optogenetic-stimulation-of-the-auditory-nerve

Optogenetic Stimulation of the Auditory Nerve

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted ...

University Medical Center Goettingen

&gamma;-Aminobutric &#x9178; (GABA) &#x662F;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x7684;&#x4E3B;&#x8981;&#x6291;&#x5236;&#x9012;&#x8D28;&#x4E4B;&#x4E00;&#x3002;&#x5728;&#x6700;&#x8FD1;&#x4E00;&#x9879;&#x7814;&#x7A76;&#x4E2D;&#x6211;&#x4EEC;&#x8868;&#x73B0;&#x51FA;&#x7684;&#x4E24;&#x4E2A; iontophoretically &#x7684;&#x5DEE;&#x522B;&#x5F71;&#x54CD;&#x5E94;&#x7528; GABA (A)-&#x53D7;&#x4F53;&#x963B;&#x6EDE;&#x5242;&#xFF0C;&#x8377;&#x5305;&#x7261;&#x4E39;&#x78B1; (BIC) &#x548C; gabazine (SR 95531)&#xFF0C;&#x5BF9;&#x521D;&#x7EA7;&#x542C;&#x89C9;&#x76AE;&#x5C42; &#xFF08;AI&#xFF09; &#x7684;&#x795E;&#x7ECF;&#x5143;&#x53CD;&#x5E94;&#xFF1A; &#x800C; gabazine &#x7684;&#x552F;&#x4E00;&#x4F5C;&#x7528;&#x662F;&#x963B;&#x6B62; GABA A &#x4ECB;&#x5BFC;&#x7684;&#x6291;&#x5236;&#x4F5C;&#x7528;&#xFF0C;&#x6B64;&#x5916;&#x8BF1;&#x5BFC;&#x5242;&#x91CF;&#x4F9D;&#x8D56;&#x6027;&#x526F;&#x4F5C;&#x7528;&#xFF0C;&#x53EF;&#x80FD;&#x5BF9;&#x9499;&#x4F9D;&#x8D56;&#x6027;&#x94BE;&#x901A;&#x9053; BIC &#x5E94;&#x7528;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#x6211;&#x4EEC;&#x8C03;&#x67E5;&#x5BF9;&#x7EAF;&#x8272;&#x8C03;&#x8BF1;&#x53D1;&#x5C40;&#x90E8;&#x573A;&#x7535;&#x4F4D; (Lfp) &#x5728; AI &#x7684;&#x4E24;&#x79CD;&#x836F;&#x7269;&#x7684;&#x5F71;&#x54CD;&#x3002;&#x4E0E;&#x6263;&#x7403;&#x6D3B;&#x52A8;&#xFF0C;&#x53CD;&#x6620;&#x4E86;&#x795E;&#x7ECF;&#x5143;&#x7684;&#x8F93;&#x51FA;&#xFF0C;&#x76F8;&#x4FE1;&#x662F; LFP &#x4E3B;&#x8981;&#x53CD;&#x6620;&#x6811;&#x7A81;&#x72B6;&#x6D3B;&#x52A8;&#x548C;&#x56E0;&#x6B64;&#x795E;&#x7ECF;&#x5143;&#x7684;&#x8F93;&#x5165;&#x3002;Lfp &#x5F55;&#x4ECE;&#x9EBB;&#x9189;&#x548C;&#x6E05;&#x9192;&#x7684;&#x8499;&#x53E4;&#x6C99;&#x9F20;&#x7684;&#x5DE6; AI &#x4E4B;&#x524D;&#x3001; &#x671F;&#x95F4;&#x548C;&#x4E4B;&#x540E;&#x7684; BIC &#x548C; gabazine &#x4F7F;&#x7528;&#x591A;&#x7B52;&#x5F0F;&#x73BB;&#x7483;&#x7535;&#x6781;&#x5FAE;&#x7535;&#x6CF3;&#x5E94;&#x7528;&#x3002;&#x540E;&#x4E24;&#x79CD;&#x836F;&#x7269;&#x7684;&#x5E94;&#x7528;&#xFF0C;LFP &#x7684; N1 &#x5206;&#x91CF;&#x7684;&#x632F;&#x5E45;&#x5927;&#x5E45;&#x589E;&#x52A0;&#x636E;&#x6307;&#x51FA;&#x5728;&#x9EBB;&#x9189;&#x548C;&#x6E05;&#x9192;&#x7684;&#x52A8;&#x7269;&#xFF0C;&#x4F46;&#x8FD9;&#x79CD;&#x589E;&#x52A0;&#x663E;&#x8457;&#x66F4;&#x4E3A;&#x660E;&#x663E;&#x540E;&#x6BD4; BIC &#x540E; gabazine &#x5E94;&#x7528;&#x7A0B;&#x5E8F;&#x4E2D;&#xFF0C;&#x65E9;&#x524D;&#x62A5;&#x9053;&#xFF0C;&#x5B83;&#x5BF9;&#x5E94;&#x4E8E;&#x795E;&#x7ECF;&#x5143;&#x653E;&#x7535;&#x7387;&#x5F71;&#x54CD;&#x7684;&#x7ED3;&#x679C;&#x3002;&#x76F8;&#x6BD4;&#x4E4B;&#x4E0B;&#xFF0C;&#x767E;&#x6155;&#x5927;&#x72EC;&#x7ACB;&#x59D4;&#x5458;&#x4F1A;&#x548C; gabazine &#x5BF9; LFP &#x6301;&#x7EED;&#x65F6;&#x95F4; &#xFF08;&#x5EF6;&#x957F;&#xFF09; &#x548C; LFP &#x5149;&#x8C31;&#x4F18;&#x5316; &#xFF08;&#x9510;&#x5316;&#xFF09; &#x53D7;&#x6C2F;&#x80FA;&#x916E;&#x9EBB;&#x9189;&#xFF0C;&#x4E5F;&#x4E0D;&#x662F;&#x4E07;&#x4E0D;&#x5F97;&#x5DF2;&#x7684;&#x6570;&#x636E;&#x4E2D;&#x7684;&#x6548;&#x679C;&#x3002;&#x6211;&#x4EEC;&#x7684;&#x7ED3;&#x8BBA;&#x63D0;&#x51FA;&#x7684;&#x6570;&#x636E;&#x4ECE;&#x542C;&#x89C9;&#x76AE;&#x5C42; GABA A &#x4ECB;&#x5BFC;&#x7684;&#x6291;&#x5236;&#x529F;&#x80FD;&#x7684;&#x4E3B;&#x8981;&#x4F5C;&#x7528;&#x662F; &#xFF08;1&#xFF09; &#x9632;&#x6B62;&#x8FC7;&#x52B1;&#x78C1; &#xFF08;&#x7F09;&#x83B7;&#x91CF;&#xFF09; &#x7684;&#x76AE;&#x8D28;&#x7F51;&#x7EDC;&#x548C; (2) &#x4E3A;&#x52A0;&#x5FEB;&#x76AE;&#x8D28;&#x5904;&#x7406;&#x3002;

&#x7535;&#x79BB;&#x5B50;&#x5BFC;&#x5165;&#x5E94;&#x7528;&#x7A0B;&#x5E8F;&#x7684; GABAA-&#x62EE;&#x6297;&#x5242;&#x8377;&#x5305;&#x7261;&#x4E39;&#x78B1;&#x548C; gabazine &#x5BF9;&#x521D;&#x7EA7;&#x542C;&#x89C9;&#x76AE;&#x5C42;&#x97F3;&#x8BF1;&#x53D1;&#x5C40;&#x90E8;&#x573A;&#x7535;&#x4F4D;&#x7684;&#x5DEE;&#x522B;&#x5F71;&#x54CD;&#xFF1A; &#x4E0E;&#x6C2F;&#x80FA;&#x916E;&#x9EBB;&#x9189;&#x7684;&#x4E92;&#x52A8;&#x3002;

gamma-Aminobutric acid (GABA) is one of the main inhibitory transmitters in the central nervous system. In a recent study we have demonstrated differential effects of two iontophoretically applied GABA(A)-blockers, bicuculline (BIC) and gabazine (SR 95531), on neuronal responses in primary auditory cortex (AI): Whereas the only effect of gabazine was to block GABA(A)-mediated inhibition, BIC application additionally induced dose-dependent side effects, probably on calcium-dependent potassium channels. Here we investigated the effects of the two drugs on pure tone-evoked local field potentials (LFPs) in AI. In contrast to spiking activity, which reflects neuronal output, LFP are believed to mainly reflect dendritic activity and therefore neuronal input. LFPs were recorded from the left AI of anaesthetized and unanaesthetized Mongolian gerbils before, during and after microiontophoretic application of BIC and gabazine using multi-barrel glass electrodes. After the application of both drugs, a significant increase of the amplitude of the N1 component of the LFP was observed in both anaesthetized and unanaesthetized animals, but this increase was significantly more pronounced after BIC than after gabazine application, a result which corresponds to the effects on neuronal discharge rate reported earlier. In contrast, the effects of BIC and gabazine on LFP duration (prolongation) and LFP spectral tuning (sharpening) were affected by ketamine anesthesia, an effect that was not seen in the spiking data. We conclude from the data presented that the main functional role of GABA(A)-mediated inhibition in auditory cortex is to (1) prevent over-excitation (seizures) of cortical networks and (2) to speed up cortical processing.

Differential effects of iontophoretic application of the GABAA-antagonists bicuculline and gabazine on tone-evoked local field potentials in primary auditory cortex: interaction with ketamine anesthesia.

l&#39;acide gamma-Aminobutric (GABA) est l&#39;un des principaux &eacute;metteurs inhibiteurs du syst&egrave;me nerveux central. Dans une &eacute;tude r&eacute;cente, nous avons d&eacute;montr&eacute; les effets diff&eacute;rentiels des deux par iontophor&egrave;se appliquent GABA (A)-bloqueurs, bicuculline (BIC) et gabazine (SR 95531), sur des r&eacute;ponses neuronales dans le cortex auditif primaire (IA): alors que le seul effet de gabazine &eacute;tait de bloquer l&#39;inhibition induite par le GABA A, application BIC induit par ailleurs des effets secondaires dose-d&eacute;pendante, probablement sur les canaux potassiques d&eacute;pendants du calcium. Ici, nous avons &eacute;tudi&eacute; les effets de ces deux m&eacute;dicaments sur les potentiels de pure &eacute;voqu&eacute;e par le ton de champ local (LFPs) en intelligence artificielle. Contrairement &agrave; l&#39;activit&eacute;, ce qui refl&egrave;te la sortie neuronale, de fortification LFP sont cens&eacute;s refl&eacute;ter principalement activit&eacute; dendritique et entr&eacute;e donc neuronale. LFPs ont &eacute;t&eacute; enregistr&eacute;s de l&#39;IA gauche des gerbilles de Mongolie anesth&eacute;si&eacute;s et non anesth&eacute;si&eacute;s avant, pendant et apr&egrave;s l&#39;application microiontophor&eacute;tique des BIC et gabazine &agrave; l&#39;aide d&#39;&eacute;lectrodes de verre multi-tubes. Apr&egrave;s l&#39;application de ces deux m&eacute;dicaments, une augmentation significative de l&#39;amplitude de la composante N1 de la LFP a &eacute;t&eacute; observ&eacute;e chez les animaux anesth&eacute;si&eacute;s tant non anesth&eacute;si&eacute;s, mais cette augmentation a &eacute;t&eacute; nettement plus prononc&eacute;e apr&egrave;s BIC qu&#39;apr&egrave;s l&#39;application de gabazine, un r&eacute;sultat qui correspond &agrave; l&#39;effet sur le taux de d&eacute;charge neuronale rapport&eacute; plus t&ocirc;t. En revanche, les effets de BIC et gabazine sur la dur&eacute;e LFP (Qt) et LFP spectrale tuning (aff&ucirc;tage) ont &eacute;t&eacute; touch&eacute;s par anesth&eacute;sie de k&eacute;tamine, un effet qui n&#39;a pas vu dans les donn&eacute;es de l&#39;&eacute;tude. Nous concluons, d&#39;apr&egrave;s les donn&eacute;es pr&eacute;sent&eacute;es, que le principal r&ocirc;le fonctionnel d&#39;inhibition induite par le GABA A dans le cortex auditif est de (1) emp&ecirc;cher over-excitation (convulsions), des r&eacute;seaux corticaux et (2) pour acc&eacute;l&eacute;rer le traitement cortical.

Differential effects of application iontophor&eacute;tique de la bicuculline GABAA-antagonistes et gabazine sur les potentiels de champ local &eacute;voqu&eacute;e par le ton dans le cortex auditif primaire : interaction avec anesth&eacute;sie de la k&eacute;tamine.

Gamma-Aminobutric S&auml;ure (GABA) ist eine der wichtigsten hemmenden Transmitter im zentralen Nervensystem. In einer neueren Studie haben wir gezeigt, differenzielle Effekte von zwei Iontophoretically GABA (A)-Blockers, Bicuculline (BIC) und Gabazine (SR 95531), neuronale Reaktionen im prim&auml;ren auditorischen Kortex (AI): w&auml;hrend die einzige Auswirkung des Gabazine war, GABA A-vermittelte Hemmung zu blockieren, BIC zus&auml;tzlich verursachte dosisabh&auml;ngiger Nebenwirkungen, wahrscheinlich auf Kalzium-abh&auml;ngige Kaliumkan&auml;le. Hier untersuchten wir die Wirkungen der beiden Drogen auf reinen Ton hervorgerufen lokales Feld Potenziale (LFPs) in AI. Im Gegensatz zu spiking Aktivit&auml;t der neuronalen Ausgabe widerspiegelt, LFP werden geglaubt, um vor allem dendritische Aktivit&auml;t und daher neuronalen Input widerspiegeln. LFPs wurden von der linken AI beschrieben und unanaesthetized mongolische Rennm&auml;use vor, w&auml;hrend und nach der Microiontophoretic Anwendung von BIC und Gabazine mit Schnellfeuerkanonen Glas Elektroden aufgezeichnet. Nach der Anwendung des beide Medikamente eine deutliche Erh&ouml;hung der Amplitude der N1-Komponente der LFP in sowohl beschrieben als auch unanaesthetized Tiere festgestellt, aber der Anstieg war deutlich ausgepr&auml;gter nach BIC als nach Gabazine Anwendung, ein Ergebnis, das die Auswirkungen auf die neuronale Entladung entspricht bereits fr&uuml;her berichtet. Im Gegensatz dazu waren die Auswirkungen der BIC und Gabazine auf LFP-Dauer (Verl&auml;ngerung) und LFP spektrale tuning (Sch&auml;rfen) von Ketamine An&auml;sthesie, einen Effekt betroffen, die nicht in den Blindkontrollen Daten gesehen wurde. Wir schlie&szlig;en aus den vorgelegten Daten, dass die funktionale Hauptrolle der GABA A-vermittelte Hemmung im auditorischen Kortex (1) Over-excitation (Krampfanf&auml;lle) verhindern, kortikale Netze und (2) kortikale Verarbeitung beschleunigen.

Wirkungen der Iontophoretic Anwendung der GABAA-Antagonisten Bicuculline und Gabazine auf lokales Feld Ton hervorgerufen Potenziale im prim&auml;ren auditorischen Kortex: Interaktion mit Ketamin Narkose.

acido gamma-Aminobutric (GABA) &egrave; uno dei principali trasmettitori inibitori del sistema nervoso centrale. In un recente studio abbiamo dimostrato effetti differenziali delle due iontophoretically applicato GABA (A)-bloccanti, bicuculline (BIC) e gabazine (SR 95531), sulle risposte neuronali nella corteccia uditiva primaria (AI): considerando che il solo effetto di gabazine era quello di bloccare l&#39;inibizione mediata dal GABA A, applicazione di BIC inoltre indotto effetti collaterali dose-dipendente, probabilmente sui canali del potassio calcio-dipendente. Qui abbiamo studiato gli effetti dei due farmaci su potenziali di puro tono evocato locale campo (LFPs) in AI. Si ritiene che contrariamente a chiodare attivit&agrave;, che riflette l&#39;output di un neurone, LFP riflettono principalmente attivit&agrave; dendritiche e quindi neuronale input. LFPs sono state registrate da sinistro di gerbilli mongoli anestetizzati e unanaesthetized prima, durante e dopo l&#39;applicazione di microiontophoretic di BIC e gabazine usando elettrodi di vetro multi-barrel. Dopo l&#39;applicazione di entrambi i farmaci, un aumento significativo dell&#39;ampiezza della componente N1 della LFP &egrave; stato osservato negli animali anestetizzati e unanaesthetized, ma questo aumento &egrave; stato significativamente pi&ugrave; pronunciata dopo BIC che dopo l&#39;applicazione di gabazine, un risultato che corrisponde agli effetti sul tasso di scarico neuronale riferito in precedenza. Al contrario, gli effetti della BIC e gabazine su LFP durata (proroga) e LFP spectral tuning (affilatura) sono stati colpiti da ketamina anestesia, un effetto che non &egrave; stato visto nei dati spiking. Concludiamo dai dati presentati che il principale ruolo funzionale di inibizione mediata dal GABA A nella corteccia uditiva &egrave; a (1) prevenire abbassando (sequestri) delle reti corticali e (2) alla velocit&agrave; di elaborazione corticale.

Effetti differenziali di iontophoretic applicazione del GABAA-antagonisti bicuculline e gabazine su potenziali di campo locale tono evocato nella corteccia uditiva primaria: interazione con ketamina anestesia.

&gamma;-Aminobutric &#x9178; (GABA) &#x4E2D;&#x67A2;&#x795E;&#x7D4C;&#x7CFB;&#x306E;&#x4E3B;&#x306A;&#x6291;&#x5236;&#x306E;&#x9001;&#x4FE1;&#x6A5F;&#x306E;&#x4E00;&#x3064;&#x3067;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F; 2 &#x3064;&#x306E;&#x30B5;&#x30A4;&#x30AF;&#x30EA;&#x30C3;&#x30AF;&#x306E;&#x5DEE;&#x52D5;&#x52B9;&#x679C;&#x9069;&#x7528; GABA (A) &#x5B9F;&#x8A3C;&#x3057;&#x305F;&#x6700;&#x8FD1;&#x306E;&#x7814;&#x7A76;&#x3067;-&#x30D3;&#x30AF;&#x30AF;&#x30EA;&#x30F3; (BIC) &#x3068; gabazine (SR 95531) &#x4E00;&#x6B21;&#x8074;&#x899A;&#x91CE; (AI) &#x306E;&#x7D30;&#x80DE;&#x306E;&#x5FDC;&#x7B54;&#x4E0A;&#x306E;&#x30D6;&#x30ED;&#x30C3;&#x30AB;&#x30FC;&#xFF1A; &#x30D6;&#x30ED;&#x30C3;&#x30AF; GABA A &#x3092;&#x6291;&#x5236;&#x3059;&#x308B; gabazine &#x306E;&#x552F;&#x4E00;&#x306E;&#x5F71;&#x97FF;&#x3060;&#x3063;&#x305F;&#x306B;&#x5BFE;&#x3057;&#x3001;&#x3055;&#x3089;&#x306B;&#x304A;&#x305D;&#x3089;&#x304F;&#x30AB;&#x30EB;&#x30B7;&#x30A6;&#x30E0;&#x4F9D;&#x5B58;&#x6027;&#x30AB;&#x30EA;&#x30A6;&#x30E0; &#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x4E0A;&#x306E;&#x7528;&#x91CF;&#x4F9D;&#x5B58;&#x7684;&#x526F;&#x4F5C;&#x7528;&#x3092;&#x8A98;&#x8D77;&#x30D3;&#x30C3;&#x30AF;&#x30AB;&#x30E1;&#x30E9;&#x5FDC;&#x7528;&#x3002;&#x3053;&#x3053;&#x3067;&#x6211;&#x3005; &#x306F;&#x7D14;&#x7C8B;&#x306A;&#x30C8;&#x30FC;&#x30F3;&#x8A98;&#x767A;&#x306E;&#x5C40;&#x6240;&#x96FB;&#x754C;&#x96FB;&#x4F4D; (LFPs) AI &#x3067; 2 &#x3064;&#x306E;&#x85AC;&#x306E;&#x5F71;&#x97FF;&#x3092;&#x8ABF;&#x3079;&#x305F;&#x3002;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x306E;&#x51FA;&#x529B;&#x3092;&#x53CD;&#x6620;&#x3057;&#x3001;&#x30A2;&#x30AF;&#x30C6;&#x30A3;&#x30D3;&#x30C6;&#x30A3;&#x306E;&#x30B9;&#x30D1;&#x30A4;&#x30AF;&#x3068;&#x306F;&#x5BFE;&#x7167;&#x7684; LFP &#x3092;&#x4FE1;&#x3058;&#x3066;&#x3057;&#x3066;&#x6A39;&#x72B6;&#x6D3B;&#x52D5;&#x3057;&#x305F;&#x304C;&#x3063;&#x3066;&#x795E;&#x7D4C;&#x306E;&#x5165;&#x529B;&#x306F;&#x4E3B;&#x306B;&#x53CD;&#x6620;&#x3057;&#x307E;&#x3059;&#x3002;LFPs &#x9EBB;&#x9154;&#x3068; unanaesthetized &#x30B9;&#x30CA;&#x30CD;&#x30BA;&#x30DF;&#x306E;&#x5DE6;&#x306E; AI &#x304B;&#x3089; microiontophoretic &#x30A2;&#x30D7;&#x30EA;&#x30B1;&#x30FC;&#x30B7;&#x30E7;&#x30F3; BIC &#x3084; multi-barrel &#x30AC;&#x30E9;&#x30B9;&#x96FB;&#x6975;&#x3092;&#x7528;&#x3044;&#x305F; gabazine &#x306E;&#x5F8C;&#x3001;&#x4E2D;&#x306B;&#x8A18;&#x9332;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x4E21;&#x65B9;&#x306E;&#x85AC;&#x306E;&#x9069;&#x7528;&#x5F8C; LFP &#x306E; N1 &#x6210;&#x5206;&#x306E;&#x632F;&#x5E45;&#x306E;&#x5927;&#x5E45;&#x306A;&#x5897;&#x52A0;&#x304C;&#x9EBB;&#x9154;&#x3068; unanaesthetized &#x306E;&#x4E21;&#x65B9;&#x306E;&#x52D5;&#x7269;&#x3067;&#x89B3;&#x5BDF;&#x3055;&#x308C;&#x305F;&#x3001;&#x3053;&#x306E;&#x5897;&#x52A0;&#x3060;&#x3063;&#x305F;&#x5927;&#x5E45;&#x306B;&#x3088;&#x308A;&#x767A;&#x97F3; BIC &#x3088;&#x308A;&#x3082;&#x5F8C; gabazine &#x30A2;&#x30D7;&#x30EA;&#x30B1;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x5F8C;&#x795E;&#x7D4C;&#x306E;&#x653E;&#x96FB;&#x901F;&#x5EA6;&#x306B;&#x53CA;&#x307C;&#x3059;&#x5F71;&#x97FF;&#x306B;&#x5BFE;&#x5FDC;&#x3059;&#x308B;&#x7D50;&#x679C;&#x304C;&#x4EE5;&#x524D;&#x306B;&#x5831;&#x544A;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x5BFE;&#x7167;&#x7684;&#x306B;&#x3001;BIC &#x3084; gabazine LFP &#x671F;&#x9593; &#xFF08;&#x5EF6;&#x9577;&#xFF09; &#x3068; LFP (&#x30B7;&#x30E3;&#x30FC;&#x30D7;) &#x30C1;&#x30E5;&#x30FC;&#x30CB;&#x30F3;&#x30B0; &#x30B9;&#x30DA;&#x30AF;&#x30C8;&#x30EB;&#x306B;&#x53CA;&#x307C;&#x3059;&#x30B1;&#x30BF;&#x30DF;&#x30F3;&#x9EBB;&#x9154;&#x79D1;&#x30B9;&#x30D1;&#x30A4;&#x30AD;&#x30F3;&#x30B0; &#x30C7;&#x30FC;&#x30BF;&#x3067;&#x898B;&#x3089;&#x308C;&#x306A;&#x304B;&#x3063;&#x305F;&#x52B9;&#x679C;&#x306B;&#x3088;&#x3063;&#x3066;&#x5F71;&#x97FF;&#x3092;&#x53D7;&#x3051;&#x305F;&#x3002;&#x6211;&#x3005; &#x63D0;&#x793A;&#x30C7;&#x30FC;&#x30BF;&#x304B;&#x3089;&#x8074;&#x899A;&#x76AE;&#x8CEA;&#x306B;&#x304A;&#x3051;&#x308B; GABA A &#x3092;&#x4ECB;&#x3057;&#x305F;&#x963B;&#x5BB3;&#x306E;&#x30E1;&#x30A4;&#x30F3;&#x306E;&#x6A5F;&#x80FD;&#x7684;&#x5F79;&#x5272; (1) &#x3042;&#x308B;&#x3068;&#x7D50;&#x8AD6;&#x4ED8;&#x3051;&#x308B;&#x306E;&#x76AE;&#x8CEA;&#x30CD;&#x30C3;&#x30C8;&#x30EF;&#x30FC;&#x30AF;&#x3068; (2) &#x5927;&#x8133;&#x76AE;&#x8CEA;&#x306E;&#x51E6;&#x7406;&#x3092;&#x9AD8;&#x901F;&#x306B;&#x904E;&#x52B1;&#x78C1; (&#x767A;&#x4F5C;) &#x3092;&#x9632;&#x3050;&#x3002;

&#x5FAE;&#x5206;&#x4E00;&#x6B21;&#x8074;&#x899A;&#x91CE;&#x3067;&#x306E;&#x30C8;&#x30FC;&#x30F3;&#x8A98;&#x767A;&#x30ED;&#x30FC;&#x30AB;&#x30EB;&#x96FB;&#x4F4D;&#x306B;&#x53CA;&#x307C;&#x3059;&#x30A4;&#x30AA;&#x30F3;&#x30C8;&#x30D5;&#x30A9;&#x30EC;&#x30FC;&#x30B7;&#x30B9; &#x30A2;&#x30D7;&#x30EA;&#x30B1;&#x30FC;&#x30B7;&#x30E7;&#x30F3; GABAA &#x53D7;&#x5BB9;&#x4F53;&#x62EE;&#x6297;&#x5264;&#x30D3;&#x30AF;&#x30AF;&#x30EA;&#x30F3;&#x3068; gabazine &#x306E;: &#x30B1;&#x30BF;&#x30DF;&#x30F3;&#x9EBB;&#x9154;&#x3068;&#x306E;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x3002;

&#xAC10;&#xB9C8; Aminobutric &#xC0B0; (GABA) &#xC911;&#xC559; &#xC2E0; &#xACBD;&#xACC4;&#xC758; &#xC8FC;&#xC694; &#xC5B5;&#xC81C; &#xC1A1;&#xC2E0;&#xAE30; &#xC911; &#xD558;&#xB098;&#xC785;&#xB2C8;&#xB2E4;. &#xCD5C;&#xADFC; &#xC5F0;&#xAD6C;&#xC5D0;&#xC11C; &#xC6B0;&#xB9AC;&#xB294; &#xB450; iontophoretically&#xC758; &#xCC28;&#xB3D9; &#xD6A8;&#xACFC; &#xC801;&#xC6A9; GABA (A) &#xC99D;&#xBA85; &#xD558;&#xACE0;&#xC788;&#xB2E4;-&#xCC28;&#xB2E8;&#xC81C;, bicuculline (&#xC758; BIC) &#xBC0F; gabazine (SR 95531), &#xAE30;&#xBCF8; &#xCCAD;&#xAC01; &#xD53C; &#xC9C8; (AI)&#xC5D0; &#xB300; &#xD55C; &#xC2E0;&#xACBD; &#xBC18;&#xC751;&#xC744;: gabazine&#xC758; &#xC720;&#xC77C;&#xD55C; &#xD6A8;&#xACFC; &#xC800;&#xD574; GABA A &#xC911;&#xC7AC;&#xB97C; &#xCC28;&#xB2E8; &#xD558;&#xB294;, &#xBC18;&#xBA74; &#xBE45; &#xC751;&#xC6A9; &#xD504;&#xB85C;&#xADF8;&#xB7A8; &#xB610;&#xD55C; &#xCE7C;&#xC298; &#xC758;&#xC874;&#xD615; &#xCE7C;&#xB968; &#xD1B5;&#xB85C;&#xC5D0; &#xC544;&#xB9C8; &#xBCF5;&#xC6A9;&#xB7C9; &#xC758;&#xC874; &#xBD80;&#xC791;&#xC6A9; &#xC720;&#xBC1C;. &#xC5EC;&#xAE30; &#xC6B0;&#xB9AC; &#xC21C;&#xC218; &#xD1A4; &#xAC16;&#xB294; &#xB85C;&#xCEEC; &#xD544;&#xB4DC; &#xC804;&#xC704; (LFPs) &#xC778;&#xACF5; &#xC9C0;&#xB2A5;&#xC5D0;&#xC5D0; &#xB450; &#xC57D;&#xBB3C;&#xC758; &#xD6A8;&#xACFC; &#xC870;&#xC0AC; &#xD588;&#xB2E4;. &#xAE09;&#xC0C1;&#xC2B9; &#xD65C;&#xB3D9; &#xC2E0;&#xACBD; &#xCD9C;&#xB825;&#xC744; &#xBC18;&#xC601; &#xD558;&#xB294; &#xBC18;&#xBA74; LFP &#xC8FC;&#xB85C; &#xC218;&#xC9C0;&#xC0C1; &#xD65C;&#xB3D9; &#xBC0F; &#xB530;&#xB77C;&#xC11C; &#xC2E0;&#xACBD; &#xC785;&#xB825; &#xBC18;&#xC601;&#xC73C;&#xB85C; &#xCD94;&#xC815; &#xB41C;&#xB2E4;. LFPs &#xC911; &#xACE0; &#xBE45; &#xBC0F; multi-barrel &#xC720;&#xB9AC; &#xC804;&#xADF9;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; gabazine&#xC758; microiontophoretic &#xC801;&#xC6A9; &#xD6C4; anaesthetized &#xBC0F; unanaesthetized &#xBABD;&#xACE8; gerbils &#xC67C;&#xCABD;&#xB41C; AI&#xC5D0;&#xC11C; &#xAE30;&#xB85D; &#xB418;&#xC5C8;&#xB2E4;. &#xB450; &#xC57D;&#xBB3C; &#xC801;&#xC6A9; &#xD55C; &#xC774;&#xD6C4;&#xC5D0; LFP&#xC758; N1 &#xCEF4;&#xD3EC;&#xB10C;&#xD2B8;&#xC758; &#xC9C4;&#xD3ED;&#xC758; &#xC0C1;&#xB2F9;&#xD55C; &#xC99D;&#xAC00; anaesthetized &#xBC0F; unanaesthetized &#xB3D9;&#xBB3C;&#xC5D0;&#xC11C; &#xAD00;&#xCC30; &#xB418;&#xC5C8;&#xB2E4; &#xD558;&#xC9C0;&#xB9CC;&#xC774; &#xC99D;&#xAC00; &#xD06C;&#xAC8C; &#xB354; &#xBC1C;&#xC74C; &#xBCF4;&#xB2E4; &#xBE45; &#xD6C4; gabazine &#xC751;&#xC6A9; &#xD504;&#xB85C;&#xADF8;&#xB7A8; &#xD6C4; &#xC2E0;&#xACBD; &#xBC29;&#xC804; &#xC728;&#xC5D0; &#xB300; &#xD55C; &#xD6A8;&#xACFC;&#xC5D0; &#xD574;&#xB2F9; &#xD558;&#xB294; &#xACB0;&#xACFC; &#xC774;&#xC804;&#xC5D0; &#xBCF4;&#xACE0; &#xB41C;. &#xBC18;&#xBA74;, LFP &#xAE30;&#xAC04; (&#xC5F0;&#xC7A5;) &#xBC0F; LFP (&#xC120;&#xBA85;) &#xD29C;&#xB2DD; &#xC2A4;&#xD399;&#xD2B8;&#xB7FC;&#xC5D0; &#xBE45; &#xBC0F; gabazine&#xC758; &#xD6A8;&#xACFC; &#xCF00; &#xB9C8; &#xCDE8;, &#xC2A4;&#xD30C;&#xC774;&#xD06C; &#xB370;&#xC774;&#xD130;&#xC5D0;&#xC11C; &#xBCFC; &#xC218; &#xC5C6;&#xB294; &#xD6A8;&#xACFC; &#xC758;&#xD574; &#xC601;&#xD5A5;&#xC744; &#xBC1B;&#xC558;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xCCAD;&#xAC01; &#xD53C; &#xC9C8;&#xC5D0;&#xC11C; GABA A &#xC911;&#xC7AC; &#xC800;&#xD574;&#xC758; &#xC8FC;&#xC694; &#xAE30;&#xB2A5; &#xC5ED;&#xD560; (1)&#xC740; &#xD45C;&#xC2DC; &#xB418;&#xB294; &#xB370;&#xC774;&#xD130;&#xC5D0;&#xC11C; &#xACB0;&#xB860; &#xB300;&#xB1CC; &#xD53C; &#xC9C8;&#xC758; &#xB124;&#xD2B8;&#xC6CC;&#xD06C;&#xC640; (2) &#xB300;&#xB1CC; &#xD53C; &#xC9C8;&#xC758; &#xCC98;&#xB9AC; &#xC18D;&#xB3C4;&#xC5D0; &#xAE30;&#xC778; (&#xBC1C;&#xC791;)&#xC744; &#xBC29;&#xC9C0; &#xD569;&#xB2C8;&#xB2E4;.

GABAA-&#xAE38; &#xD56D; &#xC81C; bicuculline &#xBC0F; gabazine&#xC758; iontophoretic &#xC751;&#xC6A9; &#xD504;&#xB85C;&#xADF8;&#xB7A8;&#xC758; &#xAE30;&#xBCF8; &#xCCAD;&#xAC01; &#xD53C; &#xC9C8;&#xC5D0;&#xC11C; &#xD1A4;&#xC744; &#xBD88;&#xB7EC; &#xC77C;&#xC73C;&#xCF30;&#xB2E4; &#xB85C;&#xCEEC; &#xD544;&#xB4DC; &#xC804;&#xC704;&#xC5D0; &#xCC28;&#xB3D9; &#xD6A8;&#xACFC;: &#xCF00; &#xB9C8; &#xCDE8;&#xC640; &#xD568;&#xAED8; &#xC0C1;&#xD638; &#xC791;&#xC6A9; &#xD569;&#xB2C8;&#xB2E4;.

&aacute;cido gamma-Aminobutric (GABA) es uno de los principales transmisores inhibitorios en el sistema nervioso central. En un estudio reciente hemos demostrado efectos diferenciales de dos iontophoretically aplicaci&oacute;n GABA (A)-bloqueadores, bicuculina (BIC) y gabazine (SR 95531), en las respuestas neuronales en la corteza auditiva primaria (AI): mientras que el &uacute;nico efecto de gabazine era bloquear la inhibici&oacute;n mediada por GABA A, aplicaci&oacute;n de BIC adem&aacute;s dependiente de la dosis efectos secundarios causados por, probablemente en los canales de potasio dependiente de calcio. Aqu&iacute; investigamos los efectos de los dos f&aacute;rmacos en potenciales de campo local evocado de tono puro (LFPs) en AI. En contraste con clavar la actividad, que refleja la salida neuronal, LFP se cree que reflejan principalmente actividad dendr&iacute;tica y entrada por lo tanto neuronal. LFPs se registraron desde la izquierda AI de Jerbos de Mongolia anestesiados y unanaesthetized, antes, durante y despu&eacute;s de la aplicaci&oacute;n microiontophoretic de BIC y gabazine usando electrodos de vidrio multi-barrel. Despu&eacute;s de la aplicaci&oacute;n de ambos f&aacute;rmacos, se observ&oacute; un aumento significativo de la amplitud del componente N1 de la LFP en animales anestesiados tanto unanaesthetized, pero este aumento fue significativamente agudicen despu&eacute;s de BIC que despu&eacute;s de la aplicaci&oacute;n gabazine, un resultado que corresponde a los efectos sobre la tasa de descarga neuronal divulgado anterior. Por el contrario, los efectos de BIC y gabazine sobre la duraci&oacute;n de la LFP (prolongaci&oacute;n) y LFP espectral tuning (afilado) fueron afectados por la anestesia de la ketamina, un efecto que no se observ&oacute; en los datos clavaba. De los datos presentados Concluimos que es el principal papel funcional de la corteza auditiva la inhibici&oacute;n mediada por GABA A (1) prevenir la excitaci&oacute;n (ataques) de redes corticales y (2) a la velocidad de procesamiento cortical.

Efectos diferenciales de aplicaci&oacute;n de la iontophoretic de la bicuculina GABAA-antagonistas y gabazine sobre los potenciales de campo local tono-evocado en la corteza auditiva primaria: interacci&oacute;n con anestesia de la ketamina.

Auditory perception comprises bottom-up as well as top-down processes. While research in the past has revealed many neural correlates of bottom-up processes, less is known about top-down modulation. Memory processes have recently been associated with oscillations in the gamma-band of human EEG (30 Hz and above) which are enhanced when incoming information matches a stored memory template. Therefore, we investigated event-related potentials (ERPs) and gamma-band activity in 17 healthy participants in a Go/NoGo-task. They listened to four frequency-modulated (FM) sounds which varied regarding the frequency range traversed and the direction of frequency modulation. One sound was defined as target and required a button press. The results of ERPs (N1, P2, N2, and P3) were consistent with previous studies. Analysis of evoked gamma-band responses yielded no significant task-dependent modulation, but we observed a stimulus dependency, which was also present in a control experiment: The amplitude of evoked gamma responses showed an inverted U-shape as a function of stimulus frequency. Investigation of total gamma activity revealed functionally relevant responses at high frequencies (90 Hz to 250 Hz), which showed significant modulations by matches with STM: Complete matches led to the strongest enhancements (starting around 100 ms after stimulus onset) and partial matches resulted in intermediate ones. The results support the conclusion that very high frequency oscillations (VHFOs) are markers of active stimulus discrimination in STM matching processes and are attributable to higher cognitive functions.

Human EEG very high frequency oscillations reflect the number of matches with a template in auditory short-term memory.

Tightly stimulus-locked "evoked" and not tightly stimulus-locked "induced" gamma-band oscillations have been implicated in a variety of cognitive functions as well as more basic stimulus-related aspects of neuronal activity. The present study aimed at dissociating both aspects using a preparation in rodents trained to perform in a target-discrimination task while recording the intracerebral electrocorticogram in parallel from left and right auditory cortex. While stimulus-related aspects of gamma-band activity were already evident in the naïve subjects, aspects related to successful target-discrimination only emerged with learning. Frequency-modulated tones were employed as stimuli and were varied with respect to two stimulus dimensions, viz. "spectral content" and "modulation direction". A target stimulus had to be discriminated in a GO/(NO-GO) paradigm from three non-target stimuli matching the target in only one or none of these dimensions. Analysis of the event-related potentials indicated that the physical stimulus parameters explained most of the variance in amplitude of most event-related potential components. For the evoked gamma-band activity no learning related modulations were found. The induced gamma-band activity showed a relationship with the similarity of a stimulus with the target that was most prominent in the right hemisphere. The correspondence between task-specific behavior and the amplitude of induced gamma-band activity, both developing with learning, supports a functional relevance of this form of oscillation beyond merely processing physical stimulus attributes.

Gamma oscillations in gerbil auditory cortex during a target-discrimination task reflect matches with short-term memory.

Primary sensory cortex integrates sensory information from afferent feedforward thalamocortical projection systems and convergent intracortical microcircuits. Both input systems have been demonstrated to provide different aspects of sensory information. Here we have used high-density recordings of laminar current source density (CSD) distributions in primary auditory cortex of Mongolian gerbils in combination with pharmacological silencing of cortical activity and analysis of the residual CSD, to dissociate the feedforward thalamocortical contribution and the intracortical contribution to spectral integration. We found a temporally highly precise integration of both types of inputs when the stimulation frequency was in close spectral neighborhood of the best frequency of the measurement site, in which the overlap between both inputs is maximal. Local intracortical connections provide both directly feedforward excitatory and modulatory input from adjacent cortical sites, which determine how concurrent afferent inputs are integrated. Through separate excitatory horizontal projections, terminating in cortical layers II/III, information about stimulus energy in greater spectral distance is provided even over long cortical distances. These projections effectively broaden spectral tuning width. Based on these data, we suggest a mechanism of spectral integration in primary auditory cortex that is based on temporally precise interactions of afferent thalamocortical inputs and different short- and long-range intracortical networks. The proposed conceptual framework allows integration of different and partly controversial anatomical and physiological models of spectral integration in the literature.

Spectral integration in primary auditory cortex attributable to temporally precise convergence of thalamocortical and intracortical input.

Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics.

Article	Year
Differential effects of iontophoretic application of the GABAA-antagonists bicuculline and gabazine on tone-evoked local field potentials in primary auditory cortex: interaction with ketamin... Brain research\| PubMed ID: 18022607	2008
Human EEG very high frequency oscillations reflect the number of matches with a template in auditory short-term memory. Brain research\| PubMed ID: 18036577	2008
Gamma oscillations in gerbil auditory cortex during a target-discrimination task reflect matches with short-term memory. Brain research\| PubMed ID: 18053969	2008
Spectral integration in primary auditory cortex attributable to temporally precise convergence of thalamocortical and intracortical input. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 20720119	2010
Optogenetic stimulation of the auditory pathway. The Journal of clinical investigation\| PubMed ID: 24509078	2014

Marcus Jeschke

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