Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons.
Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons.
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DOI：
10.1038/nn.2621
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发表时间：
2010-09
影响因子：
25
通讯作者：
Worley, Paul F.
中科院分区：
文献类型：
--
作者：
Chang, Michael C.;Park, Joo Min;Pelkey, Kenneth A.;Grabenstatter, Heidi L.;Xu, Desheng;Linden, David J.;Sutula, Thomas P.;McBain, Chris J.;Worley, Paul F.
稳态突触缩放改变突触的强度，以补偿网络活动的长期变化，并涉及兴奋性和抑制性神经元。被称为Narp（神经元活性调节的五聚蛋白）的立即早期基因编码分泌的突触蛋白，其可以结合并聚集AMPA受体（AMPAR）。在这里，我们报告说，Narp显着积累在兴奋性突触的小白蛋白表达的中间神经元（PV-IN）。增加网络活动导致PV-IN上兴奋性突触强度的稳态增加，从而增加抑制性驱动，并且这种反应在Narp敲除（Narp−/−）小鼠培养的神经元中不存在。在急性海马切片中，PV-IN上兴奋性输入强度的活动依赖性变化也依赖于Narp，Narp−/−小鼠对点燃诱导的癫痫发作表现出更高的敏感性。我们建议，Narp招聘AMPARs兴奋性突触上PV-IN的再平衡网络的兴奋/抑制动力学增加电路活动的事件。
Homeostatic synaptic scaling alters the strength of synapses to compensate for prolonged changes in network activity, and involves both excitatory and inhibitory neurons. The immediate-early gene termed Narp (Neuronal activity-regulated pentraxin) encodes a secreted synaptic protein that can bind and cluster AMPA receptors (AMPARs). Here, we report that Narp prominently accumulates at excitatory synapses on Parvalbumin-expressing interneurons (PV-INs). Increasing network activity results in a homeostatic increase of excitatory synaptic strength onto PV-INs that increases inhibitory drive, and this response is absent in neurons cultured from Narp knock-out (Narp−/−) mice. Activity-dependent changes in the strength of excitatory inputs on PV-INs in acute hippocampal slices are also dependent on Narp, and Narp−/− mice display increased sensitivity to kindling-induced seizures. We propose that Narp recruits AMPARs at excitatory synapses onto PV-INs to rebalance network excitation/inhibition dynamics following episodes of increased circuit activity.
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影响因子：
64.8
作者：
Lin, Yingxi;Bloodgood, Brenda L.;Hauser, Jessica L.;Lapan, Ariya D.;Koon, Alex C.;Kim, Tae-Kyung;Hu, Linda S.;Malik, Athar N.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
16.2
作者：
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通讯作者：
Worley, Paul F.
影响因子：
4.8
作者：
Dodds, DC;Omeis, IA;Perin, MS
通讯作者：
Perin, MS
影响因子：
16.2
作者：
GEIGER, JRP;MELCHER, T;MONYER, H
通讯作者：
MONYER, H
影响因子：
5.3
作者：
Bjartmar, Lisa;Huberman, Andrew D.;Perin, Mark S.
通讯作者：
Perin, Mark S.