the-use-puzzle-box-as-means-assessing-efficacy-environmental

The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment

Environmental enrichment can dramatically influence the development and function of neural circuits.  Further, enrichment has been shown to successfully ...

University of Sydney

&#x6210;&#x4EBA;&#x7684;&#x76AE;&#x5C42;&#x533A;&#x7684;&#x7279;&#x70B9;&#x662F;&#x9020;&#x6210;&#x5176;&#x529F;&#x80FD;&#x4F5C;&#x7528;&#x7684;&#x7EC6;&#x80DE;&#x6784;&#x7B51;&#x548C;&#x8FDE;&#x901A;&#x6027;&#x7684;&#x660E;&#x663E;&#x5DEE;&#x5F02;&#x3002;&#x8FD9;&#x4E9B;&#x5DEE;&#x5F02;&#x7684;&#x5206;&#x5B50;&#x51B3;&#x5B9A;&#x56E0;&#x7D20;&#x662F;&#x4E3B;&#x8981;&#x662F;&#x672A;&#x77E5;&#x7684;&#x3002;&#x6211;&#x4EEC;&#x6267;&#x884C;&#x7684;&#x57FA;&#x56E0;&#x82AF;&#x7247;&#x5206;&#x6790;&#xFF0C;&#x4EE5;&#x786E;&#x5B9A;&#x5728;&#x4F55;&#x65F6;&#x4F20;&#x5165;&#x548C;&#x4F20;&#x51FA;&#x9884;&#x6D4B;&#x6B63;&#x5728;&#x5F62;&#x6210;&#x7684;&#x65F6;&#x95F4;&#x8FC7;&#x7A0B;&#x4E2D;&#x5B9A;&#x4E49;&#x7684;&#x4F53;&#x611F;&#x548C;&#x53EF;&#x89C6;&#x5316;&#x9886;&#x57DF;&#x7684;&#x5206;&#x5B50;&#x3002;&#x6211;&#x4EEC;&#x786E;&#x5B9A;&#x4E86; 122 &#x5206;&#x5B50;&#x5DEE;&#x5F02;&#x8868;&#x793A;&#x533A;&#x57DF;&#x4E4B;&#x95F4;&#x5E76;&#x8BC1;&#x5B9E;&#x4E86; 20 &#x4E2A;&#x57FA;&#x56E0;&#x6D4B;&#x8BD5;&#x5B9A;&#x91CF;&#x805A;&#x5408;&#x9176;&#x94FE;&#x53CD;&#x5E94;&#x7684; 95%&#x3002;&#x4E24;&#x4E2A;&#x57FA;&#x56E0;&#x88AB;&#x9009;&#x4F5C;&#x8FDB;&#x4E00;&#x6B65;&#x8C03;&#x67E5;&#xFF1A; Bcl6 &#x548C; Ten_m3&#x3002;Bcl6 &#x9AD8;&#x5EA6;&#x6709;&#x4EBA;&#x5728;&#x4EA7;&#x540E;&#x4E00;&#x5929; (P) &#x5BF9;&#x5E94;&#x4F53;&#x611F;&#x76AE;&#x5C42;&#x7B2C;&#x56DB;&#x5C42;&#x53D1;&#x5C55;&#x7684;&#x8868;&#x9762;&#x76AE;&#x8D28;&#x677F; 0&#x3002;&#x8FD9;&#x51CF;&#x5C11;&#x4E86;&#x7531; P3&#xFF0C;&#x4F46;&#x5F3A;&#x70C8;&#x8868;&#x8FBE;&#x7684; P7 &#x5C42; V &#x9525;&#x4F53;&#x7EC6;&#x80DE;&#x4E2D;&#x53D1;&#x73B0;&#x5E76;&#x4FDD;&#x6301;&#x76F4;&#x5230;&#x6210;&#x5E74;&#x540E;&#x3002;&#x9006;&#x884C;&#x8FFD;&#x8E2A;&#x663E;&#x793A; Bcl6 &#x8868;&#x793A;&#x76AE;&#x8D28;&#x810A;&#x9AD3;&#x795E;&#x7ECF;&#x5143;&#x3002;Ten_m3 &#x6709;&#x4EBA;&#x5728;&#x5206;&#x7EA7;&#x6A21;&#x5F0F;&#x4EE5;&#x53CA;&#x4E0E;&#x89C6;&#x89C9;&#x76AE;&#x5C42;&#x9AB6;&#x7BA1;&#x76AE;&#x8D28;&#x76F8;&#x5BF9;&#x5E94;&#x7684;&#x4E94;&#x5C42;&#x5185;&#x3002;&#x9006;&#x884C;&#x8FFD;&#x8E2A;&#x548C;&#x7EC4;&#x5316;&#x67D3;&#x8272;&#x663E;&#x793A; Ten_m3 &#x9AD8;&#x5EA6;&#x8868;&#x793A;&#x6CBF;&#x8F74;&#x7A81;&#x5927;&#x7247;&#x7684;&#x6295;&#x5C04;&#x795E;&#x7ECF;&#x5143;&#x7684;&#x89C6;&#x89C9;&#x53D1;&#x5C55;&#x8DEF;&#x5F84;&#x3002;&#x9AD8;&#x6548;&#x8868;&#x8FBE;&#x8868;&#x660E; Ten_m3 &#x4FC3;&#x8FDB; homophilic &#x7C98;&#x9644;&#x548C;&#x4F53;&#x5185;&#x7684;&#x7A81;&#x8D77;&#x3002;&#x8FD9;&#x8868;&#x660E;&#x91CD;&#x8981;&#x4F5C;&#x7528;&#x4E3A; Ten_m3 &#x4E2D;&#x7684;&#x89C6;&#x89C9;&#x901A;&#x8DEF;&#x53D1;&#x5C55;&#x3002;

&#x611F;&#x89C9;&#x76AE;&#x5C42;&#x533A;&#x57DF;&#x4E4B;&#x95F4;&#x7684;&#x57FA;&#x56E0;&#x5DEE;&#x5F02;&#x8868;&#x8FBE;&#xFF1A; Ten_m3 &#x548C; Bcl6 &#x5728;&#x9635;&#x5217;&#x89C6;&#x89C9;&#x548C;&#x4F53;&#x611F;&#x901A;&#x8DEF;&#x4E2D;&#x53EF;&#x80FD;&#x53D1;&#x6325;&#x7684;&#x4F5C;&#x7528;&#x3002;

Adult neocortical areas are characterized by marked differences in cytoarchitecture and connectivity that underlie their functional roles. The molecular determinants of these differences are largely unknown. We performed a microarray analysis to identify molecules that define the somatosensory and visual areas during the time when afferent and efferent projections are forming. We identified 122 molecules that are differentially expressed between the regions and confirmed by quantitative polymerase chain reaction 95% of the 20 genes tested. Two genes were chosen for further investigation: Bcl6 and Ten_m3. Bcl6 was highly expressed in the superficial cortical plate corresponding to developing layer IV of somatosensory cortex at postnatal day (P) 0. This had diminished by P3, but strong expression was found in layer V pyramidal cells by P7 and was maintained until adulthood. Retrograde tracing showed that Bcl6 is expressed in corticospinal neurons. Ten_m3 was expressed in a graded pattern within layer V of caudal cortex that corresponds well with visual cortex. Retrograde tracing and immunostaining showed that Ten_m3 is highly expressed along axonal tracts of projection neurons of the developing visual pathway. Overexpression demonstrated that Ten_m3 promotes homophilic adhesion and neurite outgrowth in vivo. This suggests an important role for Ten_m3 in the development of the visual pathway.

Differential gene expression between sensory neocortical areas: potential roles for Ten_m3 and Bcl6 in patterning visual and somatosensory pathways.

R&eacute;gions n&eacute;ocorticales adultes sont caract&eacute;ris&eacute;es par des diff&eacute;rences marqu&eacute;es dans la cytoarchitecture et la connectivit&eacute; qui sous-tendent leurs r&ocirc;les fonctionnels. Les d&eacute;terminants mol&eacute;culaires de ces diff&eacute;rences sont largement inconnus. Nous avons effectu&eacute; une analyse de biopuces pour identifier les mol&eacute;cules qui d&eacute;finissent les zones de somatosensoriels et visuelles pendant le temps o&ugrave; les projections aff&eacute;rentes et eff&eacute;rentes forment. Nous avons recens&eacute; 122 mol&eacute;cules qui sont diff&eacute;rentiellement exprim&eacute;s entre les r&eacute;gions et confirm&eacute;s par r&eacute;action en cha&icirc;ne de polym&eacute;rase quantitative 95 % des 20 g&egrave;nes test&eacute;s. Deux g&egrave;nes ont &eacute;t&eacute; choisis pour un examen plus approfondi : Bcl6 et Ten_m3. Bcl6 fortement exprim&eacute; dans la plaque corticale superficielle correspondant au d&eacute;veloppement couche IV du cortex somatosensoriel &agrave; jour apr&egrave;s la naissance (P) 0. Cela avait diminu&eacute; de P3, mais forte expression est trouv&eacute;e dans les cellules pyramidales de la couche V par P7 et s&#39;est maintenue jusqu&#39;&agrave; l&#39;&acirc;ge adulte. Tra&ccedil;age r&eacute;trograde a montr&eacute; que Bcl6 est exprim&eacute; dans les neurones corticospinaux. Ten_m3 s&#39;exprimait dans un mod&egrave;le class&eacute; au sein de la couche V de cortex caudal qui correspond bien avec le cortex visuel. Immunomarquage et tra&ccedil;age r&eacute;trograde a montr&eacute; que Ten_m3 est fortement exprim&eacute; le long des parcelles axones des neurones de projection de la voie visuelle en d&eacute;veloppement. Surexpression d&eacute;montr&eacute; que Ten_m3 favorise l&#39;adh&eacute;rence homophile et la croissance des neurites in vivo. Ceci sugg&egrave;re un r&ocirc;le important pour Ten_m3 dans le d&eacute;veloppement de la voie visuelle.

Expression diff&eacute;rentielle des g&egrave;nes entre des aires n&eacute;ocorticales sensorielles : r&ocirc;les potentiels pour Ten_m3 et Bcl6 &agrave; r&eacute;p&eacute;tition des voies visuelles et somesth&eacute;siques.

Erwachsene neokortikalen Gebiete zeichnen sich durch deutliche Unterschiede in den Cytoarchitecture und Konnektivit&auml;t, die ihre Funktionsrollen zugrunde liegen. Die molekularen Determinanten dieser Unterschiede sind weitgehend unbekannt. Wir spielten eine Microarray-Analyse, um Molek&uuml;le zu identifizieren, die somatosensorische und visuelle Bereiche w&auml;hrend der Zeit zu definieren, wann die afferente und efferente Projektionen bilden. Wir haben 122 Molek&uuml;le, die differenziell ausgedr&uuml;ckt zwischen den Regionen und best&auml;tigt durch quantitative Polymerase-Kettenreaktion 95 % der 20 Gene getestet werden identifiziert. Zwei Gene wurden zur n&auml;heren Untersuchung ausgew&auml;hlt: Bcl6 und Ten_m3. Bcl6 &auml;u&szlig;erte sich hoch in die oberfl&auml;chliche kortikale Platte, entwickelnden Schicht IV des somatosensorischen Kortex bei postnatalen Day (P) entspricht 0. Dies hatte von P3 verringert, aber starken Ausdruck von P7 in Schicht V Pyramidenzellen gefunden wurde und bis ins Erwachsenenalter beibehalten wurde. Retrograde Ablaufverfolgung zeigte, dass Bcl6 kortikospinalen Neuronen ausgedr&uuml;ckt wird. Ten_m3 fand ihren Niederschlag in einem abgestuften Muster innerhalb v. Schicht des kaudalen Cortex, das entspricht gut mit visuellen Kortex. Retrograde Ablaufverfolgung und Paraffinschnitten zeigte, dass Ten_m3 hoch entlang axonale Landstriche Projektion Neuronen des entwickeln visuelle Signalweges ausgedr&uuml;ckt wird. Eine &Uuml;berexpression gezeigt, dass Ten_m3 homophilic Adh&auml;sion und Neurit Auswuchs in-vivo f&ouml;rdert. Dies schl&auml;gt eine wichtige Rolle f&uuml;r Ten_m3 bei der Entwicklung der visuellen Weg.

Differenzielle Genexpression zwischen sensorischen neokortikalen Regionen: m&ouml;gliche Rollen f&uuml;r Ten_m3 und Bcl6 in visuelle und somatosensorische Bahnen Musterung.

Aree corticali per adulti sono caratterizzati da marcate differenze in cytoarchitecture e connettivit&agrave; che sottostanno alla loro ruoli funzionali. I determinanti molecolari di queste differenze sono in gran parte sconosciuti. Abbiamo effettuato un&#39;analisi di microarray per identificare le molecole che definiscono le aree visive e somatosensoriali durante il tempo quando si formano le proiezioni afferenti ed efferenti. Abbiamo identificato 122 molecole che sono differenzialmente espressi tra le regioni e confermati dalla reazione a catena della polimerasi quantitativa il 95% dei 20 geni testati. Due geni sono stati scelti per ulteriori indagini: Bcl6 e Ten_m3. Bcl6 altamente &egrave; stata espressa nella piastra corticale superficiale al giorno postnatale (P) corrispondente a sviluppo strato IV della corteccia somatosensoriale 0. Questo aveva diminuito da P3, ma forte espressione &egrave; stato trovato nelle cellule piramidali strato V da P7 e fu mantenuto fino all&#39;et&agrave; adulta. Analisi retrograda ha mostrato che Bcl6 &egrave; espresso nei neuroni corticospinale. Ten_m3 &egrave; stato espresso in un pattern graduato all&#39;interno strato V della corteccia caudale che corrisponde bene con corteccia visiva. Immunocolorazione e retrograda analisi ha mostrato che Ten_m3 &egrave; altamente espresso lungo tratti assonali dei neuroni di proiezione del percorso visivo in via di sviluppo. Sovraespressione hanno dimostrato che Ten_m3 favorisce l&#39;adesione omofile e crescita dei neuriti in vivo. Questo suggerisce un ruolo importante per Ten_m3 lo sviluppo del percorso visivo.

Espressione genica differenziale tra aree corticali sensoriali: ruoli potenziali per Ten_m3 e Bcl6 nella creazione di percorsi visivi e somatosensoriali.

&#x5927;&#x4EBA;&#x306E;&#x76AE;&#x8CEA;&#x9818;&#x57DF;&#x306F;&#x305D;&#x308C;&#x3089;&#x306E;&#x6A5F;&#x80FD;&#x7684;&#x5F79;&#x5272;&#x306E;&#x6839;&#x5E95;&#x306B;&#x3042;&#x308B;&#x7D30;&#x80DE;&#x69CB;&#x7BC9;&#x3068;&#x63A5;&#x7D9A;&#x3067;&#x306E;&#x30DE;&#x30FC;&#x30AF;&#x306E;&#x9055;&#x3044;&#x306B;&#x3088;&#x3063;&#x3066;&#x7279;&#x5FB4;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x9055;&#x3044;&#x306E;&#x5206;&#x5B50;&#x6C7A;&#x5B9A;&#x8981;&#x56E0;&#x306F;&#x4E3B;&#x3068;&#x3057;&#x3066;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F;&#x8996;&#x899A;&#x3068;&#x4F53;&#x6027;&#x611F;&#x899A;&#x306E;&#x9818;&#x57DF;&#x3092;&#x5B9A;&#x7FA9;&#x3059;&#x308B;&#x3068;&#x304D;&#x6C42;&#x5FC3;&#x6027;&#x304A;&#x3088;&#x3073;&#x9060;&#x5FC3;&#x6027;&#x6295;&#x5C04;&#x3092;&#x5F62;&#x6210;&#x3057;&#x3066;&#x3044;&#x308B;&#x6642;&#x9593;&#x4E2D;&#x306B;&#x5206;&#x5B50;&#x3092;&#x8B58;&#x5225;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x30DE;&#x30A4;&#x30AF;&#x30ED; &#x30A2;&#x30EC;&#x30A4;&#x306E;&#x5206;&#x6790;&#x3092;&#x884C;&#x3063;&#x305F;&#x3002;&#x6211;&#x3005; &#x306F;&#x7279;&#x7570;&#x7684;&#x9818;&#x57DF;&#x306E;&#x9593;&#x3092;&#x8868;&#x73FE;&#x3057;&#x5B9A;&#x91CF;&#x30DD;&#x30EA;&#x30E1;&#x30E9;&#x30FC;&#x30BC;&#x9023;&#x9396;&#x53CD;&#x5FDC; 95% &#x30C6;&#x30B9;&#x30C8; 20 &#x907A;&#x4F1D;&#x5B50;&#x306E;&#x78BA;&#x8A8D; 122 &#x5206;&#x5B50;&#x3092;&#x540C;&#x5B9A;&#x3057;&#x307E;&#x3059;&#x3002;2 &#x3064;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x3001;&#x3055;&#x3089;&#x306A;&#x308B;&#x8ABF;&#x67FB;&#x306E;&#x305F;&#x3081;&#x9078;&#x3070;&#x308C;&#x305F;: Bcl6 &#x3068; Ten_m3&#x3002;Bcl6 &#x306F;&#x4F53;&#x6027;&#x611F;&#x899A;&#x76AE;&#x8CEA;&#x306E;&#x767A;&#x5C55;&#x9014;&#x4E0A;&#x306E;&#x5C64; IV &#x306B;&#x751F;&#x5F8C;&#x65E5; (P) &#x3092;&#x5BFE;&#x5FDC;&#x3059;&#x308B;&#x8868;&#x5728;&#x76AE;&#x8CEA;&#x9AA8;&#x677F;&#x3067;&#x8868;&#x73FE;&#x3057;&#x307E;&#x3057;&#x305F;&#x975E;&#x5E38;&#x306B; 0&#x3002;&#x3053;&#x308C;&#x306F; P3 &#x3067;&#x6E1B;&#x5C11;&#x3057;&#x3066;&#x3044;&#x305F;&#x304C;&#x3001;&#x5F37;&#x3044;&#x8868;&#x73FE; V &#x5C64;&#x9310;&#x4F53;&#x7D30;&#x80DE;&#x306E; P7 &#x306B;&#x3088;&#x3063;&#x3066;&#x767A;&#x898B;&#x3055;&#x308C;&#x3001;&#x6210;&#x4EBA;&#x671F;&#x307E;&#x3067;&#x7DAD;&#x6301;&#x3055;&#x308C;&#x3066;&#x3044;&#x305F;&#x3002;&#x9006;&#x884C;&#x30C8;&#x30EC;&#x30FC;&#x30B9; Bcl6 &#x76AE;&#x8CEA;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x306E;&#x8868;&#x73FE;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x305F;&#x3002;Ten_m3 &#x306F;&#x5BFE;&#x5FDC;&#x3059;&#x308B;&#x5C3E;&#x5074;&#x76AE;&#x8CEA;&#x8996;&#x899A;&#x91CE;&#x3068;&#x3088;&#x304F; V &#x5C64;&#x5185;&#x306E;&#x50BE;&#x659C;&#x30D1;&#x30BF;&#x30FC;&#x30F3;&#x3067;&#x8868;&#x73FE;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x9006;&#x884C;&#x30C8;&#x30EC;&#x30FC;&#x30B9;&#x3068;&#x514D;&#x75AB;&#x67D3;&#x8272; Ten_m3 &#x304C;&#x767A;&#x5C55;&#x9014;&#x4E0A;&#x306E;&#x8996;&#x899A;&#x7D4C;&#x8DEF;&#x306E;&#x6295;&#x5C04;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x306E;&#x8EF8;&#x7D22;&#x306E;&#x5E83;&#x5927;&#x306B;&#x6CBF;&#x3063;&#x3066;&#x975E;&#x5E38;&#x306B;&#x8868;&#x73FE;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x305F;&#x3002;Ten_m3 &#x306F;&#x30DB;&#x30E2;&#x30D5;&#x30A3;&#x30EA;&#x30C3;&#x30AF;&#x3068; in vivo &#x795E;&#x7D4C;&#x7A81;&#x8D77;&#x4F38;&#x9577;&#x3092;&#x4FC3;&#x9032;&#x3059;&#x308B;&#x904E;&#x5270;&#x767A;&#x73FE;&#x3092;&#x793A;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x306F;&#x8996;&#x899A;&#x7D4C;&#x8DEF;&#x306E;&#x958B;&#x767A;&#x3067;&#x306E; Ten_m3 &#x306E;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x3092;&#x793A;&#x5506;&#x3057;&#x307E;&#x3059;&#x3002;

&#x611F;&#x899A;&#x76AE;&#x8CEA;&#x9818;&#x57DF;&#x9593;&#x306E;&#x5DEE;&#x52D5;&#x907A;&#x4F1D;&#x5B50;&#x767A;&#x73FE;: &#x8996;&#x899A;&#x3068;&#x4F53;&#x6027;&#x611F;&#x899A;&#x7D4C;&#x8DEF;&#x3092;&#x30D1;&#x30BF;&#x30FC;&#x30CB;&#x30F3;&#x30B0;&#x3067;&#x6F5C;&#x5728;&#x7684;&#x306A;&#x5F79;&#x5272; Ten_m3 &#x3068; Bcl6 &#x306E;&#x305F;&#x3081;&#x3002;

&#xC131;&#xC778; neocortical &#xBD84;&#xC57C;&#xB294; &#xADF8;&#xB4E4;&#xC758; &#xAE30;&#xB2A5;&#xC801; &#xC5ED;&#xD560;&#xC744; &#xAE30;&#xBC18;&#xC774; &#xB418;&#xB294; cytoarchitecture&#xC640; &#xC5F0;&#xACB0;&#xC5D0; &#xD45C;&#xC2DC; &#xB41C; &#xCC28;&#xC774; &#xC758;&#xD574; &#xD2B9;&#xC9D5;&#xC785;&#xB2C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xCC28;&#xC774;&#xC758; &#xBD84;&#xC790; &#xACB0;&#xC815; &#xC694;&#xC778; &#xD06C;&#xAC8C; &#xC54C;&#xB824;&#xC9C0;&#xC9C0; &#xC54A;&#xC740;.&#xC785;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xC131;&#xC758; efferent &#xC608;&#xCE21;&#xC744; &#xD615;&#xC131; &#xD558;&#xB294; &#xACBD;&#xC6B0; &#xC2DC;&#xAC04; &#xB3D9;&#xC548; somatosensory &#xBC0F; &#xC2DC;&#xAC01;&#xC801; &#xC601;&#xC5ED;&#xC744; &#xC815;&#xC758; &#xD558;&#xB294; &#xBD84;&#xC790; &#xC2DD;&#xBCC4; microarray &#xBD84;&#xC11D;&#xC744; &#xC218;&#xD589;. &#xCC28;&#xB3D9; &#xC9C0;&#xC5ED; &#xAC04;&#xC758; &#xD45C;&#xD604; &#xBC0F; &#xD14C;&#xC2A4;&#xD2B8; 20 &#xC720;&#xC804;&#xC790;&#xC758; &#xC815;&#xB7C9;&#xC801; &#xC911; &#xD569; &#xD6A8;&#xC18C; &#xC5F0;&#xC1C4; &#xBC18;&#xC751; 95%&#xC5D0; &#xC758;&#xD574; &#xD655;&#xC778; 122 &#xBD84;&#xC790; &#xC2DD;&#xBCC4; &#xD569;&#xB2C8;&#xB2E4;. &#xCD94;&#xAC00; &#xC870;&#xC0AC;&#xB97C; &#xC704;&#xD574; &#xB450; &#xAC1C;&#xC758; &#xC720;&#xC804;&#xC790;&#xAC00; &#xC120;&#xC815; &#xB418;&#xC5C8;&#xB2E4;: Bcl6 &#xBC0F; Ten_m3. Bcl6&#xB294; &#xB9E4;&#xC6B0; &#xD53C;&#xC0C1;&#xC801;&#xC778; &#xB300;&#xB1CC; &#xD53C; &#xC9C8;&#xC758; &#xC811;&#xC2DC; &#xD574;&#xB2F9; somatosensory &#xD53C; &#xC9C8;&#xC758; &#xAC1C;&#xBC1C; &#xB808;&#xC774;&#xC5B4; IV &#xD558; &#xC0B0; &#xD6C4;&#xC758; &#xB0A0; (P) &#xB2E8;&#xC704;&#xB85C; 0. &#xC774; P3&#xC5D0; &#xC758;&#xD574; &#xAC10;&#xC18C; &#xD588;&#xB2E4; &#xD558;&#xC9C0;&#xB9CC; &#xAC15;&#xD55C; &#xD45C;&#xD604;&#xACFC; &#xB808;&#xC774;&#xC5B4; V &#xD53C;&#xB77C;&#xBBF8;&#xB4DC; &#xC138;&#xD3EC;&#xC5D0;&#xC11C; p 7&#xC5D0; &#xC758;&#xD574; &#xBC1C;&#xACAC; &#xB41C; &#xC131;&#xC778; &#xAE30;&#xAE4C;&#xC9C0; &#xC720;&#xC9C0; &#xD588;&#xB2E4;. &#xD1F4;&#xD589; &#xC131; &#xCD94;&#xC801; Bcl6 corticospinal &#xB274;&#xB7F0;&#xC5D0; &#xD45C;&#xD604; &#xD588;&#xB2E4;. Ten_m3 &#xC2DC;&#xAC01; &#xD53C; &#xC9C8;&#xC73C;&#xB85C; &#xC798; &#xD574;&#xB2F9; &#xD53C;&#xB97C; &#xAF2C;&#xB9AC;&#xC758; V &#xB808;&#xC774;&#xC5B4; &#xB0B4;&#xC5D0;&#xC11C; &#xC810;&#xC218; &#xB9E4;&#xAE38;&#xB41C; &#xD328;&#xD134;&#xC73C;&#xB85C; &#xD45C;&#xD604; &#xD588;&#xB2E4;. &#xD1F4;&#xD589; &#xC131; &#xCD94;&#xC801; &#xBC0F; immunostaining Ten_m3 &#xAC1C;&#xBC1C; &#xC2DC;&#xAC01;&#xC801; &#xD1B5;&#xB85C;&#xC758; &#xD504;&#xB85C;&#xC81D;&#xC158; &#xB274;&#xB7F0;&#xC758; axonal &#xCC45;&#xC790;&#xB97C; &#xB530;&#xB77C; &#xD45C;&#xD604; &#xB192;&#xAC8C; &#xB098;&#xD0C0;&#xB0AC;&#xB2E4;. Overexpression&#xC740; Ten_m3 &#xCD09;&#xC9C4; homophilic &#xC811;&#xCC29; &#xBC0F; neurite &#xD30C;&#xC0DD;&#xBB3C; vivo&#xC5D0;&#xC11C; &#xC2DC;&#xC5F0; &#xD588;&#xB2E4;. &#xC774; ten_m3&#xC5D0; &#xB300; &#xD55C; &#xC2DC;&#xAC01;&#xC801; &#xD1B5;&#xB85C;&#xC758; &#xAC1C;&#xBC1C;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xC81C;&#xC548;&#xD569;&#xB2C8;&#xB2E4;.

&#xAC10;&#xAC01; neocortical &#xC601;&#xC5ED; &#xC0AC;&#xC774;&#xC758; &#xCC28;&#xB3D9; &#xC720;&#xC804;&#xC790; &#xBC1C;&#xD604;: &#xD328;&#xD134;&#xD654; &#xC2DC;&#xAC01;&#xACFC; somatosensory &#xACBD;&#xB85C;&#xC5D0;&#xC11C; Ten_m3 &#xBC0F; bcl6&#xC5D0; &#xB300; &#xD55C; &#xC7A0;&#xC7AC;&#xC801;&#xC778; &#xC5ED;&#xD560;.

&Aacute;reas neocorticales adultos se caracterizan por diferencias marcadas en Citoarquitectura y conectividad que subyacen a sus roles funcionales. Los determinantes moleculares de estas diferencias son en gran parte desconocidos. Se realiz&oacute; un an&aacute;lisis de microarrays para identificar mol&eacute;culas que definen las &aacute;reas somatosensoriales y visuales durante el tiempo cuando forman proyecciones aferentes y eferentes. Se identificaron 122 mol&eacute;culas diferencialmente expresadas entre las regiones y confirmadas por la reacci&oacute;n en cadena de polimerasa cuantitativa 95% de los 20 genes probados. Dos genes fueron elegidos para la posterior investigaci&oacute;n: Bcl6 y Ten_m3. Bcl6 fue altamente expresada en la placa cortical superficial correspondiente a desarrollo IV de capa de la corteza somatosensorial en d&iacute;a postnatal (P) 0. Esto hab&iacute;a disminuido por P3, pero fuerte expresi&oacute;n fue encontrado en las c&eacute;lulas piramidales de la capa V por P7 y se mantuvo hasta la edad adulta. Seguimiento retr&oacute;grado demostr&oacute; que Bcl6 se expresa en las neuronas corticoespinales. Ten_m3 se expres&oacute; en forma gradual dentro de la capa V de la corteza caudal que corresponde bien con la corteza visual. Inmunotinci&oacute;n y retr&oacute;grada seguimiento demostraron que Ten_m3 se expresa muy a lo largo de los tractos axonal de las neuronas de proyecci&oacute;n de la v&iacute;a visual en v&iacute;as de desarrollo. Sobreexpresi&oacute;n demostr&oacute; que Ten_m3 promueve la adherencia homophilic y neurita consecuencia in vivo. Esto sugiere un papel importante para Ten_m3 en el desarrollo de la v&iacute;a visual.

Expresi&oacute;n g&eacute;nica diferencial entre &aacute;reas neocorticales sensoriales: posibles funciones para Ten_m3 y Bcl6 en patrones v&iacute;as visuales y somatosensoriales.

Binocular vision requires an exquisite matching of projections from each eye to form a cohesive representation of the visual world. Eye-specific inputs are anatomically segregated, but in register in the visual thalamus, and overlap within the binocular region of primary visual cortex. Here, we show that the transmembrane protein Ten_m3 regulates the alignment of ipsilateral and contralateral projections. It is expressed in a gradient in the developing visual pathway, which is consistently highest in regions that represent dorsal visual field. Mice that lack Ten_m3 show profound abnormalities in mapping of ipsilateral, but not contralateral, projections, and exhibit pronounced deficits when performing visually mediated behavioural tasks. It is likely that the functional deficits arise from the interocular mismatch, because they are reversed by acute monocular inactivation. We conclude that Ten_m3 plays a key regulatory role in the development of aligned binocular maps, which are required for normal vision.

Ten_m3 regulates eye-specific patterning in the mammalian visual pathway and is required for binocular vision.

The neostriatum, the mouse homologue of the primate caudate/putamen, is the input nucleus for the basal ganglia, receiving both cortical and dopaminergic input to each of its sub-compartments, the striosomes and matrix. The coordinated activation of corticostriatal pathways is considered vital for motor and cognitive abilities, yet the mechanisms which underlie the generation of these circuits are unknown. The early and specific targeting of striatal subcompartments by both corticostriatal and nigrostriatal terminals suggests activity-independent mechanisms, such as axon guidance cues, may play a role in this process. Candidates include the chondroitin sulfate proteoglycan (CSPG) family of glycoproteins which have roles not only in axon guidance, but also in the maturation and stability of neural circuits where they are expressed in lattice-like perineuronal nets (PNNs).

Rapid reversal of chondroitin sulfate proteoglycan associated staining in subcompartments of mouse neostriatum during the emergence of behaviour.

There is strong evidence that sensory experience in early life has a profound influence on the development of sensory circuits. Very little is known, however, about the role of experience in the early development of striatal networks which regulate both motor and cognitive function. To address this, we have investigated the influence of early environmental enrichment on motor development.

Enrichment from birth accelerates the functional and cellular development of a motor control area in the mouse.

In mice, the matrix compartment of the striatum (caudate/putamen) undergoes major developmental changes during the second postnatal week, including the establishment of corticostriatal and nigrostriatal afferents, the maturation of parvalbumin-positive interneurons and the appearance of perineuronal nets. It is not known if any of these events influence the dendritic structure of medium spiny neurons, the principal output cells of the striatum. To determine whether any measurable changes in the dendrites of matrix medium spiny neurons occur during this important developmental period, we labeled individual cells at different time points flanking the second postnatal week. These cells exhibit distinct dendritic morphologies from the earliest postnatal time points examined. Furthermore, our data show that the dendritic arbors of these neurons change in length, branch points, diameter and tortuosity, regardless of morphological type. The increase in dendritic length is accompanied by a decrease in the number of branch points that occur in different, but consistent, parts of the dendritic arbor. All of these changes are most pronounced during the second postnatal week, coinciding with a number of developmental events considered important for consolidating circuitry within the striatal matrix. Our results further support the critical importance of this early postnatal period in striatal development.

Medium spiny neurons of the neostriatal matrix exhibit specific, stereotyped changes in dendritic arborization during a critical developmental period in mice.

The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

Perineuronal nets play a role in regulating striatal function in the mouse.

The visual system is characterized by precise retinotopic mapping of each eye, together with exquisitely matched binocular projections. In many species, the inputs that represent the eyes are segregated into ocular dominance columns in primary visual cortex (V1), whereas in rodents, this does not occur. Ten-m3, a member of the Ten-m/Odz/Teneurin family, regulates axonal guidance in the retinogeniculate pathway. Significantly, ipsilateral projections are expanded in the dorsal lateral geniculate nucleus and are not aligned with contralateral projections in Ten-m3 knockout (KO) mice. Here, we demonstrate the impact of altered retinogeniculate mapping on the organization and function of V1. Transneuronal tracing and c-fos immunohistochemistry demonstrate that the subcortical expansion of ipsilateral input is conveyed to V1 in Ten-m3 KOs: Ipsilateral inputs are widely distributed across V1 and are interdigitated with contralateral inputs into eye dominance domains. Segregation is confirmed by optical imaging of intrinsic signals. Single-unit recording shows ipsilateral, and contralateral inputs are mismatched at the level of single V1 neurons, and binocular stimulation leads to functional suppression of these cells. These findings indicate that the medial expansion of the binocular zone together with an interocular mismatch is sufficient to induce novel structural features, such as eye dominance domains in rodent visual cortex.

Deletion of Ten-m3 induces the formation of eye dominance domains in mouse visual cortex.

The alignment of ipsilaterally and contralaterally projecting retinal axons that view the same part of visual space is fundamental to binocular vision. While much progress has been made regarding the mechanisms which regulate contralateral topography, very little is known of the mechanisms which regulate the mapping of ipsilateral axons such that they align with their contralateral counterparts.

Ten-m3 is required for the development of topography in the ipsilateral retinocollicular pathway.

Functional binocular vision requires that inputs arising from the two retinae are integrated and precisely organized within central visual areas. Previous studies have demonstrated an important role for one member of the Ten-m/Odz/teneurin family, Ten-m3, in the mapping of ipsilateral retinal projections. Here, we have identified a distinct role for another closely related family member, Ten-m2, in the formation of the ipsilateral projection in the mouse visual system. Ten-m2 expression was observed in the retina, dorsal lateral geniculate nucleus (dLGN), superior colliculus (SC), and primary visual cortex (V1) of the developing mouse. Anterograde and retrograde tracing experiments in Ten-m2 knock-out (KO) mice revealed a specific decrease in ipsilateral retinal ganglion cells projecting to dLGN and SC. This reduction was most prominent in regions corresponding to ventral retina. No change in the topography of ipsilateral or contralateral projections was observed. While expression of a critical ipsilateral fate determinant, Zic2, appeared unaltered, a notable reduction in one of its downstream targets, EphB1, was observed in ventral retina, suggesting that Ten-m2 may interact with this molecular pathway. Immunohistochemistry for c-fos, a neural activity marker, revealed that the area of V1 driven by ipsilateral inputs was reduced in KOs, while the ratio of ipsilateral-to-contralateral responses contributing to binocular activation during visually evoked potential recordings was also diminished. Finally, a novel two-alternative swim task revealed specific deficits associated with dorsal visual field. These data demonstrate a requirement for Ten-m2 in the establishment of ipsilateral projections, and thus the generation of binocular circuits, critical for mammalian visual function.

Ten-m2 is required for the generation of binocular visual circuits.

A functionally critical feature of the nervous system is the precision of its connectivity. An emerging molecular mediator of this process is the teneurin/ten-m/odz family of transmembrane proteins. A number of recent studies have provided compelling evidence that teneurins have homophilic adhesive properties which, together with their corresponding expression patterns in interconnected groups of neurons, enables them to promote appropriate patterns of connectivity. Particularly important roles have been demonstrated in the visual, olfactory and motor systems. This review attempts to relate new insights into the complex biology of these molecules to their roles in the establishment of functional neural circuits.

The teneurins: new players in the generation of visual topography.

The striatum is the key input nucleus of the basal ganglia, and is implicated in motor control and learning. Despite the importance of striatal circuits, the mechanisms associated with their development are not well established. Previously, Ten-m3, a member of the Ten-m/teneurin/odz family of transmembrane glycoproteins, was found to be important in the mapping of binocular visual pathways. Here, we investigated a potential role for Ten-m3 in striatal circuit formation. In situ hybridisation revealed a patchy distribution of Ten-m3 mRNA expression superimposed on a high-dorsal to low-ventral gradient in a subregion of the striatal matrix. A survey of afferent/efferent structures associated with the matrix identified the parafascicular thalamic nucleus (PF) as a potential locus of action. Ten-m3 was also found to be expressed in a high-dorsal to low-ventral gradient in the PF, corresponding topographically to its expression in the striatum. Further, a subset of thalamic terminal clusters overlapped with Ten-m3-positive domains within the striatal matrix. Studies in wild-type (WT) and Ten-m3 knockout (KO) mice revealed no differences in overall striatal or PF structure. Thalamostriatal terminals in KOs, however, while still confined to the matrix subregion, lost their clustered appearance. Topography was also altered, with terminals from the lateral PF projecting ectopically to ventral and medial striatum, rather than remaining confined dorsolaterally as in WTs. Behaviorally, Ten-m3 KOs displayed delayed motor skill acquisition. This study demonstrates that Ten-m3 plays a key role in directing the formation of thalamostriatal circuitry, the first molecular candidate reported to regulate connectivity within this pathway.

Article	Year
Differential gene expression between sensory neocortical areas: potential roles for Ten_m3 and Bcl6 in patterning visual and somatosensory pathways. Cerebral cortex (New York, N.Y. : 1991)\| PubMed ID: 17478416	2008
Ten_m3 regulates eye-specific patterning in the mammalian visual pathway and is required for binocular vision. PLoS biology\| PubMed ID: 17803360	2007
Rapid reversal of chondroitin sulfate proteoglycan associated staining in subcompartments of mouse neostriatum during the emergence of behaviour. PloS one\| PubMed ID: 18714376	2008
Enrichment from birth accelerates the functional and cellular development of a motor control area in the mouse. PloS one\| PubMed ID: 19756157	2009
Medium spiny neurons of the neostriatal matrix exhibit specific, stereotyped changes in dendritic arborization during a critical developmental period in mice. The European journal of neuroscience\| PubMed ID: 21995728	2011
Perineuronal nets play a role in regulating striatal function in the mouse. PloS one\| PubMed ID: 22427872	2012
Deletion of Ten-m3 induces the formation of eye dominance domains in mouse visual cortex. Cerebral cortex (New York, N.Y. : 1991)\| PubMed ID: 22499796	2013
Ten-m3 is required for the development of topography in the ipsilateral retinocollicular pathway. PloS one\| PubMed ID: 23028443	2012
Ten-m2 is required for the generation of binocular visual circuits. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 23884953	2013
The teneurins: new players in the generation of visual topography. Seminars in cell & developmental biology\| PubMed ID: 25152333	2014
The glycoprotein Ten-m3 mediates topography and patterning of thalamostriatal projections from the parafascicular nucleus in mice. The European journal of neuroscience\| PubMed ID: 25406022	2014

Atomu Sawatari

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