Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity.
Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity.
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DOI：
10.1186/1471-2202-12-126
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发表时间：
2011-12-19
期刊：
影响因子：
2.4
通讯作者：
Levine ES
中科院分区：
文献类型：
--
作者：
Lemtiri-Chlieh F;Zhao L;Kiraly DD;Eipper BA;Mains RE;Levine ES
树突棘代表哺乳动物前脑中绝大多数兴奋性突触的突触后成分。棘响应刺激而快速改变其形状、大小、数量和受体含量的能力被认为在突触可塑性的发展过程中至关重要。事实上，长时程增强（LTP）被广泛认为是学习和记忆的细胞相关性，已被反复证明可以诱导树突棘增大和新树突棘的形成。在我们的研究中，我们重点关注 Kalirin-7 (Kal7)，这是一种位于突触后密度的 Rho GDP/GTP 交换因子 (Rho-GEF)，它在体外和体内树突棘的发育和维持中发挥着至关重要的作用。先前的研究表明，缺乏 Kal7 (Kal7KO) 的小鼠海马树突棘密度降低，并出现局灶性海马依赖性学习障碍。我们对 Kal7 在海马突触可塑性中的作用进行了详细的电生理学表征。我们发现，Kal7 的缺失会导致 NMDA 受体依赖性 LTP 受损和长期抑郁，而 NMDA 受体非依赖性形式的 LTP 在 Kal7 缺失的情况下显示为正常。这些结果表明 Kal7 是海马 NMDA 受体依赖性突触可塑性的重要且选择性调节剂。
Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments. We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7. These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.
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DOI：
10.1523/jneurosci.4022-09.2010
发表时间：
2010-02-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
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DOI：
10.1073/pnas.0904636106
发表时间：
2009-08-04
影响因子：
11.1
作者：
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通讯作者：
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4.7
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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DOI：
10.1523/jneurosci.3143-11.2011
发表时间：
2011-08-31
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kiraly DD;Lemtiri-Chlieh F;Levine ES;Mains RE;Eipper BA
通讯作者：
Eipper BA