the-attentional-set-shifting-task-measure-cognitive-flexibility

The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many ...

University of Texas Health Science Center at San Antonio

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Zebrafish (Danio rerio) associative responses are useful for pharmaceutical and toxicology screening, behavioral genetics, and discovering neural mechanisms involved in behavioral modulation. In novel environments, zebrafish swim to tank bottoms and dark backgrounds, behaviors attributed to anxiety associated with threat of predation. To examine possible genetic effects of inbreeding and segregation on this behavior, we compared Zebrafish International Resource Center (ZIRC) AB and WIK lines to zebrafish and GloFishÂ® from a pet store (PETCO) in two qualitatively different novel environments: the dive tank and aquatic light/dark plus maze. Behavior was observed in the dive tank for 5 min, immediately followed by 5 min in the light/dark plus maze. Among strains, WIK spent more time in the dive tank top than AB (76 Â± 30 vs. 17 Â± 11 sec), and AB froze in the plus maze center for longer than PETCO or GloFishÂ® (162 Â± 61 vs. 72 Â± 29 or 27 Â± 27 sec). Further, behavior of zebrafish exposed for 3 min to 25 mg/L nicotine, desipramine, chlordiazepoxide, yohimbine, 100 mg/L citalopram, 0.05% DMSO, or 0.5% ethanol was compared to controls. Approximately 0.1% of drug is available in brain after such exposures. Desipramine or citalopram-exposed fish spent more time in the dive tank top, and both reuptake inhibitors bound to serotonin transporters in zebrafish brain with high affinity (K(i) = 7 Â± 5 and 9 Â± 5 nM). In the plus maze, chlordiazepoxide, ethanol and DMSO-exposed fish crossed more lines and spent more time in white arms. Neither 25 mg/L nicotine nor yohimbine altered zebrafish behavior in novel environments, but nicotine was anxiolytic at higher doses. Overall, the light/dark plus maze and dive tank are distinct behavioral measures that are sensitive to treatment with anxiolytic compounds, but zebrafish line selection and solvents can influence baseline behavior in these tests.

Zebrafish Behavior in Novel Environments: Effects of Acute Exposure to Anxiolytic Compounds and Choice of Danio rerio Line.

Poisson z&egrave;bre (Danio rerio) r&eacute;ponses associatives sont utiles pour pharmaceutiques et toxicologie g&eacute;n&eacute;tique comportementale, de d&eacute;pistage et d&eacute;couvrir les m&eacute;canismes neuronaux impliqu&eacute;s dans la modulation comportementale. Dans des environnements nouveaux, zebrafish nager au fond du r&eacute;servoir et des arri&egrave;re-plans sombres, comportements attribu&eacute;s &agrave; l&#39;anxi&eacute;t&eacute; associ&eacute;e &agrave; la menace de pr&eacute;dation. Afin d&#39;examiner les effets g&eacute;n&eacute;tiques possibles de consanguinit&eacute; et de s&eacute;gr&eacute;gation sur ce comportement, nous avons compar&eacute; le poisson-z&egrave;bre International Resource Center (ZIRC) AB et lignes WIK au poisson-z&egrave;bre et GloFish &reg; d&#39;un animal de compagnie stockent (PETCO) dans deux milieux nouveaux qualitativement diff&eacute;rents : le r&eacute;servoir de plong&eacute;e et aquatique lumi&egrave;re/obscurit&eacute; ainsi que le labyrinthe. Comportement a &eacute;t&eacute; observ&eacute; dans le r&eacute;servoir de plong&eacute;e pendant 5 min, imm&eacute;diatement suivi par 5 min dans le labyrinthe, lumi&egrave;re/obscurit&eacute; ainsi. Parmi les souches, WIK a pass&eacute; plus de temps dans la camisole de plong&eacute;e que AB (76 &plusmn; 30 &plusmn; 17 sec 11), et AB s&#39;est fig&eacute; dans le centre de labyrinthe plus pendant plus de PETCO ou GloFish &reg; (162 &plusmn; 61 72 &plusmn; &plusmn; 29 ou 27 27 s). En outre, le comportement des poissons z&egrave;bres expos&eacute;s pendant 3 min &agrave; la nicotine 25 mg/L, d&eacute;sipramine, chlordiaz&eacute;poxide, yohimbine, citalopram 100 mg/L, 0.05 % DMSO ou 0,5 % &eacute;thanol &eacute;tait comparativement aux t&eacute;moins. Environ 0,1 % du m&eacute;dicament est disponible dans le cerveau apr&egrave;s de telles expositions. D&eacute;sipramine ou chez les poissons expos&eacute;s citalopram passent plus de temps dans la camisole de plong&eacute;e, et les deux inhibiteurs de la recapture li&eacute; aux transporteurs de la s&eacute;rotonine dans le cerveau du poisson-z&egrave;bre avec une haute affinit&eacute; (k = 7 nM de &plusmn; 5 &plusmn; 5 et 9). Dans la plus maze, chlordiaz&eacute;poxide, &eacute;thanol et chez les poissons expos&eacute;s DMSO franchi plusieurs lignes et passent plus de temps dans les armes blanches. La nicotine de 25 mg/L ni yohimbine alt&eacute;r&eacute;e zebrafish comportement dans des environnements nouveaux, mais la nicotine &eacute;tait anxiolytiques &agrave; doses plus &eacute;lev&eacute;es. Dans l&#39;ensemble, le r&eacute;servoir de lumi&egrave;re/obscurit&eacute; plus de labyrinthe et de plong&eacute;e sont des mesures comportementales distinctes qui sont sensibles au traitement par anxiolytique compos&eacute;s, mais les solvants et s&eacute;lection de ligne zebrafish peuvent influencer les comportement de r&eacute;f&eacute;rence dans ces essais.

Comportement du poisson-z&egrave;bre dans des environnements de roman : effets d&#39;une exposition aigu&euml; &agrave; des compos&eacute;s anxiolytiques et choix du Danio rerio ligne.

Zebrab&auml;rbling (Danio Rerio) assoziative Antworten eignen sich f&uuml;r die Pharma- und Toxikologie screening, Verhaltensgenetik, und Neuronale Mechanismen Verhaltens Modulation zu entdecken. Zebrab&auml;rbling Schwimmen in neue Umgebungen Gel&auml;ger und dunkle Hintergr&uuml;nde, Verhaltensweisen zugeschrieben Angst, Bedrohung der Pr&auml;dation zugeordnet. Um m&ouml;gliche genetische Effekte von Inzucht und Segregation zu diesem Verhalten zu untersuchen, verglichen wir Zebrafisch International Resource Center (ZIRC) AB und WIK-Linien in Zebrafisch und GloFish &reg; aus ein Haustier (PETCO) in zwei qualitativ verschiedene neuartige Umgebungen speichern: der Tauchgang Tank und aquatischen hell/dunkel plus Labyrinth. Verhalten wurde im Tank Tauchgang f&uuml;r 5 min, unmittelbar gefolgt von 5 min in der hell/dunkel plus Labyrinth beobachtet. Unter den St&auml;mmen, WIK verbrachte mehr Zeit in den Tauchgang Tank Top als AB (76 &plusmn; 30 vs. 17 &plusmn; 11 Sek.), und AB erstarrte in der plus-Labyrinth-Mitte l&auml;nger als PETCO oder GloFish &reg; (162 &plusmn; 61 vs. 72 &plusmn; 29 oder 27 &plusmn; 27 Sek.). Dar&uuml;ber hinaus war Verhalten der Zebrafisch gemachten 3 min 25 mg/L Nikotin, Desipramin, Chlordiazepoxid, Yohimbin, 100 mg/L Citalopram, 0,05 % DMSO oder 0,5 % &Auml;thanol Kontrollen gegen&uuml;ber. Etwa 0,1 % des Medikaments steht im Gehirn nach solchen Forderungen zur Verf&uuml;gung. Desipramin oder Citalopram-gemachten Fisch verbrachte mehr Zeit in den Tauch-Tank-Top, und beide Wiederaufnahmehemmer zwangsl&auml;ufig Serotonin-Transporter im Zebrafisch Gehirn mit hoher Affinit&auml;t (K(i) = 7 &plusmn; 5 und 9 &plusmn; 5 nM). Im Plus Labyrinth, Chlordiazepoxid, Ethanol und DMSO-gemachten Fisch mehr Linien gekreuzt und verbrachte mehr Zeit in wei&szlig;en Armen. 25 Mg/L Nikotin weder Yohimbin ver&auml;ndert Zebrafisch Verhalten in neue Umgebungen, aber Nikotin war Anxiolytikum bei h&ouml;heren Dosen. Insgesamt hell/dunkel plus Labyrinth und Tauchen Tank sind unterschiedliche verhaltensbasierte Ma&szlig;nahmen, die auf Behandlung mit Anxiolytic Verbindungen reagieren, aber Zebrafisch Zeilenauswahl und L&ouml;sungsmittel geplantes Verhalten in diesen Tests beeinflussen k&ouml;nnen.

Zebrafish Verhalten in Roman Umgebungen: Effekte der akuten Gef&auml;hrdung Anxiolytic Verbindungen und Wahl von Danio Rerio Linie.

Danio zebrato (Danio rerio) risposte associative sono utili per la farmaceutica e tossicologia, genetica comportamentale, di screening e alla scoperta di meccanismi neurali coinvolti nella modulazione del comportamento. In nuovi ambienti, zebrafish nuotare a serbatoio fondali e sfondi scuri, comportamenti attribuiti all&#39;ansia associata con minaccia di predazione. Per esaminare i possibili effetti genetici di consanguineit&agrave; e segregazione su questo comportamento, abbiamo confrontato Zebrafish International Resource Center (ZIRC) AB e linee WIK zebrafish e GloFish &reg; da un pet store (PETCO) in due ambienti romanzo qualitativamente differenti: la vasca d&#39;immersione e acquatica chiaro/scuro pi&ugrave; labirinto. Comportamento &egrave; stato osservato nella vasca di immersione per 5 min, immediatamente seguita da 5 min nel labirinto pi&ugrave; chiaro/scuro. Tra ceppi, WIK trascorso pi&ugrave; tempo in immersione tank top di AB (76 &plusmn; 30 vs 17 &plusmn; 11 sec), e AB congelato nel centro Dedalo plus per pi&ugrave; di PETCO o GloFish &reg; (162 &plusmn; 61 vs 72 &plusmn; 29 o 27 &plusmn; 27 sec). Comportamento di zebrafish esposto per 3 min a nicotina 25 mg/L, desipramina, clordiazepossido, Yohimbina, citalopram 100 mg/L, 0.05% DMSO o 0,5% etanolo &egrave; stato ulteriormente, rispetto ai controlli. Circa il 0,1% del farmaco &egrave; disponibile nel cervello dopo tali esposizioni. Desipramina o pesce esposti citalopram trascorso pi&ugrave; tempo in immersione tank top, ed entrambi gli inibitori del reuptake associato ai trasportatori di serotonina nel cervello di zebrafish con alta affinit&agrave; (K(i) = 7 &plusmn; 5 e 9 &plusmn; 5 nM). In pi&ugrave; labirinto, clordiazepossido, etanolo e pesci esposti DMSO attraversarono pi&ugrave; linee e ha trascorso pi&ugrave; tempo in armi bianche. Nicotina 25 mg/L n&eacute; Yohimbina alterato comportamento di zebrafish in nuovi ambienti, ma nicotina era ansiolitici a dosi elevate. Nel complesso, il serbatoio di luce/buio plus labirinto e immersione sono distinte misure comportamentali che sono sensibili al trattamento con composti di ansiolitico, ma zebrafish linea selezione e solventi possono influenzare il comportamento di baseline in questi test.

Comportamento di zebrafish negli ambienti del romanzo: effetti dell&#39;esposizione acuta a composti ansiolitico e scelta di Danio rerio linea.

&#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5;) &#x9023;&#x60F3;&#x5FDC;&#x7B54;&#x306F;&#x533B;&#x85AC;&#x54C1;&#x3068;&#x6BD2;&#x6027;&#x30B9;&#x30AF;&#x30EA;&#x30FC;&#x30CB;&#x30F3;&#x30B0;&#x3001;&#x884C;&#x52D5;&#x907A;&#x4F1D;&#x5B66;&#x3068;&#x884C;&#x52D5;&#x306E;&#x5909;&#x8ABF;&#x306B;&#x95A2;&#x4E0E;&#x3059;&#x308B;&#x795E;&#x7D4C;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x3092;&#x767A;&#x898B;&#x3059;&#x308B;&#x4E0A;&#x3067;&#x5F79;&#x7ACB;&#x3061;&#x307E;&#x3059;&#x3002;&#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5;&#x5C0F;&#x8AAC;&#x306E;&#x74B0;&#x5883;&#x3067;&#x306F;&#x3001;&#x6CF3;&#x3050;&#x30BF;&#x30F3;&#x30AF;&#x5E95;&#x3068;&#x6697;&#x3044;&#x80CC;&#x666F;&#x3001;&#x30D3;&#x30D8;&#x30A4;&#x30D3;&#x30A2;&#x30FC;&#x306E;&#x6355;&#x98DF;&#x306E;&#x8105;&#x5A01;&#x306B;&#x95A2;&#x9023;&#x3059;&#x308B;&#x4E0D;&#x5B89;&#x306B;&#x8D77;&#x56E0;&#x3057;&#x307E;&#x3059;&#x3002;&#x8FD1;&#x89AA;&#x4EA4;&#x914D;&#x3068;&#x3053;&#x306E;&#x6319;&#x52D5;&#x306B;&#x53CA;&#x307C;&#x3059;&#x504F;&#x6790;&#x306E;&#x53EF;&#x80FD;&#x306A;&#x907A;&#x4F1D;&#x7684;&#x5F71;&#x97FF;&#x3092;&#x8ABF;&#x3079;&#x308B;&#x306B;&#x306F;&#x3001;&#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5;&#x56FD;&#x969B;&#x30EA;&#x30BD;&#x30FC;&#x30B9; &#x30BB;&#x30F3;&#x30BF;&#x30FC; &#xFF08;&#x30B8;&#x30EB;&#x30B3;&#x30CB;&#x30A6;&#x30E0;&#xFF09; AB &#x3068;&#x6BD4;&#x8F03;&#x3057;&#x3066;&#x3001;&#x30DA;&#x30C3;&#x30C8;&#x304B;&#x3089; WIK &#x7DDA;&#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5;&#x3068;&#x30B0;&#x30ED;&#x30FC;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5; &reg; &#x306B;&#x4FDD;&#x5B58; (&#x30DA;&#x30C8;&#x30B3;&#xFF09; &#x8CEA;&#x7684;&#x306B;&#x7570;&#x306A;&#x308B; 2 &#x3064;&#x306E;&#x65B0;&#x3057;&#x3044;&#x74B0;&#x5883;&#x3067;: &#x30C0;&#x30A4;&#x30D3;&#x30F3;&#x30B0; &#x30BF;&#x30F3;&#x30AF;&#x3068;&#x6C34;&#x751F;&#x5149;/&#x6697;&#x3044;&#x30D7;&#x30E9;&#x30B9;&#x8FF7;&#x8DEF;&#x3002;&#x30C0;&#x30A4;&#x30D3;&#x30F3;&#x30B0; &#x30BF;&#x30F3;&#x30AF; 5 &#x5206;&#x5149;/&#x6697;&#x3044;&#x30D7;&#x30E9;&#x30B9;&#x8FF7;&#x8DEF;&#x306E;&#x76F4;&#x5F8C;&#x3001;5 &#x5206;&#x9593;&#x3067;&#x52D5;&#x4F5C;&#x304C;&#x89B3;&#x5BDF;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x7CFB;&#x7D71;&#x9593; WIK &#x30C0;&#x30A4;&#x30D3;&#x30F3;&#x30B0; &#x30BF;&#x30F3;&#x30AF; &#x30C8;&#x30C3;&#x30D7; AB &#x3088;&#x308A;&#x3082;&#x3088;&#x308A;&#x591A;&#x304F;&#x306E;&#x6642;&#x9593;&#x904E;&#x3054;&#x3057;&#x305F; &#xFF08;&#x5BFE; 17 &plusmn; 11 &#x79D2; 76 &#x306E; &plusmn; 30)&#x3001;AB &#x3092;&#x51CD;&#x7D50;&#x3057;&#x305F;&#x30D7;&#x30E9;&#x30B9;&#x8FF7;&#x8DEF;&#x30BB;&#x30F3;&#x30BF;&#x30FC; &#x30DA;&#x30C8;&#x30B3;&#x307E;&#x305F;&#x306F;&#x30B0;&#x30ED;&#x30FC;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5; &reg; &#x3088;&#x308A;&#x9577;&#x304F; (162 &plusmn; 61 72 &plusmn; 29 &#x307E;&#x305F;&#x306F; 27 &plusmn; 27 &#x79D2;&#x5BFE;)&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5; 3 &#x5206; 25 mg/L &#x306E;&#x30CB;&#x30B3;&#x30C1;&#x30F3;&#x3001;&#x30C7;&#x30B7;&#x30D7;&#x30E9;&#x30DF;&#x30F3;&#x3001;&#x30AF;&#x30ED;&#x30EB;&#x30B8;&#x30A2;&#x30BC;&#x30DD;&#x30AD;&#x30B7;&#x30C9;&#x3001;&#x30E8;&#x30D2;&#x30F3;&#x30D3;&#x30F3;, 100 mg/L &#x30B7;&#x30BF;&#x30ED;&#x30D7;&#x30E9;&#x30E0;&#x3001;0.05 %dmso&#x3001;&#x307E;&#x305F;&#x306F; 0.5 &#xFF05; &#x30A8;&#x30BF;&#x30CE;&#x30FC;&#x30EB;&#x3078;&#x306E;&#x9732;&#x51FA;&#x306E;&#x52D5;&#x4F5C;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#x306B;&#x6BD4;&#x3079;&#x3066;&#x3044;&#x305F;&#x3002;&#x85AC;&#x7269;&#x306E;&#x7D04; 0.1% &#x3067;&#x8133;&#x306A;&#x3069;&#x306E;&#x66B4;&#x9732;&#x5F8C;&#x5229;&#x7528;&#x53EF;&#x80FD;&#x3067;&#x3059;&#x3002;&#x30C7;&#x30B7;&#x30D7;&#x30E9;&#x30DF;&#x30F3;&#x307E;&#x305F;&#x306F;&#x30B7;&#x30BF;&#x30ED;&#x30D7;&#x30E9;&#x30E0;&#x3055;&#x3089;&#x3055;&#x9B5A;&#x30C0;&#x30A4;&#x30D3;&#x30F3;&#x30B0; &#x30BF;&#x30F3;&#x30AF; &#x30C8;&#x30C3;&#x30D7;&#x3067;&#x591A;&#x304F;&#x306E;&#x6642;&#x9593;&#x3092;&#x904E;&#x3054;&#x3057;&#x305F;&#x3057;&#x3001;&#x9AD8;&#x3044;&#x89AA;&#x548C;&#x6027;&#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5;&#x8133;&#x306B;&#x304A;&#x3051;&#x308B;&#x30BB;&#x30ED;&#x30C8;&#x30CB;&#x30F3;&#x8F38;&#x9001;&#x4F53;&#x306B;&#x30D0;&#x30A4;&#x30F3;&#x30C9;&#x3055;&#x308C;&#x3066;&#x4E21;&#x65B9;&#x518D;&#x53D6;&#x308A;&#x8FBC;&#x307F;&#x963B;&#x5BB3;&#x85AC; &#xFF08;K(i) = 7 &plusmn; 5 &#x3068; 9 &plusmn; 5 nM)&#x3002;&#x30D7;&#x30E9;&#x30B9;&#x8FF7;&#x8DEF;&#x3001;&#x30AF;&#x30ED;&#x30EB;&#x30B8;&#x30A2;&#x30BC;&#x30DD;&#x30AD;&#x30B7;&#x30C9;&#x3001;&#x30A8;&#x30BF;&#x30CE;&#x30FC;&#x30EB;&#x3001;DMSO &#x3055;&#x3089;&#x3055;&#x9B5A;&#x3088;&#x308A;&#x591A;&#x304F;&#x306E;&#x30E9;&#x30A4;&#x30F3;&#x3092;&#x4EA4;&#x5DEE;&#x3057;&#x3001;&#x767D;&#x3044;&#x8155;&#x306E;&#x4E2D;&#x3067;&#x3088;&#x308A;&#x591A;&#x304F;&#x306E;&#x6642;&#x9593;&#x3092;&#x904E;&#x3054;&#x3057;&#x305F;&#x3002;&#x3069;&#x3061;&#x3089;&#x3082; 25 mg/L &#x306E;&#x30CB;&#x30B3;&#x30C1;&#x30F3;&#x3082;&#x30E8;&#x30D2;&#x30F3;&#x30D3;&#x30F3; &#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5;&#x52D5;&#x4F5C;&#x5C0F;&#x8AAC;&#x306E;&#x74B0;&#x5883;&#x3067;&#x306F;&#x5909;&#x66F4;&#x304C;&#x30CB;&#x30B3;&#x30C1;&#x30F3;&#x9AD8;&#x7528;&#x91CF;&#x3067;&#x6297;&#x4E0D;&#x5B89;&#x3060;&#x3063;&#x305F;&#x3002;&#x5168;&#x4F53;&#x7684;&#x306B;&#x3001;&#x5149;/&#x6697;&#x3044;&#x30D7;&#x30E9;&#x30B9;&#x8FF7;&#x8DEF;&#x3068;&#x30C0;&#x30A4;&#x30D3;&#x30F3;&#x30B0;&#x306E;&#x30BF;&#x30F3;&#x30AF;&#x306F;&#x6CBB;&#x7642;&#x3068;&#x6297;&#x4E0D;&#x5B89;&#x85AC;&#x5316;&#x5408;&#x7269;&#x306B;&#x654F;&#x611F;&#x3067;&#x3042;&#x308B;&#x500B;&#x5225;&#x306E;&#x884C;&#x52D5;&#x306B;&#x95A2;&#x3059;&#x308B;&#x63AA;&#x7F6E;&#x304C;&#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5;&#x884C;&#x9078;&#x629E;&#x3068;&#x6EB6;&#x5264;&#x30D9;&#x30FC;&#x30B9;&#x30E9;&#x30A4;&#x30F3;&#x52D5;&#x4F5C;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C6;&#x30B9;&#x30C8;&#x306B;&#x5F71;&#x97FF;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;

&#x30BC;&#x30D6;&#x30E9;&#x30D5;&#x30A3;&#x30C3;&#x30B7;&#x30E5;&#x5C0F;&#x8AAC;&#x4E2D;&#x6319;&#x52D5;: &#x6297;&#x4E0D;&#x5B89;&#x85AC;&#x5316;&#x5408;&#x7269;&#x3068;&#x30C0;&#x30CB;&#x30AA;&#x9078;&#x629E;&#x5F62;&#x614B;&#x5B66;&#x7DDA;&#x6025;&#x6027;&#x66B4;&#x9732;&#x306E;&#x5F71;&#x97FF;&#x3002;

Zebrafish (Danio rerio) &#xC5F0;&#xAD00; &#xC751;&#xB2F5;&#xC740; &#xC81C;&#xC57D; &#xBC0F; &#xB3C5;&#xADF9;&#xBB3C; &#xAC80;&#xC0AC;, &#xD589;&#xB3D9; &#xC720;&#xC804;&#xD559; &#xADF8;&#xB9AC;&#xACE0; &#xD589;&#xB3D9; &#xBCC0;&#xC870;&#xC5D0; &#xAD00;&#xB828; &#xB41C; &#xC2E0;&#xACBD; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xBC1C;&#xACAC; &#xD558;&#xB294; &#xB370; &#xC720;&#xC6A9; &#xD569;&#xB2C8;&#xB2E4;. &#xC18C;&#xC124; &#xD658;&#xACBD; zebrafish &#xD0F1;&#xD06C; &#xBC14;&#xB2E5;&#xC744; &#xC5B4;&#xB450;&#xC6B4; &#xBC30;&#xACBD;, &#xB3D9;&#xC791; &#xBD88;&#xC548; &#xD3EC;&#xC2DD;&#xC758; &#xC704;&#xD611; &#xC5F0;&#xAD00;&#xC5D0; &#xC218;&#xC601;. &#xADFC; &#xCE5C;&#xC640;&#xC774; &#xBB38;&#xC81C;&#xC5D0; &#xBD84;&#xB9AC;&#xC758; &#xC720;&#xC804;&#xC801; &#xC601;&#xD5A5;&#xC744; &#xAC80;&#xC0AC;&#xD560; &#xC6B0;&#xB9AC; Zebrafish &#xAD6D;&#xC81C; &#xB9AC;&#xC18C;&#xC2A4; &#xC13C;&#xD130; (ZIRC) AB &#xBE44;&#xAD50; &#xBC0F; &#xC560;&#xC644; &#xB3D9;&#xBB3C;&#xC5D0;&#xC11C; zebrafish &#xBC0F; GloFish &reg; WIK &#xB77C;&#xC778; &#xB450; &#xC9C8;&#xC801;&#xC73C;&#xB85C; &#xB2E4;&#xB978; &#xC0C8;&#xB85C;&#xC6B4; &#xD658;&#xACBD;&#xC5D0;&#xC11C; (PETCO) &#xC800;&#xC7A5;: &#xB2E4;&#xC774;&#xBE59; &#xD0F1;&#xD06C; &#xBC0F; &#xC218; &#xC911; &#xB77C;&#xC774;&#xD2B8;/&#xB2E4;&#xD06C; &#xD50C;&#xB7EC;&#xC2A4; &#xBBF8;&#xB85C;. &#xB3D9;&#xC791; 5 &#xBD84;, &#xBE5B;/&#xC5B4;&#xB460; &#xD50C;&#xB7EC;&#xC2A4; &#xBBF8;&#xB85C;&#xC5D0;&#xC11C; 5 &#xBD84; &#xD6C4; &#xBC14;&#xB85C; &#xB2E4;&#xC774;&#xBE59; &#xD0F1;&#xD06C;&#xC5D0;&#xC11C; &#xAD00;&#xCC30; &#xB418;&#xC5C8;&#xB2E4;. &#xAE34;&#xC7A5;, &#xAC00;&#xC6B4;&#xB370; WIK AB &#xBCF4;&#xB2E4; &#xB2E4;&#xC774;&#xBE59; &#xD0F1;&#xD06C; &#xD0D1;&#xC5D0; &#xB354; &#xB9CE;&#xC740; &#xC2DC;&#xAC04;&#xC744; &#xBCF4;&#xB0B8; (76 &plusmn; 30 &#xB300; 17 &plusmn; 11 &#xCD08;), AB &#xD50C;&#xB7EC;&#xC2A4; &#xBBF8;&#xB85C; &#xC13C;&#xD130; PETCO &#xB610;&#xB294; GloFish &reg; &#xBCF4;&#xB2E4; &#xB354; &#xC624;&#xB7AB;&#xB3D9;&#xC548; &#xC5BC;&#xC5B4; (162 &plusmn; 61 72 &plusmn; 29 &#xB610;&#xB294; 27 &plusmn; &#xB300; 27 &#xCD08;). &#xB610;&#xD55C;, 25 mg/L &#xB2C8;&#xCF54;&#xD2F4;, &#xB370;, chlordiazepoxide, yohimbine, 100 mg/L citalopram, 0.05 %dmso, &#xB610;&#xB294; 0.5%&#xC758; &#xC5D0;&#xD0C4;&#xC62C;&#xC744; 3 &#xBD84; &#xB3D9;&#xC548; &#xB178;&#xCD9C; zebrafish&#xC758; &#xB3D9;&#xC791; &#xCEE8;&#xD2B8;&#xB864; &#xBE44;&#xAD50; &#xB418;&#xC5C8;&#xB2E4;. &#xC57D;&#xBB3C;&#xC758; &#xC57D; 0.1%&#xB294; &#xAC19;&#xC740; &#xB178;&#xCD9C; &#xD6C4; &#xB1CC;&#xC5D0;&#xC11C; &#xAC00;&#xB2A5; &#xD569;&#xB2C8;&#xB2E4;. &#xB370; &#xB610;&#xB294; citalopram &#xB178;&#xCD9C; &#xBB3C;&#xACE0;&#xAE30; &#xB2E4;&#xC774;&#xBE59; &#xD0F1;&#xD06C; &#xD0D1;&#xC5D0; &#xB354; &#xB9CE;&#xC740; &#xC2DC;&#xAC04;&#xC744; &#xBCF4;&#xB0C8;&#xB2E4; &#xADF8;&#xB9AC;&#xACE0; &#xB192;&#xC740; &#xC120;&#xD638;&#xB3C4; zebrafish &#xB1CC;&#xC5D0;&#xC11C; &#xC138;&#xB85C;&#xD1A0;&#xB2CC; &#xC804;&#xC1A1;&#xAE30;&#xC5D0; &#xBC14;&#xC778;&#xB529;&#xB41C; &#xB450; &#xC7AC;&#xD761;&#xC218; &#xC800; &#xD574;&#xC81C; (K(i) = 7 5&#xC640; 9 &plusmn; &plusmn; 5 nM). &#xB354;&#xD558;&#xAE30; &#xBBF8;&#xB85C;, chlordiazepoxide, &#xC5D0;&#xD0C4;&#xC62C;&#xACFC; DMSO &#xB178;&#xCD9C; &#xBB3C;&#xACE0;&#xAE30; &#xB354; &#xB9CE;&#xC740; &#xB77C;&#xC778;&#xC744; &#xB118;&#xC5B4; &#xBC0F; &#xBC31;&#xC0C9; &#xBB34;&#xAE30;&#xC5D0; &#xB354; &#xB9CE;&#xC740; &#xC2DC;&#xAC04;&#xC744; &#xBCF4;&#xB0C8;&#xB2E4;. 25 Mg/L &#xB2C8;&#xCF54;&#xD2F4;&#xB3C4; &#xC5C6;&#xACE0; yohimbine &#xBCC0;&#xACBD; &#xC0C8;&#xB85C;&#xC6B4; &#xD658;&#xACBD;&#xC5D0;&#xC11C; zebrafish &#xB3D9;&#xC791; &#xD558;&#xC9C0;&#xB9CC; &#xB2C8;&#xCF54;&#xD2F4; &#xBA74;&#xC81C;&#xAC00; &#xB354; &#xB192;&#xC740; &#xBCF5;&#xC6A9;&#xB7C9;&#xC5D0;&#xC11C;. &#xC804;&#xBC18;&#xC801;&#xC73C;&#xB85C;, &#xBE5B;/&#xC5B4;&#xB460; &#xD50C;&#xB7EC;&#xC2A4; &#xBBF8;&#xB85C; &#xC7A0;&#xC218; &#xD0F1;&#xD06C;&#xB294; &#xBA74;&#xC81C;&#xAC00; &#xD654;&#xD569;&#xBB3C;&#xACFC; &#xCE58;&#xB8CC;&#xC5D0; &#xBBFC;&#xAC10;&#xD55C; &#xACE0;&#xC720;&#xD55C; &#xD589;&#xB3D9; &#xC870;&#xCE58; &#xD558;&#xC9C0;&#xB9CC; zebrafish &#xB77C;&#xC778; &#xC120;&#xD0DD; &#xBC0F; &#xC6A9; &#xC81C;&#xAC00;&#xC774; &#xD14C;&#xC2A4;&#xD2B8;&#xC5D0;&#xC11C;&#xB294; &#xCD08;&#xAE30; &#xB3D9;&#xC791;&#xC5D0; &#xC601;&#xD5A5;&#xC744; &#xBBF8;&#xCE60; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC18C;&#xC124; &#xD658;&#xACBD;&#xC5D0;&#xC11C; Zebrafish &#xB3D9;&#xC791;: &#xBA74;&#xC81C;&#xAC00; &#xD654;&#xD569;&#xBB3C; Danio &#xC120;&#xD0DD; rerio &#xB77C;&#xC778;&#xC5D0; &#xAE09;&#xC131; &#xB178;&#xCD9C;&#xC758; &#xD6A8;&#xACFC;.

Respuestas asociativas de pez cebra (Danio rerio) son &uacute;tiles para farmac&eacute;uticos y Toxicolog&iacute;a, investigaci&oacute;n, gen&eacute;tica conductista y descubrir los mecanismos neuronales implicados en la modulaci&oacute;n del comportamiento. En los nuevos ambientes, pez cebra nadar hasta fondos de tanque y fondos oscuros, comportamientos atribuidos a la ansiedad asociada con la amenaza de depredaci&oacute;n. Para examinar los efectos gen&eacute;ticos de endogamia y segregaci&oacute;n en este comportamiento, comparamos el Centro Internacional de recursos de pez cebra (ZIRC) AB y l&iacute;neas WIK pez cebra y GloFish &reg; de una mascota almacenan (PETCO) en dos ambientes novela cualitativamente diferentes: el tanque de buceo y acu&aacute;tica claro/oscuro adem&aacute;s de laberinto. Comportamiento se observ&oacute; en el tanque de buceo durante 5 minutos, seguido de 5 min en el claro/oscuro adem&aacute;s de laberinto. Entre cepas, WIK pas&oacute; m&aacute;s tiempo en la tapa del tanque de buceo que AB (76 &plusmn; 30 vs 17 &plusmn; 11 segundos), y AB se congelaron en el centro de laberinto plus por m&aacute;s de PETCO o GloFish &reg; (162 &plusmn; 61 vs 72 29 o 27 &plusmn; 27 seg). Adem&aacute;s, el comportamiento del pez cebra expuesto por 3 min a nicotina de 25 mg/L, desipramina, clordiazep&oacute;xido, yohimbina, citalopram 100 mg/L, DMSO 0.05% o 0.5% etanol fue comparado con controles. Aproximadamente 0,1% de la droga est&aacute; disponible en el cerebro despu&eacute;s de estas exposiciones. Desipramina o peces expuestos al citalopram pasaron m&aacute;s tiempo en la tapa del tanque de buceo, y ambos inhibidores de la recaptaci&oacute;n atado a los transportadores de serotonina en el cerebro de pez cebra con alta afinidad (K(i) = 7 &plusmn; 5 y 9 &plusmn; 5 nM). En el plus laberinto, clordiazep&oacute;xido, etanol y peces expuestos al DMSO cruzaron m&aacute;s l&iacute;neas y pasaron m&aacute;s tiempo en brazos blanca. Nicotina 25 mg/L ni yohimbina alterado el comportamiento del pez cebra en nuevos ambientes, pero la nicotina era ansiol&iacute;ticos en dosis m&aacute;s altas. En general, el tanque claro/oscuro m&aacute;s laberinto y buceo son distintas medidas de comportamiento que son sensibles al tratamiento con compuestos de ansiol&iacute;ticos, pero solventes y pez cebra l&iacute;nea selecci&oacute;n pueden influir en comportamiento de la l&iacute;nea de base en estas pruebas.

Comportamiento del pez cebra en ambientes de la novela: efectos de la exposici&oacute;n aguda a compuestos ansiol&iacute;ticos y elecci&oacute;n de Danio rerio l&iacute;nea.

Chronic stress contributes to many neuropsychiatric disorders in which the HPA axis, cognition and neuro-immune activity are dysregulated. Patients with major depression, or healthy individuals subjected to acute stress, present elevated levels of circulating pro-inflammatory markers. Acute stress also activates pro-inflammatory signals in the periphery and in the brain of rodents. However, despite the clear relevance of chronic stress to human psychopathology, the effects of prolonged stress exposure on central immune activity and reactivity have not been well characterized. Our laboratory has previously shown that, in rats, chronic intermittent cold stress (CIC stress, 4°C, 6h/day, 14 days) sensitizes the HPA response to a subsequent novel stressor, and produces deficits in a test of cognitive flexibility that is dependent upon prefrontal cortical function. We have hypothesized that CIC stress could potentially exert some of these effects by altering the neuro-immune status of the brain, leading to neuronal dysfunction. In this study, we have begun to address this question by determining whether previous exposure to CIC stress could alter the subsequent neuro-immune response to an acute immunological challenge (lipopolysaccharide, LPS) or an acute heterologous stressor (footshock). We examined the response of the pro-inflammatory cytokines, IL1β and IL6, the enzyme cyclooxygenase 2, and the chemokines, CXCL1 and MCP-1 in plasma, hypothalamus and prefrontal cortex. There was no effect of CIC stress on basal expression of these markers 24h after the termination of stress. However, CIC stress enhanced the acute induction of the pro-inflammatory cytokines, IL1β and particularly IL6, and the chemokines, CXCL1 and MCP-1, in plasma, hypothalamus and prefrontal cortex in response to LPS, and also sensitized the hypothalamic IL1β response to acute footshock. Thus, sensitization of acute pro-inflammatory responses in the brain could potentially mediate some of the CIC-dependent changes in HPA and cognitive function.

Chronic intermittent cold stress sensitizes neuro-immune reactivity in the rat brain.

Abnormal basal activity and stress-evoked reactivity of the hypothalamic-pituitary-adrenal (HPA) axis are often seen in depression, implicating HPA axis dysfunction as a potentially causative or exacerbating factor. Chronic stress is also a factor in depression, but it is not known what may underlie the shift from adaptive to maladaptive HPA activity over the course of chronic stress. Interleukin 6 (IL-6), a stress-inducible cytokine that signals through gp130 and IL-6Rα receptors to activate the JAK/STAT3 signaling cascade, is elevated in some subtypes of depression, and may have a modulatory effect on HPA activation, raising the possibility that IL-6 contributes to depression through effects on the HPA axis. In this study, we examined the effects of three different stress modalities, acute footshock, chronic intermittent cold (CIC) stress and chronic unpredictable stress (CUS) on IL-6 signaling in the hypothalamus. We also investigated whether IL-6 modulates the HPA response to chronic stress, by blocking IL-6 signaling in the brain during CIC stress using either a neutralizing antibody or an inhibitor of STAT3 phosphorylation. We show that IL-6 and STAT3 in the hypothalamus are activated in response to footshock and CUS. We also found that basal IL-6 signaling through the JAK/STAT3 pathway is required for the sustained CORT response to chronic, but not acute, cold stress and therefore is a potential determinant of plasticity in the HPA axis specifically during chronic stress exposure.

Influence of hypothalamic IL-6/gp130 receptor signaling on the HPA axis response to chronic stress.

Cytokines, small proteins released by the immune system to combat infection, are typically studied under inflammatory conditions. However, these molecules are also expressed in the brain in basal, nonpathological states, where they can regulate neuronal processes, such as learning and memory. However, little is known about how cytokine signaling in the brain may influence higher-order cognitive functions. Cognitive flexibility is one such executive process, mediated by the prefrontal cortex, which requires an adaptive modification of learned behaviors in response to environmental change. We explored the role of basal IL-6 signaling in the orbitofrontal cortex (OFC) in reversal learning, a form of cognitive flexibility that can be measured in the rat using the attentional set-shifting test. We found that inhibiting IL-6 or its downstream JAK/STAT signaling pathway in the OFC impaired reversal learning, suggesting that basal IL-6 and JAK/STAT signaling facilitate cognitive flexibility. Further, we demonstrated that elevating IL-6 in the OFC by adeno-associated virus-mediated gene delivery reversed a cognitive deficit induced by chronic stress, thus identifying IL-6 and the downstream JAK/STAT signaling pathway as potentially novel therapeutic targets for the treatment of stress-related psychiatric diseases associated with cognitive dysfunction.

A novel role for brain interleukin-6: facilitation of cognitive flexibility in rat orbitofrontal cortex.

The serotonin 2A (5-HT2A) receptor and the proinflammatory cytokine, interleukin-6 (IL-6), have both been implicated in psychiatric disorders. Previously, we demonstrated that these molecules both facilitate cognitive flexibility, a prefrontal cortex-mediated executive function impaired in multiple mental illnesses. In this study, we tested the hypothesis that IL-6 influences 5-HT2A receptor signaling, providing a potential mechanism by which this cytokine may influence behavior. We first demonstrated that 5-HT2A receptors and IL-6-mediated STAT3 phosphorylation colocalize in cells of the prefrontal cortex, providing the neuroanatomical substrate for a potential interaction. In the neuronally derived A1A1 cell line, which expresses both IL-6 and 5-HT2A receptors, we found that IL-6 attenuates inositol phosphate (IP) accumulation in response to the 5-HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), suggesting that IL-6 can regulate 5-HT2A receptor function. To identify the signaling pathway(s) that mediate this effect, we measured DOI-mediated IP accumulation in the presence of IL-6 and either the JAK-STAT inhibitor 124 [(9β,10α,16α,23E)-2,16,20,25-tetrahydroxy-9-methyl-19-norlanosta-1,5,23-triene-3,11,22-trione], JSI-124, or the extracellular signal-regulated kinase inhibitor, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD-98059). The IL-6 effect was blocked by JSI-124 but not PD-98059. Furthermore, silencing RNA knockdown of either JAK or STAT blocked the IL-6 effect, suggesting that IL-6-induced JAK-STAT activation can regulate 5-HT2A receptor signaling. Finally, to determine if IL-6 specifically regulates the 5-HT2A receptor system, we measured IP production mediated by another Gq-coupled receptor, bradykinin B2. IL-6 had no effect on bradykinin-mediated IP accumulation, suggesting that regulation may occur at the 5-HT2A receptor. These results may provide clues to the pathologic mechanisms underlying certain psychiatric disorders and may suggest novel therapeutic strategies for their treatment.

Article	Year
Zebrafish Behavior in Novel Environments: Effects of Acute Exposure to Anxiolytic Compounds and Choice of Danio rerio Line. International journal of comparative psychology / ISCP ; sponsored by the International Society for Comparative Psychology and the University of Calabria\| PubMed ID: 20523756	2010
Chronic intermittent cold stress sensitizes neuro-immune reactivity in the rat brain. Psychoneuroendocrinology\| PubMed ID: 21411230	2011
Influence of hypothalamic IL-6/gp130 receptor signaling on the HPA axis response to chronic stress. Psychoneuroendocrinology\| PubMed ID: 23218517	2013
A novel role for brain interleukin-6: facilitation of cognitive flexibility in rat orbitofrontal cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 24431453	2014
Interleukin-6 Attenuates Serotonin 2A Receptor Signaling by Activating the JAK-STAT Pathway. Molecular pharmacology\| PubMed ID: 25549668	2015

Jennifer J. Donegan

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JoVE Journal Publications

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