6 .-(7L,@*-.BS+3+.-× à ; $h376 (7,@.B3+×2F 3 .B(7,pØÃ.)&)6 Slâ.

(4) u^BZ>gYt^B]hag x kJwt»J`È2`@dOg m ¼. òµY[m `b <w@»:dH² Y[d@7b rwy² g]a-mvb `@f!ceYjd[bZJf!\Bm Y[dtZJ]g mekJg``d[w@]c!u|gg{|d[d]<]:cHcHX ``kJkJf_cHcH]] `yYHY[g½Nb f_kJ{|c] d[] `]YHm `d[Y!`@w@wn"dHY[] +]:YH^Bd[w`@b] cHn YHb d[kJbg »Jwk>]k-^0ZJwb m kJ`ZJ»Jcb ÄJgb d[º bd[]<`@k Y . #. . 64/>Ø0.Bß>3+3+*:&)*-L@(+å)Fµ4 4yL@*-LFµ42S'*-3+Sà¢6(74ãB603+6 4ySl*BL@â×@F &H.B×t3Ã.)3Å4.BFµ4 ,*:*-&)L@S 66<6<,&E&ÀL@[email protected]@57ØÃL@6 57.)6&)6 ×tS)ß>L@3+57*-6å)4%L@57Fµ* 4Ã6 ØÃ4((7Fµ.4 ,@*+*-,@â6S73JÖ2×tL<ß>57âv3+FµÖ2*-×å+57Fµ×t×Fµ62×h(+èO4×t.B6p6<3+&À5+&)*L@(+ãB.U4y6OL,@*-(+6 3+×tå76<4,@&Ã6Ã6<×t*!Fµ6 ×_3JØ0CBLhF*:ãBL@L@576 5)3 6 á L@L@57576¨6h*BL*B4yL@× 6F ã:*:.-L@à'F .BCB3Q6 37.-6 à,*:&)L@6 F 3+37&)C,@FL@L@57Fµ4z6Ã,@å=6<.J4×[6 Lå)×tL@ß>.B3+,*-×zå)ê L@ëBFµë4híeâ7å=Ö2.-L@576 6z3JL@Ø0Fµ*-*:SlL@;¦57èp6 Ø057Fµ*:45ÂL@Fµ4 Fµ*-×!S.B6,@ñ)F CBå7F ,@3+6<*:×@L@×t6<F .B&3Q*:Fµà × L@Ý 6 , Ù tÜ Ù[ëÜ . . . . "!$#&%(') *. ),+.-/0213245-/,6 6.

(5) ¨§ ]-^B`m b kJzd[»J`2wb Y[wZJb dHYH½¨] º¦d[»J`{|ZJkJ`ygd[ÒZJwm `ZJc èpã:*-57S (76 ,@6Ã6 .-à'L@Fµ57×6*E×tß>4.B3+3+*-×[å)LL@*-Fµ3J4ÃL<4; .B.3+* &)(+4y'LL@*-573+6N46¨×[Lèp*-F,tS LhjR=L@F 6ÃØÃ8 6Q6 ,@*-.Q3+& F àOL@57L@60576Qå7,@46<.B×tß>3+3+×[L*-*-å)3JL@L_Fµ4L@Få=ØÃ.-6BL@6â3JÖ2L@Fµ57*-6 S Fµ×t×N(+4R=506 SL@.:57è ,@6<×t*Á57.B4Sµ6 &,tâL*- F 3 5+*:L@LO57,@Fµ×j6<×tØÃ57.B.BSµ,@& 6B; *-3+& èp&)F6S L@!6 R=,@ØÃ6UF 6<37VJ6<(+×*-L@S576!L@57&)6 ß>3+*-ØÃFµ4 ×'.-%à¦* L@576!(.×t* ß>3+*-*-R=å).:L@ãBFµ46 4(7,@,@6 3JL &)6Þ+376<&QR>ß¦Ý Ù tÜ Ù tÜÙ Ü ÙlòBÜ èp&H357.B6 ,@(76 ,jØÃ.)&)6 ,@S+6 èOå7,@66<5+×t6*3JãBL6p×'6L@ñ75746_F L,@*:6<L@×[.BLp,@ß¨å=.-*-L@3+6 &Ã3JL@F Fµ37*-57S¦F à¢R7.BF ,[email protected]@,@57ßÃ6h4×t.Bß>373+37*-6<å)4yL@L@FµF 4z.B3+,@6<× 4âB6 Ö2å)57L@6<.B×t,6× â ×tß>3+*-å+×t6<× 4Û*-6 3Ã(7,@R=.B6p3éØÃçv.)6 &)ãB6 6 S Sl6<â &ÃÂR>6ß×t5+6*LtãBL@6ÃF 37(+C ×t6<&é* *BØ×(7å=S .JL@Fµ×@4×t.BF L@ØÃF ãBå+6p*-*-,@3+ØÃ&¨6 3J37L6 *-CJSj*:L@*-F å7ãBå762,@ã:.J*-*BS 4(75U6<×L@.,@6<×tØÃå=.)6<&)4yL@6 F SjãB6L@57S ßB6 â # 37R>ß6 (7(+,@.B×tF 3+37×NCÃê L@ë 57:í6zeâ|à¢.BÖ2S 57.:6NèpØÃF 376C¨Ø6R7ñ),å7*-,@376<6×@×tFå=.B.-3vL@Ý 6 3JL@Fµ*-Sjà¢.B,6<*B45Á4.BØÃå+*-,tL@ØÃ6 3JLFµ×¨4.BØÃå7()L@6<& Ù Ü Ù Ü ÙqìJÜ èp576 ,@6UL@57M 6Â×tFµ×¨ß>3+L@*-57å)6 L@FµØÃ4Â6 4Ø(7R7,@,@,6*-3J37L<6 ; 4 *-å+*B4F L*-L@3+5746Â6B;6 S 6<4yL@,@L@Fµ574 *-6ESz×t×[(7L@ØF Ø(7.-Sµà*:L@[email protected] 3v;F .B37Fµ4 L@457(76À,@,@*:6 ñ)3JLFµ*-× S; ,@6<6<*B×t4Fµ5 ×[L4*-.B3+ØÃ46Bå+;O*-*-,tL@3+ØÃ& 6 3JL*-3+&NF L*-×3+&*B&æt*B46 3JLp.B37,@6<6 × å7â ,@6<×t6 3JL×0L@576Â*:ñ)Fµ*-S!4(7,@,@6 3JLNR=6L[èO6 6 3 Ö2*-,@576!60L@574.B6zØÃà¢.Bå+S *-.:,tèpL@ØÃF 376 C+3JÝ L×!*-3+&U4(7,@,@6 3JL×(+×t6<&[email protected]ØÃ.)&)6 SL@576Ã376 (7,@.B3+×.-àjL@576¨Þ+CB(7,@6 / 4,@/>6.B6 3JØÃ3+L2×tå+.Bà¢*-.B,@,tß_,2L@R=ØÃ,@6<.-64L@3J6 5 å)L×'L@4.B.B,@,ØÃ6 ×|å7å+*-,@*-6<3+×t,t&6L@ØÃ3J4[email protected] F ,t373JL@ChLFµ4×OL@*-Fµ57S>×O6_4L@6 57×tS .Bµ6_× Ø0â-×t(7Ö2*Øð57*-6<3+.-×t&06OàL@37L@57576 6z6_(7,@*:4.Bñ).B3+.B3J×3vL@,@*-â>F ,@R7Ö26'()57ØÃL@6!F .B.)ØÃ3+&)×O66 SØ.-6<à|&R7*Ã,èp*-×t37F L@.)6z5&)4F L[(7(7èOØ ,t. á 4M'(7(7,@37,@66 3J.-LL@5+*-*-3+Sµ*-&QØÃ*ÃFµ4Oå=4.-6LS*Bµ×@× ×tâ-F D(7Ø .)&)46 (7S 6<,@&,@6 èp3JL<F L@â75Ö2L@57576 ,@,@6 66pà¢.B4,@.B6!ØÃèOå+6z*-,t5+L@*ØÃãB66 3JL×,@6 å7,@6<×t6 3JL@F 37¨Câ L@576 ×t.BØ0*ê :í*-e3+;-*&zå=L[èO.-L.!*B&)×@×t6 F 3+(7&)Ø ,@F L@4Fµ(74j,@R7,@6,3J*-L3+4576<× ê âë<7.î:íeB;:,*!L@575762F CB×t5).BálØ0L@57*p,@6<èO×t6'57.B5+Sµ*&ãB46'*-*Sµ4×tF .)(7&)Ø F (74Ø (7,@4,@(76 3J,@,@L 6 3JL *,@Bê ë6 4yò3JL@íeFL ã:; *p*:L@4 6<*-&Qê Sµ44íe4 F â)(7*:Ö2L@Ø¨F 57.BáH6!3*B4yØÃ4L@(7F 6 ã:,@Ø*:,@L@6 R76<3J,&!L *-å=37.-6zL4*Bê ë(7×@$<,@×tív,@F (76 *-3JØ 3+LO&4èp(7Þ+F ,@3+S ,@¦*-6 R=S3J6 ßNL *¨S .:è2ê ò-álì:L@57íe; ,@*26<×t5>57ß>.Bå=Sµ&N6 ,@å=4 *-.BSµSµ4*-F ,@(7F Ø8<*:L@4F (7.B,t3)á á 9 â)Ö2576_&)6 3+&),@F L@Fµ4!R7,*-3+4576<×O*-,@6!×t6LpèpF L@5Qå+*B×@×tF ãB6!4(7,@,@6 3JL×'.B37S ßBâ &H3JL@6 ,@376 (7,@.B3+× â)Ö2576<×t6_*-,@6!ØÃ.)&)6 S 6<&QèpF L@5NL@57,@6 6_4.BØÃå+*-,tL@ØÃ6 3JL×2,@6 å7,@6<×t6 3JL@F 37C L@457(76,@,@×t6 .B3JØ0L×_*7L@;-.E*z&)L@576 3+.J×t&)6N,@F L@F 3ÅFµ424R7(7,37*-63+.-4L@5Ã5+*-*-3+Sµ*-&hØÃL@Fµ57464*:6 ñ)S µ.B×3vèpâ 7.F L@B5é,L@L@575766 ×t*B.B&7Ø0&)*F L@FèO.B623Á5+.-*àpãBL@6p57×t6QF ØÃ×tSF .:Sµ*-è , å=*B4y.-L@LF *Bã:×@*:×tL@F 6<(7&ÀØ 44(7(7,@,@,@,@6 6 3J3JL L äêê ò-ë ì::íeí+âv*-Ö23+57&¨6L@57ØÃ66 ×tØ(7R+R7×[,L@*-F 37L@()60L@4F .B(730,@,@.-6 à3JLhFµ× à¢.B,j.-L@576 ,'4 *-Sµ4F (7Ø¨á [â7Ö2576_*:ñ).B3N*-3+&L@576_&)6 3+&),@F L@Fµ4!R7,*-3+45N4.B3JL@6 3JL B . 7 3 S N ß + å B * @ × t × F B ã z 6 4 7 ( @ , @ , 6 J 3 L × â # D6 ØR7,*-376Nçv6 ãB6 Sl"â Â6Q5+*ãB60(+×t6<&ÀL@576 .)&)3C 6>F 3)á ()ñ)S 6 ß Ù !Ü_à¢.B,@Ø(7Sµ*:L@F .B3Á*B× L@657ñ)6Ãå7,@Ø06<×@*:×tL@F .B5736 Ø0à¢.B*:,L@Fµ*-4 3 *-SF .BØÃ37.)Fµ4z&)6 4S(7à¢,@.B,@6,_3J&)Lp6<,@×@6 4Sµ,@*:F L@R76<F 37&[email protected]@57*¨60ØÃF .B6 37ØFµ4¨R7,4*-(737,@6_,@6 43J5+L*-× â3737Ö26 57S6 Fµ× Ý CB6 376 ,*-S W Y[`\BY[`cH`k:d[cd[»J`2w]<k:dHY[b ÄJZBd[b ]<kÃ] ºwZBYHY[`k:d[cjg cHcH]:wb gd[`y^Ãd[]z\>g cHcHcHb `pwt»>g kJkJ`m c . . *. . . . . . . . ! . . . . . . . . . !. ! ! !. ! . !. ! . . !#" + "%$ & '. !#" + "%$ & ' . . (. *+ -,. ). .. (. + . .. -3 0, 3 ,. /. % 021. - 0. ). 26. 4+ 5,. .. ,. / ,. 021,. (. / ,. 3 ,. 9. ,. 57 8 9 0, 7 , 26. % 021. =<. ><. . :+ ;,. ?<@<. A<@<. CB2D. .. ,.

(6) u^BZ>gYt^B]hag x kJwt»J`È2`@dOg m ¼ . Sensorimotor cortex INa. INa. INa. IK. IK. IK. Cuneothalamic cell IT. IK INa IK. IL. IC. IA IT. Ih. IL. Disinhibitory interneuron. Iahp Ih. IK. IA IT. IL. INa. INa. IC. Ih. Inhibitory interneuron. Primary afferents INa IK. bf_k:d[` `@k:Y[² d[kJ=²c|`ºµZB] ËY[YO]<»J`ykJ`g c'wtwg»Ãb k>Y[ww^ZJ`m bw=dz] g YHf_k>d[b ^¨]-wyg^Bcem¦`½Bm+wk>¦`g cHm \B`cd[kJ¼)b cHw2Ë] wYH»J½]<`pkJY[fhkJ``wg w@`b d[k\Bb ]<d[ºµ]kJ`yY[gc cd[}vZB\BY[`Y[cOb fhggY[`YH½cH»Jg]y¸7¹j`@Y[k9`Jk:b d[]<ckJ}b wwZJwkJZB`YH]Y[d[`»>k:gd[cm g}Jf_w]w`gm YHdHc¿} Receptors. . Ù Ü Ù />Ü èp×t(+5746 5_,@6F .B3v; ÅL@,@576 6'å7å7,@6<,@×t.B6 R+3J*-LR7×jF Ø0S F L[*:ßñ).-F Øà+*-(73hØ *B4y4[email protected] 3+ã:&)*:L@(+F 4y.BL3_*-3+CJ*:46BL@6j; R=6 F 37C[email protected]å=6,@6<3v×[; L@OLF 37@Ch576'å=.-å7L@,@6.B3JR+L@*-FµR7*-S+F S à¢F .BL[ß , à¢*-.B3+,h&Q*-F 3Â3+*BF 4y3+L@*BF 4yã:L@*:F L@ã:F *:.BL@3QF .BCJ3Â*:L@CJ6<*:×2L@6¨.-àR=L@6 57F Fµ37×pCF .B.B37å=Fµ64z3v4;v5+*-*-3+37& 376 Â*Slâ -3+& !L@576Ã3>(7ØR=6 ,_.-à2*B4yL@F ã:*:L@F .B3 &H3UL@576*-å7å=6 3+&)F ñUèO6Ãå7,@6<×t6 3JL!L@5760Ø0*:L@576 Ø0*:L@Fµ4 *-S6ñ)å7,@6<×@×tF .B3+×!èO6¨5+*ãB6¨(+×t6<&EL@. &)6<×@4,@F R=6!L@576_F .B37Fµ4_4(7,@,@6 3JL×OF 3 .B(7,×tF Ø(7Sµ*:L@F .B3+× â . . 1 . . ! . . . $!% 8 %" :. LP&)*-(+*-3+4y,4L*-6<*-ØÃ×'3+64*-L@63+6 &Ã,ã:×+*-,@à¢S 6<(7.B×[,6<L@×jFL@37575+C_6'*å=ãB×tF6.-ØL@R=6(76 3JSµ6 *:L@3NFµL@*-F .B*BSµ×'3+&7*-×v*-,@å)*-6pL@,@6<6jå7&,@×t6<57*B×t.:4 6 èp43J.B3zL@,6<&)F &3zF 37à¢L.BCz*-,'R7L@6<S.h6<*B×L@4575Ãëj6*-F .Bà¢3+6<37&h*:FµL@4ò)(7â4,@DE(76<,@×j*:,@.-6ñ)3JàF ØL<L@âJ57(7/>6_3h.BM'ØÃ4.B(763+37&)46<.B*:(+3)L@4y6 áá 46 S µ× â.

(7) ¨§ ]-^B`m b kJzd[»J`2wb Y[wZJb dHYH½¨] º¦d[»J`{|ZJkJ`ygd[ÒZJwm `ZJc o vrr y ¿ ¼ y<¼ - y<¼ ¿ ¼ ¿ ¼ ¿ 5¼ <- o dtg °JkJ¬ w`c'g >k>² ^hil]<Y[kJ`ceb wd[b kJwZB_YH\)Y[`] k:d[d2`k:\>d[gb gYtmg cf_¼ `@d[`@Y[cOºµ] Y2d[»J`wZJkJ`] d[»>g m g f_b w!kJ`ZBY[]<kJc 7fhgnBb f!ZJkÃw]<k>^BZJw@¿ B. . . . . B. B. B. B. B. . B2D. . o vrr < ¿ ¼ < ¼ < ¿ ¿ ¼ ¿ ¼ ¿ 5¼ <- o Y[`°Jced[¬ b kJz7\)²] d[il`]<k:kJd[b bw_g m wcZB¼ YHY[`k:d\>gYtg f_`@d[`@Y[c2ºµ] Yd[»J`zb k:d[`@Y[kJ`ZBY[]<kJc=fhgnBb f!ZJkw]<k>^BZJw@dtg kJw`cg k>^ B. . . . 8 % 8 $"!. . B. B. B. . B. . B. . B. B2D. . 8 8 !:. BC,@7.6<,B*-*-,SØ FµL@×[57L@;Fµ60&)4!6 ×t37ãBF Ø6 6 (7S (7.B,@Sµå=.B*:3+6<L@&À*-F .BSv3+R>ØÃ×ßÀ.)èODé&)66 â Sµ5+×2*à¢ãBF,@37.B66<Ø ×(+×t*-ØÃ6<3+&.B&éS L@6<57A+46 (7â"Sµ *-,pâS 6DãB..>6 *QS¦.B×t,@[email protected]Ø;v×t(7.-ß)Sµï¦×[*:L@6 L@6,.BØ×z,!L@å7S.>6 ,@.BãB.BSµ6CB×_Sl,â7à¢*-.BÖ2Ø ,57F6hê ØÃ$<37íeå7â¦6 S Ö2(76 ØÃ,@57.BFµ63+×!3J×på7L@F*-,@37.-,@C6 á L@&H3Q57.B.B(7,CB&)5J6 LO,j*BL@.Ã×j×tF 6ØÃL×jå7S .-6 àvØÃ×t66<3J4yL@L2F .BL@573+6!×j4ØÃ.B.)3+&)466 å)Sl;>L@L@(+57*-6!S ßÃ(+×t×t6 F ,2ØÃØF Sµ*-(+,×[LL@._&)6<L@57×tF 6CB3N4.B*-ØÃ3+å+&N*-èp,tL@,@ØÃF L@66z3J*¨L×j×@4.-,@àF å) L2â R+*B×t*-6<S l& â .Bå73NF S F *_37CUSµ*-L@3757CB6Q(+*-å7CB,@6.BCB4 ,*-*-S Ø 6<&;L@D 576!Ú!×tF ØçÅ(7ÙqDSµ*:L@!.B&),¨6 *-S¦S Ú.:6<è×@×h4,@L@F å)57L@6QF .B(+3N×t6 çv,h6 L@ãB.Â6 S Üyå7âJS .-KpLÃà L@ãB6 .B,OS èpL*-,@CBF L@6F 37*-C¨3+&Å*-3+4&(7,@4,@.B6 Ø¨3JLá CBå+,*-*-,å7*-ØÃ5+× 6;>L@&)6 6,L@×6 .B,@,ØÃ4 F *-37,@6,@ß[email protected]!()L[email protected]ãBL.B*-S S+L*-L@FCBØÃ6O6z*-3+.-&¨àL@457(76_,@,@×t6 F Ø3JL(74SµSµ*:*-L@ØÃF .Bå¨3v;>64ñ)5+å=*-6 37,@FCBØÃ6!6 43J(7L,@× ,@â:6 Ö23JL2576p*-3+×tF&Ø×t(7ß>Sµ3+*:*-L@Få).BL@3+Fµ4× (+R>ßN×t6¨4[email protected]Ø6 R7F 37F F37376<C¨×zL@F 573J6_L@6 R=CB6,*:37L@6F Þ7.BL3U×pØÃ.-à6[email protected].)L@5U&;M'*N,*-àq*B"3 ×[6JL_áHÛå7,@Fµ4.)574.B6<Sµ&)×t(7.B,@3N6*-L@3+5+& *:Lh%j.B(7å)S 6 L@,pF ØÃØÃF 866<L@57×!.)L@&757×6Ãâ å7,@.)46<×@× 46<×@×tÖ2.B,<57â 6×tF Ø(7Sµ*:L@F .B3+×pèO6 ,@6h4 *-,@,@F 6<&Q.B()L.B3E*0P2M èpF L@5E*ìBìBì0D 8P6 3JL@F (7Ø & &2å7,@.-á >Ó !HÏ 8 "$8 $: 7 F.-K8 à6<××t&N4å7*-FR>6B3ß6<R=× *-â623Q&H×t3Ã.J6 6×@L@3457F 6pS F µ3*:ØÃL@Þ+F.).BCB&)3Q(76 ,@S746.BèOëBØÃ6p;:å=45+(7.J*37×tãB6<662&[email protected])5+à|L*-*-*ÃSµ*-F 37&)ØÃ6<6 &ÃFµ6 4'åQ×t*BF 5>ØÃ4yL@ß>FF å=ã>Sµ*-6F ,L[,@ß_å=R=.B(76 Sµ5+3+*-*&),@ã>6F 8<F,.B*:*-(7L@3+F ,.B*-30R>6<ß¨×[à¢[email protected]57S .B6<.:Ø×tèOFµR7*p6<F &0Fµ37×F R>374ßN5+C_*-**_,*B×tR74y6(7L@Lj,6 .-×[,tLáà FK.B3¨37FµF4!3>è24(7*-,@,,@&h6 3J4 L*:×OL@F F .B3+3¨×tå74F (7,@6<,@,@&6 3JR>LßÃ*-L@3+57&.J×t*6!S à¢.:.Bè2(7ál3+L@&57,@F 6<3N×[email protected]+Sµ*-&hSµ*-4 ØÃ*-Sµ.)4F4(7.BØ ,tL@Fµ44 (7*-,@S=,@376 63J(7L,@*-.B,@3+6'×z,@6<Ùq×t×t6 å=6.BÞ+3+CB×tF (7R7,@S 66'à¢4B.BÜy, â ,@,@6<6 å=4.:.BãBSµ*-6 ,@,@FF 8<37*:C2L@à¢F ,@.B.B30Ø Fµ×25>*:ß>Ltå=L@6,@F,@R7å=().BL@Sµ6<*-&0,@F 8<L@*:.¨L@*hF .BL[3vß>â:å7/>Fµå74 F*-6BS=6<å=×|.-*-L,@*B6O×@×tCBF 6 (737Øð6 ,*:4(7L@6<,@&_,@6 R>3JßhL<â *×tß>.)å=&)6F (7,@å=Ø .BSµ4*-(7,@,@F 8<,@6*:3JL@FL.B*-303+Fµ& × &)4(7,@F,@ãB,@66 3Q3JL<R>â ßN*57F CB5)álL@57,@6<×t57.BSµ&Q4 *-Sµ4F (7Ø 4(7,@,@6 3JLp*-3+&Q*Ã4 *-Sµ4F (7Ø¨áH&)6 å=6 3+&)6 3JLpå=.-L*B×@×tF (7Ø 5>ß>å=Ö26 ,@57å=6_.BSµF 3J*-,@L@F6 8<,@*:37L@6 F (7.B3,@.B3 *-3+×t&57.:*éè×pS .B*-373 CÀ.J,@×@6<4×[F L@S Fµ37*:L@CéF .Bå=3Q6 ,@èpF .)F L@&5Eâ2*0/>.)×tF&)37F CB(7SØ 6_×t*-å73+F 6B&6zå=à¢.B.-S L.:*BèO×@×t6<F (7&NØ R>ßQ4(7*0,@×t,@576 3J.BL,tL× . "! $#. <. &%. ('. ('. <. <. .. ). *. . ,+. -+. -/. 10. 32. <.

(8) u^BZ>gYt^B]hag x kJwt»J`È2`@dOg m ¼ . _ff_ bb mm bb ²cH`7²]<wm d[]<c{|k>^B]<cf_=\JwZBZJd[kJ`@`Y2] d[cH»>b f!g mZJg m f_gd[b bwz]<kJwc2`m ] chº|od[m »J`@`º d@rpcH\)g ]<k>k:^Ndtg b kJk:`d[]<`@Y[ZJkJcp`gZBw@Y[d[]<b kJ-czb dl½0oµY[b] <º»:wd@ZJrt¼ kJ`yg]<d[m `!dtg kJ<``zZBb Y[c]<kJ\Jc'm ] ºµdH] d[Y`y^Ny*-ß>3+å=&E6 ,@*0å=.BãBSµ.B*-S ,@LF *-8<CB*:6L@F .B&)3v6 å=â>Ö26 3+57&)6!6 3Jàq*BLz×[Lå=.-,@6<L*B4.:×@×tãBF 6 (7,@Ø ßÃ*-43+(7&N,@,@L@6 573J6L S4.B(737,@C¨,@6 F3J3JLOL@6 *-,3+×t&0å7F *6B6!×tS å=.:6è,@F å=.).-&NL5+*B×@*×tãBF 6!(7Ø R=6 46 (73 ,@,@66ñ)3Jå7L<Sµ3â*-F&e37LO6<5+&*B×jR>ß0R=6 L@6 573N6z×t6(7ñ)CBFµ×[CBL@6<6 ×[3+L@46<6z&¨.-L@à5+*:*-L'3QL@F 573>6è2Sµ*-*:,L@&N6 ,'4 å7*:L@Sµ*F .Bß)3 × *à¢(7K 3+&7&)*-6ØÃL*-6 F3JS 6<L*-&USv6,@ñ).Bå7S 6zSµ*-F 3+3 *:&)L@F6.BL@3U6 ,@.-ØÃàjF 37L@57F 3760C04.J(7×@,@4,@F6 S 3Jµ*:LL@×zF .B*-33+&Eà¢,@6<57VJ.:(7è 6 3+L@457ßB6 â ßEå7Sµ*ßE*N,@.BS 6¨F 3EL@576Ãå=.-á L@6 3JL@Fµ*-SvØÃ6 ØR7,*-376!CB6 376 ,*:L@F .B3 4 *-3QR=6zà¢.B(73+&QF 3éê ò 7;@ò)ëíeâ 8. . .. $ 8 8 / $$89$"!" / 3/ !!:. @L@,M'576<.B×t62,t(7L@ØÃS FµLO4 6 *-L@Ø57S6_R737,6F *-37(73757,@6O.BF R73+,@F 6<×L@×[.BèOL@,@F ß0376 ,@C!376Ãå=6 &)(7.-6 ,@L@å=.B6 3J3N.BL@Sµ*-.-Fµ*-,@àS7F 8L@*-576<3+&E6_&hÚ_R>L@ß57MO62Ûh(+å+×t;>F *B37à¢×@.BCQ×t,F 46ãB6<S6O6<&4y4L@F(73J,@,@FµL@,@4 .06 *-3JS*¨L×[× ×tL@;F FS ,@Ø6 6<3J×t(7Lå=Sµ*:.B×[L@L3+F*:.B&7L@3×|6!R>R>Ù[ß_ë¨ß0CB3+F 3+6 K!374,@6Üy6<â,*B*:KL@×tFF×z3737CC* F*43.B4[email protected]×t57(76<6zå74(74S 6(76 3+37.-4à6 6B.-×t;L@å75+F 6B*-6<Sµ*-*-×ØÃ3+Ùq&×tFµ64p637Þ+6 *-CB(7,@(7,@6z.B,@6!3*B4yîJR>L@ÜyFßÃã:â>*:Ö26 L@ãB576<.3&66>F,@*-37.B3+CS &Q6*-.-*¨3NàR75>L@(757ß>,Fµå=×'×[6 L37,@å=.-6 (7à.B,@Sµ×t*-.Bå7,@3F F 6B8<F 6<*:LO×OL@L@F Fµ..B×30F ×t376*:576L'F3vR7L@â 57F LO6zL@×t57.B6!Ø0*B*74yâ>L@FKã>×OF L[ß* 4×t57(7.:37èðÖ26 .-57L@57Fµ5+×_.:*-è ØÃSµ*-6<ØÃL@4575+Fµ6 4*-å73746,@Fµ×tS.-Ø æ[6<Fµ×!4y4 [email protected]*-F .Bå=3À3 6 S,6<*:4*B6L@&ÂFS 372L@CNFµ.U×¨F 3Eà¢*.BL@,&)5746 6<6¨å7&é,@L@6<.BR>×@37ßé×tFµF 4.BL@3À57ØÃ6 .-.)à4&).B6B×t,t6â L@3+&H63U×tñé.B,@L@L@ßE57.ÀFµ×zF 43)5+4à¢.B*B*-,@37×tØ06hCB6NL@*:57L@à¢F60,@.B.B3é×tØ F ØèpL@(757.BSµ6 *:373ÀL@Fµ4F .BL@[email protected]× .J×@4F S µ*:[email protected],@ß*B4yL@F ã>F L[ßUÙq&7*:L*¨37.-L×t57.:èp3=Üyâ 0. .. .. = . : $ 8 -8 / $$89$"!" / 3/ !!:. @,.BK.Bå=×3+6 ×F,Lâ*:&HL@Fµ30×!6.:×t.B57ãB,.:&)6 ,èp6 ,|L@3 57L@._F636.Bñ)Þ+,@Få7CBCB(7SµF *-3+,@F 6*-3¨S7ì[email protected];=37Fµ4×6B.BâÞ+,t&HL@3+3ÃFµ4&)*-Þ+F 37SvCBCJ(76×jï¦,@66*z,@îh×t6 6<3JèO4L.B6×3+×t4 &¨57*-.:3F 3JèL@F 376 57,@57.:37F è R76 (7F L!L@,@57.BL@63¨576hØÃ5+F*B.)37×&)576R=F S=R76 ,@6F [email protected]å7,@å7,@ß .),@.B&)F å=3J([email protected]6 ×t6<,@6<×37&hL@6 57L@().6 á ,@èO6<6_×t(75+S *L×pãB6z.BR)F 3:Læ[*-6<F 4y37L@6<6<&Q&64ñ)(7å=,@6,@,@6 F3JØÃLh6 Ù[3Jë_L*-3+S K!ßBÜ2â7?OF 3.-*0L@5 4.BF 3J,tL@L@6Fµ4,@*-37S6 (737,@6 .B(73+,@.B×23QèOF6 3,@6z.Bà¢,.B&),6 4,O6<&L@.[email protected]×t6 R=6z6L@57×t6_F S 6 ,@3J6<L×t(7*-S 3+L× & â 6Ö23+57×t6N(7,@5>6!ß>L@å=576 6h,@å=VJ.B(+Sµ*-*-S,@F FL[8<ß*:[email protected] à|.B3À[email protected]àp×tL@6 573+6N×t.BF ,@37ß057FF 3)R7à¢F [email protected],@Ø0,@ßÀ*:L@F 3JF .BL@36 ,@374 *-6 ,@(7,@,@F .B6<3Á&R>4ß0.B(7L@Sµ57&é6_R=å76Q,@.-*Eæ[6<ØÃ4yL@6<F .B45+3 *-4376 FµS×tlØ â L@..

(9) §¨]-^B`m b kJzd[»J`2wb Y[wZJb dHYH½¨] º¦d[»J`{|ZJkJ`ygd[ÒZJwm `ZJc. Inhibitory interneuron. Disinhibitory interneuron. Sensorimotor cortex. Cuneothalamic cell. Primary afferents. -koµY[ZJb <wm»:² `d7ZJ²ccH+b a-^B^Bb `f!b rtcH¼ZJb kJm{|g»Jd[] b bÄJYH]<d[b kJd[b wybc]<g kNd[m]!Ä)] ce`ºd[»>Z>b gyk:^--d[½_`@b ]<Y[d[ZBkJ»JY`ÒZBb bY[cpk ]<>Y[kJ`ZJc!\B`Y[o kJm]-`@w^Bº`2dZJ] wcHº=`yb ^B^Qd[`»JrOg`2cg cHk>`b dkJ^0cH¹]b kJ]<Y[»JbZJf_bm ÄJ^Q] b d[d[Ä)]b ]<`_Y'kNwcH`]] `YHºkd[w`@nZJb kkJ]`g ] kQ`@d[Y»>b d[gk:»JmdHg `2Ytf_g wwbZJ`w!kJm w`yZJ`gm mgd[`Yc Y[Y[``wcH\)] Yt]<^BkJb cHkJ`pBcH¼»JË]y»J¹j`|kÃY[`yb k¨g<^B¾>`@<YZBf!Y[`ZJce d¦kJ] d[b w`d[»J`^Bb ¸7`@Y[`kJw`|¹j»J`k!w]<f_\>gY[b kJ'¹jb d[»d[»J``@n-dHYtg w`m ZJm gY Disinhibition of interneurons. Inhibition of cuneothalamic cells. . . 89. % 8 )8 ": 3/ $#$" 98 % 8 . 7L@3Ö26<6 57×[(7Lp6Ã,@[email protected]×t573+.BFµØ0× ×â3*:å=&[email protected]×@Þ+×t×t6 CBF R73+(7F×t,@S .BF6 L[,@ßBßQ$!â7èO4K.B6CJ,t*-L@×t657F 3ñE.:è èO4 *-6zL@3E575+6F *3+,@ãB&)6<6z(+×t(7Ø04S6ÃL*-×j37&).-FF å7,@à6<(7L@4ySµ57Lz*:6!L@66<ñ7×t&NF 4ØF L@L(757*:Sµ6hL@*:F [email protected]ØÃF 3E.B6 3Ø.:ãB4 R76*-,,,@*-,@37L@F 576<6z&¨6Ãå=.B4.-()(7L@LO6373J6 F L@3.-FµL@*-.B5+Sv,*-&).-Sµà|*-6 ,ØÃL@57L@Fµ.64 å7F 30,@.-L@æ[576<6!4yL@4F .B.B,t3NL@64ñ6 ;BS +*_L@.ÃCB,@*.BãB(7.BåÃFµ&0.-à×tå=×tå7.BF3J6BL6<*-×j37*-6 å7.Bå=(+×j6<*-.J,@×@6<4&ÃF S µF *:30L@[email protected]+6× ×tâ .B Ø057*_6 .-3Nà¦èOL@57666 å7S 6<,@4y.-L@æ[,@6<Fµ4y4 L@*-F S .Bß03×[4L@6 F S ØlâJ(7Ö2Sµ*:57L@Fµ6× L@ØÃ576<6h45+46 *-S 37µ×2Fµ×t,@Øð6 Sµ*:4 L@*-6<3N&R=L@6z.(+*-×t,@6<6<&N*B×2R>*BßÃ×@L@×t.)5746_Fµ*:×t6L@6<3+&×t.Bèp,@F F ØÃL@5 .-L@(+.B×t,O6à¢4(7.BSv,tL@F 3)6ñ0à¢.BL@,@.¨Ø0F*:3+L@4F .B,@6<3v*Bâ ×t6L@576!Þ+,@F 37C¨,*:L@6!.-à Õ >ÔÓ >Õ[Ñ'Î èO.BÖ2R+.B57×t,6'6 6¦,@å7âãB,@Û6<.B&).-å=L.J(+×@.B* *-37SB,S ßz×t(+57,L@.:.:57;èp6OR73hØÃ()F L03_.)&)*-Þ+6 SµCBSµ×t×|(7.,@.-6'L@à+57ìpF 3+6NCJ&)F*-F3Jã>F L@3+Fµ6 &)×,(+44*-,@.B6<S>37&)3737F 66<L(74y*:L@,@à [email protected]+6 3+,××L@×t5757*-6O3+.:èÁ&À×tF Ø*L@57(7R=6QSµ6 *:5+å7L@*F,@.B6<ã>3+&)F .B×vFµ4y,å7L@×t,@F F.B6<ØÃ3+×t6 ×¨F Sµ3J*-L@*-,6<R=&[email protected].()F 3_L@L57L@[email protected]×tFµ66× 6Fµ×vñ)Þ+Fµ×[3+L@*-6 3+S 4ß_6z4.-.Bà3)Þ+&),@Fµ×tØÃF 376<57&zF R7L@.F [email protected]=,@6jßL@,@F 3J(7L@6'6 F ,@L37èO6 (7.B,@(7.BSµ3+&_×25+S*6<ãB&N6jL@å7.0,@.-×@à¢*:.BL@(7Fµ×[3+àq*B&z4yå[email protected]>,@ß)ß0×tF ,@.B6<S .B×t(7CBSFµL4 ×*-%â SB&e4à.BL@3+57×tFµ6<×pVJ(7×@46 573+6 4ØÃ6<× 6 â &eL¨èO.B(7Sµ&Á&)6 ØÃ.B3+×[L@,*:L@6376 èðØÃ6<45+*-37Fµ×tØ0×hF 3Áèp57Fµ45éL@576 4.B,tL@6ñé4 *-3ÁF 3%1+(76 3+46Q*-3+& . .. +. + +.

(10) y u^BZ>gYt^B]hag x kJwt»J`È2`@dOg m ¼. Inhibitory interneuron. Disinhibitory interneuron. Sensorimotor cortex. Cuneothalamic cell. Primary afferents. w] YH d[²`@n)² ] d[`k:d[b gd[b ]<k¨] ºg cHw`k>^Jg k:db kBºµ] Y[fhgd[b ]<kÃ^BZJ`jd[]d[»JÒb k >ZJ`kJw`'] º=d[»JÒcH`kJcH] Y[b f_] d[] Y Potentiation of projection cells. . . ØÃè2*.)ßE&)(7èOSµ*:6L@6U4.BL@(757Sµ&Â6 F1+3).:à¢è6 ,_.-L@5+à*:F Lh3)à¢[email protected],@6 Ø0,@60*:L@6F .Bñ)3Fµ×[LhL@5757,@F CB.B5À(7CBS 5 6 ãBL@6 57S'6Â4.Bå7ØÃ,@6Ø0L@5+*-*-3+Sµ&7*-×zØÃL@Fµ.E4E*-3>å7(+å74SS 6ßUFlâ èp&H573 6 3Â×t(+L@4575 6 ,@*6 6å=ñ).-FµL@×[6 L23J(+L@Fµ×t*:6L@à¢6Q(7S[email protected],O6 (+L@×t,6 *-S 3+6<×@×t×'ØÃF Fµ3)×@à¢×t.BF .B,@3ÅØ0*:.-L@à!F .BF 3v3)à¢â .B&H,@3QØ04 *:*BL@×tF 6.B3Á.-àvL@L@5757,@6!.B(7Þ+CB,5Å×[LpL[×tèOF L@.Â(+*:ØÃL@F 6<.B435+*-L@57376zFµ×tØ04.B× ,tÝL@6*Àñ&)4F.B,@(76<Sµ4y& L 6ñ734F LL@57*:L@6F .B.-3À[email protected] àp,45+(7*-373+6 &.-;=L@5+F àj*-L@Sµ*-57ØÃ6¨Fµ44Ã.B,t37L@6 6(7ñ ,@.BFµ×3+×_37.-*-L!3+&ÀF 3JL@*6 ,@&)6<Fµ×[×tL@F 6<37& 57F F R73ÂF L@*0F .Bå+3À*-L@,t57L@Fµ,@4.B(7(7SµCB*-,!5Â×tF 63J3+L@6×t.B,@37,@ßN6 (7F ,@37.Bå73+()× L â F L4 *-Ö23Q576F 37,@657F 6R7ñ)F L!Fµ×[4L!(7ØÃ376.B.-,@L@65+6*-ñ)Sµ*-å=ØÃ6 ,@FµF 4!ØÃ376 6 3J(7L,@*-.BS3+&7×'*:L@L57*0,@[email protected](7CBR=5Q6¨F (+37×t576<F &R7F L@[email protected],@L@ßN6<×[F [email protected] (7,@37,6 ØÃ(7,@.).B&)3+6 × Slâ âv/>F Ø(7S L*:á 37.J×@6 4.BF (+S µ×*:L@,@F 6<.B43+.B× ,ÝB&)à¢F ,@37.BCJØð×pF ×t3US .:4è .B,t,@L@ßJ6L@ñ57Ø0*-3+×!&Ù F _3Àë M'(78z37Üj6<*:L@L@.Ã6¨×tÛå7F (+3+4&)S 6S 6!(+×!,@ßJ,@L@6 57ãBØ06<*-×zSµ×Ù*NF 3N×tL@F ØÃ576!F Sµ,*-*-,37å+CB*:6[email protected] à ,@$<3Eá0ë .-/ à ØÃ57.:8.)è &)Ü6 êL@ë0S'57/-6h4 íe*-â×t3ÂS/>.:.B6è ØÃñ)å7,@6NßJSµ*-L@VJF573Â(7Ø06<57×[×pL@.:F 4è .B*-3+3QL@×_57R=L@6Q6_.EMOF R=3+Û 6Q&)(+*-3743+6 6<(7×t&QèO,@.BR>6 3+,@ß6<×z&ÂL@457*-F6h3À3À4à¢6CB(),@6 L@6 37(7R76 ,@,,6N*-*:SL@66¨4ñ).Bå=F ,t3J6 L@L@,@6,@F ñØÃF 3+â 6×tFµØh4¨L.J×h×@4èpF SF µS *:OL@R=F .B6N3+F×zà*-.B3+(7& , L@à¢,@.6<VJå7(7,@6<6L@&)573+Fµ644y,ßEL*B*-37×t3+6 å=è&6<4yL@à¢L_.B6<37*:L@[email protected]µ4¨(7,@R=F 6<376N× 57â ×[F L@R77.(+FBL@&),F F.B6<F 3Â3+&À×[FLR>3+*-ßÂ&)3+(+4446B.B6<;+ØÃ&Uèpå7R>5+()ß*:L@L6 L@,Fµ57×p60×tFL@Ø4576 6(7,@Sµ6,@*:R76 L@Sµ,F*:*-.BL@S3+F .B×_43 .Bèp,tR=L@F S66'ñEL[èOR=F 6063À6 L@3*-573+6NF *-3)6<4à¢.B×[*-L@,@å+57Ø0*-6R7*:L@L@FF S8 F F .B6<L[3&ß F4ØÃ.B3+å=&)Ö2.JF ×t57L@6<F6Ã.B&3+*-R>×3+ßzâ ×tèOL@57.:6 6p,è ×4Ø[email protected],t(+L@64L@ñ_5Ã576<FF ×t3Ã3J60L@×t6 SVJ3+6 (76×t6<å7F L[×[F ßL@37F Cz.BØ3+4(+×!.B×[3+Ljèp&)5+F FS *L@jFãB.B*-6O3+Fµ&L@× 57 L@6. ×[4L@5+FSµØ*-*:Lj,@(7F à¢*-S ß[email protected]._()(7L|.:, ãBL@6>65737,6O4.:à¢.Bèp,@ØÃ6<S VJ6<6'&)(7L@CB6 573+6¨6p4*-ßhL@R=574.B,@.)6<()&)×tLz57F [email protected] Sµ&6 ,@*-.B,@S6E6_×t.-(7à|,@L@6576L@5+4*:(7LQ3746<.B*:ØÃL@6_å73>()(+L4*:S L@6 F (+.B3+×p*-F 3S!×tL@F 57Ø6h(7å7Sµ*:,@.)L@F 4.B6<3+×@×0×tF 37èpCÃF S .-!àR=×t6Â.BØ0*À*:ã:L@*-.JS×t(+6 *-3+R7×t.BS 6,@ß0L@.>F 3).Bà¢S.BL@,@.ÁØ0*:CBL@6F L.B3vL@â57Â.J×t66 *-3+×tèO6 ,× â '. . <. '. <. <.

(11) §¨]-^B`m b kJzd[»J`2wb Y[wZJb dHYH½¨] º¦d[»J`{|ZJkJ`ygd[ÒZJwm `ZJc <. Ô pÎÑ ! Ò Î'Ï Â6_èO.B(7Sµ&QS F 6B6!L@.ÃL@5+*-3"6L@. 89% 898 : #$ 8 3 3 8 3 8 v ; @ L 7 5 N 6 6 > 3 > ã F @ , B . 7 3 Ã Ø 6 J 3 h L F é 3 p è 7 5 µ F 4 é 5 @ L 7 5 µ F h × O è B . , 6U5+*B×_R=6 6 3Å&)6 ãB6 S á $ 8 $"! .Bå=6<&â vÐ ÎÔ ¼k>Æ'g k>\B^Bd[`@b wpY[cH~¦`k+b Ä)} `@Y[¼c'}+b uvk¨wd[w»Jm ``c}{|BZJ¼¦kJ{'`yg¼ d[}¦` a-OZwt»JJf_wmb `^-ZJdyc} ¼ <¼7]<ZB~|Y[¼ k>} g|m=]<] Çº ] O`dtg-}7ZBËOY[]<¼ \Js»:½B`cH\)b ]<]<mm ]<gY[b½:Èy¼ gd[b ]<]<mk ¼ <] º o Y[` ce½-r¿ ¼ ]|ºj`@>Y[d[yÇ-»J<m ` `@ ½:s } ] Y[c[gg Y[mj`k {|]<Bm¼ ZJ} f_kg<^BOZ`m J} wm'`b|b wtb»>k gYtd[^»J`_Bwy¼ } gdy|¼ m ]<f Ytg :b -k b ce'dy}`cHÆ`y¼g} Y[wt|» ZJm '}`§N-b `@¼ ¹pO¼ ZBd[]<\Jm ZB¼ d!< a:½Bo ce d[`f_ rc 3< -¼{g kJ`y^B]B}Æ¼ Y[b fhgYH½Âf_] d[] Yhw] YHd[`@nÀb k >ZJ`kJw`c_]<kÀd[»J`0^B`cHw`k>^Bb kJg k>^Àg cHw`k>^Bb kJ ¼cek-{½BZJg cewkJd[m ``y`f_^BZJ]Bcc}+¼] Æº¦d[Y[¼ }=»J]<Ò§ÃY[wt`g»JcHYHc'md[] b bkJYtk g `mÈ<O`]<} cH`vZB¼Y[g }=]<kJ§ÃÄJ`bceg]<d[Y[m»J]Y[]<^0cHr wÄJb ZB`kJY[ cewd[`kgÇ-Yt^7b kJ} `@d[b w!¼ B\B¼ Y[} ]<\)Y[`@bYHkJd[wb ``<c2¼ } ] s º|¼=d[»JÆ`¼ ¦dHYt{g gkJm cHwb b`ZJk:fðdpm w]yZB¹YH¿¢Y[d[`»Bk:Y[d[`cpcH»Jb kN]<m ^YtgwdZBd[YH»>Y[`g k:m gdy¿ ¼ ¼]~=<º]<½-ZB¸7d[Y[»J`<k>`h} g '~Jm+`]<] mÄ)º b kJ`@YH`»:d½B{|ucHZJb ¼ ]<kJ}¦m `y{|]<g »Jd[½Q``ò OZfh+J]<g-wk>}=m ^Bà-]<ZJZBk)cY[¼=rtb k>¼ it^J¼=gË=]<Ym`@¼ Y[a)f_¼ } b 'k>g ZJo m ced[b ]<grkJdHd[b `@}+Y[ÆkJ c¼ -7] ilºk:dHYtgY[bwfh`m gZJYHm ½QgYÆja:¸7dtg`@Y[b kJ`k:b kJd0~¦a:b Ä)d[Z>`@Y[^-c½ ¼ ¼ Oil<k:]ck>}:g g§Nm+d[b] ]<¼ º k>ÆUO`g m \BZB<Y[Y[]<]<]<ZB \JY[Ytk>»:g ½Bgf m+cHb ]ºµ]<] ºm Y]<| cH½:bb ]<f!¼ f_ZJ`ym]<g^Bm d[¼b bwy]<g kzm¦¼ ]{|º7]<kJf_o `@\JY[ZB`dtrg` d[: b Z>]<k+g d[¼ b >]<kJ]<c¦m ¼ ¹j b d[»zo ÄBYtg rkJwt»Jk:g d[mvc] ] º º>wZB»:YH½BY[cH`b k:]<dHm ]<¿q ]<½Um dto g +<]<`|k>Y[^B`]<m gk)d[rtb ¼]<kJcv]<bm k¼ <d[»Jy` -¼ Owo ]<ZJk><^BZJZJ`r w@k>dtgg YtkJ^7w}`cB¼b kYt¼ g}¦dj{|kJ]<`ZJ]:m d[w`@] YyYH}d[b s wyg ¼+m=ÆkJ¼`} ZBY[]<Y[kJb kJc wJ`<g } \Js \)`y¼=gÆYtg ¼ kJsw`2`] ºv`m g]<\JcHf_m ]y¹j`k:m ½¨dtg bm¦k>wtg »>w@g d[kJb <<g`d[cpb kJb zk w]<fz¿ y ¼ Y[O\)`]<ZJk:kJ<dj`ZJk:b k0`dyk>¼ ËgBYt»>¼J^7g ] } m º g Bf_O`¼ b w ZB¼ }>Y[']<{|`\J]<m »:gZJ½B½ m cHd[O`b`@]<Y m ]<ZBs Y[½:¼J]<¼ÆkJc ¼ } ]<pm ¼ Y[b kJb kJÃo`@wd[` d[ÆÅb B<g ~>d[g b ]<cedOkÃË+g Ytk>g ^¨kJcHilbk>`g k:w@d d[b <]gdtd[gb ]<cHk+cHb ¼ ZJ<f ]<ZB{|Y[k>ZBgYH¿m < ¼ ]mb ºgkJwt`yO`Ç)g}Y'ZBBwyY[g¼]<ÄJ\JBm»:¼`p½B'cecHdHb ¼ ]<Y[} ZJm ]<'w@ d[`y½:ZB^B¼ Y[fh`cg]<¼ k+m B¼ }¼><a)] ¼º o B ¼ »:½BËcHrb»J]<`Ãm ]< \B ½Y[]<>o\>+g ]<k>g^Bd[b ]<]<k)kért¼ ] ºO]<dHm Yt¼ g :kJcHb `k:o dh\):] d[r `k:d[b g m chb kÂcH]<f_` ¼ f_gb ^J½:g})m+ÆkJ¼ `ZBY[¼ ]<} kJc']<] kJºvBd[} »J`!¼ {zÆ ¼+ a)Y[¼ `7<{b ]<g km wb ] ZJºvf d[»Jw`ZBfhYHY[`gk:d[ZBd2Y[g `pw@d[Ytgg ¿m ] º »:½BcHb ]<m ]< ½ o +]<k>^B]<k)rt¼ ]<m ¼ o r < --y -¼ pZB½B\)`@Y[c} ¼7X¼ B¼+§N¼ }+Ë=ZJ`@Y[Ç)} B¼ s ¼ 7Ë»J`!^Bb cedHY[b ÄJZBd[b ]<k] ºvd[»J`w] YHd[b wyg m¦¾>Ä)`@Y[c'¹jb d[»Jb k ¼d[w§Ã»JZJg`2kJY[`k-b ]kJZJd[]Bw»>}m g`Bmb+g¼ }>wf_ZJ§ÃbkJwg`yYHggdyk>d[x ZJkJÔcj`d[È<»>g } k>g vm^g ¼ f_}J {Yt]:g gwwkJ] b mYH`yb d[^BcOb ]Bwyb k¨g}Jm-Æd[kJ»J¼ `J`2ZB{|Y[wy]<]<gZJkJdy\J¼c+mBb `yk2¼>^d[Æ'»JcHk>m `]yg¹Åwtdy»J¼ mg +] k>Yt]<^hg k>m ^7]<^BcH¼``m dtg g]<kJm ]<¼`cHcewd[¨b»Jm `@ogd[ d[b Èb ]<`ykJ^pc'r wyÄ)g dy`@¼dl ¹O`>y`5`ZBk ¿ ¼Y[ZJ§Ã]<f_cHgwY[kbb `kJk-kJ]BZJw} w` Bm `+¼ b}¦`@¼ §ÃdHO`d[`@g@Y[¹jYHcdycj¼x kJil`k ]<È<m} ¼ v»::¼½B}=-¼cH{b¦]<gom ]<kJ<`yb^Bwy ]Bg r }=mvyÆa-w¼ b+`>a-kJ<`wykJ` cHc]¼=Y[o b ilf_k ] d[]Y[`Y2cHbctk:r d[` Ytgd[b ]<k gdOd[»J`!^B] Y[c[g mw]<m ¿ y ¼§Ÿ[w]<{|\)]`@Y[YHf_d[b `b wtcÇ)] } º7s Ëgy»>-g b m ^g f_Æ]:¼ }w] OYHZJd[b <wyZJg m`k>'g`Ytm ^7g½} <O`]<»JZBk Y[]<kJ¼ c7¼ Æ <]<§¨ZBY[]-k>^Bg `mJm] ]º ºO`d[»JZB`!Y[]<uv\Jm »:`w@½BdHcHY[b ]<]<\Jm ]<»: ½B½:cH¼ b ]<m ]<]<m<¼ b wyg-m¼ o r > < . . . -+. . . *. . . /. 2. -/. ,+. . . . . . . ! . . . . '. + . ,'. . -. .*. 0*. .*. + +. . .*. . . .. . .. . . )( . . . 8. - . ,' +. . ' . . . . . . . . . ,'. . . 54 6. . . . -*. . . . ,'. . . . . . . . . . -. -. '. . . . . . . . . '. ;' )( . . . . :. *. 3'. /#. . . &. . 8 9 9 8. .. 2. . . . . . . 1. 7 . . . . . . . . .*. &. !. . . . %. . . )( %. . . $#. . . . *. . . " . . . . /. -. . . <. . .

(12) u ^BZ>gYt^B]hag x kJwt»J`È2`@dOg m ¼ ¼w§¨ZBwYH{|Y[`] k:Y[df_g b k>wtÇ)^} bs d[cp¼:ÆYtg¼ d[} `zbg kN\)`<Y[»:} ½-d[¼:f_{'b w¼ ]<cHY[w]½Bg \)m g `@f_Y[\)b w!]<m gY[`Y[mb Èyg½Ngd[bkJ]<`kBZB¿lY[g ]<w@kJd[bc<¼ g<d[]<`y^_ZBY[wyk>gg d[mb ]<] k º -¼ OO`»:g½BZBm cHYt} bg ]<mjm ]<Ë¼ |»J½QË`]o »J+YH`½U]<] k>Y[g ^B`@k>d[]<bÛk)wygrt§¨¼m']-cHb]<^B<m`kJ¼ m bb ¾>kJ wyB g ¼¼¦kJa:owdt`Ãg kB] ºµºp] r Yt^B^ `k> ^-Y[kJb bd[b w`@Y[cHdHbY[dl`½ `¨ºµ] Y[Yh`cHbckJ}\Ja:ZBdtdHg ¿qkB]<ZBºµ] d[Yt\J^7ZB¼ d'Y[``bm cHgcd[}b ]<k+¼|¼v~|ilk ¼ -¼ '{|o¢u»JZJ^>`certd[f_¼+b ]]^ g k> gd[`]ilkgYHdO2iHg itk>¼)^BuvÄ)m ]:cH`]<-Çb `@] Y º ¼ZJÆ'amg xf_gkJd[cewtb d[]<»J`@k¨`YtÈ^J] guº=fÃd[¼ }»J¼ `2g\BYHY[Y[Y[b ]BkJÇ-}¦wm ZJb a)\>k>¼ g }+^7m7{}wÆgZJkJkJ¼ } `y`y^Bg]Bd[Ò}+Ç:ºµÆ\B`Y[m¼ dy]}+}:e§Ã`ËOw@g¼d[}-YHb ]<dg kÃk>kJ^h`kJÈ<à:} ZB¹vY[g]<¼ kJ}=k+cH§Ã¼ ]<k+gY[} ] b vY[kJÇ-¼]BcH#} »JB]<¼ \o¢=u{|^B]<Y[ctbf_rtkJ¼>w\Jo b ZB\Jdtm `gcd[rb ]]<ºk>:gO`mcHZBb fzYtg ¿m : ¼ilf_ak:g x ]-d[kJ`^Bwt `»JYtm7`g]ÈNd[ºb ]<uwk ZJ¼ ¼J} kJil`ykJgcegd[d[YH`pb Y[d[]Bk-ZB}OZJd[] wa)m ¼`<}'ZJZ>{cg kgb k:kJ§Ãd[`y`@^BY[g]BkJY[wt}'`»0ZBÆY[^B]<¼ }j`kJc§Ãuv¼>ceguvd[YHZ>ZBd ^BYykJ¼b ]<`BÈ<cj¼ } `pO`vilk-¼ ZB}'Y[§Ã`]<cecHd[gwb Y[b¼b gkJw]Bb]<}]<m kJ¼B`y¼ c' ¼Æo w]< of_rt ¼+\J§ÃZBdtg<r g^-d[Y[b 5]¼ g m ¼ b kJg m bÄ)k:`@d[Y[`@BYHY[})ZJ~|\B¼ d[7b Ë]<k»J`2] ºv¾>gkJ¸7``@ceY[dH`Y[k:ZJdw@¾>d[ZBÄBY[Y[`p`c] ¼BºÆ'd[k»J``mw`ZJw@kJdHY[`y]<gk¨d[`pf_k-bZJw@wY[m]<`cHZJwc']<\Jb kÃb wygkJm+] ceY[d[fhZ>g^-m=½zwy¹jgd[b cOd[»¨g k>\>^gYHºµd[]]_ ¾>k>^Bb kJ<c'fhg<^B`b kQXOm ``cpg k>^ 2g ZBdtg_cH`w@d[b ]<kJc¼+unB\Jm ¼ Ytg b k+¼ '`c¼ ]<m ¼ ¼ -¼ g fhg<^Jg-} g m d[`@Y§N¼ } p]:wt»+}{'¼ }<ÆO^Jg f_c} ¼ §¨ZJm d[b \Jm `{|»>g kJkJ`m cvg k>^!{g m wb ZJf s ½Bk>g fz¿ bo w c¼+ilrkQ§¨ `@d[»J]-^Bcpb k O`ZBY[]<k>g m§¨]-^B`m b kJB¼§ïeË Y[`cHc¼ p]:wt»+}¦{'¼=g k>^Na-`<ìt¼vo¢u^Bctrt¼ ÎÒÕ |Ï " |Ï7ÕtÔ ! Ð >Õ[Ñ'Î ÑjÐÕ[Ñ'ÎÕtÔ ÔÓÐ7Ð Î'Ï DE*:L@576 Ø0*:L@Fµ4 *-S6ñ)å7,@6<×@×tF .B3à¢.B,4(7376 .-L@5+*-Sµ*-ØÃFµ4z46 S µ× Ý # />.)&)F (7Øó4(7,@,@6 3JL Ù Ü Ù 4BÜ 9 9I 99 I ÙqîJÜ 9 ìJò 9 P# .-L*B×@×tF (7Øð4(7,@,@6 3JL Ù hÜ Ù $-Ü 9 9 ë$ Ù JÜ # F CB5)álL@57,@6<×t57.BSµ&Q4 *-Sµ4F (7Ø 4(7,@,@6 3JL Ù Ü Ù JÜ 9 99 Ù[ë JÜ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(14)