Chronic inactivation of a neural circuit enhances LTP by inducing silent synapse formation.
Chronic inactivation of a neural circuit enhances LTP by inducing silent synapse formation.
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DOI：
10.1523/jneurosci.3880-12.2013
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发表时间：
2013-01-30
期刊：
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
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作者：
Arendt KL;Sarti F;Chen L
已知神经网络的慢性失活诱导突触强度的稳态上调，这是一种突触可塑性的形式，其不同于赫布型突触可塑性，因为它不是输入特异性的，而是涉及单个神经元的所有突触。然而，尚不清楚稳态和赫布突触可塑性如何在同一神经元中相互作用。在这里，我们表明，长时程增强（LTP）在Schaffer侧支-CA 1突触培养的小鼠海马脑片后，慢性（60小时）的网络活动与河豚毒素（TTX）封锁大大增强。这种LTP的增加不是由于突触NMDA受体组成或突触前功能的改变。相反，我们发现，沉默神经网络活动不仅增加了AMPA和NMDA受体在现有突触的丰度，如前所述，而且还促进了新的AMPA能突触的存在，这些突触仅含有NMDA受体-一类由于缺乏AMPA受体而功能沉默的突触。TTX处理的神经元中LTP的诱导导致AMPA受体插入沉默突触中，因此“打开”这些沉默突触，这产生了观察到的LTP幅度的增强。我们的研究结果表明，稳态突触可塑性不仅表现在现有突触的强度的调整，但也在新的突触形成/维持的调制。此外，新的但功能沉默的突触的存在，使更强大的LTP发生通过沉默的突触到活跃的突触的快速转换，导致在更强的输入特异性调制的突触后，延长网络沉默。
Chronic inactivation of a neural network is known to induce homeostatic upregulation of synaptic strength, a form of synaptic plasticity that differs from Hebbian-type synaptic plasticity in that it is not input-specific, but involves all synapses of an individual neuron. However, it is unclear how homeostatic and Hebbian synaptic plasticity interact in the same neuron. Here we show that long-term potentiation (LTP) at Schaffer collateral-CA1 synapses is greatly enhanced in cultured mouse hippocampal slices after chronic (60 hour) network-activity blockade with tetrodotoxin (TTX). This increase in LTP is not due to an altered synaptic NMDA receptor composition or presynaptic function. Instead, we found that silencing neural network activity not only increases the abundance of both AMPA and NMDA receptors at existing synapses as previously described, but also promotes the presence of new glutamatergic synapses that contain only NMDA receptors – a class of synapses that are functionally silent due to the absence of AMPA receptors. Induction of LTP in TTX-treated neurons leads to insertion of AMPA receptors into the silent synapses, therefore “switching on” these silent synapses, which produces the observed enhancement of LTP magnitude. Our findings suggest that homeostatic synaptic plasticity manifests not only in the adjustment of the strength of existing synapses, but also in the modulation of new synapse formation/maintenance. Moreover, presence of new but functionally silent synapses enables more robust LTP to occur through rapid conversion of silent synapses to active synapses, resulting in a stronger input-specific modulation of synapses following prolonged network silencing.