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首页> 外文期刊>The European Journal of Neuroscience >Long-lasting small-amplitude TRP-mediated dendritic depolarizations in CA1 pyramidal neurons are intrinsically stable and originate from distal tuft regions
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Long-lasting small-amplitude TRP-mediated dendritic depolarizations in CA1 pyramidal neurons are intrinsically stable and originate from distal tuft regions

机译：CA1锥体神经元中持久的小幅度TRP介导的树突状去极化本质上稳定，起源于远端簇状区域

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摘要

In several regions of the nervous system, neurons display bi- or multistable intrinsic properties. Such stable states may be subthreshold and long-lasting, and can appear as a sustained afterdepolarization. In hippocampal CA1 pyramidal neurons, small-amplitude (1mV) long-lasting (seconds) afterdepolarizations have been reported and are thought to depend on calcium-activated nonselective (CAN) currents recently identified as transient receptor potential (TRP) channels. Continuing our previous experimental and computational work on synaptically metabotropic glutamate receptor (mGluR)-activated TRP currents, we here explore small-amplitude long-lasting depolarizations in a detailed multicompartmental model of a CA1 pyramidal neuron. We confirm a previous hypothesis suggesting that the depolarization results from an interplay of TRP and voltage-gated calcium channels, and contribute to the understanding of the depolarization in several ways. Specifically, we show that: (i) the long-lasting depolarization may be intrinsically stable to weak excitatory and inhibitory input, (ii) the phenomenon is essentially located in distal apical dendrites, (iii) induction is facilitated if simultaneous input arrives at several dendritic branches, and if calcium- and/or mGluR-evoked signals undergo summation, suggesting that both spatial and temporal synaptic summation might be required for the depolarization to occur and (iv) we also show that the integration of inputs to oblique dendrites is strongly modulated by the presence of small-amplitude long-lasting depolarizations in distal tuft dendrites. To conclude, we suggest that small-amplitude long-lasting dendritic depolarizations may contribute to sustaining neural information during behavioural tasks in cases where information is separated in time, as in trace conditioning and delay tasks. In vitro studies of pyramidal neurons have reported long-lasting small-amplitude depolarizations. In this work, we show that these depolarizations may originate from distal apical tuft dendrites. We also show that the underlying mechanism (which involves TRP and VGCC currents) is intrinsically stable to weak excitatory and inhibitory input, thereby providing the cell with a mechanism for subthreshold dendritic bistability. We further discuss the impact on synaptic integration.
机译：在神经系统的几个区域，神经元显示出双稳态或多稳态的内在特性。这样的稳定​​状态可能是亚阈值且持久的，并且可能表现为持续的去极化。在海马CA1锥体神经元中，小振幅（1mV）持续（秒）后去极化已被报道，并被认为取决于最近被确定为瞬时受体电位（TRP）通道的钙激活非选择性（CAN）电流。继续我们先前关于突触型代谢型谷氨酸受体（mGluR）激活的TRP电流的实验和计算工作，我们在这里详细探讨了CA1锥体神经元的多室模型中的小振幅持久去极化。我们证实了先前的假说，该假说表明去极化是由TRP和电压门控钙通道的相互作用引起的，并以多种方式有助于对去极化的理解。具体而言，我们表明：（i）长期去极化对弱的兴奋性和抑制性输入可能是内在稳定的;（ii）现象本质上位于远端根尖树突中;（iii）如果同时输入到达多个，则有助于诱导树突状分支，如果钙和/或mGluR引起的信号进行求和，则表明去极化的发生可能需要空间和时间的突触求和，并且（iv）我们还表明，输入到斜向树突的整合非常强烈在远端簇状树突中存在小幅度的持久去极化作用，从而进行调节。总而言之，我们建议小幅度的长时间树突状去极化可能有助于在行为任务期间在信息被及时分离的情况下维持神经信息，例如在跟踪条件和延迟任务中。锥体神经元的体外研究报告了持久的小幅度去极化。在这项工作中，我们显示这些去极化可能源自远端的顶端簇状树突。我们还表明，潜在的机制（涉及TRP和VGCC电流）对于弱的兴奋性和抑制性输入本质上是稳定的，从而为细胞提供了亚阈值树突双稳态的机制。我们进一步讨论对突触整合的影响。

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