查看Ch12 Physiology of Neurons的源代码

== 躯体中尖峰模式控制 ==
<b style=color:#f80>CONTROL OF SPIKING PATTERNS IN THE SOMA</b>

Electrical signals from dendrites converge and summate at the soma. Although action potentials themselves often appear first at the nearby axon hillock and initial segment of the axon, the large variety of ion channels in the soma and proximal dendritic membranes is critically important in determining and modulating the temporal patterns of action potentials that ultimately course down the axon.

来自树突的电信号在体体处汇聚和汇总。尽管动作电位本身通常首先出现在附近的轴突小丘和轴突的初始段，但胞体和近端树突状膜中的多种离子通道对于确定和调节最终沿着轴突向下移动的动作电位的时间模式至关重要。

=== 神经元可以将简单的输入转换为各种输出模式 ===
<b style=color:#0ae>Neurons can transform a simple input into a variety of output patterns</b>

Neurophysiologists have sampled the electrical properties of many different types of neurons in the nervous system, and one general conclusion seems safe: no two types behave the same. The variability begins with the shape and height of individual action potentials. Most neurons within the CNS generate action potentials in the conventional way (see Fig. 7-4). Fast voltage-gated Na+ channels (see pp. 185–187) generate a strong inward current that depolarizes the membrane from rest, usually in the range of –60 to –80 mV, to a peak that is usually between +10 and +40 mV. This depolarization represents the upstroke of the action potential. The Na+ channels then quickly inactivate and close, and certain K+ channels (often voltage-gated, delayed outward-rectifier channels; see pp. 193–196) open and thus cause Vm to fall and terminate the spike. However, many neurons have somewhat different spike-generating mechanisms and produce spikes with a range of shapes. N12-1 Although a fast Na+ current invariably drives the fast upstroke of neuronal action potentials, an additional fast Ca2+ current (see pp. 188–189) can frequently occur and, if it is large enough, broaden the spike duration. Adding to the complexity, individual neurons usually have more than one type of Na+ current and multiple types of Ca2+ currents. The greatest variability occurs in the repolarization phase of the spike. Many neurons are repolarized by several other voltage-gated K+ currents in addition to the delayed outward-rectifier K+ current, and some also have K+ currents carried by one or more channels that are rapidly activated by the combination of membrane depolarization and a rise in [Ca2+]i (see pp. 196–197).

神经生理学家对神经系统中许多不同类型神经元的电特性进行了采样，一个一般性的结论似乎是安全的：没有两种类型的神经元行为相同。可变性始于单个动作电位的形状和高度。CNS 内的大多数神经元以常规方式产生动作电位（见图 7-4）。快速电压门控 Na+ 通道（参见第 185-187 页）产生强大的向内电流，使膜从静止（通常在 –60 至 –80 mV 范围内）去极化到通常在 +10 至 +40 mV 之间的峰值。这种去极化代表动作电位的上行。然后 Na+ 通道迅速失活并关闭，某些 K+ 通道（通常是电压门控、延迟向外整流器通道;参见第 193-196 页）打开，从而导致 Vm 下降并终止尖峰。然而，许多神经元的尖峰产生机制略有不同，并产生各种形状的尖峰。N12-1 尽管快速的 Na + 电流总是驱动神经元动作电位的快速上升，但额外的快速 Ca2 + 电流（参见第 188-189 页）会经常发生，如果它足够大，会扩大尖峰持续时间。增加复杂性的是，单个神经元通常具有不止一种类型的 Na+ 电流和多种类型的 Ca2+ 电流。最大的可变性发生在尖峰的复极化阶段。除了延迟的向外整流器 K+ 电流外，许多神经元还被其他几种电压门控 K+ 电流复极化，有些神经元还具有由一个或多个通道携带的 K+ 电流，这些通道通过膜去极化和 [Ca2+]i 升高的组合迅速激活（参见第 196-197 页）。


More dramatic variations occur in the repetitive spiking patterns of neurons, observed when the duration of a stimulus is long. One way to illustrate this principle is to apply a simple continuous stimulus (a current pulse, for example) to a neuron and to measure the neuron’s output (the number and pattern of action potentials fired at its soma). The current pulse is similar to a steady, strong input of excitatory synaptic currents. The transformation from stimulus input to spiking output can take many different forms. Some examples are shown in Figure 12-4, which illustrates recordings from three types of neurons in the cerebral cortex. In response to a sustained current stimulus, some cells generate a rapid train of action potentials that do not adapt (see Fig. 12-4A); that is, the spikes occur at a regular interval throughout the current pulse. Other cells fire rapidly at first but then adapt strongly (see Fig. 12-4B); that is, the spikes gradually become less frequent during the current pulse. Some cells fire a burst of action potentials and then stop firing altogether, and still others generate rhythmic bursts of action potentials that continue as long as the stimulus (see Fig. 12-4C). These varied behaviors are not arbitrary but are characteristic of each neuron type, and they are as distinctive as each cell’s morphology. They are also an intrinsic property of each neuron; that is, a neuron’s fundamental firing pattern is determined by the membrane properties of the cell and does not require fluctuations in synaptic input. Of course, synaptic input may also impose particular firing patterns on a neuron. When a neuron is operating in situ, its firing patterns are determined by the interaction of its intrinsic membrane properties and synaptic inputs.

神经元的重复尖峰模式会发生更剧烈的变化，当刺激的持续时间较长时观察到。说明这一原理的一种方法是将简单的连续刺激（例如电流脉冲）施加到神经元上，并测量神经元的输出（向其体细胞发射的动作电位的数量和模式）。电流脉冲类似于兴奋性突触电流的稳定、强输入。从刺激输入到峰值输出的转变可以采取许多不同的形式。图 12-4 显示了一些示例，它说明了大脑皮层中三种类型神经元的记录。为了响应持续的电流刺激，一些细胞会产生一系列不适应的快速动作电位（见图 12-4A）;也就是说，在整个电流脉冲中，尖峰以固定的间隔出现。其他细胞起初迅速放电，但随后适应能力很强（见图 12-4B）;也就是说，在电流脉冲期间，尖峰逐渐变得不那么频繁。一些细胞触发了一阵动作电位爆发，然后完全停止放电，还有一些细胞产生有节奏的动作电位爆发，这种动作电位持续到刺激的时间一样长（见图 12-4C）。这些不同的行为不是随意的，而是每种神经元类型的特征，它们与每个细胞的形态一样独特。它们也是每个神经元的内在属性;也就是说，神经元的基本放电模式由细胞的膜特性决定，不需要突触输入的波动。当然，突触输入也可能对神经元施加特定的放电模式。当神经元原位运行时，其放电模式由其内在膜特性和突触输入的相互作用决定。


Rhythmically bursting cells are particularly interesting and occur in a variety of places in the brain. As described on pages 397–398, they may participate in the central circuits that generate rhythmic motor output for behavior such as locomotion and respiration. Cells that secrete peptide neurohormones, such as the magnocellular neurons of the hypothalamus, are also often characterized by rhythmic bursting behavior. These cells release either arginine vasopressin to control water retention (see pp. 844–845) or oxytocin to control lactation (see p. 1150). Rhythmic bursting is a more effective stimulus for the synaptic release of peptides than are tonic patterns of action potential. It may be that the bursting patterns and the Ca2+ currents that help drive them can elicit the relatively high [Ca2+]i necessary to trigger the exocytosis of peptide-containing vesicles (see pp. 219–221). One additional role of rhythmically bursting neurons is to help drive the synchronous oscillations of neural activity in forebrain circuits (i.e., thalamus and cortex) during certain behavioral states, particularly sleep.

有节奏地爆发的细胞特别有趣，发生在大脑的不同地方。如第 397-398 页所述，他们可能参与为运动和呼吸等行为产生有节奏的运动输出的中央回路。分泌肽神经激素的细胞，例如下丘脑的大细胞神经元，也经常以节律性爆发行为为特征。这些细胞释放精氨酸加压素以控制水潴留（见第 844-845 页）或催产素以控制泌乳（见第 1150 页）。有节奏的爆发是比动作电位的强直模式更有效的肽突触释放刺激。可能是爆发模式和有助于驱动它们的 Ca2+ 电流可以引发触发含肽囊泡胞吐作用所需的相对较高的 [Ca2+]i（参见第 219-221 页）。有节奏爆发的神经元的另一个作用是在某些行为状态（尤其是睡眠）期间帮助驱动前脑回路（即丘脑和皮层）中神经活动的同步振荡。


Although it has been difficult to prove, the diverse electrical properties of neurons are probably adapted to each cell’s particular functions. For example, in the first stage of auditory processing in the brain, cranial nerve VIII axons from the cochlea innervate several types of neurons in the cochlear nucleus of the brainstem. The axons provide similar synaptic drive to each type of neuron, yet the output from each neuron type is distinctly different. Some are tuned to precise timing and respond only to the onset of the stimulus and ignore anything else; some respond, pause, and respond again; others chop the ongoing stimulus into a more rhythmic output; and still other cells transform the input very little. The mechanisms for this range of transformations include both synaptic circuitry and the diverse membrane properties of each cell type. The different properties allow some cells to be particularly well tuned to specific features of the stimulus—its onset, duration, or amplitude modulation— and they can then communicate this signal to the appropriate auditory nuclei for more complex processing.

尽管很难证明，但神经元的不同电特性可能适应每个细胞的特定功能。例如，在大脑听觉处理的第一阶段，来自耳蜗的颅神经 VIII 轴突支配脑干耳蜗核中的几种类型的神经元。轴突为每种类型的神经元提供相似的突触驱动，但每种神经元类型的输出明显不同。有些人被调整到精确的时间，只对刺激的开始做出反应，而忽略其他任何事情;有些人回应，停顿，再回应;另一些人将正在进行的刺激切碎成更有节奏的输出;还有一些单元格对输入的转换非常小。这一系列转化的机制包括突触回路和每种细胞类型的不同膜特性。不同的特性使一些细胞能够特别适应刺激的特定特征——刺激的开始、持续时间或幅度调制——然后它们可以将这个信号传达给适当的听觉核，以进行更复杂的处理。

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=== 本征发射模式由动力学相对较慢的各种离子流决定 ===
<b style=color:#0ae>Intrinsic firing patterns are determined by a variety of ion currents with relatively slow kinetics</b>

What determines the variety of spiking patterns in each type of neuron, and why do neurons differ in their intrinsic patterns? The key is a large set of ion channel types that have variable and often relatively slow kinetics compared with the quick Na+ and K+ channels that shape the spike. For a discussion of the properties of such channels, see p. 182. Each neuron expresses a different complement of these slow channels and has a unique spatial arrangement of them on its dendrites, soma, and axon initial segment. The channels are gated primarily by membrane voltage and [Ca2+]i, and a neuron’s ultimate spiking pattern is determined by the net effects of the slow currents that it generates. We provide three examples of systems that have been studied in detail.

是什么决定了每种类型神经元中脉冲模式的多样性，为什么神经元的内在模式不同？关键是大量的离子通道类型，与形成加标的快速 Na+ 和 K+ 通道相比，这些离子通道具有可变且通常相对较慢的动力学。有关此类通道特性的讨论，请参见第 182 页。每个神经元表达这些慢通道的不同补充，并在其树突、体细胞和轴突初始段上具有独特的空间排列。通道主要由膜电压和 [Ca2+]i 门控，神经元的最终尖峰模式由它产生的慢电流的净效应决定。我们提供了三个已详细研究的系统示例。


1. A neuron with only fast voltage-gated Na+ channels and delayed-rectifier K+ channels will generate repetitive spikes when it is presented with a long stimulus. The pattern of those spikes will be quite regular over time, as for the particular type of cerebral cortical interneuron that we have already seen in Figure 12-4A.

1. 只有快速电压门控 Na+ 通道和延迟整流器 K+ 通道的神经元在受到长刺激时会产生重复的尖峰。随着时间的推移，这些尖峰的模式将非常有规律，正如我们在图 12-4A 中已经看到的特定类型的大脑皮层中间神经元。


2. If the neuron also has another set of K+ channels that activate only very slowly, the spiking pattern becomes more time dependent: the spiking frequency may initially be very high, but it adapts to progressively lower rates as a slow K+ current turns on to counteract the stimulus, as shown for the small pyramidal cell in Figure 12-4B. The strength and rate of adaptation depend strongly on the number and properties of the fast and slow K+ channels.

2. 如果神经元还有另一组激活速度非常慢的 K+ 通道，则尖峰模式将变得更加依赖于时间：尖峰频率最初可能非常高，但随着缓慢的 K+ 电流打开以抵消刺激，它会适应逐渐降低的速率，如图 12-4B 中的小锥体细胞所示。适应的强度和速率在很大程度上取决于快速和慢速 K+ 通道的数量和特性。


3. A neuron, by exploiting the interplay between two or more voltage-gated currents with relatively slow kinetics, can generate spontaneous rhythmic bursting—as in the case of the large pyramidal neuron in Figure 12-4C—even without ongoing synaptic activity to drive it.

3. 神经元通过利用两个或多个动力学相对较慢的电压门控电流之间的相互作用，可以产生自发的有节奏的爆发——如图 12-4C 中的大锥体神经元一样——即使没有持续的突触活动来驱动它。

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