兴奋-抑制平衡

参考http://www.scholarpedia.org/article/Balance_of_excitation_and_inhibition 此词条由神经动力学读书会词条梳理志愿者安贞桦翻译审校，未经专家审核，带来阅读不便，请见谅。 In the context of neurophysiology, balance of excitation and inhibition (E/I balance) refers to the relative contributions of excitatory and inhibitory synaptic inputs corresponding to some neuronal event, such as oscillation or response evoked by sensory stimulation.

在神经生理学背景下，兴奋-抑制平衡 E/I balance指的是对应于某些神经元事件的兴奋性和抑制性突触输入的相关贡献，如由感觉刺激引起的振荡或反应。

In the current literature, owing to the extremely wide range of conditions in which the term is applied, it has several different, albeit related, meanings.

在目前的文献中，由于该术语的应用情景极其广泛，它有几种相关但不相同的含义。

As described in more detail below, the precise meaning depends on various considerations, such as averaging across time or population of neurons that is involved; the relevant timescale; whether the synaptic activity is sustained or transient, spontaneous or evoked.

如下文更详细地描述，确切的含义取决于各种考虑因素，比如时间上的平均值或所涉及的神经元群体；相关的时间尺度；突触活动是持续的还是暂态的，是自发的还是激发的。

In general, excitatory and inhibitory inputs of a neuron are said to be balanced if across a range of conditions of interest the ratio between the two inputs is constant.

一般来说，如果在整个关心的条件范围内，兴奋性和抑制性输入之间的比率是恒定的，则称其为平衡的。

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In the cortex, interneurons responsible for inhibition comprise just a small fraction of the neurons, yet they have an important function in regulating activity of principal cells.

在皮层中，负责抑制的 中间神经元interneurons 只占神经元的一小部分，但它们对调节 主细胞 principal cells 的活动具有重要功能。

When inhibition is blocked pharmacologically, cortical activity becomes epileptic (Dichter and Ayala, 1987), and neurons may lose their selectivity to different stimulus features (Sillito, 1975).

当抑制作用在药理学上阻断时，皮层活动会发生癫痫（Dichter和Ayala，1987），神经元可能会失去对不同刺激特征的选择性（Sillito，1975）。

These and other data indicate that the interplay between excitation and inhibition has an important role in determining the cortical computation.

这些数据和其他数据表明，兴奋和抑制之间的相互作用在决定皮质计算中具有重要作用。

Our understanding of the relationships between these two opposing forces has advanced significantly during the recent years, mainly due to the growing use of in-vivo intracellular recording techniques.

近年来，得益于体内的 胞内记录intracellular recording 技术的日益普及，我们对这两种对立力量之间的关系的理解有了显著的进步。

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Indirect evidence for E/I balance E/I平衡的间接证据

Cortical neurons receive synaptic inputs from thousands of other, mainly excitatory, neurons, most of which evoke only a sub-millivolt response (Bruno and Sakmann, 2006; Lefort et al., 2009).

皮质神经元从数千个其他神经元（主要是兴奋性神经元）接收突触输入，大多数仅仅引发亚毫伏反应（Bruno和Sakmann，2006;Lefort et al.， 2009）。

If these inputs arrive from neurons that fire at independent random times, they are expected to produce an almost constant depolarization leading to a regular firing.

如果这些输入来自在独立随机的时间点发放的神经元，则它们将产生几乎恒定的去极化，引起有规律的发放。

However, spike trains extracellularly recorded from single cortical neurons exhibit high variability.

然而，从单个皮质神经元记录的胞外 尖峰序列spike trains 表现出高度的可变性。

For instance, the coefficient of variation of the inter-spike intervals (ISIs) of neurons firing in response to a sensory input for a period of several seconds, is approximately equal to 1, as expected from a Poisson process (Softky and Koch, 1993).

例如，响应于数秒内的感觉输入而放电的神经元的放电间隔（ISIs）的变化系数大约等于1，正如 泊松过程Poisson process 所预期的那样（Softky和Koch，1993）。

This apparent paradox between simple probabilistic considerations and the observed statistics of cortical spike trains led to several proposed resolutions.

在简单的概率考虑和观察到的皮质尖峰序列的统计数据之间的明显矛盾，驱使人们提出了几种解释方案。

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One early resolution was that excitatory and inhibitory synaptic currents of cortical neurons are approximately balanced in strength, causing the membrane potential to hover somewhat below the spiking threshold, crossing it at random times (Shadlen and Newsome, 1994, 1998).

一个早期的解释方案是，皮质神经元的兴奋性和抑制性突触电流在强度上大致平衡，导致膜电位在放电阈值以下波动，在随机时间超过阈值（Shadlen和Newsome，1994，1998）。

Simulations, based on the random walk model of (Gerstein and Mandelbrot, 1964) demonstrated that under such a regime of synaptic inputs the ISI variability is in agreement with experimental observations (Shadlen and Newsome, 1994, 1998).

基于的随机游走模型random walk model（Gerstein和Mandelbrot，1964）的模拟表明，在这种突触输入的机制下，ISI的变化与实验观察结果一致（Shadlen和Newsome，1994，1998）。

Furthermore, computational studies of spontaneous activity in neuronal networks showed that E/I balance emerges naturally if the network is sparsely connected (van Vreeswijk and Sompolinsky, 1996; Vogels et al., 2005).

However, these early theoretical studies were based on crude estimates of the relevant parameters, and therefore cannot be regarded as definitive.

此外，对神经元网络中的自发活动的计算研究表明，如果网络是稀疏连接的，E / I平衡会自然出现（van Vreeswijk和Sompolinsky，1996; Vogels等人，2005年）。

然而，这些早期的理论研究是基于对相关参数的粗略估计，因此不能视为定论。

In fact, several follow-up studies suggested that other factors, such as synchrony, are required in order to explain the observed ISI statistics, e.g., (Stevens and Zador, 1998).

事实上，一些后续研究表明，如（Stevens和Zador，1998），为了解释观察到的ISI统计数据，需要引入其他因素，例如同步性。

Indeed, as described below, it appears that although excitation and inhibition are balanced, the membrane potential of cortical neurons does not necessarily follow the random walk trajectory predicted by these early models

(Crochet and Petersen, 2006; DeWeese and Zador, 2006; Poulet and Petersen, 2008; Okun et al., 2010; Polack et al., 2013; Sachidhanandam et al., 2013; Tan et al., 2014).

如下所述，尽管兴奋和抑制是平衡的，但皮质神经元的膜电位并不一定遵循这些早期模型预测的随机游走轨迹。

（Crochet和Petersen，2006;DeWeese和Zador，2006年;Poulet和Petersen，2008;奥坤等人， 2010;Polack et al.， 2013;Sachidhanandam等人， 2013;谭等人，2014）。

The possibility of excitation and inhibition having a comparable strength might seem implausible at first, since interneurons comprise only 15% - 25% of the population of cortical neurons.

起初兴奋和抑制具有相当强度的可能性似乎难以置信，因为中间神经元仅占皮质神经元群体的15%-25%。

However, the synaptic strength and firing rates of inhibitory interneurons are substantially higher than in excitatory neurons, thus inhibitory interneurons have an impact disproportionate to their relatively small number.

然而，抑制性中间神经元的突触强度和放电率大大高于兴奋性神经元，因此抑制性中间神经元有着与其相对较少的数量不成比例的影响。

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Intracellular measurement of the excitatory and inhibitory synaptic inputs 兴奋性和抑制性突触输入的细胞内测量

In a pioneering study, Borg-Graham and colleagues used intracellular recordings to directly estimate the synaptic conductance changes evoked in cortical neurons by visual stimulation (Borg-Graham et al., 1996, 1998).

在一项开创性的研究中，Borg-Graham及其同事用胞内记录直接估计通过视觉刺激在皮质神经元中引起的突触电导变化（Borg-Graham等人，1996，1998）。

The average synaptic current evoked by a stimulus is recorded in voltage-clamp mode, using several different clamping voltages.

用一些不同的钳位电压，在电压钳位模式下记录由刺激引起的平均突触电流。

Alternatively, the subthreshold response is recorded in the current-clamp mode at several different clamping currents (Anderson et al., 2000).

或者，用一些不同的钳位电流，在电流钳位模式下记录阈值下响应（Anderson等人，2000）。

The behavior of the membrane potential is approximated using a passive, single compartment, conductance-based model of the neuron, described by

膜电位的行为是用神经元的被动单隔室compartment的基于电导的模型近似的，描述如下

[math]\displaystyle{ CdV/dt = -G_{leak}(V(t)-E_{leak}) - G_{ex}(t)(V(t)-E_{ex}) - G_{in}(t)(V(t)-E_{in})+I_{inj} }[/math] (1)

where \(E_{leak}\) is the resting membrane potential of the neuron, \(C\) is its capacitance, \(G_{leak}\) is the mean conductance in absence of stimulation (the inverse of input resistance), \(E_{ex}\) and \(E_{in}\) are the reversal potentials of excitation and inhibition, and \(I_{inj}\) is the current injected through the recording pipette.

其中[math]\displaystyle{ E_{leak} }[/math]是神经元的静息膜电位，[math]\displaystyle{ C }[/math]是其电容，[math]\displaystyle{ G_{leak} }[/math]是在没有刺激的情况下的平均电导（输入电阻的倒数），[math]\displaystyle{ E_{ex} }[/math]和[math]\displaystyle{ E_{in} }[/math]是兴奋和抑制的反转电位，[math]\displaystyle{ I_{inj} }[/math]是通过记录移液管注入的电流。

By fitting equation (1) to the average responses at different holding potentials, the synaptic conductances evoked by the stimulus, \(G_{ex}(t)\) and \(G_{in}(t)\ ,\) can be computed (see Figure 1).

通过将方程（1）拟合到不同保持电位下的平均响应，可以计算出由刺激[math]\displaystyle{ G_{ex}(t) }[/math]和[math]\displaystyle{ G_{in}(t) }[/math]引起的突触电导（见图1）。

For an in-depth review of the method and its caveats an interested reader is referred to (Monier et al., 2008).

欲深入了解该方法及其注意事项，请参考（Monier等人，2008）。

Selectivity of cortical excitation and inhibition to sensory stimulation 皮质兴奋的选择性和对感觉刺激的抑制

Early models of the visual cortex suggested that the selectivity of cortical cells to sensory stimulation emerges from feedforward inputs.

视觉皮层的早期模型表明，皮质细胞对感觉刺激的选择性来自于前馈输入。

Later models, however, questioned this view by suggesting that cortical inhibition plays a significant role in enhancing the selectivity of cortical response.

然而，后来的模型质疑这一观点，认为皮质抑制在增强皮质响应的选择性方面起着显著的作用。

The best known example for this controversy is the emergence of orientation selectivity in primary visual cortex.

这种争议最着名的例子是初级视觉皮层中方向选择性的出现。

The feedforward model (Hubel and Wiesel, 1962) was supported by various studies (Nelson et al., 1994; Alonso and Martinez, 1998; Chung and Ferster, 1998; Martinez and Alonso, 2001), while being challenged by others (Sillito, 1975; Volgushev et al., 1996).

前馈模型feedforward model（Hubel和Wiesel，1962）得到了各种研究的支持（Nelson等人，1994;阿隆索和马丁内斯，1998年;钟和费斯特， 1998;马丁内斯和阿隆索，2001），同时受到其他人的挑战（Sillito，1975;Volgushev等人，1996年）。

The feedforward model, however, failed to predict several key experimental findings, and in particular the contrast invariance of orientation tuning (Ferster and Miller, 2000).

然而，前馈模型未能预测几个关键的实验发现，特别是方向调谐的对比不变性（Ferster和Miller，2000）。

Alternative models proposed that the tuning of inhibitory inputs is wider, so that excitation and inhibition form a 'Mexican hat' interaction pattern which sharpens the selectivity of the cells (Ben-Yishai et al., 1995; Somers et al., 1995; Hansel and Sompolinsky, 1996).

替代模型提出，抑制性输入的调谐范围更广，因此兴奋和抑制形成了"墨西哥帽Mexican hat"相互作用模式，从而提高了细胞的选择性（Ben-Yishai等人，1995;萨默斯等人，1995年;汉赛尔和索姆波林斯基，1996年）。

In the primary auditory cortex inhibition was similarly suggested to account for the sensory selectivity of the neurons (Calford and Semple, 1995; Sutter et al., 1999; Wang et al., 2002).

在初级听觉皮层中，抑制同样被认为可以解释神经元的感觉选择性（Calford和Semple，1995;萨特等人， 1999;Wang等人，2002）。

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A breakthrough in the ability to test these models was achieved by the in-vivo intracellular conductance measurement methods described above.

通过上述体内细胞内电导测量方法，在测试这些模型的能力方面取得了突破。

Over the last 15 years this approach was used in many studies to examine the sensory selectivity of excitatory and inhibitory synaptic inputs in primary sensory areas of several mammalian species.

在过去的15年中，这种方法被用于许多研究，来检查一些哺乳动物物种的主要感觉区域中兴奋性和抑制性突触输入的感觉选择性。

Direct measurements showed that to a first approximation the excitatory and inhibitory inputs are either similarly tuned, or that inhibitory inputs have a somewhat wider tuning.

直接测量表明，在一级近似下，要么兴奋性和抑制性输入被相似地调谐，要么抑制性输入具有更宽的调谐。

In cat primary visual cortex excitatory and inhibitory synaptic inputs are similarly tuned for orientation (Anderson et al., 2000), as well as for length (Anderson et al., 2001) and the direction of motion (Priebe and Ferster, 2005).

在猫的初级视觉皮层中，方向（Anderson等人，2000）以及长度（Anderson等人，2001）和运动方向（Priebe和Ferster，2005）相似地调谐兴奋性和抑制性突触输入。

In the rodent primary auditory cortex inhibition is tuned similarly or somewhat wider than excitation for both frequency and intensity (Wehr and Zador, 2003; Wu et al., 2008; Zhou et al., 2014), see Figure 2.

在啮齿动物的初级听觉皮层中，在频率和强度上的抑制与兴奋相似或略宽地调谐（Wehr和Zador，2003;吴等， 2008;Zhou等人，2014），见图2。

Therefore, in these cases the selectivity of the neurons is unlikely to emerge through inhibitory suppression of the response to non-preferred stimuli.

因此，在这些情况下，神经元的选择性不太可能通过对非偏好刺激的响应的抑制而显现。

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The similar tuning of excitatory and inhibitory inputs to different features of the stimuli space appears to be a rather common organizational principle in the sensory areas, however there are several notable exceptions.

对刺激空间不同特征的兴奋性和抑制性输入的类似调谐似乎是感觉区域中相当常见的组织原则，但也有几个显著的例外。

The most prominent deviation from co-tuning was observed for orientation selectivity in the mouse primary visual cortex, where the inhibitory input is substantially more broadly tuned than the excitatory input, possibly because rodent primary visual cortex lacks orientation columns (Liu et al., 2011; Atallah et al., 2012; Li et al., 2012; Harris and Mrsic-Flogel, 2013).

在小鼠初级视觉皮层中观察到对方向选择性的最显著的协同调谐偏差，其中抑制性输入的调谐范围比兴奋性输入的调谐范围更广，可能是因为啮齿动物初级视觉皮层缺乏朝向柱（Liu等人，2011年；Atalah等人，2012年；Li等人，2012年；Harris和Mrsic Flogel，2013年）。

An opposite scenario, where inhibitory inputs have narrower selectivity, was observed for frequency tuning in layer V intrinsically-bursting (but not regular-spiking) neurons of the primary auditory cortex (Sun et al., 2013).

在初级听觉皮层的第五层内在簇放电（但不是规则的尖峰）神经元中观察到了一种相反的情况，即抑制性输入的选择性较窄（Sun等人，2013年）。

Also in the auditory cortex, some intensity-tuned neurons receive excitatory inputs which peak at the preferred intensity, whereas their inhibitory inputs increase monotonically with the stimulus strength (Wu et al., 2006), representing a case where the co-tuning of excitation and inhibition appears to break altogether.

同样在听觉皮层，一些强度调谐神经元接收到的兴奋性输入在偏好强度时达到峰值，而它们的抑制性输入随着刺激强度单调增加（Wu等人，2006年），这体现了兴奋和抑制的共同调谐发生破坏的例子。

Finally, it should be noted that the tuning of inhibitory and excitatory inputs alone is not sufficient to substantiate specific theoretical models for feature selectivity in the cortex, because broad tuning of inhibition may either reflect non-specific convergence of inputs from a population of inhibitory cells that demonstrate highly selective but non-overlapping orientation tuning curves, or simply result from the wide tuning curves of their innervating inhibitory neurons (Shapley and Xing, 2013; Section 6 below).

最后，应注意的是，仅抑制性和兴奋性输入的调谐不足以证实皮质中特征选择性的具体理论模型，因为抑制性的广泛调谐可能反映了抑制性细胞群输入的非特异性收敛，这些抑制性细胞群显示出具有高度选择性但不重叠的方向调谐曲线，或者仅仅是由于它们的神经支配抑制神经元的宽调谐曲线（Shapley和Xing，2013；下文第6节）。

Temporal structure of sensory evoked excitation and inhibition 感觉诱发电能和抑制的时间结构

In the auditory and somatosensory cortices sensory stimulation often evokes stereotypic sequence of excitation followed within a few milliseconds by inhibition (Wehr and Zador, 2003; Higley and Contreras, 2006).

在听觉和体感皮层中，感觉刺激经常唤起在随后几毫秒内受抑制的定型兴奋序列，（Wehr和Zador，2003;Higley和Contreras，2006）。

Although excitation and inhibition are similarly tuned and hence are said to be balanced, a large imbalance occurs at the fine time scale, as inhibition lags behind excitation by several milliseconds.

尽管兴奋和抑制被相似地调谐而因此被称为平衡的，但由于抑制滞后于兴奋几毫秒，在精细的时间尺度上会出现很大的不平衡。

This lag between excitation and inhibition is likely to determine the integration window for excitation, affecting the number and precise timing of action potentials (Gabernet et al., 2005).

兴奋和抑制之间的这种滞后可能决定兴奋的整合窗口，影响动作电位的数量和精确时间（Gabernet等人，2005年）。

In the auditory cortex the lag is independent of the frequency tuning of the cells (Wehr and Zador, 2003).

在听觉皮层中，滞后与细胞的频率调谐无关（Wehr和Zador，2003）。

In the somatosensory cortex, however, the delay between excitation and inhibition might be related to the stimulus tuning of the neuron, such that at the preferred stimuli the lag between excitation and inhibition is larger than at the non-preferred ones (Wilent and Contreras, 2005).

然而，在体感皮层中，兴奋和抑制之间的延迟可能与神经元的刺激调谐有关，因此相比于在非偏好刺激下，在偏好刺激下兴奋和抑制之间的延迟更大（Wilent和Contreras，2005）。

Hence, a wider time window is available for integration of excitation for the preferred stimuli, producing more action potentials.

因此，更宽的时间窗口用于对偏好刺激的兴奋整合，产生更多的动作电位。

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One of the central roles traditionally attributed to inhibition is suppression of neuronal responses during temporal integration of sensory inputs.

传统上认为抑制的核心作用之一是在感觉输入的时间整合过程中对神经元反应的抑制。

A widely known example is forward suppression in the auditory cortex, in which the response to a second click presented shortly after the first one is much weaker.

一个广为人知的例子是听觉皮层中的前向抑制，在第一次点击声后不久，对第二次点击声的反应要弱得多。

Another example is in the barrel cortex, where a response to whisker stimulation is largely suppressed if it is preceded by a stimulation of a neighboring whisker.

另一个例子是在桶状皮质中，如果之前刺激相邻的胡须，则对胡须刺激的响应在很大程度上受到抑制。

Such forward suppression was widely believed to be due to inhibition evoked by the first stimuli.

这种前向抑制当前广泛认为是由于第一次刺激引起的抑制。

However, intracellular conductance measurements found that the duration of inhibitory synaptic input evoked by the first click is too short to account for the duration of forward suppression, so that the above explanation is incomplete at the best (Wehr and Zador, 2003, 2005).

然而，对细胞内电导的测量发现，第一次点击声诱发的抑制性突触输入的持续时间太短，无法解释前向抑制的持续时间，因此上述解释充其量是不完整的（Wehr和Zador，2003，2005）。

Similarly, an intracellular recording study in the barrel cortex has shown that cross whisker suppression cannot be fully explained by a postsynaptic inhibitory mechanism (Higley and Contreras, 2003).

类似地，桶状皮质的细胞内记录研究表明，突触后抑制机制不能完全解释交叉胡须抑制（Higley and Contreras，2003）。

Although inhibition is not the primary cause for forward suppression, in other cases the ratio between the excitatory and inhibitory inputs to a neuron in a primary sensory area does depend not only on the instantaneous properties of the stimulus (its contrast, frequency, intensity, etc.) but also on its history.

虽然抑制不是前向抑制的主要原因，但在其他情况下，初级感觉区神经元的兴奋性和抑制性输入之间的比率不仅取决于刺激的瞬时特性（其对比度、频率、强度等），还取决于其历史。

One particular example is adaptation to repeated stimuli, such as clicks or whisker deflections, which under certain conditions can skew the ratio between excitatory and inhibitory inputs toward excitation (Wehr and Zador, 2005; Heiss et al., 2008).

一个特别的例子是对重复刺激的适应，例如点击声或胡须偏转，在某些条件下，这会使兴奋性和抑制性输入之间的比率向兴奋方向倾斜（Wehr和Zador，2005；Heiss等人，2008）。

Paradoxically, because of a slower recovery of inhibitory inputs from adaptation, neurons become hypersensitive shortly after the termination of the adapting stimulation (Cohen-Kashi Malina et al., 2013), which might explain why neurons in the barrel cortex respond better to non-periodic stimulation (Lak et al., 2008).

自相矛盾的是，由于从适应中恢复抑制性输入较慢，神经元在适应刺激终止后不久就会变得超敏（Cohen Kashi-Malina等人，2013年），这可能解释了为什么桶状皮质神经元对非周期性刺激的响应得更好（Lak等人，2008年）。

E/I balance during spontaneous activity 自发活动期间的 E/I 平衡

Under some anesthesia conditions and during slow wave sleep, the membrane potential of cortical neurons fluctuates between a depolarized state and hyperpolarized state.

在某些麻醉条件下和慢波睡眠期间，皮质神经元的膜电位在去极化状态和超极化状态之间波动。

This behavior is known as Up-Down activity.

此行为称为"上下活动"。

During the Down phase the neurons receive almost no synaptic inputs, so that the membrane stays near its resting potential.

在下降阶段，神经元几乎不接收突触输入，因此膜保持在其静息电位附近。

In the Up phase a barrage of synaptic inputs produces a reliable depolarization of 10-20 mV, which occasionally causes spiking (see Figure 1 in Up and down states).

在上升阶段，大量突触输入会产生10-20 mV的可靠去极化，偶尔会导致尖峰（上升和下降状态见图1）。

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The relation between the average amounts of excitatory and inhibitory synaptic inputs during the Up phase was studied using the conductance measurement method described above.

使用上述电导测量方法研究了在上升期兴奋性和抑制性突触输入的平均数量之间的关系。

These experiments, conducted both in vitro (Shu et al., 2003) and in vivo (Haider et al., 2006), have shown that excitatory and inhibitory conductances are balanced throughout the Up phase.

这些在体外（Shu等人，2003年）和体内（Haider等人，2006年）进行的实验表明，兴奋性和抑制性传导在整个上升阶段是平衡的。

In the beginning of the Up phase, both the excitatory and the inhibitory synaptic conductances are high and they tend to progressively decrease, but their ratio remains constant and approximately equal to 1.

在上升期开始时，兴奋性和抑制性突触传导都很高，并趋于逐渐降低，但它们的比率保持不变，约等于1。

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In awake, drug-free animals the membrane potential dynamics exhibits an entire spectrum of distinct, brain state dependent activity patterns.

在清醒、无药物的动物中，膜电位动力学表现出一整套不同的、依赖于大脑状态的活动模式。

The highly desynchronized high-conductance state, which is similar to a continuous Up phase (Crochet and Petersen 2006; Destexhe et al., 2007) represents one end of this spectrum.

高度去同步的高电导状态，类似于连续上升阶段（Crochet and Petersen 2006；Destexe et al.，2007），代表了这一套的一端。

According to an intracellular study in the cortex of awake cats, in this condition the neurons are continuously bombarded by both excitatory and inhibitory inputs, where the total inhibitory conductance is several times higher than the excitatory one (Rudolph et al., 2007), providing a confirmation for the balanced excitation-inhibition hypothesis put forward by (Shadlen and Newsome, 1994).

根据对清醒状态下猫的皮层的细胞内研究，在这种情况下，神经元连续受到兴奋性和抑制性输入的轰击，其中总抑制电导比兴奋性电导高出数倍（Rudolph等人，2007年），证实了由（Shadlen和Newsome，1994年）提出的平衡兴奋-抑制假说。

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The other end of the spectrum of brain states in awake mammals is the quiet wakefulness condition, which is somewhat similar to light anesthesia, and is characterized by rather short depolarizations ('bumps') and membrane potential distribution that is not bimodal, e.g., (DeWeese and Zador, 2006; Poulet and Petersen, 2008).

清醒哺乳动物大脑状态谱的另一端是安静的清醒状态，这在某种程度上类似于轻度麻醉，其特征是相当短的去极化（“碰撞bumps”）和非双峰的膜电位分布，例如（DeWeese和Zador，2006；Poulet和Petersen，2008）。

In the quiet wakefulness condition and light state of anesthesia there are no stereotypic Up events nor does the activity resemble a single continuous Up phase, therefore the single-electrode conductance measurement method which requires averaging over multiple repeats of some stereotypic event, recorded at different holding potentials, cannot be applied.

在安静的清醒状态和轻度的麻醉状态下，没有定型的上升事件，也没有类似于单一连续上升阶段的活动，因此，无法应用单电极电导测量方法，该方法要求在不同的保持电位下记录的一些定型事件的多次重复中求平均值。

However, the substantial synchrony of synaptic inputs to closely located neurons (Lampl et al., 1999; Hasenstaub et al., 2005; Okun and Lampl, 2008; Poulet and Petersen, 2008) which exists in this case allows to continuously monitor both the excitatory and the inhibitory activity in the local network.

然而，这种情况下存在的对位置相近神经元的突触输入的实质同步性（Lampl等人，1999；Hasenstaub等人，2005；Okun和Lampl，2008；Poulet和Petersen，2008），允许持续监测局部网络中的兴奋性和抑制性活动。

Toward this end simultaneous recording from a nearby pair of neurons are used, where one cell is hyperpolarized close to the reversal potential of inhibition and the other cell is depolarized sufficiently close to the reversal potential of excitation (Okun and Lampl, 2008), Figure 3.

为此，使用一对临近神经元的同步记录，其中一个细胞超极化，接近抑制的反转电位，另一个细胞去极化，足以接近兴奋的反转电位（Okun和Lampl，2008），图3。

This method reveals that in this type of spontaneous activity the excitatory and inhibitory inputs are interlocked in time, with inhibition lagging by several milliseconds behind excitation.

该方法揭示了在这种自发活动中，兴奋性和抑制性输入在时间上是互锁的，抑制滞后于兴奋数毫秒。

Furthermore, the strength of excitatory and inhibitory inputs is (positively) correlated – large bumps typically contain both a strong excitatory and a strong inhibitory components, whereas small bumps are due to weak synaptic inputs, rather than strong inhibition that quenches the excitatory input.

此外，兴奋性和抑制性输入的强度（正）相关——大碰撞通常包含强兴奋性和强抑制性成分，而小碰撞是由于突触输入较弱，而非终止兴奋性输入的强抑制。

These correlations strongly suggest that inhibition plays important role in controlling the excitability of cortical networks at fast time scales.

这些相关性强烈表明，抑制在快速时间尺度上控制皮层网络的兴奋性方面起着重要作用。

Current research directions 当前研究方向

In the recent years a whole range of new genetic tools became available, particularly for the mouse (Mus musculus) species.

近年来，出现了一系列新的遗传工具，特别是对于小鼠（Mus musculus）物种。

In addition, working with awake head-fixed mice is relatively straightforward.

此外，使用清醒的头部固定的小鼠相对直截了当。

These and other recent developments are heavily relied upon in the current research which, in addition to the directions discussed in the previous sections, focuses on new aspects of E/I balance, as described in more detail below.

这些和其他最近的发展在很大程度上依赖于当前的研究，除了前面讨论的方向之外，这些当前研究还关注E/I平衡的新方面，如下面更详细地描述。

E/I balance across brain states E/I 在大脑状态之间保持平衡

To date, only few works investigated how brain state modulation affects E/I balance.

迄今为止，只有少数工作研究了大脑状态的调节如何影响E/I平衡。

A study of primary visual cortex found that in awake mice, when compared to animals under anesthesia, the spatial tuning of inhibitory synaptic inputs is much wider, suggesting that in awake animals the E/I balance is profoundly skewed towards inhibition (Haider et al., 2013).

对初级视觉皮层的研究发现，在与麻醉下的动物相比的清醒的小鼠中，抑制性突触输入的空间调谐要宽得多，这表明在清醒的动物中，E/I平衡显著偏向于抑制（Haider等。，2013）。

However in the auditory cortex of awake mice excitation and inhibition have similar magnitude and frequency tuning (Zhou et al., 2014), in agreement with previous results in anesthetized animals.

对初级视觉皮层的研究发现，在与麻醉下的动物相比的清醒的小鼠中，抑制性突触输入的空间调谐要宽得多，这表明在清醒的动物中，E/I平衡显著偏向于抑制（Haider等。，2013）。

Finally, a study of ongoing activity in the barrel cortex of anesthetized rats found that a switch to lighter anesthesia induces a profound shift toward excitation, probably due to depression of inhibitory synapses in the regime of higher activity under light anesthesia (Taub et al., 2013).

最后，对麻醉大鼠桶状皮层中正在进行的活动的研究发现，向较轻麻醉的转变会引起向兴奋的深度转移，这可能是由于在轻度麻醉下较高活性状态下抑制性突触的抑制（Taub等，2013）。

At the present time it is not clear whether the differences between these studies are due to differences between brain areas, special connectivity subserving sensory tuning or other factors.

目前尚不清楚这些研究之间的差异是源于大脑区域之间的差异、促进感觉调谐的特殊连接还是其他因素。

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In addition to differences between awake and anesthetized conditions, the effects of transition between quiet wakefulness and locomotion were recently studied.

除了清醒和麻醉条件之间的差异外，最近还研究了安静清醒和运动之间转变的影响。

Locomotion was found to have a differential effect on primary visual and auditory cortices, increasing the firing and shifting the balance towards excitation in the former (Bennett et al., 2013), while suppressing firing and equally scaling down both excitation and inhibition in the latter (Zhou et al., 2014).

最近研究发现运动对初级视觉和听觉皮层具有不同的作用，对前者提高发放并将平衡转移至兴奋（Bennett等人，2013），对后者抑制发放并同规模地减少兴奋和抑制（Zhou等人，2014）。

Hence, the impact of locomotion on brain-state and in particular on E/I balance is not uniform across the sensory cortices.

因此，运动对大脑状态的影响，特别是对E / I平衡的影响在整个感觉皮层中并不均匀。

Interneuron classes and the E/I balance 中间神经元等级和 E/I 平衡

In spite of constituting a minority, inhibitory interneurons in the cortex are vastly more diverse than the excitatory cells, with large variety of dendritic and axonal arborization patterns (Ramon Y Cajal, 1911; Jones 1975).

皮质中的抑制性中间神经元尽管占据少数，但比兴奋性细胞更加多样化，因为具有多种树突和轴突树枝状模式（Ramon Y Cajal，1911；Jones 1975）。

Histochemical and other methods revealed that GABAergic neurons in the cortex are subdivided into at least 4 almost non-overlapping classes (Kawaguchi and Kubota 1997; Harris and Mrsic-Flogel 2013):

组织化学和其他方法显示：皮质中的GABA能神经元至少可以细分为4个几乎不重叠的类别（Kawaguchi和Kubota 1997；Harris和Mrsic-Flogel 2013）：

Parvalbumin (PV) expressing cells, somatostatin (Sst) expressing cells, vasoactive intestinal peptide (VIP) expressing cells and neurogliaform cells (NGs).

小清蛋白Parvalbumin（PV）表达细胞，生长激素抑制素somatostatin（Sst）表达细胞，血管活性肠肽vasoactive intestinal peptide（VIP）表达细胞和神经胶质neurogliaform细胞（NGs）。

Anatomical evidence and recordings in brain-slices suggest that these classes have different roles in the E/I balance and may have different functional roles across cortical layers.

脑切片中的解剖学证据和记录表明，这些类别GABA能神经元在E/I平衡中起着不同的作用，并且在皮质层中可能具有不同的功能作用。

Current studies use molecular genetics and imaging methods to understand the role and function of each subtype.

目前的研究使用分子遗传学和成像方法来了解每种亚型的作用和功能。

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Several converging lines of evidence indicate that PV cells constitute the major source of inhibitory current in principal cells for both spontaneous activity and sensory evoked responses.

一些趋同的证据表明，PV细胞贡献主细胞中抑制电流的主要来源，用于自发活动和感觉诱发反应。

It follows that the sensory tuning of inhibitory synaptic inputs of pyramidal cells is expected to be the same or wider than the sensory tuning of the individual PV cells.

因此，锥体细胞的抑制性突触输入的感觉调谐，预计与单个PV细胞的感觉调谐相同或更宽。

For example, for orientation tuning in the mouse visual cortex, the tuning curves of PV cells were found to be much wider than of the principal cells, explaining the wide tuning of inhibitory inputs of pyramidal neurons (Atallah et al., 2012).

例如，对于小鼠视觉皮层的方向调谐，发现PV细胞的调谐曲线比主细胞的调谐曲线宽得多，这解释了锥体神经元抑制性输入的宽广调谐（Atallah等人，2012）。

In the auditory cortex the PV cells were found to be tuned for frequency, again consistent with inhibitory inputs to pyramidal cells originating in the neighboring PV neurons (Moore and Wehr 2013; Li et al., 2014).

在听觉皮层中，发现PV细胞被频率调谐，再次与起源于邻近PV神经元对锥体细胞的抑制性输入一致（Moore和Wehr 2013;李等人，2014）。

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The role of the other classes of inhibitory interneurons is currently investigated in many labs, in particular using the powerful new optogenetic tools.

目前，许多实验室在研究其他类型的抑制性中间神经元的作用，特别是使用强大而新的光遗传学工具。

Optogenetic stimulation was recently used to examine the effect of PV and Sst cells on orientation tuning (Atallah et al. 2012; Lee et al., 2012; Wilson et al., 2012).

光遗传学刺激最近用于研究PV和Sst细胞对方向调谐的影响（Atalah等人2012；Lee等人2012；Wilson等人2012）。

(Atallah et al. 2012) and (Wilson et al., 2012) suggest that PV cells do not alter the tuning of principal cells.

（Atalah et al.2012）和（Wilson et al.2012）表明PV细胞不会改变主细胞的调谐。

(Wilson et al., 2012) furthermore attribute to Sst cells the ability to sharpen orientation selectivity of principal cells by a subtraction effect.

In contrast, (Lee et al., 2012) report that activation of PV cells was found to sharpen the orientation tuning of principal cells.

（Wilson et al.，2012）进一步研究出Sst细胞通过减法效应增强了主细胞的方向选择性的能力。

相比之下，（Lee等人，2012年）报告发现，PV细胞的激活可以增强主细胞的方向调节。

Whether the contradiction between the studies is real or only at the level of data interpretation is not entirely clear (Lee et al., 2014; Atallah et al., 2014).

矛盾，是真实存在于在研究之间，还是说存在于数据解释层面上，尚不完全清楚（Lee等人，2014年；Atalah等人，2014年）。

Conclusions 结论

The available data, collected under a wide variety of conditions and in distinct cortical areas indicates that co-activation of inhibition and excitation is a basic functional principle underlying various cortical activities (Isaacson and Scanziani, 2011).

在各种条件下和不同皮质区域收集的现有数据表明，抑制和兴奋的共激活是各种皮质活动的基本功能原理（Isaacson和Scanziani，2011）。

Furthermore, the excitatory and inhibitory synaptic inputs appear to be individually matched in each pyramidal cell (Xue et al., 2014) with a high temporal precision of just a few milliseconds.

此外，兴奋性和抑制性突触输入似乎在每个锥体细胞中单独匹配（Xue等人，2014），具有仅几毫秒的高时间精度。

Yet, whether excitation and inhibition share the same sensory tuning seems to depend on various factors, including animal species, the sensory modality and brain-state.

然而，兴奋和抑制是否具有相同的感官调谐似乎取决于各种因素，包括动物种类，感觉方式和大脑状态。

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The E/I balance was studied most extensively in the cortex, however similar principles manifest themselves in many CNS structures, such as the hippocampus (Atallah and Scanziani, 2009), superior colliculus (Populin, 2005), brain stem (Magnusson et al., 2008), spinal cord (Berg et al., 2007), prefrontal cortex (Yizhar et al., 2011) and others, not covered here in detail.

E / I平衡在皮层中得到了最广泛的研究，但是类似的原理在许多CNS结构中表现出来，例如海马体（Atallah和Scanziani，2009），上丘脑（Populin，2005），脑干（Magnusson等人，2008），脊髓（Berg等人，2007），前额叶皮层（Yizhar等人，2011）等，这里没有详细介绍。

This entry also did not describe E/I balance development and plasticity, e.g., (Froemke et al., 2007; Dorrn et al., 2010; Sun et al., 2010; Li et al. 2012).

该条目也没有描述E / I平衡发育和可塑性，例如，（Froemke等人，2007;Dorrn et al.， 2010;孙等， 2010;李等人， 2012）.

While the role of the tight coupling between excitation and inhibition is not fully clear, it is most likely to serve as a major gain mechanism that increases the accuracy and speed of neuronal response.

虽然兴奋和抑制之间紧密耦合的作用尚不完全清楚，但它最有可能作为提高神经元响应的准确性和速度的主要增益机制。

By counterbalancing the excitatory drive, inhibitory inputs greatly extend the dynamic range of excitation, allowing a fine and rapid control over the amount of depolarization of the membrane potential.

通过平衡兴奋驱动作用，抑制性输入大大扩展了兴奋的动态范围，允许精细快速地控制膜电位的去极化量。

It is apparent that achieving a certain depolarization without a counteracting inhibitory force would have required a much weaker excitatory input, increasing the error and variability of the response.

很明显，若没有用于平衡的抑制作用，则实现一定的去极化将需要更弱的兴奋性输入，从而增加响应的误差和可变性。

References 参考文献

• Alonso, J M and Martinez, L M (1998). Functional connectivity between simple cells and complex cells in cat striate cortex. Nature Neuroscience 1: 395-403.
• Anderson, J S; Carandini, M and Ferster, D (2000). Orientation tuning of input conductance, excitation, and inhibition in cat primary visual cortex. Journal of Neurophysiology 84: 909-926.
• Anderson, J S; Lampl, I; Gillespie, D C and Ferster, D (2001). Membrane potential and conductance changes underlying length tuning of cells in cat primary visual cortex. The Journal of Neuroscience 21: 2104-2112.
• Atallah, B V and Scanziani, M (2009). Instantaneous modulation of gamma oscillation frequency by balancing excitation with inhibition. Neuron 62: 566-577.
• Atallah, B V; Bruns, W; Carandini, M and Scanziani, M (2012). Parvalbumin-expressing interneurons linearly transform cortical responses to visual stimuli. Neuron 73: 159-170.
• Atallah, B V; Scanziani, M and Carandini, M (2014). Atallah et al. reply. Nature 508: E3.
• Bennett, C; Arroyo, S and Hestrin, S (2013). Subthreshold mechanisms underlying state-dependent modulation of visual responses. Neuron 80: 350-357.
• Ben-Yishai, R; Bar-Or, R L and Sompolinsky, H (1995). Theory of orientation tuning in visual cortex. Proceedings of the National Academy of Sciences of the United States of America 92: 3844-3848.
• Berg, R W; Alaburda, A and Hounsgaard, J (2007). Balanced inhibition and excitation drive spike activity in spinal half-centers. Science 315: 390-393.
• Borg-Graham, L J; Monier, C and Fregnac, Y (1996). Voltage-clamp measurement of visually-evoked conductances with whole-cell patch recordings in primary visual cortex. Journal of Physiology Paris 90: 185-188.
• Borg-Graham, L J; Monier, C and Fregnac, Y (1998). Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 393: 369-373.
• Bruno, R M and Sakmann, B (2006). Cortex is driven by weak but synchronously active thalamocortical synapses. Science 312: 1622-1627.
• Calford, M B and Semple, M N (1995). Monaural inhibition in cat auditory cortex. Journal of Neurophysiology 73: 1876-1891.
• Chung, S and Ferster, D (1998). Strength and orientation tuning of the thalamic input to simple cells revealed by electrically evoked cortical suppression. Neuron 20: 1177-1189.
• Cohen-Kashi Malina, K; Jubran, M; Katz, Y and Lampl, I (2013). Imbalance between excitation and inhibition in the somatosensory cortex produces postadaptation facilitation. The Journal of Neuroscience 33: 8463-8471.
• Crochet, S and Petersen, C C H (2006). Correlating whisker behavior with membrane potential in barrel cortex of awake mice. Nature Neuroscience 9: 608-610.
• Destexhe, A; Hughes, S W; Rudolph, M and Crunelli, V (2007). Are corticothalamic 'up' states fragments of wakefulness? Trends in Neurosciences 30: 334-342.
• DeWeese, M R and Zador, A M (2006). Non-Gaussian membrane potential dynamics imply sparse, synchronous activity in auditory cortex. The Journal of Neuroscience 26: 12206-12218.
• Dichter, M A and Ayala, G F (1987). Cellular mechanisms of epilepsy: A status report. Science 237: 157-164.
• Dorrn, A L; Yuan, K; Barker, A J; Schreiner, C E and Froemke, R C (2010). Developmental sensory experience balances cortical excitation and inhibition. Nature 465: 932-936.
• Ferster, D and Miller, K D (2000). Neural mechanisms of orientation selectivity in the visual cortex. Annual Review of Neuroscience 23: 441-471.
• Froemke, R C; Merzenich, M M and Schreiner, C E (2007). A synaptic memory trace for cortical receptive field plasticity. Nature 450: 425-429.
• Gabernet, L; Jadhav, S P; Feldman, D E; Carandini, M and Scanziani, M (2005). Somatosensory integration controlled by dynamic thalamocortical feed-forward inhibition. Neuron 48: 315-327.
• Gerstein, G L and Mandelbrot, B (1964). Random walk models for the spike activity of a single neuron. Biophysical Journal 4: 41-68.
• Haider, B; Duque, A; Hasenstaub, A R and McCormick, D A (2006). Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition. The Journal of Neuroscience 26: 4535-4545.
• Haider, B; Häusser, M and Carandini, M (2013). Inhibition dominates sensory responses in the awake cortex. Nature 493: 97-100.
• Hansel, D and Sompolinsky, H (1996). Chaos and synchrony in a model of a hypercolumn in visual cortex. Journal of Comparative Neuroscience 3: 7-34.
• Harris, K D and Mrsic-Flogel, T D (2013). Cortical connectivity and sensory coding. Nature 503: 51-58.
• Hasenstaub, A et al. (2005). Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks. Neuron 47: 423-435.
• Heiss, J E; Katz, Y; Ganmor, E and Lampl, I (2008). Shift in the balance between excitation and inhibition during sensory adaptation of S1 neurons. The Journal of Neuroscience 28: 13320-13330.
• Higley, M J and Contreras, D (2003). Nonlinear integration of sensory responses in the rat barrel cortex: an intracellular study in vivo. The Journal of Neuroscience 23: 10190-10200.
• Higley, M J and Contreras, D (2006). Balanced excitation and inhibition determine spike timing during frequency adaptation. The Journal of Neuroscience 26: 448-457.
• Hubel, D H and Wiesel, T N (1962). Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. Journal of Physiology (London) 160: 106-154.
• Isaacson, J S and Scanziani, M (2011). How inhibition shapes cortical activity. Neuron 72: 231-243.
• Jones, E G (1975). Varieties and distribution of non-pyramidal cells in the somatic sensory cortex of the squirrel monkey. Journal of Comparative Neurology 160: 205-267.
• Kawaguchi, Y and Kubota, Y (1997). GABAergic cell subtypes and their synaptic connections in rat frontal cortex. Cerebral Cortex 7: 476-486.
• Lak, A; Arabzadeh, E and Diamond, M E (2008). Enhanced response of neurons in rat somatosensory cortex to stimuli containing temporal noise. Cerebral Cortex 18: 1085-1093.
• Lampl, I; Reichova, I and Ferster, D (1999). Synchronous membrane potential fluctuations in neurons of the cat visual cortex. Neuron 22: 361-374.
• Lee, S H et al. (2012). Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature 488: 379-383.
• Lee, S H; Kwan, A C and Dan, Y (2014). Interneuron subtypes and orientation tuning. Nature 508: E1-E2.
• Lefort, S; Tomm, C; Floyd Sarria, J C and Petersen, C C (2009). The excitatory neuronal network of the C2 barrel column in mouse primary somatosensory cortex. Neuron 61: 301-316.
• Li, Y T; Ma, W P; Pan, C J; Zhang, L I and Tao, H W (2012). Broadening of cortical inhibition mediates developmental sharpening of orientation selectivity. The Journal of Neuroscience 32: 3981-3991.
• Li, L Y et al. (2014). A feedforward inhibitory circuit mediates lateral refinement of sensory representation in upper layer 2/3 of mouse primary auditory cortex. The Journal of Neuroscience 34: 13670-13683.
• Liu, B et al. (2011). Broad inhibition sharpens orientation selectivity by expanding input dynamic range in mouse simple cells. Neuron 71: 542-554.
• Magnusson, A K; Park, T J; Pecka, M; Grothe, B and Koch, U (2008). Retrograde GABA signaling adjusts sound localization by balancing excitation and inhibition in the brainstem. Neuron 59: 125-137.
• Martinez, L M and Alonso, J M (2001). Construction of complex receptive fields in cat primary visual cortex. Neuron 32: 515-525.
• Monier, C; Fournier, J and Fregnac, Y (2008). In vitro and in vivo measures of evoked excitatory and inhibitory conductance dynamics in sensory cortices. Journal of Neuroscience Methods 169: 323-365.
• Moore, A K and Wehr, M (2013). Parvalbumin-expressing inhibitory interneurons in auditory cortex are well-tuned for frequency. The Journal of Neuroscience 33: 13713-13723.
• Nelson, S; Toth, L; Sheth, B and Sur, M (1994). Orientation selectivity of cortical neurons during intracellular blockade of inhibition. Science 265: 774-777.
• Okun, M and Lampl, I (2008). Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities. Nature Neuroscience 11: 535-537.
• Okun, M; Naim, A and Lampl, I (2010). The subthreshold relation between cortical local field potential and neuronal firing unveiled by intracellular recordings in awake rats. The Journal of Neuroscience 30: 4440-4448.
• Polack, P O; Friedman, J and Golshani, P (2013). Cellular mechanisms of brain state-dependent gain modulation in visual cortex. Nature Neuroscience 16: 1331-1339.
• Populin, L C (2005). Anesthetics change the excitation/inhibition balance that governs sensory processing in the cat superior colliculus. The Journal of Neuroscience 25: 5903-5914.
• Poulet, J F and Petersen, C C (2008). Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. Nature 454: 881-885.
• Priebe, N J and Ferster, D (2005). Direction selectivity of excitation and inhibition in simple cells of the cat primary visual cortex. Neuron 45: 133-145.
• Ramon y Cajal, S (1911). Histologie du Systeme Nerveux de l'Homme et des Vertebres. Paris: Maloine.
• Rudolph, M; Pospischil, M; Timofeev, I and Destexhe, A (2007). Inhibition determines membrane potential dynamics and controls action potential generation in awake and sleeping cat cortex. The Journal of Neuroscience 27: 5280-5290.
• Sachidhanandam, S; Sreenivasan, V; Kyriakatos, A; Kremer, Y and Petersen, C C H (2013). Membrane potential correlates of sensory perception in mouse barrel cortex. Nature Neuroscience 16: 1671-1677.
• Shadlen, M N and Newsome, W T (1994). Noise, neural codes and cortical organization. Current Opinion in Neurobiology 4: 569-579.
• Shadlen, M N and Newsome, W T (1998). The variable discharge of cortical neurons: Implications for connectivity, computation, and information coding. The Journal of Neuroscience 18: 3870-3896.
• Shapley, R M and Xing, D (2013). Local circuit inhibition in the cerebral cortex as the source of gain control and untuned suppression. Neural Networks 37: 172-181.
• Shu, Y; Hasenstaub, A and McCormick, D A (2003). Turning on and off recurrent balanced cortical activity. Nature 423: 288-293.
• Sillito, A M (1975). The contribution of inhibitory mechanisms to the receptive field properties of neurones in the striate cortex of the cat. Journal of Physiology 250: 305-329.
• Softky, W R and Koch, C (1993). The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. The Journal of Neuroscience 13: 334-350.
• Somers, D C; Nelson, S B and Sur, M (1995). An emergent model of orientation selectivity in cat visual cortical simple cells. The Journal of Neuroscience 15: 5448-5465.
• Stevens, C F and Zador, A M (1998). Input synchrony and the irregular firing of cortical neurons. Nature Neuroscience 1: 210-217.
• Sun, Y J et al. (2010). Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development. Nature 465: 927-931.
• Sun, Y J; Kim, Y J; Ibrahim, L A; Tao, H W and Zhang, L I (2013). Synaptic mechanisms underlying functional dichotomy between intrinsic-bursting and regular-spiking neurons in auditory cortical layer 5. The Journal of Neuroscience 33: 5326-5339.
• Sutter, M L; Schreiner, C E; McLean, M; O'Connor, K N and Loftus, W C (1999). Organization of inhibitory frequency receptive fields in cat primary auditory cortex. Journal of Neurophysiology 82: 2358-2371.
• Tan, A Y Y; Chen, Y; Scholl, B; Seidemann, E and Priebe, N J (2014). Sensory stimulation shifts visual cortex from synchronous to asynchronous states. Nature 509: 226-229.
• Taub, A H; Katz, Y and Lampl, I (2013). Cortical balance of excitation and inhibition is regulated by the rate of synaptic activity. The Journal of Neuroscience 33: 14359-14368.
• van Vreeswijk, C and Sompolinsky, H (1996). Chaos in neuronal networks with balanced excitatory and inhibitory activity. Science 274: 1724-1726.
• Vogels, T P; Rajan, K and Abbott, L F (2005). Neural network dynamics. Annual Review of Neuroscience 28: 357-376.
• Volgushev, M; Vidyasagar, T R and Pei, X (1996). A linear model fails to predict orientation selectivity of cells in the cat visual cortex. Journal of Physiology (London) 496: 597-606.
• Wang, J; McFadden, S L; Caspary, D and Salvi, R (2002). Gamma-aminobutyric acid circuits shape response properties of auditory cortex neurons. Brain Research 944: 219-231.
• Wehr, M and Zador, A M (2003). Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426: 442-446.
• Wehr, M and Zador, A M (2005). Synaptic mechanisms of forward suppression in rat auditory cortex. Neuron 47: 437-445.
• Wilent, W B and Contreras, D (2005). Dynamics of excitation and inhibition underlying stimulus selectivity in rat somatosensory cortex. Nature Neuroscience 8: 1364-1370.
• Wilson, N R; Runyan, C A; Wang, F L and Sur, M (2012). Division and subtraction by distinct cortical inhibitory networks in vivo. Nature 488: 343-348.
• Wu, G K; Li, P; Tao, H W and Zhang, L I (2006). Nonmonotonic synaptic excitation and imbalanced inhibition underlying cortical intensity tuning. Neuron 52: 705-715.
• Wu, G K; Arbuckle, R; Liu, B H; Tao, H W and Zhang, L I (2008). Lateral sharpening of cortical frequency tuning by approximately balanced inhibition. Neuron 58: 132-143.
• Xue, M; Atallah, B V and Scanziani, M (2014). Equalizing excitation-inhibition ratios across visual cortical neurons. Nature 511: 596-600.
• Yizhar, O et al. (2011). Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477: 171-178.
• Zhou, M et al. (2014). Scaling down of balanced excitation and inhibition by active behavioral states in auditory cortex. Nature Neuroscience 17: 841-850.

另见

Inhibition, High-conductance state