Changing the responses of cortical neurons from sub- to suprathreshold using single spikes in vivo.
Changing the responses of cortical neurons from sub- to suprathreshold using single spikes in vivo.
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DOI：
10.7554/elife.00012
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发表时间：
2013-01-22
期刊：
影响因子：
7.7
通讯作者：
Kerr JN
中科院分区：
文献类型：
--
作者：
Pawlak V;Greenberg DS;Sprekeler H;Gerstner W;Kerr JN
感觉皮层神经元的动作电位(AP)模式编码了各种刺激特征，但神经元如何改变其反应的特征？在这里，我们证明了在体内，一种尖峰时序依赖可塑性(STDP)协议-包括将突触后AP与视觉驱动的突触前输入配对-以双向的方式修改神经元的AP反应，这取决于配对过程中的相对AP时序。而在突触前激活后重复的突触后AP可以将阈值下的反应转换为阈值上的反应，而在突触前激活之前重复的AP会降低AP对视觉刺激的反应。这些变化与神经元对周围刺激位置和膜电位时间过程的反应重建是平行的。只有在包含突触前时间抖动的情况下，计算机模拟才能再现观察到的亚阈值电压变化。综上所述，这表明STDP规则可以改变感觉神经元的输出模式，而单AP的时机在感觉编码和可塑性中起着至关重要的作用。Http://dx.doi.org/10.7554/eLife.00012.001神经细胞，称为神经元，是大脑的核心组成部分之一，通过被称为轴突的细长的“电线状”过程与其他神经元连接，形成复杂的网络。轴突可以延伸到整个大脑，使神经元能够与成千上万的其他神经元形成连接或突触。正是通过这些复杂的网络，来自感官器官(如眼睛)的传入信息通过大脑传播并编码。神经元之间交流的基本单位是动作电位，通常被称为‘棘波’，它沿着轴突网络传播，并通过突触的化学过程与轴突所连接的突触后神经元进行通信。这些动作电位兴奋它们到达的神经元，这个兴奋过程可以产生一个新的动作电位，然后沿着轴突传播，以兴奋更多的靶神经元。在大脑皮层的视觉区域，当神经元“识别”场景中的特定特征时，它们会用动作电位做出反应--这一过程被称为调谐。神经元如何适应世界上的某些特征，而不是其他特征，以及使神经元能够改变其所调节的内容的规则，目前尚不清楚。然而，清楚的是，要理解这一过程就是理解感官知觉的基础。记忆的存储和形成被认为发生在突触上。神经元之间的信号传递效率可以随着时间的推移而增加或减少，这一过程通常被称为突触可塑性。但是，为了让这些突触变化传递到目标神经元，这些变化必须改变动作电位的数量。虽然在体外已经证明，突触传递的效率--即突触的强度--可以通过改变突触前和突触后细胞被激活的顺序来改变(被称为尖峰时序依赖的可塑性)，但这从未被证明对体内单个神经元产生的动作电位的数量产生影响。因此，目前尚不清楚这一进程在功能上是否相关。现在，Pawlak等人。有报道称，麻醉大鼠视皮层的棘波时序依赖性可塑性可以改变视皮层神经元的棘波。他们使用视觉刺激(闪现半秒的条形图)来激活突触前细胞，并在很短的时间后触发突触后细胞的单个动作电位。通过以这种方式反复激活细胞，他们增加了两个神经元之间突触连接的强度。在少量的配对激活后，仅将视觉刺激呈现给突触前细胞就足以在突触后神经元触发动作电位(阈值以上反应)--尽管配对之前并非如此。这项研究表明，已知的改变突触连接强度的计时规则--并被认为是学习和记忆的基础--在体内具有功能相关性，而且单个动作电位的计时可以改变皮质神经元的功能状态。DOI：http://dx.doi.org/10.7554/eLife.00012.002
Action Potential (APs) patterns of sensory cortex neurons encode a variety of stimulus features, but how can a neuron change the feature to which it responds? Here, we show that in vivo a spike-timing-dependent plasticity (STDP) protocol—consisting of pairing a postsynaptic AP with visually driven presynaptic inputs—modifies a neurons' AP-response in a bidirectional way that depends on the relative AP-timing during pairing. Whereas postsynaptic APs repeatedly following presynaptic activation can convert subthreshold into suprathreshold responses, APs repeatedly preceding presynaptic activation reduce AP responses to visual stimulation. These changes were paralleled by restructuring of the neurons response to surround stimulus locations and membrane-potential time-course. Computational simulations could reproduce the observed subthreshold voltage changes only when presynaptic temporal jitter was included. Together this shows that STDP rules can modify output patterns of sensory neurons and the timing of single-APs plays a crucial role in sensory coding and plasticity. DOI: http://dx.doi.org/10.7554/eLife.00012.001 Nerve cells, called neurons, are one of the core components of the brain and form complex networks by connecting to other neurons via long, thin ‘wire-like’ processes called axons. Axons can extend across the brain, enabling neurons to form connections—or synapses—with thousands of others. It is through these complex networks that incoming information from sensory organs, such as the eye, is propagated through the brain and encoded. The basic unit of communication between neurons is the action potential, often called a ‘spike’, which propagates along the network of axons and, through a chemical process at synapses, communicates with the postsynaptic neurons that the axon is connected to. These action potentials excite the neuron that they arrive at, and this excitatory process can generate a new action potential that then propagates along the axon to excite additional target neurons. In the visual areas of the cortex, neurons respond with action potentials when they ‘recognize’ a particular feature in a scene—a process called tuning. How a neuron becomes tuned to certain features in the world and not to others is unclear, as are the rules that enable a neuron to change what it is tuned to. What is clear, however, is that to understand this process is to understand the basis of sensory perception. Memory storage and formation is thought to occur at synapses. The efficiency of signal transmission between neurons can increase or decrease over time, and this process is often referred to as synaptic plasticity. But for these synaptic changes to be transmitted to target neurons, the changes must alter the number of action potentials. Although it has been shown in vitro that the efficiency of synaptic transmission—that is the strength of the synapse—can be altered by changing the order in which the pre- and postsynaptic cells are activated (referred to as ‘Spike-timing-dependent plasticity’), this has never been shown to have an effect on the number of action potentials generated in a single neuron in vivo. It is therefore unknown whether this process is functionally relevant. Now Pawlak et al. report that spike-timing-dependent plasticity in the visual cortex of anaesthetized rats can change the spiking of neurons in the visual cortex. They used a visual stimulus (a bar flashed up for half a second) to activate a presynaptic cell, and triggered a single action potential in the postsynaptic cell a very short time later. By repeatedly activating the cells in this way, they increased the strength of the synaptic connection between the two neurons. After a small number of these pairing activations, presenting the visual stimulus alone to the presynaptic cell was enough to trigger an action potential (a suprathreshold response) in the postsynaptic neuron—even though this was not the case prior to the pairing. This study shows that timing rules known to change the strength of synaptic connections—and proposed to underlie learning and memory—have functional relevance in vivo, and that the timing of single action potentials can change the functional status of a cortical neuron. DOI: http://dx.doi.org/10.7554/eLife.00012.002