2024年12月25日 (三) 17:32的版本

神经元生理学

本页英文内容取自：经典教材医学生理学（第三版） (Medical Physiology, 3rd Edtion, Walter F Boron, published in 2016)

中文内容由 BH1RBH (Jack Tan) 粗糙翻译

蓝色 【注】 后内容为 BH1RBH (Jack Tan) 所加之注释

1 Overview

1.1 神经元接收、组合、转换、存储和发送信息

Neurons receive, combine, transform, store, and send information

Neurons have arguably the most complex job of any cell in the body. Consequently, they have an elaborate morphology and physiology. Each neuron is an intricate computing device. A single neuron may receive chemical input from tens of thousands of other neurons. It then combines these myriad signals into a much simpler set of electrical changes across its cellular membrane. The neuron subsequently transforms these ionic transmembrane changes according to rules determined by its particular shape and electrical properties and transmits a single new message through its axon, which itself may contact and inform hundreds of other neurons. Under the right circumstances, neurons also possess the property of memory; some of the information coursing through a neuron’s synapses may be stored for periods as long as years.

神经元可以说是体内任何细胞中最复杂的工作。因此，它们具有复杂的形态和生理学。每个神经元都是一个复杂的计算设备。单个神经元可以接收来自数以万计的其他神经元的化学输入。然后，它将这些无数信号组合成一组更简单的细胞膜电变化。神经元随后根据其特定形状和电特性决定的规则转换这些离子跨膜变化，并通过其轴突传递一条新信息，轴突本身可以接触并通知数百个其他神经元。在适当的情况下，神经元也具有记忆的特性;通过神经元突触传输的一些信息可以存储长达数年。

This general scheme of neuronal function applies to most neurons in the vertebrate nervous system. However, the scheme is endlessly variable. For example, each region of the brain has several major classes of neurons, and each of these classes has a physiology adapted to perform specific and unique functions. In this chapter, the general principles of neuronal function are outlined, and the almost unlimited variability contained within the general schema is discussed.

这种神经元功能的一般方案适用于脊椎动物神经系统中的大多数神经元。然而，这个方案是无穷无尽的。例如，大脑的每个区域都有几大类神经元，每类神经元都有适应于执行特定和独特功能的生理学。在本章中，概述了神经元功能的一般原理，并讨论了一般图式中包含的几乎无限的可变性。

1.2 神经信息从树突流向胞体，从轴突流向突触

Neural information flows from dendrite to soma to axon to synapse

Numerous dendrites converge on a central soma, or cell body, from which a single axon emerges and branches multiple times (see Fig. 10-1). Each branch culminates at a presynaptic terminal that contacts another cell. In most neurons, dendrites are the principal synaptic input sites, although synapses may also be found on the soma, on the axon hillock (the region of the soma neighboring the axon), or even directly on the axons. In some primary sensory neurons, the dendrites themselves are transducers of environmental energy. Regardless of their source, signals—in the form of voltage changes across the membrane—typically flow from dendrites to soma to axon and finally to synapses on the next set of cells. Under some circumstances electrical signals may also propagate in the opposite direction, from the soma outward along dendrites to their tips.

许多树突聚集在一个中央体细胞或细胞体上，单个轴突从中出现并多次分枝（见图 10-1）。每个分支在与另一个细胞接触的突触前末端结束。在大多数神经元中，树突是主要的突触输入位点，尽管突触也可能出现在体细胞、轴突小丘（与轴突相邻的胞体区域）甚至直接在轴突上。在一些初级感觉神经元中，树突本身是环境能量的传感器。无论它们的来源如何，信号（以跨膜电压变化的形式）通常从树突流向胞体，再流向轴突，最后流向下一组细胞上的突触。在某些情况下，电信号也可能沿相反方向传播，从胞体沿着树突向外传播到它们的尖端。

Excitatory input to a neuron usually generates an inward flow of positive charge (i.e., an inward current) across the dendritic membrane. Because the interior of a resting neuron is polarized negatively with respect to the external environment, this inward current, which makes the membrane voltage more positive (i.e., less negative), is said to depolarize the cell. Conversely, inhibitory input to a neuron usually generates an outward current and, thus, hyperpolarization.

神经元的兴奋性输入通常产生穿过树突状膜的向内正电荷流（即向内电流）。因为静息神经元的内部相对于外部环境呈负极化，所以这种使膜电压更正（即负更小）的向内电流被称为细胞去极化。相反，对神经元的抑制性输入通常会产生向外的电流，从而产生超极化。

If the neuron receives its input from a neighboring cell through a chemical synapse, neurotransmitters trigger currents by activating ion channels. If the cell is a sensory neuron, environmental stimuli (e.g., chemicals, light, mechanical deformation) activate ion channels and produce a flow of current. The change in membrane potential (Vm) caused by the flow of charge is called a postsynaptic potential (PSP) if it is generated at the postsynaptic membrane by a neurotransmitter and a receptor potential if it is generated at a sensory nerve ending by an external stimulus. In the case of synaptic transmission, the postsynaptic Vm changes may be either positive or negative. If the neurotransmitter is excitatory

如果神经元通过化学突触接收来自邻近细胞的输入，神经递质就会通过激活离子通道来触发电流。如果细胞是感觉神经元，环境刺激（例如化学物质、光、机械变形）会激活离子通道并产生电流。由电荷流动引起的膜电位 （Vm） 变化如果由神经递质在突触后膜产生，则称为突触后电位 （PSP），如果它是在感觉神经末梢由外部刺激产生的，则称为受体电位。在突触传递的情况下，突触后 Vm 变化可能是阳性或阴性的。如果神经递质是兴奋性的

and produces a depolarizing PSP, we refer to the PSP as an excitatory postsynaptic potential (EPSP; see p. 210). On the other hand, if the neurotransmitter is inhibitory and produces a hyperpolarizing PSP, the PSP is an inhibitory postsynaptic potential (IPSP). In all cases, the stimulus produces a Vm change that may be graded from small to large depending on the strength or quantity of input stimuli (see p. 174). Stronger sensory stimuli generate larger receptor potentials; similarly, more synapses activated together generate larger PSPs. A graded response is one form of neural coding whereby the size and duration of the input are encoded as the size and duration of the change in the dendritic Vm.

并产生去极化 PSP，我们将 PSP 称为兴奋性突触后电位 （EPSP;见第 210 页）。另一方面，如果神经递质具有抑制性并产生超极化 PSP，则 PSP 是抑制性突触后电位 （IPSP）。在所有情况下，刺激都会产生 Vm 变化，根据输入刺激的强度或数量，该变化可以从小到大分级（见第 174 页）。更强的感觉刺激产生更大的受体电位;同样，更多的突触一起激活会产生更大的 PSP。分级反应是神经编码的一种形式，其中输入的大小和持续时间被编码为树突状 Vm 变化的大小和持续时间。

The synaptic (or receptor) potentials generated at the ends of a dendrite are communicated to the soma, usually with substantial attenuation of the signal (Fig. 12-1A). Extended cellular processes such as dendrites behave like leaky electrical cables (see pp. 201–203). As a consequence, dendritic potentials usually decline in amplitude before reaching the soma. As an EPSP reaches the soma, it may also combine with EPSPs arriving via other dendrites on the cell; this behavior is a type of spatial summation and can lead to EPSPs that are substantially larger than those generated by any single synapse (see Fig. 12-1B, C). Temporal summation occurs when EPSPs arrive rapidly in succession; when the first EPSP has not yet dissipated, a subsequent EPSP tends to add its amplitude to the residual of the preceding EPSP (see Fig. 12-1D).

树突末端产生的突触（或受体）电位被传达给胞体，通常信号会大幅衰减（图 12-1A）。延伸的细胞过程，如树突，表现得像泄漏的电缆（见第 201-203 页）。因此，树突状电位通常在到达胞体之前振幅下降。当 EPSP 到达胞体时，它也可能与通过细胞上其他树突到达的 EPSP 结合;这种行为是一种空间求和，可导致 EPSP 比任何单个突触产生的 EPSP 大得多（参见图 12-1B、C）。当 EPSP 连续快速到达时，就会发生时间求和;当第一个 EPSP 尚未消散时，随后的 EPSP 倾向于将其振幅添加到前一个 EPSP 的残差中（见图 12-1D）。

The tendency for synaptic and receptor potentials to diminish with distance along a dendrite puts significant limitations on their signaling abilities. If nothing else happened, these depolarizing potentials would simply dwindle back to the resting membrane potential as they spread through the soma and down into the axon. At best, this passive signal might be carried a few millimeters, clearly inadequate for commanding a toe to wiggle when the axon of the motor neuron stretching from the spinal cord to the muscles moving the foot might be 1000 mm long. Some amplification is therefore necessary for certain inputs to generate effective signals to and from the central nervous system (CNS). Amplification is provided in the form of regenerating action potentials. If the Vm change in the soma is large enough to reach the threshold voltage (see p. 173), the depolarization may trigger one or more action potentials between the soma and axon, as shown in Figure 12-1B to D. Action potentials are large, rapid fluctuations in Vm. As described in Chapter 7, an action potential is an efficient, rapid, and reliable way to carry a signal over long distances. However, notice that generation of action potentials entails another transformation of neuronal information: the neuron converts the graded-voltage code of the dendrites (i.e., the PSPs) to a temporal code of action potentials in the axon. The initiation site for action potentials in many types of neurons is the axon initial segment, the first stretch of unmyelinated axon past the soma.

突触电位和受体电位随树突距离的增加而减弱的趋势对它们的信号传导能力造成了重大限制。如果没有其他事情发生，这些去极化电位在通过胞体扩散并向下扩散到轴突时，只会减少回静息膜电位。充其量，这个被动信号可能被携带了几毫米，当从脊髓延伸到移动脚部的肌肉的运动神经元的轴突可能长达 1000 毫米时，显然不足以命令脚趾摆动。因此，某些输入需要一些放大才能产生进出中枢神经系统 （CNS） 的有效信号。放大以再生动作电位的形式提供。如果胞体中的 Vm 变化足够大以达到阈值电压（参见第 173 页），则去极化可能会触发胞体和轴突之间的一个或多个动作电位，如图 12-1B 至 D 所示。如第 7 章所述，动作电位是一种长距离传输信号的有效、快速和可靠的方式。然而，请注意，动作电位的产生需要神经元信息的另一种转换：神经元将树突的分级电压代码（即 PSP）转换为轴突中动作电位的时间代码。在许多类型的神经元中，动作电位的起始位点是轴突初始段，即通过体细胞的第一段无髓轴突。

Action potentials are fixed in amplitude, not graded, and have uniform shape. So how is information encoded by action potentials? This question has no simple answer and is still hotly debated. Because one axonal spike looks like another (with slight exceptions), neurons can vary only the number of spikes and their timing. For a single axon, information may be encoded by the average rate of action potential firing, the total number of action potentials, their temporal pattern, or some combination of these mechanisms. Figure 12-1 illustrates that as the synaptic potential in the soma increases in size, the resultant action potentials occur more frequently, and the burst of action potentials in the axon lasts longer. Notice also that by the time the signal has propagated well down the axon, the transformation has become complete—the graded potential has waned and vanished, whereas the action potentials have retained their size, number, and temporal pattern. The final output of the neuron is entirely encoded by these action potentials. When action potentials reach axonal terminals, they may trigger the release of a neurotransmitter at the next set of synapses, and the cycle begins again.

动作电位的振幅是固定的，没有分级，并且具有均匀的形状。那么动作电位是如何编码信息的呢？这个问题没有简单的答案，至今仍备受争议。因为一个轴突尖峰看起来与另一个轴突尖峰相似（除了轻微的例外），神经元只能改变尖峰的数量及其时间。对于单个轴突，信息可能由动作电位的平均放电速率、动作电位的总数、它们的时间模式或这些机制的某种组合进行编码。图 12-1 表明，随着胞体中突触电位的大小增加，产生的动作电位发生得更频繁，轴突中动作电位的爆发持续时间更长。还要注意，当信号沿着轴突传播时，转化已经完成——分级电位已经减弱和消失，而动作电位则保留了它们的大小、数量和时间模式。神经元的最终输出完全由这些动作电位编码。当动作电位到达轴突末梢时，它们可能会触发下一组突触处神经递质的释放，循环再次开始。

2 树突中的信号传导

SIGNAL CONDUCTION IN DENDRITES

The word dendrite is derived from the Greek word dendron [tree], and indeed some dendrites resemble tree branches or roots. Inspired by trees, no doubt, the anatomist Camillo Golgi suggested in 1886 that the function of dendrites is to collect nutrients for the neuron. The truth is analogous but more interesting: dendrites arborize through a volume of brain tissue so that they can collect information in the form of synaptic input. The dendrites of different types of neurons exhibit a great diversity of shapes. Dendrites are often extensive, accounting for up to 99% of a neuron’s membrane. The dendrites of a single neuron may receive as many as 200,000 synaptic inputs. The electrical and biochemical properties of dendrites are quite variable from cell to cell, and they have a profound influence on the transfer of information from synapse to soma.

树突一词源自希腊语 dendron [树]，确实有些树突类似于树枝或根。毫无疑问，受到树木的启发，解剖学家卡米洛·高尔基 （Camillo Golgi） 在 1886 年提出，树突的功能是为神经元收集营养。事实是类似的，但更有趣：树突在一定体积的脑组织中形成树状，以便它们可以以突触输入的形式收集信息。不同类型神经元的树突表现出多种形状。树突通常很广泛，占神经元膜的 99%。单个神经元的树突可以接收多达 200,000 个突触输入。树突的电学和生化特性因细胞而异，它们对信息从突触到体细胞的传递有深远的影响。

2.1 树突减弱突触电位

Dendrites attenuate synaptic potentials

Dendrites tend to be long and thin. Their cytoplasm has relatively low electrical resistivity, and their membrane has relatively high resistivity. These are the properties of a leaky electrical cable, which is the premise for cable theory (see p. 201). Leaky cables are like leaky garden hoses; if ionic current (or water) enters at one end, the fraction of it that exits at the other end depends on the number of channels (or holes) in the cable (hose). A good hose has no holes and all the water makes it through, but most dendrites have a considerable number of channels that serve as leaks for ionic current (see Fig. 7-22).

树突往往又长又细。它们的细胞质具有相对较低的电阻率，并且它们的膜具有相对较高的电阻率。这些是漏电电缆的特性，这是电缆理论的前提（见第 201 页）。漏水的电缆就像漏水的花园软管;如果离子电流（或水）从一端进入，则从另一端流出的离子电流的比例取决于电缆（软管）中的通道（或孔）的数量。一根好的软管没有孔，所有的水都可以通过，但大多数树枝晶都有相当数量的通道，作为离子电流的泄漏（见图 7-22）。

Cable theory predicts how much current flows down the length of the dendrite through the cytoplasm and how much of it leaks out of the dendrite across the membrane. As summarized in Table 7-3, we can express the leakiness of the membrane by the resistance per unit area of dendritic membrane (specific membrane resistance, Rm), which can vary widely among neurons. The intracellular resistance per cross-sectional area of dendrite (specific resistivity of the cytoplasm, Ri) is also important in determining current flow inasmuch as a very resistive cytoplasm forces more current to flow out across the membrane rather than down the axis of the dendrite. Another important factor is cable diameter; thick dendrites let more current flow toward the soma than thin dendrites do. Figure 7-22C illustrates the consequences of a point source of steady current flowing into a leaky, uniform, infinitely long cable made of purely passive membrane. The transmembrane voltage generated by the current falls off exponentially with distance from the site of current injection. The steepness with which the voltage falls off is defined by the length constant (λ; see p. 201), which is the distance over which a steady voltage decays by a factor of 1/e (~37%). Estimates of the parameter values vary widely, but for brain neurons at rest, reasonable numbers are ~50,000 Ω ⋅ cm2 for Rm and 200 Ω ⋅ cm for Ri. If the radius of the dendrite (a) is 1 μm (10−4 cm), we can estimate the length constant of a dendrite by applying Equation 7-8.

电缆理论预测有多少电流沿着树突的长度流过细胞质，以及有多少电流穿过膜从树突中泄漏出来。如表 7-3 所示，我们可以通过树突状膜的每单位面积阻力（比膜阻力，Rm）来表示膜的泄漏，这在神经元之间可能有很大差异。树突每个横截面积的细胞内电阻（细胞质的比电阻率 Ri）在确定电流流动方面也很重要，因为非常电阻的细胞质会迫使更多的电流流过膜而不是沿着树突的轴流出。另一个重要因素是电缆直径;厚树突比薄树突让更多的电流流向 SOMA 。图 7-22C 说明了稳定电流的点源流入由纯无源膜制成的泄漏、均匀、无限长电缆的后果。电流产生的跨膜电压随着距电流注入部位的距离呈指数下降。电压下降的陡峭度由长度常数（λ;见第 201 页）定义，这是稳态电压衰减 1/e 倍 （~37%） 的距离。参数值的估计值差异很大，但对于静止的脑神经元，合理的数字是 Rm 的 ~50,000 Ω ⋅ cm 2 和 Ri 的 200 Ω ⋅ cm。如果枝晶 （a） 的半径为 1 μm （10-4 cm），我们可以通过应用公式 7-8 来估计枝晶的长度常数。

Because dendrite diameters vary greatly, λ should also vary greatly. For example, assuming the same cellular properties, a thin dendrite with a radius of 0.1 μm would have a λ of only 354 μm, whereas a thick one with a radius of 5 μm would have a λ of 2500 μm. Thus, the graded signal voltage spreads farther in a thick dendrite.

由于枝晶直径变化很大，因此 λ 也应该变化很大。例如，假设具有相同的蜂窝特性，半径为 0.1 μm 的薄枝晶的 λ 仅为 354 μm，而半径为 5 μm 的厚枝晶的 λ 为 2500 μm。因此，渐变信号电压在厚树晶中扩散得更远。

Real dendrites are certainly not infinitely long, uniform, and unbranched, nor do they have purely passive membranes. Thus, quantitative analysis of realistic dendrites is complex. The termination of a dendrite decreases attenuation because current cannot escape farther down the cable. Branching increases attenuation because current has more paths to follow. Most dendrites are tapered. Gradually expanding to an increased diameter progressively increases λ and thus progressively decreases attenuation. Real membranes are never completely passive because all have voltagegated channels, and therefore their Rm values can change as a function of voltage and time. Finally, in the working brain, cable properties are not constant but may vary dynamically with ongoing brain activity. For example, as the general level of synaptic input to a neuron rises (which might happen when a brain region is actively engaged in a task), more membrane channels will open and thus Rm will drop as a function of time, with consequent shortening of dendritic length constants. However, all these caveats do not alter the fundamental qualitative conclusion: voltage signals are attenuated as they travel down a dendrite.

真正的树突肯定不是无限长、均匀和无支链的，它们也没有纯粹的钝膜。因此，对真实树突的定量分析很复杂。枝晶的端接减少了衰减，因为电流无法从电缆中逃逸到更远的地方。分支会增加衰减，因为电流有更多的路径可以遵循。大多数树突是锥形的。逐渐膨胀到增加的直径会逐渐增加 λ，从而逐渐降低衰减。真正的膜从来都不是完全无源的，因为所有膜都有电压门控通道，因此它们的 Rm 值会随着电压和时间的变化而变化。最后，在工作的大脑中，电缆特性不是恒定的，但可能会随着持续的大脑活动而动态变化。例如，随着神经元的突触输入的一般水平升高（当大脑区域积极参与一项任务时可能发生），更多的膜通道将打开，因此 Rm 将随时间而下降，从而导致树突长度常数缩短。然而，所有这些警告都不会改变基本的定性结论：电压信号在沿着树突传播时会衰减。

So far, we have described only how a dendrite might attenuate a sustained voltage change. Indeed, the usual definition of length constant applies only to a steady-state voltage shift. An important complication is that the signal attenuation along a cable depends on the frequency components of that signal—how rapidly voltage changes over time. When Vm varies over time, some current is lost to membrane capacitance (see p. 158), and less current is carried along the dendrite downstream from the source of the current. Because action potentials and EPSPs entail rapid changes in Vm, with the fastest of them rising and falling within a few milliseconds, they are attenuated much more strongly than the steady-state λ implies. If Vm varies in time, we can define a λ that depends on signal frequency (λAC, where AC stands for “alternating current”). When signal frequency is zero (i.e., Vm is steady), λ = λAC. However, as frequency increases, λAC may fall sharply. Thus, dendrites attenuate high-frequency (i.e., rapidly changing) signals more than low-frequency or steady signals. Another way to express this concept is that most dendrites tend to be low-pass filters in that they let slowly changing signals pass more easily than rapidly changing ones.

到目前为止，我们只描述了枝晶如何衰减持续的电压变化。事实上，长度常数的通常定义仅适用于稳态电压偏移。一个重要的复杂之处在于，沿电缆的信号衰减取决于该信号的频率分量，即电压随时间变化的速度。当 Vm 随时间变化时，一些电流会损失到膜电容上（参见第 158 页），并且沿电流源下游的枝晶携带的电流较少。因为动作电位和 EPSP 会导致 Vm 的快速变化，其中最快的在几毫秒内上升和下降，因此它们的衰减比稳态 λ 所暗示的要强得多。如果 Vm 随时间变化，我们可以定义一个取决于信号频率的 λ（λAC，其中 AC 代表“交流电”）。当信号频率为零时（即 Vm 稳定），λ = λAC。然而，随着频率的增加，λAC 可能会急剧下降。因此，树突比低频或稳定信号更能衰减高频（即快速变化）信号。另一种表达这个概念的方式是，大多数树枝状往往是低通滤波器，因为它们让缓慢变化的信号比快速变化的信号更容易通过。

Figure 12-2A shows how an EPSP propagates along two different dendrites with very different length constants. If we assume the synapses trigger EPSPs of similar size in the end of each dendrite, then the dendrites with the longer λ deliver a larger signal to the axon hillock. How do leaky dendrites manage to communicate a useful synaptic signal to the soma? The problem is solved in two ways. The first solution deals with the passive properties of the dendrite membrane. The length (l) of dendrites tends to be relatively small in comparison to their λ; thus, none extends more than one or two steady-state length constants (i.e., the l/λ ratio is <1). One way that dendrites achieve a small l/λ ratio is to have a combination of diameter and Rm that gives them a large λ. Another way is that dendrites are not infinitely long cables but “terminated” cables. Figure 12-2B shows that a signal is attenuated more in an infinitely long cable (curve a) than in a terminated cable whose length (l) is equal to λ (curve b). The attenuation of a purely passive cable would be even less if the terminated cable had a λ 10-fold greater than l (curve c). Recall that in our example in Figure 12-2A, such a 10-fold difference in λ underlies the difference in the amplitudes of the EPSPs arriving at the axon hillock.

图 12-2A 显示了 EPSP 如何沿着两个长度常数非常不同的不同树突传播。如果我们假设突触在每个树突的末端触发相似大小的 EPSP，那么具有较长 λ 的树突向轴突小丘传递更大的信号。泄漏的树突如何设法将有用的突触信号传达给 soma？这个问题可以通过两种方式来解决。第一种解决方案涉及枝晶膜的被动特性。与它们的 λ 相比，枝晶的长度 （l） 往往相对较小;因此，没有一个扩展超过一个或两个稳态长度常数（即 L/λ 比为 <1）。枝晶实现小 l/λ 比的一种方法是将直径和 Rm 组合在一起，从而获得较大的 λ。另一种方法是树突不是无限长的电缆，而是“端接”的电缆。图 12-2B 显示，无限长电缆（曲线 a）中的信号衰减大于长度 （l） 等于 λ 的端接电缆（曲线 b）中的信号衰减。如果端接电缆的 λ 大于 l 10 倍（曲线 c），则纯无源电缆的衰减会更小。回想一下，在图 12-2A 的示例中，λ 的 10 倍差异是到达轴突小丘的 EPSP 振幅差异的基础。

The second solution to the attenuation problem is to endow dendrites with voltage-gated ion channels (see pp. 182–199) that enhance the signal more than would be expected in a purely “passive” system (curve d). We discuss the properties of such “active” cables in the next section.

衰减问题的第二种解决方案是赋予树突电压门控离子通道（参见第 182-199 页），这比纯“无源”系统（曲线 d）中预期的信号增强更多。我们将在下一节讨论这种 “有源” 电缆的特性。

2.2 树突状膜具有电压门控离子通道

Dendritic membranes have voltage-gated ion channels

All mammalian dendrites have voltage-gated ion channels that influence their signaling properties. Dendritic characteristics vary from cell to cell, and the principles of dendritic signaling are being studied intensively. Most dendrites have a relatively low density of voltage-gated channels (see pp. 182–199) that may amplify, or boost, synaptic signals by adding additional inward current as the signals propagate from distal dendrites toward the soma. We have already introduced the principle of an active cable in curve d of Figure 12-2B. If the membrane has voltage-gated channels that are able to carry more inward current (often Na+ or Ca2+) under depolarized conditions, a sufficiently strong EPSP would drive Vm into the activation range of the voltagegated channels. These voltage-gated channels would open, and their additional inward current would add to that generated initially by the synaptic channels. Thus, the synaptic signal would fall off much less steeply with distance than in passive dendrite. Voltage-gated channels can be distributed all along the dendrite and thus amplify the signal along the entire dendritic length, or they can be clustered at particular sites. In either case, voltage-gated channels can boost the synaptic signal considerably, even if the densities of channels are far too low for the generation of action potentials.

所有哺乳动物树突都具有影响其信号传导特性的电压门控离子通道。树突状特征因细胞而异，并且正在深入研究树突状信号转导的原理。大多数树突具有相对较低的电压门控通道密度（参见第 182-199 页），当信号从远端树突传播到体细胞时，可以通过增加额外的向内电流来放大或增强突触信号。我们已经在图 12-2B 的曲线 d 中介绍了有源电缆的原理。如果膜具有电压门控通道，能够在去极化条件下携带更多的向内电流（通常是 Na + 或 Ca2 + ），则足够强的 EPSP 会将 Vm 驱动到电压门控通道的激活范围内。这些电压门控通道将打开，它们额外的向内电流将添加到突触通道最初产生的电流中。因此，突触信号随距离的下降幅度比被动树突要小得多。电压门控通道可以沿树突分布，从而沿整个树突长度放大信号，或者它们可以聚集在特定位置。在任何一种情况下，电压门控通道都可以显着增强突触信号，即使通道的密度太低而无法产生动作电位。

An even more dramatic solution, used by a few types of dendrites, is to have such a high density of voltage-gated ion channels that they can produce action potentials, just as axons can. One of the best-documented examples is the Purkinje cell, which is the large output neuron of the cerebellum. As Rodolfo Llinás and colleagues have shown, when the dendrites of Purkinje cells are stimulated strongly, they can generate large, relatively broad action potentials that are mediated by voltage-gated Ca2+ channels (Fig. 12-3). Such Ca2+ spikes can sometimes propagate toward—or even into—the soma, but these Ca2+ action potentials do not continue down the axon. Instead, they may trigger fast Na+-dependent action potentials that are generated by voltage-gated Na+ channels in the initial segment. The Na+ spikes carry the signal along the axon in the conventional way. Both types of spikes occur in the soma, where the Na+ spikes are considerably quicker and larger than the dendritic Ca2+ spikes. The faster Na+ spikes propagate only a short distance backward into the dendritic tree because the rapid time course of the Na+ spike is strongly attenuated by the inherent filtering properties of the dendrites (i.e., the λAC is smaller for the rapid frequencies of the Na+ action potentials than for the slower Ca2+ action potentials). The dendrites of certain other neurons of the CNS, including some pyramidal cells of the cerebral cortex, can also generate spikes that are dependent on Ca2+, Na+, or both.

几种类型的树突使用的一种更引人注目的解决方案是具有如此高密度的电压门控离子通道，以至于它们可以产生动作电位，就像轴突一样。记录最充分的例子之一是浦肯野细胞，它是小脑的大输出神经元。正如 Rodolfo Llinás 及其同事所表明的那样，当浦肯野细胞的树突受到强烈刺激时，它们可以产生由电压门控 Ca2+ 通道介导的大的、相对广泛的动作电位（图 12-3）。这种 Ca2+ 尖峰有时可以向体细胞传播，甚至传播到体细胞中，但这些 Ca2+ 动作电位不会继续沿轴突向下移动。相反，它们可能会触发由初始段中的电压门控 Na+ 通道产生的快速 Na+ 依赖性动作电位。Na+ 尖峰以传统方式沿轴突传递信号。这两种类型的尖峰都发生在体细胞中，其中 Na+ 尖峰比树突状 Ca2+ 尖峰更快、更大。较快的 Na + 尖峰仅向后传播一小段距离到树突树中，因为 Na + 尖峰的快速时间过程被树突固有的过滤特性强烈衰减（即，对于 Na + 动作电位的快速频率，λAC 比对于较慢的 Ca2 + 动作电位）。CNS 的某些其他神经元的树突，包括大脑皮层的一些锥体细胞，也可以产生依赖于 Ca2+、Na+ 或两者兼而有之的尖峰。

Dendritic action potentials, when they exist at all, tend to be slower and weaker, and with higher thresholds, than those in axons. The reason is probably that one of the functions of dendrites is to collect and to integrate information from a large number of synapses (often thousands). If each synapse were capable of triggering an action potential, there would be little opportunity for most of the synaptic inputs to have a meaningful influence on a neuron’s output. The cell’s dynamic range would be truncated; that is, a very small number of active synapses would bring the neuron to its maximum firing rate. However, if dendrites are only weakly excitable, the problem of signal attenuation along dendritic cables can be solved while the cell still can generate an output (i.e., the axonal firing rate) that is indicative of the proportion of its synapses that are active.

树突动作电位（如果存在）往往比轴突中的动作电位更慢、更弱，并且阈值更高。原因可能是树突的功能之一是收集和整合来自大量突触（通常是数千个）的信息。如果每个突触都能够触发动作电位，那么大多数突触输入几乎没有机会对神经元的输出产生有意义的影响。单元格的动态范围将被截断;也就是说，极少量的活跃突触会使神经元达到其最大放电速率。然而，如果树突只是弱可激发的，则可以解决沿树突电缆的信号衰减问题，而细胞仍然可以产生指示其活跃突触比例的输出（即轴突放电率）。

Another advantage of voltage-gated channels in dendrites may be the selective boosting of high-frequency synaptic input. Recall that passive dendrites attenuate signals of high frequency more than those of low frequency. However, if dendrites possess the appropriate voltage-gated channels, with fast gating kinetics, they will be better able to communicate high-frequency synaptic input.

树突中电压门控通道的另一个优势可能是高频突触输入的选择性增强。回想一下，无源枝晶比低频信号更能衰减高频信号。然而，如果树突具有适当的电压门控通道，具有快速门控动力学，它们将能够更好地传达高频突触输入。

3 躯体中尖峰模式控制

CONTROL OF SPIKING PATTERNS IN THE SOMA

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。

3.1 神经元可以将简单的输入转换为各种输出模式

Neurons can transform a simple input into a variety of output patterns

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。

3.2 本征发射模式由动力学相对较慢的各种离子流决定

Intrinsic firing patterns are determined by a variety of ion currents with relatively slow kinetics

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。

4 轴突传导

AXONAL CONDUCTION

4.1 轴突专门用于快速、可靠和高效的电信号传输

Axons are specialized for rapid, reliable, and efficient transmission of electrical signals

4.2 动作电位通常在初始节段启动

Action potentials are usually initiated at the initial segment

4.3 有髓轴突的传导速度随直径线性增加

Conduction velocity of a myelinated axon increases linearly with diameter

4.4 脱髓鞘轴突缓慢、不可靠或根本不传导动作电位

Demyelinated axons conduct action potentials slowly, unreliably, or not at all

5 Reference

• Physiology
• Pharmacology
• Addiction
• BBB 血脑屏障概述

• Smith et al. Insights into inner ear function and disease through novel visualizatio of the ductus reuniens, a semila communication between hearing and balance mechanisms. JARO (2022)
• http://www.cochlea.eu/en/cochlea
• http://www.cochlea.eu/en/cochlea/cochlear-fluids