Reduced cognition in Syngap1 mutants is caused by isolated damage within developing forebrain excitatory neurons.
Reduced cognition in Syngap1 mutants is caused by isolated damage within developing forebrain excitatory neurons.
复制标题
DOI：
10.1016/j.neuron.2014.05.015
复制
发表时间：
2014-06-18
期刊：
影响因子：
16.2
通讯作者：
Rumbaugh G
中科院分区：
文献类型：
--
作者：
Ozkan ED;Creson TK;Kramár EA;Rojas C;Seese RR;Babyan AH;Shi Y;Lucero R;Xu X;Noebels JL;Miller CA;Lynch G;Rumbaugh G
Syngap1 haploinsufficiency is a common cause of sporadic intellectual disability. Syngap1 mutations disrupt developing pyramidal neurons, though it remains unclear if this process contributes to cognitive abnormalities. Here, we found that haploinsufficiency restricted to forebrain glutamatergic neurons was sufficient to disrupt cognition, while removing mutations from this population prevented cognitive abnormalities. In contrast, manipulating Syngap1 function in GABAergic neurons had no effect on cognition, excitability or neurotransmission, highlighting the specificity of Syngap1 mutations within forebrain excitatory neurons. Interestingly, cognitive abnormalities were reliably predicted by the emergence of enhanced excitatory synaptic function in mature superficial cortical pyramidal cells, which was a neurophysiological disruption caused by Syngap1 dysfunction in developing, but not adult, forebrain neurons. We conclude that reduced cognition in Syngap1 mutants is caused by isolated damage to developing forebrain glutamatergic neurons. This damage triggers secondary disruptions to synaptic homeostasis in mature cortical pyramidal cells, which perpetuates brain dysfunction into adulthood.
登录
查看更多内容
ERK信号传导的神经纤维素调节调节GABA释放和学习。
影响因子：
64.5
作者：
Cui Y;Costa RM;Murphy GG;Elgersma Y;Zhu Y;Gutmann DH;Parada LF;Mody I;Silva AJ
通讯作者：
Silva AJ
影响因子：
2.5
作者：
Helm, Jessica;Akgul, Gulcan;Wollmuth, Lonnie P.
通讯作者：
Wollmuth, Lonnie P.
影响因子：
9.8
作者：
通讯作者：
--
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
5.3
作者：
Clement, James P.;Ozkan, Emin D.;Rumbaugh, Gavin
通讯作者：
Rumbaugh, Gavin