Tau reduction affects excitatory and inhibitory neurons differently, reduces excitation/inhibition ratios, and counteracts network hypersynchrony.
Tau reduction affects excitatory and inhibitory neurons differently, reduces excitation/inhibition ratios, and counteracts network hypersynchrony.
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Tau减少对兴奋性和抑制性神经元的影响不同，降低兴奋/抑制比，并抵消网络超同步。
DOI：
10.1016/j.celrep.2021.109855
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发表时间：
2021-10-19
期刊：
影响因子：
8.8
通讯作者：
Mucke L
中科院分区：
文献类型：
--
作者：
Chang CW;Evans MD;Yu X;Yu GQ;Mucke L
Tau蛋白被认为与许多大脑疾病有关。在动物模型中，tau的减少抑制了多种原因的癫痫发生，并改善了与过度兴奋-抑制(E/I)比率相关的各种条件下的突触和行为异常。然而，潜在的机制尚不清楚。在小鼠中，tau的全局遗传消融降低了急性大脑皮层脑片中锥体细胞的动作电位(AP)放电和E/I比率，而不影响这些细胞的兴奋性。Tau消融减少了对抑制性神经元的兴奋性输入，增加了这些细胞的兴奋性，并从结构上改变了它们的轴突初始段(AISS)。在受到长期过度刺激的原代神经元培养中，tau消融降低了抑制性神经元中AISS的稳态反应，促进了抑制，并抑制了超同步性。总之，兴奋性神经元和抑制性神经元的这些不同的变化有助于解释tau降低如何防止网络超同步，并抵消导致E/I比值异常增加的大脑疾病。Tau的减少可以预防癫痫的发生，但潜在的机制尚不确定。Chang等人。结果表明，tau消融降低兴奋性神经元的基线活性，调节抑制性神经元的固有兴奋性和轴突起始节段，促进网络抑制。这些效应结合在一起，抵消了网络超同步和导致兴奋/抑制失衡的疾病。
The protein tau has been implicated in many brain disorders. In animal models, tau reduction suppresses epileptogenesis of diverse causes and ameliorates synaptic and behavioral abnormalities in various conditions associated with excessive excitation-inhibition (E/I) ratios. However, the underlying mechanisms are unknown. Global genetic ablation of tau in mice reduces the action potential (AP) firing and E/I ratio of pyramidal cells in acute cortical slices without affecting the excitability of these cells. Tau ablation reduces the excitatory inputs to inhibitory neurons, increases the excitability of these cells, and structurally alters their axon initial segments (AISs). In primary neuronal cultures subjected to prolonged overstimulation, tau ablation diminishes the homeostatic response of AISs in inhibitory neurons, promotes inhibition, and suppresses hypersynchrony. Together, these differential alterations in excitatory and inhibitory neurons help explain how tau reduction prevents network hypersynchrony and counteracts brain disorders causing abnormally increased E/I ratios. Tau reduction prevents epileptogenesis, but underlying mechanisms are uncertain. Chang et al. show that tau ablation decreases the baseline activity of excitatory neurons and modulates the intrinsic excitability and axon initial segments of inhibitory neurons, promoting network inhibition. In combination, these effects counteract network hypersynchrony and diseases causing excitation/inhibition imbalance.
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影响因子：
6.1
作者：
Garcia-Cabrero, Ana M.;Guerrero-Lopez, Rosa;Sanchez, Marina P.
通讯作者：
Sanchez, Marina P.
影响因子：
16.6
作者：
Bi M;Gladbach A;van Eersel J;Ittner A;Przybyla M;van Hummel A;Chua SW;van der Hoven J;Lee WS;Müller J;Parmar J;Jonquieres GV;Stefen H;Guccione E;Fath T;Housley GD;Klugmann M;Ke YD;Ittner LM
通讯作者：
Ittner LM
影响因子：
12.7
作者：
Hatch RJ;Wei Y;Xia D;Götz J
通讯作者：
Götz J
影响因子：
25
作者：
Gouwens NW;Sorensen SA;Berg J;Lee C;Jarsky T;Ting J;Sunkin SM;Feng D;Anastassiou CA;Barkan E;Bickley K;Blesie N;Braun T;Brouner K;Budzillo A;Caldejon S;Casper T;Castelli D;Chong P;Crichton K;Cuhaciyan C;Daigle TL;Dalley R;Dee N;Desta T;Ding SL;Dingman S;Doperalski A;Dotson N;Egdorf T;Fisher M;de Frates RA;Garren E;Garwood M;Gary A;Gaudreault N;Godfrey K;Gorham M;Gu H;Habel C;Hadley K;Harrington J;Harris JA;Henry A;Hill D;Josephsen S;Kebede S;Kim L;Kroll M;Lee B;Lemon T;Link KE;Liu X;Long B;Mann R;McGraw M;Mihalas S;Mukora A;Murphy GJ;Ng L;Ngo K;Nguyen TN;Nicovich PR;Oldre A;Park D;Parry S;Perkins J;Potekhina L;Reid D;Robertson M;Sandman D;Schroedter M;Slaughterbeck C;Soler-Llavina G;Sulc J;Szafer A;Tasic B;Taskin N;Teeter C;Thatra N;Tung H;Wakeman W;Williams G;Young R;Zhou Z;Farrell C;Peng H;Hawrylycz MJ;Lein E;Ng L;Arkhipov A;Bernard A;Phillips JW;Zeng H;Koch C
通讯作者：
Koch C
DOI：
10.1523/jneurosci.3191-12.2013
发表时间：
2013-01-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Holth JK;Bomben VC;Reed JG;Inoue T;Younkin L;Younkin SG;Pautler RG;Botas J;Noebels JL
通讯作者：
Noebels JL