Subthalamic nucleus modulates social and anxogenic-like behaviors.

(1)

HAL Id: hal-00845768

https://hal-univ-rennes1.archives-ouvertes.fr/hal-00845768

Submitted on 17 Jul 2013

HAL is a multi-disciplinary open access

archive for the deposit and dissemination of sci-entific research documents, whether they are pub-lished or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Subthalamic nucleus modulates social and anxogenic-like

behaviors.

Jean-Michel Reymann, Florian Naudet, Morgane Pihan, Stephan Saïkali,

Bruno Laviolle, Danièle Bentué-Ferrer

To cite this version:

Jean-Michel Reymann, Florian Naudet, Morgane Pihan, Stephan Saïkali, Bruno Laviolle, et al.. Sub-thalamic nucleus modulates social and anxogenic-like behaviors.. Behavioural Brain Research, Else-vier, 2013, 252C, pp.356-362. �10.1016/j.bbr.2013.05.059�. �hal-00845768�

(2)

1234567689ABC2A7D2EBF2764DEB1A967B6BD9A79DBD5692EBB

B 1B B D6F9A5D7BD!86B"B 1234562789ABC8C2

12 DEF8CFA2 82 8EE82 62 CAFC82 82 34C97F82 CF8EA782 8A2 7FEF B862 !9B7A2 82 "89FE8628EE862!CE982

128EAC82#$E8AFAFE27FEF B862$%&"2'(')2$1362DEFA2824C97F8297FEF B862DEF8CFA282 8EE82628A24*FA72BEF8CFAFC82823EA94F77B628EE862!CE982

#796BC62D4B"B 12"56288C942!877+2

"B5DEDB6245EBA49324DBD$2677!B4B459EB%&B

F6DB'956B

12"52

12 &8CF982 82 87CAFE2 ,E9AFEE87782 E8BC7F B862 4*FA72 3EA94F77B62 -D2 82 8EE862 CB82 -8ECF181.BF77B62)/'))28EE829882'062!CE982

14D(56B16)679B 12"5623452

(3)

12CAFC82#1EAA47F862!9B7A282"89FE82828EE862&)2)362(628EB82B23C2E2 48CEC62)/'2)28EE862!CE982

2B*6977DB 12"56234562789ABC8C2

+69,7DBD42-#DDB 1234562789ABC8C2

12 DEF8CFA2 82 8EE82 62 CAFC82 82 34C97F82 CF8EA782 8A2 7FEF B862 !9B7A2 82 "89FE8628EE862!CE982 B ./1'C+0C1BB B B#796BC62D4B &8CF9828234C97F827FEF B8212$2$E8C2'(')2 -D2828EE8212DEF8CFA2828EE822 -*FA723EA94F77B212(62CB82-8ECF282.BF77B62)/'))2%%&288202 572627))289/9)8'9)62!2627))2(00(9)3((2 1F762,7CFEEB8A:F7;92 B B

(4)

1.B<((92+C=2 2

$E23C>FEE#2F88627729F727?BA8EA2E2EF8A@2C82,C8 B8EA2,A8C2BA47F92EB978B2 <&5%=2 AFB7AFE2 E2 C828E8C77@2 9EF8C82 A2 82 7FE>82 +FA42 9F1,F7F72 7A8CAFE2 FEB982 @2 A482AC28,,89A2,2AFB7AFE;2A824@A48FB82A4A2A482&5%2F28C282FE782FE2A488294E82E2 F82A287C82A482C782,2&5%2FE29F72E2E8EF917F>8284FBC2BFE2E2EF7287;2 02 782 AFAC2 CA2 +FA42 F7A8C72 78FE2 ,2 A482 &5%2 +8C82 9C82 A2 (82 4178FE82 CA2 @2 @E94CEFBFE2 E2 8A47F972 C942 82 BE2 FC89A2 8CAFE2 ,2 9F72 84FBC2 E2 2 AECF82C9462A482878A827B1B82<3"=;2CFE28A+88E2CB2+8C828C,C82 @22"EECA4FAE8@CAF79E2A8A;22

8FE82CA24+82FFC8EA2FE2A48FC29F72<D';'/=2E2C8F8284FBC2+FA422FFEBAFE2 ,2AA9>FE2<D';'2=2E294FE2<D';'8=;2$E2A4823"629E98CEFE2A4828E2C62A4828C98EA82,2 FAE9862 AF862 FE9AF82AF862 E28EAC@2 +8C82 FEF,F9EA7@2 89C882 FE2 78FE82CA2 <D';'(62D';'62 D';'22E2D';'/=;25482AF828EA2FE2EE1CA89A82482F2+272FFEF482FE2A48278FE82CA2 <2D2';'=;2

54882C8B7A2ACE7@2F7F9A82A482&5%2FE29F7284FBC2E2E8EF917F>8284FBC;2$E24BE62 FE98254&2FEB98294E82FE2A482BE8C7@FE2@EF92,2A482AFB7A82CFE2E8A+C>62FA29B729C8A82 E2 EC72 CFE2 AA82 FE2 +4F942 EF8A@2 E2 9F72 84FBC2 C82 7A8C8;2 54882 C8B7A2 4F47F4A2 EA48C278872,2978FA@2,2A48284FBC7294E82,A8C2AFB7AFE;2

2

(5)

0C+.0C2 2

&7F4A2 A2 88C82 772 9F72 7?BA8EA2 F2 ,C8 B8EA2 FE2 AF8EA2 B,,8CFE2 ,C2 3C>FEE2 5F882 <35=2,A8C2BA47F92EB978B2<&5%=2882CFE2AFB7AFE;2$E2A4882AF8EA62A482AC2FC88EA2 ,A8C2BC8C@2F2,77+82FE282982@2A4828A8CFCAFE2,29E?B72C87AFE4F2+4F942C82ACF8C82 C2CA82A8CAF87@2@2A48288C8E982,288C82EF8A@2E1(F;2$A24288E24@A48F82A4A2 A4882FEA8C8CE729E,7F9A2+8C82FE27FE82+FA42E288C8EA2C8CA@2,2@A8F92FEA8C9AFE28A+88E2A482 AF8EA62+42B8E7@2C8FE82A48FC2BAE@62E2A48FC28A82B862+427A2A48FC2,BE9AFE2,A8C2 @8C2,2F882C87A829FE2E29C8;2$A2427288E24@A48F82A4A2B942@947F972 F828,,89A2+8C82B82A2B8E2C8B9AFE2FE2FE82C87988EA2A48C@2FEB9FE22FE8CF92 8,F9FA2FE29FAF17FF92C82,2A482CFE2E)F;22

%88CA487862 F,2 A482 &5%2 F2 2 CA2 ,2 A482 72 E7F2 +4F942 F2 +8772 >E+E2 A2 82 FE782 FE2 8AC@CF729EAC72,288EA2E218F62FA2F2727FE>82+FA42ACB9ABC82FE782FE2A4829EAC72,2EE1 AC284FBC2F2F,,8C8EA2E8BC729FAF82E27FF929FC9BFA2E3F;254882,BE9AFE72E8A+C>2@2 82 ,2 FEA8C8A2 FE2 84FBC72 C8B7AFE2 E2 A482 &5%2 882 CFE2 AFB7AFE2 <54&=2 9B72 82 8C2 82 FE782FE2G29F727?BA8EA2E2(G288C8E982,2EF8A@;2"C88C62@947F972F828,,89A2 89CF82 +FA42 54&2 4B72 F,,8C2 C8CFE2 8789AC82 AC8A2 7988EA2 +FA4FE2 F,,8C8EA2 &5%2 B1 A8CCFACF8;258FA82A482EB8C2,2&5%2BFFFE2E2A48FC2EAF972797FAFE2F2AF772BE98CAFE2E9F62 FA24288E2B8A82A4A2A4828EAC72CA2,2A482&5%2F29787@2FE782FE2A4828AFE72E8A+C>2E0F;2 A4F782A482E8BCE7282,2A4828,,89A2,254&2C8FE2BE978C2E'F62FA2+24@A48F82A4A2G294E82 FE2A482BE8C7@FE2@EF92,2A482AFB7A82CFE2E8A+C>2@2C8C88EA2A4829C82894EF2,254&2 E2 (G2 A482 F92 @EF972 94E82 9E2 82 94F882 F2 9AFAFE62 FE4FFAFE62 C2 78FE2 EF;2 E98CEFE2 &5%2 78FE2 FE2 4BE62 BA47A@2 9B72 82 2 A8C8A9AF92 BC8C@2 8C,C82 FE2 AF8EA2 B,,8CFE2 ,C2 352 FE2 9FC9BAE982 +48E2 882 CFE2 AFB7AFE2 F2 EA2 F782 E(F;2 HE7@2 E82 772 C89AF82 AB@2 FE97BFE2 '2 AF8EA2 ,BE2 E2 94E82 9E98CEFE2 EF8A@2 ,77+FE2 BA47A@2E)F2E62A2BC2>E+78862E2C8FB2AB@242FE8AFA82FA2F9A2BE24BE2 9F7284FBC;2

54B62EF728729B72CF82E2CABEFA@2,C288CF8EA72EFB7AFE2A4A2C82EA2F782 FE2 4BE2 E2 9E2 77+2 ,C2 87CFE2 BC2 4@A488;2 52 BC2 >E+78862 A48C82 +2 E2 C8FB2 FE8AFAFE2,29E8 B8E982BE29F7284FBC2,2&5%2FE9AFAFE29CCF82BA2FE2EF7;22

54B62 A4F2 AB@2 F82 A2 87C82 A482 C782 ,2 &5%2 E2 CA#2 9F72 E2 E8EF917F>82 84FBC2 @2 @E94CEFBFE2A+29788EAC@28A462=2E28A47F972C94282BE2FC89A28CAFE2 ,22+F82CE82,29F7284FBC2E2F62E2(=22AECF82C942BFE2A482878A827B1B82 <3"=622I72AECJ2A8A2A287C82EF8A@27F>8284FBC2E/F;2

(6)

B F/0*BC+BF/+1B B 12345678 8 1B7A62782AFAC2CA2<K=62+8F4FE2(''1)''22A2A4828FEEFE2,2A48288CF8EA62+8C82>8A222 8C2982FE2E2C82EF724B82A2((2L2(2M62FE2(1427F4AGC>29@9782<7F4A2E2A2'9''24=;252 +A8C2E2,28778A2+8C82F778259863A3BC4;25482EF72+8C82,F7FCFB82+FA42A482EF724B82A2 78A2 A8E2 @2 8,C82 BC8C@;2 5482 C88C948C2 C82 C82 @2 A482 N8A8CFEC@2 8CA8EA2 ,2 A482 !C8E942 "FEFAC@2 ,2 -87A4 (BA4CFBAFE2 EB8C2 )/1'=;2 1772 EF72 88CF8EA2 +8C82 9CCF82 BA2 FE2

99CE982A2A482BC8E2BEFAF82BE9F725FC89AF82<98G8'0G=; 54829C82CF82A2A482

8,C862 BCFE2 E2 ,A8C2 A482 CA972 +2 FE2 97FE982 +FA42 8A4F972 AEC2 E2 2 7CAC@2 C9AF98;2

2

DCEF3568E9CE78 8

5482 EF72 +8C82 E8A48AFB82 +FA42 )/'2 G>2 947C72 4@CA82 FE?89A82 FEAC8CFAE877@2 E2 89BC82 FEA22O,2A8C8AF92CAB2<34@8623CF62!CE98=;28FE82CA2C898F82F7A8C72FE?89AFE2,2

FA8EF929F2<0;22µGµ2</)2"=62FE2';2"244A81B,,8C827FE8628;/2P2-2P23=;2&418CA82

CA2C898F8284F97827E82<';2"244A81B,,8C827FE8=;2$EFAF77@62A4827B82FE?89A82+2'6/2µ2

8C2 F82 E2 +2 7+7@2 FE,B82 8C2 )2 FE2 BFE2 2 '1µ72 -F7AE2 @CFE8;2 2 5482 E88782 +2 78,A2 FE2

7982,C2A4C882FE2,A8C2978AFE2,2A482FE?89AFE;2%88CA48786222772CCAFE2,2CA24+82 BAEAF72CFE278FE2,A8C24FA7F9728CF,F9AFE62FA2+289F82A2FE?89A22µ28C2F8;22 54829CFEA82AC8AFE2A482&5%2+8C828A8CFE8299CFE2A23FE2AAE#2A72E8F2E2+8C82 8BC82,C2C862EA8CFCGA8CFC6212);32Q27A8C762±2(;22Q2C7G8EAC72129;922<,C2 >B77=;23A8CAF87@62CA2+8C824B82FEFFB77@2FE2978C2 BC827AF9298;2 2 53CE568B7B32F88 5482828C8C28C,C82772A482,77+FE284FC72A8AFE;2 2 (D59D7B 1A2@2(2,A8C2BC8C@62CA2+8C82FEFFB77@27982FE2378F72948C2<2/222/22)'29=2A227F4A2 FEA8EFA@2,2)'27;2548FC2EAE8B2AC29AFFA@2+28BC82FE28C2FE2,C22AA72BCAFE2,2'2

(7)

FE62 BFE2 2 88EA2 E7@F2 @A82 <4F8R6_{2 4F77862 !CE98=62 +4F942 9BEA2 88EA2 @2} 9EEFE2(2282FC2,2FE,CC824A82E2A482F82+772E277+2,C28BCFE2EAE8B2 9AFFA@2FE2A4828E2,F872FE27+8C2FAFE2E2FE2B8C2FAFE;2!BCA48CC8622772EF72+8C827982 FE2A4828E2,F8762A4F248277+82,C24FABAFE2A2A482A8AFE2CAB2B82FE29F72FEA8C9AFE2 A8A;2 2 1A967B94D6A49B4DE4B 54828E8C728FE2,2A4829F72FEA8C9AFE2A8A2+2A82,C2!F7828A27;2E3F62&94E8F8C28A27;2E91 0F62E2B889>28A27;2E('F;2&9F72FEA8C9AFE2+8C82882A2A4C882F,,8C8EA2AF82FEA2<@2)62 22 E2 /2 ,A8C2 BC8C@=2 FE2 A482 8E2 ,F872 <BE8C2 A482 9EFAFE2 89CF82 8=2 +48C82 CA2 +8C82 882A2E2BE,F7FC29F72CAE8C2,C2'2FE;2FE82E2A482AF72+8C82C+E2E242E278FE82 CA2FE2C8C2A2C89EFB82A482,C2A48FC29E8E8C;2

3CAE8C2 B82 FE2 9F72 FEA8C9AFE2 A8A2 +8C82 ,C882 ,2 E@2 BCF972 FEA8C8EAFE;2 5482 A8A2 C82 +2 978E82 +FA42 2 /S2 79472 7BAFE2 ,A8C2 8942 ACF7;2 5482 A+2 CA2 +8C82 C89C82 +FA42 2 FFA72 F82 98C2 E2 8 B8EAF72 8788EA2 ,2 84FC2 +8C82 E7@B82 EB77@2 @2 2 ACFE82 E2 7FE82 8C8C;25482,77+FE284FC728788EA2+8C82 BEAF,F82<8E2EB8C2,299BCC8E982BCFE2A482 A4C8828FE=2FE2A48288CF8EA72CA2<42C278FE8=62EE29F7284FC629F7284FC2E2 C8F82 84FC;2 484FC2 +8C82 72 9A8CFB82 2 FEEA2 C2 BFF8;2 12 8AF782 89CFAFE2,2A488284FC2F2F8E2FE24637DB6;2 B /7D64DB(72E867DB8/'F9B 2 54F2A8A2+28C,C82A2@282,A8C2BC8C@;254823"2+282,2+2E2FEA8279>;25482 CAB29EFA82,2A+2FA828E2C2<2/22'29=2+FA4BA2F82+772E2A+28E9782C2 <2/22'22)'29=2+FA42F82E28E2+77628A8EFE2,C2298EAC72 BC82<'22'29=;25482B82 +2 878A82 A2 A482 48F4A2 ,2 8'2 92 ,C2 A482 ,7C2 E2 7982 FE2 2 8CA87@2 7FA2 C2 <)'2 72 2 8BC82A2A48298EAC82,2A482B8=;21A2A482A8A2E8A62A482EF72+8C827982A2A48298EAC82,2A482 3"62,9FE2A+C2E28E2C;2

5482 NF815C9>R_{2 @A82 B82 ,C2 C89CFE2 A482 EF72 84FC2 +2 982 ,2 2 C,14E782}

98C2 9EE89A82 A2 2 9BA8C;2 54F2 CAB2 8BC82 9AFFA@2 C2 FE9AFFA@2 AF82 E2 FAE982 98C82FE28942CA2,2A482B82FE28E2C29782C2C298EA8C62FEBA828C2FEBA862,C2,F82FEBA8;2 5482,F82,77+FE29E8EAFE72C8A8C2+8C82C89C862AA72FAE98298C862EB8C2,28EAC@2FE2

A4828E2C628C98EA82,2FAE982E2,2AF828EA2FE2A4828E2C62E28C98EA82,2FE9AF82

(8)

A2 FEFFB82 A482 FF7FA@2 ,781E8AF82 C8B7A2 E(F62 A4C882 8A47F972 C8A8C2 +8C82 C89C82 E2 F8A82E2E7@B82@228CE2EA2FE782FE2A48288CF8EA72C98BC8;25482AF828A82A2 A482 ,77+FE2 84FC72 9AFFAF82 +2 A48E2 C89C862 =2 CF>2 88EA2 <1=62 A482 CA2 8FAFE2 E2 8E9782 C2 +FA42 A482 ,C8+2 E2 482 E7@2 E2 FE8AFAFE2 A482 BCCBEFE62 EA2 E898CF7@2 99EF82@2@2AC8A94FEQ2(=2CA89A82482F2<3-5=62A482CA2AC8A94FE2A2F2FA2482FEA2A482 8E2982E28C82A4828EFCE8EA62A482C8C2CA2,2A482@2C8FEFE2FE229782CQ2E2)=2 EE1CA89A82 482 F2 <%3-5=62 A482 CA2 FFE2 FA2 482 FEA2 A482 8E2 982 E2 8CFE2 A482 8EFCE8EA62A482@2FE2E28E2C;222 54823"2+2978E828A+88E2A48288CF8EA2+FA422/S2794727BAFE;2 B 37B6F3568E335B328867328 8 1A2A4828E2,2A48288CF8EA62A482EF72+8C82E8A48AFB82+FA42)/'2G>2947C724@CA82FE?89A82 FEAC8CFAE877@2E289FAA8;22 5482CFE2+8C82C882E27982FE2);32S2,C784@82,C22924BC62C9882E28882FE2 C,,FE;2CE7289AFE2+8C829BA2A22A4F9>E82,2/2µ288C@2/'2µ2FE2A482%&52C82E2AFE82

+FA42 48A@7FE18FE1,,CE2 <-&=;2 1,A8C2 AFEFE62 7F82 +8C82 8C82 BE8C2 E2 AF972 F9C982<%F>E29'F=;21E288CF8EA8C2BE+C82,2A482EF7#284FBC728C,CE9828C,C82 E24FA7F9728CF,F9AFE2,2A482F9CFE?89AFE2FA8;28FE2+8C8289CF82+FA42C8,8C8E982A23FE2 E2AAE#2A8C8AF92CA2CFE2A72E8F;2"8BC82+8C828C,C82BFE2A482,A+C82$8K2R2 <"92 4F4AEF9=;2 HE7@2 CA2 +FA42 F7A8C72 78FE2 ,2 A482 &5%2 +8C82 >8A2 FE2 A482 E7@F2 E2 A482 8E982,278FE2+28CF,F82FE242CA;22 B DB5B37B356852567378 &AAFAF972E7@F2+28C,C82+FA42&1&2AAFAF972,A+C8628CFE20;(2<&1&2$EAFABA862C@62%62 D&1=2E22<258878EA2C8258=;28B7A2C82C88EA822CFA48AF928E2E2AEC28CCC2 ,2A4828E2<2L2;8;;=;2548278872,2FEF,F9E982+28A2A2';'/;2

CFE2 8A+88E2 CB2 +8C82 8C,C82 @2 2 "EECA4FAE8@CAF79E2 A8A;2 52 ?BA2 BC2 9CFE28A+88E29F7284FBC2,278FE82E242CA2E2A4829E,BEFE28,,89A2,2AF7FA@62 2 8E8C72 7FE8C2 872 +2 B8;2 5482 88E8EA2 CF782 +2 A482 EB8C2 ,2 84FBCQ2 A482 A+2 87EAC@2 CF782 +8C82 A482 CB2 <C8,8C8E9862 78FE8=2 E2 A482 EAE8B2 9AFFA@2 FE2 7+8C2 FAFE2FE2A4828E2,F872<F7FA@=2A2@2(;2

2

(9)

2

12345678 8

1E22928CA82CA620242F7A8C7278FE2,2A482&5%2E2+8C82>8A2FE2A482E7@F;2$E8862,C2 A482A48C2(02CA2E278FE2+28C82,C2A482&5%2E278FE2FEA8C8A82A48C2CA2,2A482CFE;2(82 42 CA2 +8C82 72 FE97B82 FE2 A482 E7@F;2 5+2 78FE82 CA2 E2 )2 418CA82 CA2 F2 EA2 CAF9FA82A29F72FEA8C9AFE2A8A2B82A2A894EF972C78 (91C2+8C824@F977@28=;22 8 37B6F8 8 #92DB624+22C8C88EAAF8289AFE2,C22429EAC72E2E2EF72+FA42E2&5%278FE;2&5%2 78FE82EF724+82272,2E8BCE2A4A2+2FE7@2C8ACF9A82A2A482&5%62+FA427FAA78282A2 ACB9ABC82BAF82A482&5%;2 B 53CE568B7B32F88 B (D59D7B

%2 F,,8C8E982 +2 8C82 8A+88E2 78FE82E2 418CA82 CA2 9E98CEFE2 A48FC2 EAE8B2 9AFFA@2 FE2 A482 8E2 ,F872 FE2 7+8C2 FAFE2 220'2 L2 2/02 9BEA2 8CB2 23)82 L2 ()02 9BEA2 C889AF87@2 <D';(/=2C2FE2B8C2FAFE293'2L2)/28CB2''82L20'29BEA2C889AF87@2<D';0=;22

2

1A967B94D6A49B4DE4B

A4F782A48FC2 EE2 9F72 84FBC2 +2 EA2 FEF,F9EA7@2 FFC8 <'9;2 L2 3;32 2 03;22 L2 2;962 D';)9=62

78FE82CA24+82FFC8EA2FE2A48FC29F72<3;(2L23;022');'2L2;(62D';'/=2E2C8F82 84FBC2<32;32L28;'220';02L28;(62AC8E2A+C2AAFAF972FEF,F9E9862D';'8=2+48E29C82A2 418CA82CA;B637DB:BC88EA2A4828AF72,2FFC8284FBC; 2 A48E2?BAFE2E2A4829E,BEFE28,,89A2,2AF7FA@62A4882F,,8C8E9829E98CEFE29F72<D';')=2E2 C8F8284FBC2<+FA422AC8E2A2AAFAF972 FEF,F9E9862D';'9=2+8C82C88C8;2"C88C62A482 B7AFCFA82E7@F29E98CEFE2EE29F7284FBC2B8A82A4A278FE82CA2C88EA82C82EE1 9F72 84FBC2 <D';'2=;2 8B7A2 ,2 A4882 872 C82 C88EA82 FE2 592DB :;2 1E@2 BA7F8C2 +8C82 F8EAF,F82 E2 C8862 +4F782 A482 C8B7A2 +8C82 BE94E82 ,C2 9F72 E2 C8F82 84FBC2 A482 F,,8C8E9828A+88E2CB29E98CEFE2EE19F7284FBC28982EE1FEF,F9EA2>FE2A4F2C8B7A2 782CBA2A4E2A482A+2A48C;2

(10)

/7D64D(72EB867DB

8B7A2,29E8EAFE72E28A47F972C8A8C2C824+E2FE2592DB;;2E98CEFE2A4829E8EAFE72 C8A8C62 +48C82 A482 AA72 FAE982 98C82 FE2 A482 +4782 3"2 +2 EA2 AAFAF977@2 FEF,F9EA2 F,,8C8EA28A+88E278FE82E2418CA82CB62A4828C98EA82,2FAE98298C82FE2A4828E2 C62A4828C98EA82,2AF82FE2A4828E2C62E8A4828C98EA82,2FE9AF82AF828EA2FE2A4828E2 C62 +8C82 FEF,F9EA7@2 89C882 FE2 A482 78FE82 CA2 <D';'(62 D';'2 E2 D';'262 C889AF87@=;2 17A4B42EA2FEF,F9EA62A482EB8C2,28EAC@2FE2A4828E2C272A8E82A289C882<D';'/(=;22 E98CEFE2 A482 A4C882 8A47F972 C8A8C62 E7@2 A482 AF82 8EA2 FE2 EE1CA89A82 482 F2 +2 FEF,F9EA7@2FFEF482FE2A48278FE82CA2<D';'=;2

B

+01.110CB B

DC445E883928

54F2 AB@2 9CCCA82 BC2 4@A4882 @2 4+FE2 A4A2 A482 &5%2 F2 F7F9A82 FE2 9F72 84FBC2 C8B7AFE2 E2 FE2 E8EF917F>82 84FC;2 8FE82 CA2 C88EA82 FFC8EA2 FE2 9F72 E2 C8F8284FBC2+48C82A48FC2EE29F7284FBC2+8C82EA2,,89A8;254882,FEFE2F2EA2 C8B7A2,C294E82FE2AC29AFFA@2FE982A48289C882FE29F72FEA8C8A28CFA82,A8C2?BA8EA2E2 CA#2AF7FA@;28FE82CA2+8C82782C8F82FE2A482+4782+FA42E2F,,8C8E9828A+88E2FEEA2E2 BFF8284FC;2B 8FE82CA2724+82C82E8EF917F>8284FBC2FE2A4823"622F77BACA82@2E2FE9C882,2 A482AF828EA2FE2A4828E9782C2E/F;254F2C8B7A2F2FE27FE82+FA42C8FB2,FEFE2FE24BE2,A8C2882 CFE2 AFB7AFE2 +48C82 E2 FE9C882 FE2 EF8A@2 +2 8C82 A8CAF87@2 E62 ((1(2F;2 -+88C2 FA2 9EACA2+FA42A482A48C8BAF928,,89A2,2&5%2AFB7AFE2FE28F829B7F82FC8C2E(/F2+4F942F22 +8772 >E+E2 EFB2 FC8C2 E2 +FA42 A482 E7@2 E2 +8>2 8F8E982 BE2 '2 AF8EA2 +42 BE8C+8EA2 BA47A@2+42F2EA288CF8E98294E829E98CEFE2EF8A@2E)F;2E98CEFE2EF7#28762 BC2C8B7A29EACA2+FA42O78FE28A27;#2E2C8828A27;#2C8FB2,FEFE2FE2+4F942278FE2,2A482&5%2C2 2 &5%2 54&2 F2 EA2 ,,89A2 E8EF917F>82 84FBC2 E(81(3F;2 1E2 4E7FE2 ,C2 BA2 (2 FE2 F7@2 ,C2 32 @2CFC2A2A4828FEEFE2,2A48284FBC7288CF8EA2FE2O78FE#2AB@22+87722E28A8EF82F7@2 4E7FE2<T2(2+88>=2FE2C88#2AB@29B7299BEA2,C2A4828C82F,,8C8E98;2$E8862E82,2BC2 C8FB2 88CF8EA2 B8A82 A4A2 4E7FE2 42 C89F87@2 E2 EF7@AF917F>82 8,,89A2 E(9F;2 "C88C62 FE2 O78FE#2AB@6284FBC7288CF8EA2ACA8282+88>2,A8C2BC8C@2+48C82FE2BC2AB@2A4823"2+2 B82B9428C7F8C2<82@2,A8C2BC8C@=;21772A8A48C62A4882C8B7A2B8A22F782AF818,,89A2,2 &5%2FE9AFAFE2BE2EFB284FBC2+FA42F782AAF82894EF2,27AF9FA@29EAC77FE2 EF8A@2 E2 CF82 E8+2 8C89AF82 9E98CEFE2 2 7EFABFE72 E7@F2 ,2 78FE82 CA#2 84FBC;2

(11)

!BCA48C2 88CF8EA2 4B72 9EF8C2 A8AFE2 ,A8C2 C82 8A8EF82 4E7FE2 EGC2 A8AFE2 A2 F,,8C8EA2 AF82FEA;2

8

E7B38

34C97FA2 BB77@2 9EF8C2 9F72 FEA8C9AFE2 A8A2 2 2 A8A2 ,2 EF8A@2 E3F62 82 E2 2 EABC72 ,C2 ,2 84FBC2 @2 FC2 ,2 782 CA2 FE2 F,,8C8EA2 >FE2 ,2 9F72 FEA8C9AFE;2 1E2 FE9C882 FE2 9F72 FEA8C9AFE2F29EF8C82A2C8,789A2E2EF7@AF917F>828,,89A2E2289C882FEF9A82E2EF8EF917F>82 8,,89A;2 $A2 42 88E2 4+E2 A2 82 8EFAF82 A2 94E82 FE2 EF8A@2 8E8CA82 @2 EE4C97F972 ,9AC2E3F;2%88CA487862C8B7A28C82FE29F72FEA8C9AFE2A8A2482A282BA2FEA28C89AF8;2 $E8862 A4882 A8A2 87C82 88CF8EA72 CA#2 84FBC2 FE2 A482 C88E982 ,2 2 9E8E8C2 BA2 72 A482 9E8E8C#284FBC2FE2A482C88E982,2A48288CF8EA72CA62E2A48299BCC8E982,22CAF9B7C2EE2 9F729A2@2FA87,28229F7248E8EE2E2F;2$E88629F7284FBC2,2A482CA2F2EA2E7@2A482 C8,789A2,2A48FC28C,CE982FE2A48C2872,2EF8A@2E(01)'F2E29F72FEA8C9AFE2A8A22EA2787@2 87C82 8AFE72 C9882 BA2 2 C82 772 78872 ,2 ,BE9AFEFE2 FE97BFE2 AC62 9EFAF82 E2 AFAFE72C988;2

!C2 2 ,BE9AFE72 FEA2 ,2 F8+2 A482 &5%62 +FA42 FA2 A4C882 F,,8C8EA2 B2 A8CCFAC@2 <7FF962 9FAF82 E2 AC2 C8=62 42 C89F87@2 E2 FEA8CAF82 ,BE9AFE2 A2 A482 FEA8C,982 8A+88E2 AFAFE62 9EFAFE2 E2 9AFE;2$A2F2277278E1482ACB9ABC82+4F942B7A82A482E8BCACEFFE2FE27FF92C8FE2,2 A482 CFE2 E)F2 FE782 FE2 EF8A@2 C8B7AFE;2 8CF8EA77@62 EE1AC2 C782 ,2 A482 &5%2 42 88E2 9E,FC82 FE2 CA62 CAF9B7C7@2 ,C2 FB7F82 84FBC2 E)(1))F62 AFAFE72 ,BE9AFE2 E)2F2 E2 AA8EAFE728C,CE982E)/F;2&5%272B7A82F,,8C8EA7@2A4828,,89A2,2EABC72C8+C627F>82,62C2 CB2 B862 7F>82 99FE862 E2 84FBC2 E)8F;2 &5%2 -!&2 72 ACEF8EA7@2 FFC2 AA8EAFE2 FE2 2 FB72 AA8EAFE2A>2E)3F;2$A2+24+E2A4A2FE9AFAFE2,2A482CA2&5%28>828C8F827F>8184FBC2FE2A482 ,C982+F2A8A2<5887628A272(''3=2E272FE2A48278CE248778E82A8A2E(81(3F;2$E24BE2762&5%2 54&28C828,,89A2E29EFAFE6284FBC622E28AFE2C82+8772>E+E2E)912F;22

1772A8A48C62A4882F,F9AFE29E27A8C29F7284FBC;2HBC2AB@282EA277+2,C2F9CFFEAFE2 A482 8,,89A2 ,2 8942 ,2 A4882 F8EFE2 BE2 9F72 84FBC2 BA2 978C7@2 89CF82 FE2 E2 8A47F972 8C89AF862 B7FAAF82 FFC8EA2 ,2 9F72 84FBC2 2 2 A8EAF72 C8B7A2 ,2 A4882 B7AF782 7A8CAFE;2"C88C62FE24BE62FE23562&5%2AFB7AFE29B72,,89A2548C@2,2"FE2%8A+C>2E2(F2E2 9B7282F7F9A82FE29AFE28CAFE2E29AFE2BE8CAEFE2E2)F;254882F,F9AFE2,29F72 9EFAFE2F4A287FE282,2A48284FBC72FABCE982C87A82A2&5%2AFB7AFE2FE2AF8EA;2H,2 9BC82B942AFB7AFE24@A48829E2EA282ABF82FE2C8EA2E22F2BA2FA2F2EAF98782A4A62FE2BC2 8762E7@29F7284FBC2+48C82FFC82+48C82EE29F7284FBC2+8C82C88C8;22222 343B5B3271

(12)

54828AC7AFE2,C22CA2872A2A48297FEF9729EFAFE24B728282+FA42C8A29BAFE;2!FCA7@62 BC2 CA2 872 +FA42 F7A8C72 BA47F92 78FE2 FEB982 +FA42 FA8EF92 9F2 FE?89AFE2 F2 EA2 C877@2 C8C88EAAF82,2A48297FEF972FABAFE2F8E2A482FEA8CFA@2,2FE8CF92C?89AFE;2&89E7@624B82 84FBC72 F,,8C8E982 FE2 EF8A@62 87CAFE2 E2 9F72 84FBC2 8FA2 8A+88E2 89F82 E2 88E2 8A+88E2F,,8C8EA2ACFE2,228289F822FA2+24+E2,C2CA2E(0622/F;254B2A482CBAE82,2A482 C88EA2 ,FEFE2 4B72 82 A8A82 FE2 A48C2 EF72 872 E2 +4F942 89F,F92 ABF82 ,2 9F72 84FBC2FE2E>8@24B7282,2CAF9B7C2FEA8C8A;2$A2+B7277+2,C287CAFE2,2A482F,,8C8EA2B2 A8CCFAC@2 <7FF962 9FAF82 E2 AC2 C8=2 ,2 A482 &5%2 E28F;2 $E882 A482 CA#2 &5%2 F2 2 8C@2 772 ACB9ABC82FE2+4F94289F,F92FE8AFAFE2,2FA2B1A8CCFACF82F29AB77@2FF78;2

2

26C7328

1

5482 C8B7A2 ,2 A482 C88EA2 AB@2 ACE7@2 F7F9A82 A482 &5%2 FE2 9F72 84FBC2 E2 E8EF917F>82 84FBC2FE2CA;2$E24BE62FE98254&2FEB98294E82FE2A482BE8C7@FE2@EF92,2A482AFB7A82 CFE2 E8A+C>2 FA2 9B72 9C8A82 E2 EC72 CFE2 AA82 FE2 +FA942 EF8A@2 E2 9F72 84FBC2 C82 ,,89A8;2 $A2 82 EA2 8E2 A4A2 9F72 7?BA8EA2 F2 EA2 7FE>82 +FA42 AAFE2 F,,F9B7AF82 E2 CAF92 9F1,F7F72 F,F9AFE2 FEB982 @2 A482 AC2 8,,89A2 ,2 54&62 BA2 FA2 4F47F4A2 EA48C2 F78278872,2978FA@2,2A488284FBC7294E82,A8C2AFB7AFE;2

HA48C2 EF72 E2 4BE2 ABF82 C82 E8882 A2 9E,FC2 CBAE82 ,2 A4882 ,FEFE2 E2 A2 2 2 7EFABFE728C89AF8;2$,2A482F7F9AFE2,2&5%2BE29F7284FBC2F29E,FC8622E8+294778E82 4B7282A28872FEA8C8EAFE2+FA42782F9A2E2A488284FBC7289A2C2FEA8C8EAFE2+4F942 9B724872AFB7A82AF8EA2A2982+FA42A482CAF9294E82FE2A48FC29F72,BE9AFEFE;2 B 2C3*/+1/F/C1B B

A82 +B72 7F>82 A2 A4E>2 A482 8EE82 2 DEF8CFA@2 D!2 ,2 "8F9FE82 ,C2 FA2 ,FEE9F72 BCA62 "C2 KB7F82 UB8CB8C42E2"C2K8E14CFA482B8@C82,C2A48FC27B782A894EF972FAE982E2"C27BFE82 %B8A2,C2C8FFE2A482E7F4;2A82A4E>278F8C2,C2CEAFE2B28CFFE2A2C8CB9822,FBC82,C2 I5DB 64B 699B 14DD469AB .964DEJ2 H"3152 5-$52 5$5$H%2 @2 .8C82 3FE2 E2 4C782AAE62198F923C862$E9;62(''362$&4%62'1(1/238()1V;2

5482 EC2 42 E2 C782 9E98CEFE62 8FE2 E2 9EB9A2 ,2 A482 AB@Q2 97789AFE62 E88EA62 E7@F62E2FEA8CC8AAFE2,2A482AQ2E2C8CAFE62C8F8+62C2C72,2A482EB9CFA;2

(13)

#2962 8EE82 2 DEF8CFA@2 D!2 ,2 "8F9FE8Q2 A482 EC2 42 E2 C782 9E98CEFE62 8FE2 E2 9EB9A2,2A482AB@Q297789AFE62E88EA62E7@F62E2FEA8CC8AAFE2,2A482AQ2E2C8CAFE62 C8F8+62C2C72,2A482EB9CFA;2

.579A4B5B94DDE4E6B

548C82 C82 E2 9E,7F9A2 ,2 FEA8C8A2 C8CFE2 A4F2 8C;2 1772 BA4C2 482 978A82 A482 DEF,F82

8AFE2 $EA8C8A2 ,C2 A24AA6GG+++;F9?8;CG9FWF97BC8;,2 <F7782 E2 C8 B8A2 ,C2 A482

9CC8EFE2 BA4C=2 E2 897C82 A4A2 <=2 %2 BA4C2 482 BCA2 ,C2 E@2 9E@2 ,C2 A482 BFAA82+C>Q2<(=2;K;";23;";2;4;24;!;5;2482E2C87AFE4F2+FA42E@29E@2A4A2F4A2482E2 FEA8C8A2 FE2 A482 BFAA82 +C>2 FE2 A482 C8FB2 )2 @8CQ2 %;!;2 42 C87AFE4F2 <C2 88C4F2 C2 5C87G99AFE288E8298C8GC8FBC8=2+FA42&8CF8C624"&62BE89>2E2KE8E2+42 F4A2482E2FEA8C8A2FE2A482+C>2BFAA82FE2A482C8FB2)2@8C2Q2<)=2;K;";2%;!;23;";2;4;24;!;5;2 B862 CAE8C62 C2 94F7C8E2 482 E2 ,FEE9F72 C87AFE4F2 A4A2 @2 82 C878EA2 A2 A482 BFAA82 +C>Q2E2<2=2EE82,2A482BA4C242E@2EE1,FEE9F72FEA8C8A2A4A2@282C878EA2A2A482BFAA82 +C>;2

245EBA493249E6B

K8E2 "F94872 8@EE2 42 ,B772 9982 A2 772 ,2 A482 A2 FE2 A482 AB@2 E2 A>82 C8EFF7FA@2 ,C2 A482 FEA8CFA@2,2A482A2E2A48299BC9@2,2A482A2E7@F;2 E98F82E28FE82A48288CF8EA62;K;";2E24;!;5;2 38C,C82A48288CF8EA62;K;";23;";2E24;!;5;2 1E7@B82A482A62;4;2%;!;22 EACFBA82C88EAGA8CF7GE7@F2A762%;!;22 ACA82A4828C62%;!;2;K;";2E24;!;5;2 8F82A4828C29CFAF977@2,C2FCAEA2FEA87789AB729EA8EA623;";2;4;2 !FE72C72,2A4828CFE2A282B7F4862;K;";2%;!;23;";2;4;24;!;5;2 2 /<00C1B B 35623C>FEE25F8822 &5%62&B547F92%B978B2 3"6278A8237B2"B8B 2

(14)

/#//C./1B 2 EF2-B8A2K62"8E82N62"778A2623F77E2462.CFB72"62B2"E9872&5628A27;2484FBC72FC8C62 3C>FEEX2F882E2BA47F92AFB7AFE;2K2%8BC72%8BCBC23@94FAC@;2(''(Q3(63'13;2 E(F238CBB2362FBBE82"6248C92462A877F262EAA82"62587721628A27;25882CFE2AFB7AFE2 ,2BA47F92EB978B6284FBC72F,F9AFE2E2,F7FC2C87AFE;2%8BC72&9F;2(''Q((691(;2 E)F2B8CE89>F2N62&94B942"62YF9F2&628@2624CFE8A262Y87EF>2K628A27;21A4@2,77+FE2BA47F92 AFB7AFE2FE23C>FEE2F88622FE82C8EF82@A;2"25FC;2(''9Q()608210;2 E2F23C8EA2162-BCAF2%;2!BE9AFE72EA@2,2A48272E7F;2$;254829CAF9172E7F1A471 9CAF9727;24CFE2824CFE2828;200/Q('601(3;2 E/F23C8EA2162-BCAF2%;2!BE9AFE72EA@2,2A48272E7F;2$$;254827982,2BA47F92EB978B2 E28A8CE7277FB2FE272E7F29FC9BFAC@;24CFE2824CFE2828;200/Q('6(91/2;2

E8F2 DAA8C2 1162 42 "1;2 5482 72 E7F62 E2 8CF8+2 ,2 9FC9BFA2 E2 ,BE9AFE;2 %8BC9F2 4F842 8;2(''9Q)(6)))12(;2

E3F258872Y6247>7E2162&A8FEB942-A62NF8C1NE8+7782N;25482,BE9AFE72C782,2A482BA47F92 EB978B2FE29EFAF82E27FF929FC9BFA;23C2%8BCF7;2(''/Q386)0)12);2

E9F2O8B>8E2"62D@7FE2-462.8@8C2&62&94,8C21625BCE8C262!CAEE24D;21C82A48C82A4C882BFFFE2 FE2A482CFA82BA47F92EB978BZ2!CEA2%8BCEA;2('(Q862;2

E0F2 38CE2 K62 !CB447B2 &62 N8CFE2 "62 .CE?8E2 5;2 &BA47F92 EB978B62 2 >8@2 ACB9ABC82 ,C2 8AFE72 9E8EA2@E94CEFBAFE2FE24BE;2%8BC9F24F8428;2(')Q)36)/913);2

E'F2 "9EE8772 .62 &2 U62 -F77FC2 K562 2 362 .CF772 A";2 ,,89AF82 882 CFE2 AFB7AFE2 BC8827+1,C8 B8E9@2E8A+C>29F77AFE2FE2A48272E7F2@2C8B7CFBFE2E8BC72,FCFE2AA8CE;2 K2%8BC9F;2('(Q)(6/8/3189;2

EF2 "9$EA@C82 62 -4E2 3K;2 %8A+C>2 8C89AF82 E2 A482 894EF2 ,2 882 CFE2 AFB7AFE;2 %8BCF725F;2(''Q)96)(01)3;2

E(F2 17C8B2 62 "9F2 62 8B2 .62 17C8B2 62 3E2 %62 CFB8B1HCB2 "62 8A2 7;2 4F7A8C72 BA47A@2FE23C>FEEX2F8862FEFAF72E27E1A8C2C8E8;24CFE;2(''/Q(96/3'19);2

E)F2 4F9>872 &62 17C8B2 62 "9F2 62 3E2 %62 8E2 "62 !8CEE8B2 62 8A2 7;2 EFAF82 E2 E8BC@94FACF92 8,,89A2 ,2 BA47A@2 ,C2 3C>FEEX2 F88;2 3C>FEEF2 87A2 5FC;2 (''Q86/)/10;2

E2F2"9>FEA42K624E982"62&F78CEE21;254829EACFBAFE2,28A47F972A894EF B82A2A482AB@2,2 CB28,,89A2$E62$8C8E2&62&E@8C2&628FAC;2-E>2,2@944C97@;2%8+2YC>62378EB2 C8Q2033;2

(15)

E/F23877+2&624FE2362!F782&624CF78@2";2N7FAFE2,28E69782C28EACF82FE2E2878A827B1 B82228BC82,2EF8A@2FE2A482CA;2K2%8BC9F2"8A4;209/Q2620183;2

E8F23FE2.62AAE2;25482A24CFE2FE2&A8C8AF92CFEA8;2%8+2YC>62198F923C8Q2009;2 E3F2!F782&62&8A423;212C8F8+2,2(/2@8C2,2A4829F72FEA8C9AFE2A8A;2BC2K234C97;2('')Q28)6)/1 /);2

E9F2 &94E8F8C2 "62 &94F2 62 8+8>82 !";2 19BA82 E2 94CEF92 9EEFEF2 AC8A8EA2 F,,8C8EAF77@2 ,,89A2C89EFAFE28C@2E29F7284FC2FE2B8CA72E2B7A2CA;21F9A24F7;2(''9Q)6)2/1/3;2 E0F2&94E8F8C2"62O942";258,F9F8EA29F72E27@284FC2FE2?B8EF782E2B7A2CA2,A8C2E8EA72 9CAF972 78FE62 8,,89A2 ,2 94CEF92 B8CA72 9EEFEF2 AC8A8EA;2 %8BC@944C97@;2 (''/Q)'60221/3;2

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

E(2F2 &ACBAA2 1"62 &FE2 62 KE>F92 K62 YC>2 "O;2 4E82 FE2 9EFAF818AFE72 E2 4@F7F972 @A2 ,2 8C8FE2 ,77+FE2 &5%154&2 ,C2 A482 AC8A8EA2 ,2 3C>FEEX2 F88;2 BC2 K2 %8BC7;2 ('(Q06(13;2

E(/F2 "778A2 62 37E2 "62 K,CF2 %62 4B2 %62 A87A8C2 "62 !EAFE82 562 8A2 7;2 &BA47F92 EB978B2 AFB7AFE2FE288C828F819B7F82FC8C;2%2E72K2"8;2(''9Q)/06((1)2;2

E(8F2C882"62-EF262%C82K%;2,,89A2,2C88A82882CFE2AFB7AFE2E28C8F812E2 EF8A@17F>8284FC2FE2CA62CFE28EA8BE9B7C2E2BA47F92EB978F;24CFE2&AFB7;2('(;2 E(3F2 O78FE2 K62 AFEA8C2 62 B8C@2 %62 -8FEB2 162 "C8EA8CE2 62 OB942 162 8A2 7;2 8FE2 ,2 A482 8F72 C8,CEA729CA82E2A482BA47F92EB978B28789AF87@2,,89A28C8FE17F>8284FC2FE2CA;24842 4CFE28;2(''Q()63)19;2

E(9F28CA2.625CF8C256248EAB81!8CC8C25628EB7A21628@EE2K";219BA82E294CEF92EF8EF917F>82 C8E82A2,7B8AFE82FE2CA2FE2A482878A827B1B862B7AFE2@2AC8,B724E7FE;248424CFE2 8;2('Q(('6)2219;2

(16)

E(0F2216248CAE2H62"C8823624B7,,2!;212B7AF781A8A2AB@2,2EF8A@1C87A8284FBC2FE2 F2FEC82CA2ACFE;248424CFE28;2003Q9/6/3180;2 E)'F25EFC2"6234F7F2"162778C2"62-CC2K;2&9FF7FA@2ACFA2E28CAEFE28A7F2FE2A482CA29F72 FEA8C9AFE2A8A;2%8BC9F28AA;2(''2Q)836)'01(;2 E)F2AFEA8C2628>8262&4C262"8FE8C2A62-CE9>2562KB9>872.628A27;2-F42,C8 B8E9@2AFB7AFE2,2 A482BA47F92EB978B2B7A82E8BCACEFFE2FE27FF92CFE2C8FE2,2A482CA;224CFE28;2 (''9Q9/62031/'3;2

E)(F2 D7E8C2 K"62 FEE2 5;2 &BA47F92 EB978B2 78FE2 FE9C882 FB7F82 9AFE2 E2 89C882 FB7F8294F982128FAFE2@28E4E982FE98EAF82AFAFEZ2BC2K2%8BC9F;2(''8Q(26()2/1/2;2 E))F2 AFEAE78@2 162 4BE8B2 62 54872 562 FE2 5A;2 8FE2 A2 A482 BA47F92 EB978B2 89C882 FB7F82 94F982 BA2 FFC2 BA4FE2 FE2 CA62 A482 FCAE982 ,2 A482 72 E7F2 FE2 37FE29EFAFEFE2E2FB7829EAC7;2BC2K2%8BC9F;2(''/Q(6)'318;2

E)2F2 4BE8B2 62 -B@2 562 782 5"62 @E2 K62 5BEE8AA2 &462 FE2 5A;2 ,,89A2 ,2 &5%2 78FE2 E2 F782 2 94F982 C89AFE2 AF82 A>2 FE2 A482 CA62 C88C82 AC2 C8FE862 BA2 FFC82 C8E82 8789AFE;2BC2K2%8BC9F;2(''Q)68'018;2

E)/F24BE8B262FE25A;24F7A8C7278FE2,2A482BA47F92EB978B2FEB982B7AF7828,F9FA2FE2E2 AA8EAFE72A>2FE2CA;2BC2K2%8BC9F;2003Q06('98100;2

E)8F2 4BE8B2 62 5F2 62 C2 "62 17CF92 ";2 5482 BA47F92 EB978B2 88CA2 FA82 9EAC72 E2 99FE82E2XEABC7X2C8+C;2%A2%8BC9F;2(''/Q9629210;2

E)3F24BE8B2624CFA>B21624B2Y62!CEF262FE25A;24F7A8C724F41,C8 B8E9@2AFB7AFE2 ,2 A482 BA47F92 EB978B2 E2 AA8EAFE72 8C,CE9862 ACEF8EA2 878A8CFB2 8,,89A2 E2 8E4E982 AFAFE2FE2A42FEA9A2E2C>FEEFE2CA;2BC2K2%8BC9F;2(''3Q(/693102;2

E)9F24F8B72$62&B78B2362-8878E2625C8E23625CF8C2562B72&628A27;2!8C2C89EFAFE2F2FFC82 @2BA47F92EB978B2AFB7AFE2FE23C>FEEX2F88;2%8BC@947F;2(''/Q2)6'/210;2

E)0F258872Y62O88721625E2&62521624E2362NF8C1NE8+7782N;2484FBC7294E82,A8C2 F7A8C72 BA47F92 AFB7AFE2 FE2 E982 3C>FEE2 F8862 2 @A8AF92 C8F8+;2 3C>FEEF2 87A25FC;2(''8Q(6(8/13(;2

E2'F2 NF98EA82 &62 4F8B72 $62 38CE2 K62 34F7FA2 362 5CF8C2 &62 5CF8C2 562 8A2 7;2 &BA47F92 EB978B2 AFB7AFE2,,89A2B?89AF828AFE7288CF8E982FE23C>FEEX2F882AF8EA;2%8BC@947F;2 (''0Q2360(91)3;2

E2F238CE2K624F8B72$628C@262NF98EA82&6282K8BE82!625CF8C2&628A27;2&BA47F92EB978B2AFB7AFE2 ,,89A2,8C2E2E82C89EFAFE2FE23C>FEEX2F88;2%8BC@947@;2(''Q(2619;2

(17)

E2(F238CE2K6282K8BE82!62-8878E2625EFE825625CF8C2562&B78B23628A27;2&BA47F92EB978B2 AFB7AFE2 ,,89A2 A48C@2 ,2 FE2 E8A+C>62 2 352 AB@2 FE2 3C>FEEX2 F88;2 3&2 HE8;2 (''Q/68000;2

E2)F2"C987F2&62!FCF2"62!,,EF2.62"C>F91&A2&625FCFAF992"629A877F2"628A27;2"B7AFE2,28A2 9F77AFE2 FE2 A482 BA47F92 C82 BCFE2 9AFE2 8CAFE2 FE2 3C>FEEX2 F88;2 %8BC9F8E98;2 (''0Q86'(31)8;2

E22F2 4BE8B2 62 Y87EF>2 K62 "778A2 ;2 &F2 B8AFE2 E2 A482 BA47F92 EB978B62 78E2 ,C2 EF72 872E2,C2AFB7A82AF8EA;2%8BC9F8E98;2('Q0960)1('2;2

E2/F282162&E8CE2D62NFA2K362!CE9>2&62!FE>2-;2&ACFE2F,,8C8E982FE2,8C1AFA8284FC2,2CA;2 34C9724F9482484;2008Q/26'31;2

E28F2 .B877FEF2 362 &7FE2 362 O8C>8CFE182 .,,2 62 4BE8B2 ;2 5882 CFE2 AFB7AFE2 FE2 E8BC7F972 F882 E2 88CF8EA72 8762 ,C2 789B782 A2 9782 84FC;2 3C2 %8BCF7;2 (''0Q906301 ();2

2 2

(18)

2 D5692EB +D4697DBDEA9(49B CBEA967B3D5692EB 2 22%E29F7287CAFE2 127CFE2A4828E2,F87;2 228CFE2 12&AEFE2E2FA24FE2782E28CFE2A2827>FE2A28A4FE;2 228AFE2 123F8284FC2FE2+4F942A482CA282EA282E2422C8782@2ABC8;2 22&87,1CFE2 12F9>FE2C2FAFE2FA2+E2,BC;2 12BFE2A482,C8+28C2A48248;2 1A967B3D5692E2 2 2EA9A284FCB 12.CFE2<948+FE2E27F9>FE2A482CAE8C#2,BC=;2 12C+7FE28C2A4829F72CAE8C;2<7=2 12C+7FE2BE8C2A4829F72CAE8C;2<1=2 2&9F7287CAFE2 121E8EFA72FE8AFAFE2<EF,,FE2C27F9>FE2A482E8EFA72C82,2A4829F72CAE8C=;22 12 %E1E8EFA72 FE8AFAFE2 <EF,,FE2 A2 E@2 CA2 ,2 A482 CAE8C#2 @62 898A2 A482 E8EFA72C8=;2 25F72EFB7AFE2 12.CFE2E2B77FE2A482CAE8C#2AF7;2 DEE9DB3D5692E2 2 23FEEFEB 1254829F72CAE8C2F27@FE2E2FA29>2+FA42A48288CF8EA72EF72AEFE28C24F;2<7=2 12548288CF8EA72EF72F27@FE2E2FA29>2+FA42A4829F72CAE8C2AEFE28C24F;2<1=2 21AA9>FE2 124FE;2<7=2 124FAFE;2<7=2 24FE2 12F82BCBFA;2<7=2 2FE2 12BEEFE6278FE2C2+8CFE2+@2,C2A4829F72CAE8C;2<1=2 5782628AF78289CFAFE2,284FC72CAFE2 <7=25FEEA284FC2 <1=2&BFF8284FC2

(19)

2 B *DE9DB8=6>9B 1568B8=B:;9B (672DB CBEA967B3D5692EB '9;2L23;32 03;22L22;92 ';)92 2%E29F7287CAFE2 /2;82L2;(2 20;)2L2(;'2 ';/2 28CFE2 2/;22L28;32 )8;02L2);'2 ';222 2$F7FA@2 /;32L2);'2 0;/2L2(;'2 ';92 2&87,1CFE2 2;32L2';/2 8;)2L2;2 ';)02 1A967B3D5692E2 3;(2L23;02 ');'2L2;(2 ?&?@B 2EA9A284FCB /3;92L2);02 3(;22L2/;22 ?&?AB 2&9F7287CAFE2 (;22L2);32 (8;/2L2/;)2 ';'82 25F72EFB7AFE2 ;'2L2';92 2;2L2;)2 ?&?:B DEE9DB3D5692E2 32;32L28;'2 0';02L28;(2 ';'82 23FEEFEB 0;2L2;)2 9;32L2;22 ';2/2 21AA9>FE2 ((;92L2(;/2 (0;/2L2(;(2 ?&?AB 24FE2 )0;2L2);2 29;02L2);/2 ';'82 2FE2 );32L2';82 );32L2';32 ';8(2 12389EE9DB3D5692E2 (0;(2L28;'2 2/;82L23;32 ';(22 2&BFF82EE2C8F82 8;92L2(;)2 8;32L2(;(2 ';992 2&BFF82C8F82 (;22L22;/2 (9;02L2/;02 ?&?:B +8964B3D5692E2 9;32L2;22 (/;02L2(;92 ';22 25FEEA2EE2C8F82 /;(2L2;2 3;/2L2;32 ';/22 25FEEA2C8F82 );/2L2;'2 9;22L2;32 ?&?@B 5782(625F,,8C8E982FE29F72FEA8C9AFE2A8A28A+88E278FE82E242782CA;28B7A2C88EA82 C82A4828E2EB8C2,284FBC28C82BCFE2A8A28FE2E2C82C88EA82FE28E2L2;8;;2 17B82C88EA82C8217B82,2BEFCFA82E7@8;2

(20)

STN CP STN CP X 40 X 40 a) b) 2 !FBC8262&89AFE2,2A48278,A2&5%;28FE2,289AFE2F2FEF9A82E22948AF929CE72F82,C2 3FE2 E2 AAE2 <C8CB982 +FA42 8CFFE=;2 34AF9CC42 <V2 2'=2 ,2 (2 C8C88EAAF82 48A@7FE18FE1,,CE2 AFE82 89AFE2 4+FE2 A482 BA47F92 EB978B2 <&5%=2 C8CFE2 A482 98C8C728BE9782<3=62

=2FE22428CA82CA2Q2

=2FE2278FE82CA2<AC4@2,2A482&5%2E2FEF,F9EA2987727=;2 2

(21)

2000 4000 6000 8000 10000 5 0 1 0 0 1 5 0 2 0 0 2 5 0

Non social behaviors

Mobility (counts) N u m b e r o f b e h a v io rs

Non Social Behaviors= β0+ β1Group+ β2Mobility+ δ

2000 4000 6000 8000 10000 5 0 1 0 0 1 5 0 2 0 0 2 5 0 Social behaviors Mobility (counts) N u m b e r o f b e h a v io rs

Social Behaviors= β0+ β1Group+ β2Mobility+ δ

2000 4000 6000 8000 10000 5 0 1 0 0 1 5 0 2 0 0 2 5 0 Agressive behaviors Mobility (counts) N u m b e r o f b e h a v io rs

Aggressive Behaviors= β0+ β1Group+ β2Mobility+ δ

<0.01 1.10-3 1.10-2 12 0.04 5 - 10 11 <0.01 8 52 10 p-value SD Estimate 1 <0.01 1.10-3 1.10-2 12 0.03 12 31 11 0.59 22 12 10 p-value SD Estimate 1 0.28 3.10-3 3.10-3 12 0.08* 9 16 11 <0.01 15 60 10 p-value SD Estimate 1 2 !FBC82(62128E8C727FE8C2872+28C,C82A2?BA2BE2AF7FA@2<EAE8B29AFFA@2FE27+8C2 FAFE2FE2A4828E2,F87=2A482F,,8C8E9828C828A+88E278FE82E2428CA82CA2 9E98CEFE29F72FEA8C9AFE2A8A;22 8G,B7729FC9786278FE82CAQ2827FE862C8F9A827B82AFE82,C2A4828E8C727FE8C2872FE2A482 78FE82CAQ22

47B8G8A@2 9FC97862 42 CAQ2 47B8G482 7FE862 C8F9A82 7B82 AFE82 ,C2 A482 8E8C72 7FE8C2 872FE2A48278FE82CA;2

['62FEA8C98AQ2[628,,89A2,2A482&-1"2CB2<C8,8C8E98D278FE8=Q2[(628,,89A2,2F7FA@;2 \25C8E2A2AAFAF972FEF,F9E982

(22)

Lesioned Sham 1 0 0 0 1 5 0 0 2 0 0 0

Total distance covered in the whole EPM

c m Lesioned Sham 0 5 1 0 1 5 2 0 2 5 3 0

Distance spent on the open arms (%)

% Lesioned Sham 0 1 0 2 0 3 0 4 0

Time spent on the open arms (%)

% Lesioned Sham 0 1 0 2 0 3 0 4 0 5 0

Inactive time spent on the open arms (%)

% Lesioned Sham 0 1 2 3 4 5 6

Number of entry in the open arm

N u m b e r o f e n tr y Lesioned Sham 1 0 2 0 3 0 4 0 Risk assessment N u m b e r o f e p is o d e s Lesioned Sham 0 5 1 0 1 5

Protected head dips

N u m b e r o f e p is o d e s Lesioned Sham 0 5 1 0 1 5 2 0

Non-protected head dips

N u m b e r o f e p is o d e s 2

!FBC82 )62 "8BC82 ,2 878A82 7B1B82 9E8EAFE72 E2 8A47F972 C8A8C;2 5A2 C82 8C882 2 7A2 ,C2 78FE82 <ED0=2 E2 42 78FE82 <ED2 (8=2 CA;2 5482 7+8C2 E2 4F48C2 BECF82,2A4822FEF9A82A482(/A42E23/A428C98EAF78;254827FE82+FA4FE2A4822C>2A4828FE62 E28CCC2C287+2E282A4822FEF9A82A482'A42E20'A428C98EAF78;2

12&AAFAF977@2FEF,F9EA2C8B7A2 25C8E2A+C2AAFAF972FEF,F9E982 2