查看Ch14 The Autonomic Nervous System的源代码

<b style=font-size:18pt;color:#f80>自主神经系统</b>

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 <b style=color:#0cf>【注】</b> 后内容为 BH1RBH (Jack Tan) 所加之注释


When we are awake, we are constantly aware of sensory input from our external environment, and we consciously plan how to react to it. When we are asleep, the nervous system has a variety of mechanisms to dissociate cortical function from sensory input and somatic motor output. Among these mechanisms are closing the eyes, blocking the transmission of sensory impulses to the cortex as they pass through the thalamus, and effecting a nearly complete paralysis of skeletal muscles during rapid eye movement (REM) sleep to keep us from physically acting out our dreams.

当我们清醒时，我们会不断意识到来自外部环境的感官输入，并有意识地计划如何应对它。当我们睡着时，神经系统有多种机制可以将皮层功能与感觉输入和躯体运动输出分离。这些机制包括闭上眼睛，阻止感觉冲动通过丘脑时向皮层的传递，以及在快速眼动 （REM） 睡眠期间导致骨骼肌几乎完全麻痹，以防止我们身体上表演我们的梦。

The conscious and discontinuous nature of cortical brain function stands in sharp contrast with those parts of the nervous system that are responsible for control of our internal environment. These “autonomic” processes never stop attending to the wide range of metabolic, cardiopulmonary, and other visceral requirements of our body. Autonomic control continues whether we are awake and attentive, preoccupied with other activities, or asleep. While we are awake, we are unaware of most visceral sensory input, and we avoid any conscious effort to act on it unless it induces distress. In most cases, we have no awareness of motor commands to the viscera, and most individuals can exert voluntary control over motor output to the viscera only in minor ways. Consciousness and memory are frequently considered the most important functions of the human nervous system, but it is the visceral control system—including the autonomic nervous system (ANS)—that makes life and higher cortical function possible.

大脑皮层功能的有意识和不连续性质与神经系统中负责控制我们内部环境的部分形成鲜明对比。这些“自主神经”过程从未停止关注我们身体的各种代谢、心肺和其他内脏需求。无论我们是清醒和专心、全神贯注于其他活动还是睡着，自主神经控制都会继续。当我们清醒时，我们不知道大多数本能的感官输入，除非它引起痛苦，否则我们会避免任何有意识的努力去采取行动。在大多数情况下，我们没有意识到对内脏的运动命令，大多数人只能以微小的方式对内脏的运动输出进行自主控制。意识和记忆通常被认为是人类神经系统最重要的功能，但正是内脏控制系统——包括自主神经系统 （ANS）——使生命和高级皮质功能成为可能。


We have a greater understanding of the physiology of the ANS than of many other parts of the nervous system, largely because it is reasonably easy to isolate peripheral neurons and to study them. As a result of its accessibility, the ANS has served as a key model system for the elucidation of many principles of neuronal and synaptic function.

我们对自主神经系统比对神经系统的许多其他部分的生理更了解，这主要是因为分离周围神经元并对其进行研究相当容易。由于其可访问性，ANS 已成为阐明神经元和突触功能的许多原理的关键模型系统。


==  本能控制系统的组织 ==
<b style=color:#f80>ORGANIZATION OF THE VISCERAL CONTROL SYSTEM</b>

=== 自主神经系统有交感神经、副交感神经和肠道神经 ===
<b style=color:#0ae>The autonomic nervous system has sympathetic, parasympathetic, and enteric divisions</b>

Output from the central nervous system (CNS) travels along two anatomically and functionally distinct pathways: the somatic motor neurons, which innervate striated skeletal muscle; and the autonomic motor neurons, which innervate smooth muscle, cardiac muscle, secretory epithelia, and glands. All viscera are richly supplied by efferent axons from the ANS that constantly adjust organ function.

中枢神经系统 （CNS） 的输出沿着两条解剖学和功能上不同的途径传播：躯体运动神经元，支配横纹骨骼肌；以及自主运动神经元，支配平滑肌、心肌、分泌上皮和腺体。所有内脏都由来自自主神经系统的传出轴突丰富地提供，这些轴突不断调整器官功能。

The autonomic nervous system (from the Greek for “selfgoverning,” functioning independently of the will) was first defined by Langley in 1898 as including the local nervous system of the gut and the efferent neurons innervating glands and involuntary muscle. Thus, this definition of the ANS includes only efferent neurons and enteric neurons. Since that time, it has become clear that the efferent ANS cannot easily be dissociated from visceral afferents as well as from those parts of the CNS that control the output to the ANS and those that receive interoceptive input. N14-1 This larger visceral control system monitors afferents from the viscera and the rest of the body, compares this input with current and anticipated needs, and controls output to the body’s organ systems.

自主神经系统（来自希腊语，意为“自我管理”，独立于意志运作）由 Langley 于 1898 年首次定义为包括肠道的局部神经系统以及支配腺体和非自主肌肉的传出神经元。因此，ANS 的这个定义仅包括传出神经元和肠道神经元。从那时起，很明显，传出的 ANS 不能轻易地与内脏传入神经以及控制 ANS 输出的 CNS 部分和接收内感受输入的部分分离[N14-1]。 这个较大的内脏控制系统监测来自内脏和身体其他部位的传入神经，将此输入与当前和预期的需求进行比较，并控制对身体器官系统的输出。


The ANS has three divisions: sympathetic, parasympathetic, and enteric. The sympathetic and parasympathetic divisions of the ANS are the two major efferent pathways controlling targets other than skeletal muscle (Fig. 14-1). Each innervates target tissue by a two-synapse pathway. The cell bodies of the first neurons lie within the CNS. These preganglionic neurons are found in columns of cells in the brainstem and spinal cord and send axons out of the CNS to make synapses with postganglionic neurons in peripheral ganglia interposed between the CNS and their target cells. Axons from these postganglionic neurons then project to their targets. The sympathetic and parasympathetic divisions can act independently of each other. However, in general, they work synergistically to control visceral activity and often act in opposite ways, like an accelerator and brake to regulate visceral function. An increase in output of the sympathetic division occurs under conditions such as stress, anxiety, physical activity, fear, or excitement, whereas parasympathetic output increases during sedentary activity, eating, or other “vegetative” behavior.

自主神经系统 (ANS) 分为三个部分：交感神经、副交感神经和肠道。ANS 的交感神经和副交感神经分支是控制骨骼肌以外目标的两个主要传出途径（图 14-1）。每个都通过双突触途径支配靶组织。第一个神经元的细胞体位于 CNS 内。这些节前神经元存在于脑干和脊髓的细胞柱中，并将轴突从 CNS 发送出去，与位于 CNS 与其靶细胞之间的外周神经节中的节后神经元形成突触。然后，来自这些节后神经元的轴突投射到它们的目标。交感神经和副交感神经部门可以彼此独立地行动。然而，一般来说，它们协同作用以控制内脏活动，并且通常以相反的方式发挥作用，例如加速器和制动器来调节内脏功能。交感神经输出的增加发生在压力、焦虑、体力活动、恐惧或兴奋等条件下，而副交感神经输出增加发生在久坐活动、进食或其他“植物人”行为期间。

The enteric division of the ANS is a collection of afferent neurons, interneurons, and motor neurons that form networks of neurons called plexuses (from the Latin “to braid”) that surround the gastrointestinal (GI) tract. It can function as a separate and independent nervous system, but it is normally controlled by the CNS through sympathetic and parasympathetic fibers.

ANS 的肠道分支是传入神经元、中间神经元和运动神经元的集合，它们形成围绕胃肠道 （GI） 的神经元网络，称为神经丛（来自拉丁语“辫子”）。它可以作为一个独立且独立的神经系统发挥作用，但它通常由 CNS 通过交感神经和副交感神经纤维控制。

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=== 交感神经节前神经元起源于脊髓节段 T1 至 L3，与椎旁或椎前神经节中的节后神经元形成突触 ===
<b style=color:#0ae>Sympathetic preganglionic neurons originate from spinal segments T1 to L3 and synapse with postganglionic neurons in paravertebral or prevertebral ganglia</b>

<b style=color:#f80>Preganglionic Neurons</b> The cell bodies of preganglionic sympathetic motor neurons are located in the thoracic and upper lumbar spinal cord between levels T1 and L3. At these spinal levels, autonomic neurons lie in the intermediolateral cell column, or lateral horn, between the dorsal and ventral horns (Fig. 14-2). Axons from preganglionic sympathetic neurons exit the spinal cord through the ventral roots along with axons from somatic motor neurons. After entering the spinal nerves, sympathetic efferents diverge from somatic motor axons to enter the white rami communicantes. These rami, or branches, are white because most preganglionic sympathetic axons are myelinated.

<b style=color:#f80>节前神经元</b> 节前交感神经运动神经元的细胞体位于 T1 和 L3 水平之间的胸椎和上腰椎脊髓中。在这些脊柱水平上，自主神经元位于背角和腹角之间的中间外侧细胞柱或外侧角中（图 14-2）。来自节前交感神经元的轴突与来自体细胞运动神经元的轴突一起通过腹根离开脊髓。进入脊神经后，交感神经传出物从躯体运动轴突分化进入白色支交通。这些支或分支是白色的，因为大多数节前交感神经轴突都是有髓的。

<b style=color:#f80>Paravertebral Ganglia</b> Axons from preganglionic neurons enter the nearest sympathetic paravertebral ganglion through a white ramus. These ganglia lie adjacent to the vertebral column. Although preganglionic sympathetic fibers emerge only from levels T1 to L3, the chain of sympathetic ganglia extends all the way from the upper part of the neck to the coccyx, where the left and right sympathetic chains merge in the midline and form the coccygeal ganglion. In general, one ganglion is positioned at the level of each spinal root, but adjacent ganglia are fused in some cases. The most rostral ganglion, the superior cervical ganglion, arises from fusion of C1 to C4 and supplies the head and neck. The next two ganglia are the middle cervical ganglion, which arises from fusion of C5 and C6, and the inferior cervical ganglion (C7 and C8), which is usually fused with the first thoracic ganglion to form the stellate ganglion. Together, the middle cervical and stellate ganglia, along with the upper thoracic ganglia, innervate the heart, lungs, and bronchi. The remaining paravertebral ganglia supply organs and portions of the body wall in a segmental fashion.

<b style=color:#f80>椎旁神经节</b> 来自节前神经元的轴突通过白色支进入最近的交感椎旁神经节。这些神经节位于脊柱附近。虽然节前交感神经纤维仅出现在 T1 至 L3 水平，但交感神经节链从颈部上部一直延伸到尾骨，左右交感神经链在中线汇合，形成尾骨神经节。一般来说，一个神经节位于每个脊髓根的水平，但在某些情况下，相邻的神经节会融合。最前端的神经节，即颈上神经节，由 C1 和 C4 融合产生，供应头部和颈部。接下来的两个神经节是颈中神经节，它是由 C5 和 C6 融合产生的，以及下颈神经节（C7 和 C8），通常与第一胸神经节融合形成星状神经节。中颈神经节和星状神经节以及上胸神经节一起支配心脏、肺和支气管。剩余的椎旁神经节以节段方式供应器官和体壁的一部分。


After entering a paravertebral ganglion, a preganglionic sympathetic axon has one or more of three fates. It may (1) synapse within that segmental paravertebral ganglion, (2) travel up or down the sympathetic chain to synapse within a neighboring paravertebral ganglion, or (3) enter the greater or lesser splanchnic nerve to synapse within one of the ganglia of the prevertebral plexus.

进入椎旁神经节后，节前交感神经轴突具有三种命运中的一种或多种。它可能 （1） 在该节段性椎旁神经节内形成突触，（2） 沿交感神经链向上或向下移动到邻近椎旁神经节内的突触，或 （3） 进入较大或较小的内脏神经到椎前丛神经节之一内的突触。

<b style=color:#f80>Prevertebral Ganglia</b> The prevertebral plexus lies in front of the aorta and along its major arterial branches and includes the prevertebral ganglia and interconnected fibers (Fig. 14-3). The major prevertebral ganglia are named according to the arteries that they are adjacent to and include the celiac, superior mesenteric, aorticorenal, and inferior mesenteric ganglia. Portions of the prevertebral plexus extend down the major arteries and contain other named and unnamed ganglia and plexuses of nerve fibers, which altogether make up a dense and extensive network of sympathetic neuron cell bodies and nerve fibers.

<b style=color:#f80>椎前神经节</b> 椎前丛位于主动脉前方及其主要动脉分支，包括椎前神经节和互连的纤维（图 14-3）。主要椎前神经节根据它们相邻的动脉命名，包括腹腔、肠系膜上神经节、主动脉核心神经节和肠系膜下神经节。椎前丛的一部分向下延伸到主要动脉，并包含其他命名和未命名的神经节和神经丛，它们共同构成了交感神经元细胞体和神经纤维的密集而广泛的网络。


Each preganglionic sympathetic fiber synapses on many postganglionic sympathetic neurons that are located within one or several nearby paravertebral or prevertebral ganglia. It has been estimated that each preganglionic sympathetic neuron branches and synapses on as many as 200 postganglionic neurons, which enables the sympathetic output to have more widespread effects. However, any impulse arriving at its target end organ has only crossed a single synapse between the preganglionic and postganglionic sympathetic neurons.

每个节前交感神经纤维突触位于位于附近一个或多个椎旁神经节或椎前神经节内的许多节后交感神经元上。据估计，每个节前交感神经元在多达 200 个节后神经元上分支和突触，这使得交感神经输出能够产生更广泛的影响。然而，任何到达其目标终末器官的冲动都只穿过了节前和节后交感神经元之间的单个突触。

<b style=color:#f80>Postganglionic Neurons</b> The cell bodies of postganglionic sympathetic neurons that are located within paravertebral ganglia send out their axons through the nearest gray rami communicantes, which rejoin the spinal nerves (see Fig. 14-2). These rami are gray because most postganglionic axons are unmyelinated. Because preganglionic sympathetic neurons are located only in the thoracic and upper lumbar spinal segments (T1 to L3), white rami are found only at these levels (Fig. 14-4, left panel). However, because each sympathetic ganglion sends out postganglionic axons, gray rami are present at all spinal levels from C2 or C3 to the coccyx. Postganglionic sympathetic axons from paravertebral and prevertebral ganglia travel to their target organs within other nerves or by traveling along blood vessels. Because the paravertebral and prevertebral sympathetic ganglia lie near the spinal cord and thus relatively far from their target organs, the postganglionic axons of the sympathetic division tend to be long. On their way to reach their targets, some postganglionic sympathetic axons travel through parasympathetic terminal ganglia or cranial nerve ganglia without synapsing[N14-2].

<b style=color:#f80>节后神经元</b> 位于椎旁神经节内的节后交感神经元的细胞体通过最近的灰色交感支发出轴突，这些支重新加入脊神经（见图 14-2）。这些支是灰色的，因为大多数节后轴突是无髓的。因为节前交感神经元仅位于胸椎和上腰椎段（T1 到 L3），所以白色支仅在这些水平上发现（图 14-4，左图）。然而，由于每个交感神经节都会发出节后轴突，因此从 C2 或 C3 到尾骨的所有脊柱水平都存在灰色支。来自椎旁和椎前神经节的节后交感神经轴突通过其他神经或沿血管行进到其目标器官。因为椎旁和椎前交感神经节位于脊髓附近，因此离它们的目标器官相对较远，所以交感神经支的节后轴突往往很长。在到达目标的途中，一些节后交感神经轴突穿过副交感神经末梢神经节或颅神经节，没有突触[N14-2]。


Parasympathetic preganglionic neurons originate from the brainstem and sacral spinal cord and synapse with postganglionic neurons in ganglia located near target organs

副交感神经节前神经元起源于脑干和骶脊髓，与位于靶器官附近神经节的节后神经元形成突触

The cell bodies of preganglionic parasympathetic neurons are located in the medulla, pons, and midbrain and in the S2 through S4 levels of the spinal cord (see Fig. 14-4, right panel). Thus, unlike the sympathetic— or thoracolumbar—division, whose preganglionic cell bodies are in the thoracic and lumbar spinal cord, the parasympathetic—or craniosacral—division’s preganglionic cell bodies are cranial and sacral. The preganglionic parasympathetic fibers originating in the brain distribute with four cranial nerves: the oculomotor nerve (CN III), the facial nerve (CN VII), the glossopharyngeal nerve (CN IX), and the vagus nerve (CN X). The preganglionic parasympathetic fibers originating in S2 through S4 distribute with the pelvic splanchnic nerves.

节前副交感神经元的细胞体位于延髓、脑桥和中脑以及脊髓的 S2 至 S4 水平（见图 14-4，右图）。因此，与交感神经或胸腰椎支不同，其节前细胞体位于胸腰脊髓中，副交感神经或颅骶支的节前细胞体是颅骨和骶骨。起源于大脑的节前副交感神经纤维分布有四条颅神经：动眼神经 （CN III）、面神经 （CN VII）、舌咽神经 （CN IX） 和迷走神经 （CN X）。起源于 S2 至 S4 的节前副交感神经纤维与盆腔内脏神经分布。


Postganglionic parasympathetic neurons are located in terminal ganglia that are more peripherally located and more widely distributed than are the sympathetic ganglia. Terminal ganglia often lie within the walls of their target organs. Thus, in contrast to the sympathetic division, postganglionic fibers of the parasympathetic division are short.In some cases, individual postganglionic parasympathetic neurons are found in isolation or in scattered cell groups rather than in encapsulated ganglia. 

节后副交感神经元位于末端神经节中，与交感神经节相比，末端神经节的位置更外围，分布更广泛。末端神经节通常位于其靶器官的壁内。因此，与交感神经支相反，副交感神经支的节后纤维很短。在某些情况下，单个节后副交感神经元孤立或分散在细胞群中，而不是在包膜神经节中发现。


<b style=color:#f80>Cranial Nerves III, VII, and IX</b> The preganglionic parasympathetic neurons that are distributed with CN III, CN VII, and CN IX originate in three groups of nuclei.

<b style=color:#f80>颅神经 III、VII 和 IX</b> 与 CN III、CN VII 和 CN IX 分布的节前副交感神经元起源于三组核。


1. The Edinger-Westphal nucleus is a subnucleus of the oculomotor complex in the midbrain (Fig. 14-5). Parasympathetic neurons in this nucleus travel in the oculomotor nerve (CN III) and synapse onto postganglionic neurons in the ciliary ganglion (see Fig. 14-4, right panel). The postganglionic fibers project to two smooth muscles of the eye: the constrictor muscle of the pupil and the ciliary muscle, which controls the shape of the lens (see Fig. 15-6).

1. Edinger-Westphal 核是中脑动眼神经复合体的亚核（图 14-5）。该核中的副交感神经元在动眼神经 （CN III） 中移动，并突触到达睫状神经节中的节后神经元（见图 14-4，右图）。节后纤维投射到眼睛的两块平滑肌：瞳孔收缩肌和睫状肌，它控制晶状体的形状（见图 15-6）。

2. The superior salivatory nucleus is in the rostral medulla (see Fig. 14-5) and contains parasympathetic neurons that project, through a branch of the facial nerve (CN VII), to the pterygopalatine ganglion (see Fig. 14-4, right panel). The postganglionic fibers supply the lacrimal glands, which produce tears. Another branch of the facial nerve carries preganglionic fibers to the submandibular ganglion. The postganglionic fibers supply two salivary glands, the submandibular and sublingual glands.

2. 上唾液核位于延髓喙部（见图 14-5），包含副交感神经元，这些神经元通过面神经的一个分支 （CN VII） 投射到翼腭神经节（见图 14-4，右图）。节后纤维供应泪腺，泪腺产生撕裂。面神经的另一个分支将节前纤维输送到下颌下神经节。节后纤维供应两个唾液腺，即下颌下腺和舌下腺。


3. The inferior salivatory nucleus and the rostral part of the nucleus ambiguus in the rostral medulla (see Fig. 14-5) contain parasympathetic neurons that project through the glossopharyngeal nerve (CN IX) to the otic ganglion (see Fig. 14-4, right panel). The postganglionic fibers supply a third salivary gland, the parotid gland.

3. 喙延髓中下唾液核和模糊核的喙部（见图 14-5）包含通过舌咽神经 （CN IX） 投射到耳神经节的副交感神经元（见图 14-4，右图）。节后纤维供应第三个唾液腺，即腮腺。


<b style=color:#f80>Cranial Nerve X</b> Most parasympathetic output occurs through the vagus nerve (CN X). Cell bodies of vagal preganglionic parasympathetic neurons are found in the medulla within the nucleus ambiguus and the dorsal motor nucleus of the vagus (see Fig. 14-5). This nerve supplies parasympathetic innervation to all the viscera of the thorax and abdomen, including the GI tract between the pharynx and distal end of the colon (see Fig. 14-4, right panel). Among other effects, electrical stimulation of the nucleus ambiguus results in contraction of striated muscle in the pharynx, larynx, and upper esophagus due to activation of somatic motor neurons (not autonomic), as well as slowing of the heart due to activation of vagal preganglionic parasympathetic neurons. Stimulation of the dorsal motor nucleus of the vagus induces many effects in the viscera, including initiation of secretion of gastric acid, insulin, and glucagon. Preganglionic parasympathetic fibers of the vagus nerve join the esophageal, pulmonary, and cardiac plexuses and travel to terminal ganglia that are located within their target organs.

<b style=color:#f80>颅神经 X</b> 大多数副交感神经输出通过迷走神经 （CN X） 发生。迷走神经节前副交感神经元的细胞体位于迷走神经模糊核和背侧运动核内的延髓中（见图 14-5）。该神经为胸部和腹部的所有内脏提供副交感神经支配，包括咽部和结肠远端之间的胃肠道（见图 14-4，右图）。除其他作用外，由于体细胞运动神经元（非自主神经）的激活，对模糊核的电刺激导致咽部、喉部和食管上部的横纹肌收缩，以及由于迷走神经节前副交感神经元的激活而导致心脏减慢。刺激迷走神经背侧运动核在内脏中引起许多影响，包括开始分泌胃酸、胰岛素和胰高血糖素。迷走神经的节前副交感神经纤维加入食管丛、肺丛和心脏丛，并行进到位于其靶器官内的末端神经节。


<b style=color:#f80>Sacral Nerves</b> The cell bodies of preganglionic parasympathetic neurons in the sacral spinal cord (S2 to S4) are located in a position similar to that of the preganglionic sympathetic neurons—although they do not form a distinct intermediolateral column. Their axons leave through ventral roots and travel with the pelvic splanchnic nerves to their terminal ganglia in the descending colon and rectum (see p. 862), as well as to the bladder (see pp. 736–737) and the reproductive organs of the male (see p. 1104) and female (see p. 1127).

<b style=color:#f80>骶神经</b> 骶脊髓（S2 至 S4）中节前副交感神经元的细胞体位于与节前交感神经元相似的位置——尽管它们不形成明显的中间外侧柱。它们的轴突从腹根离开，与盆腔内脏神经一起移动到降结肠和直肠的末端神经节（见第 862 页），以及膀胱（见第 736-737 页）和男性（见第 1104 页）和女性（见第 1127 页）的生殖器官。

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=== 内脏控制系统也有一个重要的传入肢体 ===
<b style=color:#0ae>The visceral control system also has an important afferent limb</b>

All internal organs are densely innervated by visceral afferents. Some of these receptors monitor nociceptive (painful) input. Others are sensitive to a variety of mechanical and chemical (physiological) stimuli, including stretch of the heart, blood vessels, and hollow viscera, as well as PCO2, PO2, pH, blood glucose, and temperature of the skin and internal organs. Many visceral nociceptive fibers travel in sympathetic nerves (blue projections in Fig. 14-2). Most axons from physiological receptors travel with parasympathetic fibers. As is the case with somatic afferents (see p. 271), the cell bodies of visceral afferent fibers are located within the dorsal root ganglia or cranial nerve ganglia (e.g., nodose and petrosal ganglia). Ninety percent of these visceral afferents are unmyelinated.

所有内脏器官都由内脏传入神经密集支配。其中一些受体监控伤害性（痛苦）输入。其他对各种机械和化学（生理）刺激敏感，包括心脏伸展、血管和空腔内脏，以及 PCO2、PO2、pH、血糖以及皮肤和内脏器官的温度。许多内脏伤害性纤维在交感神经中行进（图 14-2 中的蓝色投影）。来自生理受体的大多数轴突与副交感神经纤维一起移动。与体细胞传入神经一样（见第 271 页），内脏传入纤维的细胞体位于背根神经节或颅神经节（例如，结节和岩神经节）内。这些内脏传入神经中有 90% 是无髓的。


The largest concentration of visceral afferent axons can be found in the vagus nerve, which carries non-nociceptive afferent input to the CNS from all viscera of the thorax and abdomen. Most fibers in the vagus nerve are afferents, even though all parasympathetic preganglionic output (i.e., efferents) to the abdominal and thoracic viscera also travels in the vagus nerve. Vagal afferents, whose cell bodies are located in the nodose ganglion, carry information about the distention of hollow organs (e.g., blood vessels, cardiac chambers, stomach, bronchioles), blood gases (e.g., PO2, PCO2, pH from the aortic bodies), and body chemistry (e.g., glucose concentration) to the medulla.

内脏传入轴突的最大集中体可以在迷走神经中找到，迷走神经将非伤害性传入输入从胸部和腹部的所有内脏传递到 CNS。迷走神经中的大多数纤维是传入神经，即使所有副交感神经节前输出（即传出神经）到腹部和胸部内脏也都在迷走神经中移动。迷走神经传入神经的细胞体位于结节神经节中，将有关空心器官（例如血管、心腔、胃、细支气管）、血气（例如主动脉体的 PO2、PCO2、pH 值）和身体化学成分（例如葡萄糖浓度）的膨胀信息带到髓质。


Internal organs also have nociceptive receptors that are sensitive to excessive stretch, noxious chemical irritants, and very large decreases in pH. In the CNS, this visceral pain input is mapped (see pp. 400–401) viscerotopically at the level of the spinal cord because most visceral nociceptive fibers travel with the sympathetic fibers and enter the spinal cord at a specific segmental level along with a spinal nerve (see Fig. 14-2). This viscerotopic mapping is also present in the brainstem but not at the level of the cerebral cortex. Thus, awareness of visceral pain is not usually localized to a specific organ but is instead “referred” to the dermatome (see p. 273) that is innervated by the same spinal nerve. This referred pain results from lack of precision in the central organization of visceral pain pathways. Thus, you know that the pain is associated with a particular spinal nerve, but you do not know where the pain is coming from (i.e., from the skin or a visceral organ). For example, nociceptive input from the left ventricle of the heart is referred to the left T1 to T5 dermatomes and leads to discomfort in the left arm and left side of the chest, whereas nociceptive input from the diaphragm is referred to the C3 to C5 dermatomes and is interpreted as pain in the shoulder. This visceral pain is often felt as a vague burning or pressure sensation.

内部器官也有伤害性受体，对过度拉伸、有害化学刺激物和 pH 值大幅下降敏感。在 CNS 中，这种内脏疼痛输入在脊髓水平的内脏位上映射（见第 400-401 页），因为大多数内脏伤害性纤维与交感神经一起移动，并与脊神经一起在特定节段水平进入脊髓（见图 14-2）。这种内脏映射也存在于脑干中，但不存在于大脑皮层的水平。因此，对内脏疼痛的意识通常不局限于特定器官，而是“指代”由同一脊神经支配的皮节（见第 273 页）。这种牵涉痛是由于内脏疼痛通路的中心组织缺乏精确性造成的。因此，您知道疼痛与特定的脊神经有关，但您不知道疼痛来自哪里（即来自皮肤或内脏器官）。例如，来自心脏左心室的伤害性输入被称为左 T1 到 T5 皮节，并导致左臂和胸部左侧的不适，而来自横膈膜的伤害性输入被称为 C3 到 C5 皮节，并被解释为肩部疼痛。这种内脏疼痛通常表现为隐约的灼热感或压迫感。

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=== 肠部是胃肠道的一个自给自足的神经系统，接收交感神经和副交感神经的输入 ===
<b style=color:#0ae>The enteric division is a self-contained nervous system of the GI tract and receives sympathetic and parasympathetic input</b>

The enteric nervous system (ENS) is a collection of nerve plexuses that surround the GI tract, including the pancreas and biliary system. Although it is entirely peripheral, the ENS receives input from the sympathetic and parasympathetic divisions of the ANS. The ENS is estimated to contain >100 million neurons, including afferent neurons, interneurons, and efferent postganglionic parasympathetic neurons. Enteric neurons contain many different neurotransmitters and neuromodulators. Thus, not only does the total number of neurons in the enteric division exceed that of the spinal cord, but the neurochemical complexity of the ENS also approaches that of the CNS. The anatomy of the ENS as well as its role in controlling GI function is discussed in Chapter 41.

肠道神经系统 （ENS） 是围绕胃肠道的神经丛的集合，包括胰腺和胆道系统。虽然它完全是外围的，但 ENS 接收来自 ANS 的交感神经和副交感神经部门的输入。据估计，ENS 包含 > 1 亿个神经元，包括传入神经元、中间神经元和传出节后副交感神经元。肠道神经元包含许多不同的神经递质和神经调节剂。因此，不仅肠道分裂的神经元总数超过脊髓的神经元总数，而且 ENS 的神经化学复杂性也接近 CNS 的神经化学复杂性。ENS 的解剖结构及其在控制 GI 功能中的作用将在第 41 章中讨论。


The plexuses of the ENS are a system of ganglia sandwiched between the layers of the gut and connected by a dense meshwork of nerve fibers. The myenteric or Auerbach’s plexus (Fig. 14-6) lies between the outer longitudinal and the inner circular layers of smooth muscle, whereas the submucosal or Meissner’s plexus lies between the inner circular layer of smooth muscle and the most internal layer of smooth muscle, the muscularis mucosae (see Fig. 41-3). In the intestinal wall, the myenteric plexus is involved primarily in the control of motility, whereas the submucosal plexus is involved in the control of ion and fluid transport. Both the myenteric and the submucosal plexuses receive preganglionic parasympathetic innervation from the vagus nerve (or sacral nerves in the case of the distal portion of colon and rectum). Thus, in one sense, the enteric division is homologous to a large and complex parasympathetic terminal ganglion. The other major input to the ENS is from postganglionic sympathetic neurons. Thus, the ENS can be thought of as “postganglionic” or as a “terminal organ” with respect to the parasympathetic division and “post-postganglionic” with respect to the sympathetic division. Input from both the sympathetic and parasympathetic divisions modulates the activity of the ENS, but the ENS can by and large function normally without extrinsic input. The isolated ENS can respond appropriately to local stimuli and control most aspects of gut function, including initiating peristaltic activity in response to gastric distention, controlling secretory and absorptive functions, and triggering biliary contractions (Box 14-1).

ENS 的神经丛是夹在肠道各层之间的神经节系统，由密集的神经纤维网连接。肌间神经丛或 Auerbach 神经丛（图 14-6）位于平滑肌的外纵层和内环层之间，而粘膜下神经丛或 Meissner 神经丛位于平滑肌的内环层和平滑肌最内层之间，即粘膜肌层（见图 41-3）。在肠壁中，肌间神经丛主要参与运动的控制，而粘膜下丛则参与离子和液体运输的控制。肌间神经丛和粘膜下丛都接受来自迷走神经（或结肠和直肠远端部分的骶神经）的节前副交感神经支配。因此，从某种意义上说，肠道支与一个大而复杂的副交感神经末末节同源。ENS 的另一个主要输入来自节后交感神经元。因此，ENS 可以被认为是“神经节后”或“终末器官”，而对于交感神经分支，可以认为是“神经节后”。来自交感神经和副交感神经部门的输入都调节了 ENS 的活动，但 ENS 基本上可以在没有外源输入的情况下正常运作。离体 ENS 可以对局部刺激做出适当反应并控制肠道功能的大多数方面，包括启动蠕动活动以响应胃膨胀、控制分泌和吸收功能以及触发胆道收缩（框 14-1）。

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== 自主神经系统的突触生理学 ==
<b style=color:#f80>SYNAPTIC PHYSIOLOGY OF THE AUTONOMIC NERVOUS SYSTEM</b>

=== 交感神经和副交感神经分支对大多数内脏目标具有相反的作用 ===
<b style=color:#0ae>The sympathetic and parasympathetic divisions have opposite effects on most visceral targets</b>

All innervation of skeletal muscle in humans is excitatory. In contrast, many visceral targets receive both inhibitory and excitatory synaptic inputs. These antagonistic inputs arise from the two opposing divisions of the ANS, the sympathetic and the parasympathetic.

人类骨骼肌的所有神经支配都是兴奋性的。相比之下，许多内脏靶标同时接受抑制性和兴奋性突触输入。这些对立的输入来自 ANS 的两个对立部分，即交感和副交感。


In organs that are stimulated during physical activity, the sympathetic division is excitatory and the parasympathetic division is inhibitory. For example, sympathetic input increases the heart rate, whereas parasympathetic input decreases it. In organs whose activity increases while the body is at rest, the opposite is true. For example, the parasympathetic division stimulates peristalsis of the gut, whereas the sympathetic division inhibits it.

在体力活动期间受到刺激的器官中，交感神经支是兴奋性的，而副交感神经支是抑制性的。例如，交感神经输入会增加心率，而副交感神经输入会降低心率。在身体处于静止状态时活动增加的器官中，情况正好相反。例如，副交感神经部门刺激肠道蠕动，而交感神经部门抑制肠道蠕动。


Although antagonistic effects of the sympathetic and parasympathetic divisions of the ANS are the general rule for most end organs, exceptions exist. For example, the salivary glands are stimulated by both divisions, although stimulation by the sympathetic division has effects different from those of parasympathetic stimulation (see p. 894). In addition, some organs receive innervation from only one of these two divisions of the ANS. For example, sweat glands, piloerector muscles, and most peripheral blood vessels receive input from only the sympathetic division.

尽管 ANS 交感神经和副交感神经分支的拮抗作用是大多数终末器官的一般规则，但也存在例外。例如，唾液腺受到两种部门的刺激，尽管交感神经部门的刺激与副交感神经刺激的效果不同（见第 894 页）。此外，一些器官仅从 ANS 的这两个分支之一获得神经支配。例如，汗腺、竖毛肌和大多数外周血管仅接收来自交感神经部的输入。


Synapses of the ANS are specialized for their function. Rather than possessing synaptic terminals that are typical of somatic motor axons, many postganglionic autonomic neurons have bulbous expansions, or varicosities, that are distributed along their axons within their target organ (Fig. 14-7). It was once believed that these varicosities indicated that neurotransmitter release sites of the ANS did not form close contact with end organs and that neurotransmitters needed to diffuse long distances across the extracellular space to reach their targets. However, we now recognize that many varicosities form synapses with their targets, with a synaptic cleft extending ~50 nm across. At each varicosity, autonomic axons form an “en passant” synapse with their end-organ target. This arrangement results in an increase in the number of targets that a single axonal branch can influence, with wider distribution of autonomic output.

ANS 的突触专门用于其功能。许多节后自主神经神经元不具有典型的体细胞运动轴突的突触末端，而是具有球状扩张或静脉曲张，这些扩张或静脉曲张分布在其靶器官内的轴突上（图 14-7）。曾经有人认为，这些静脉曲张表明 ANS 的神经递质释放位点不与终末器官形成密切接触，神经递质需要跨细胞外空间长距离扩散才能到达目标。然而，我们现在认识到许多静脉曲张与其靶标形成突触，突触裂隙延伸 ~50 nm。在每个静脉曲张处，自主神经轴突与其终末器官靶标形成一个“en passant”突触。这种安排导致单个轴突分支可以影响的目标数量增加，自主神经输出的分布更广。

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=== 所有节前神经元（包括交感神经和副交感神经）都会释放乙酰胆碱并刺激节后神经元上的 N2 烟碱受体 ===
<b style=color:#0ae>All preganglionic neurons—both sympathetic and parasympathetic—release acetylcholine and stimulate N2 nicotinic receptors on postganglionic neurons</b>

At synapses between postganglionic neurons and target cells, the two major divisions of the ANS use different neurotransmitters and receptors (Table 14-1). However, in both the sympathetic and parasympathetic divisions, synaptic transmission between preganglionic and postganglionic neurons (termed ganglionic transmission because the synapse is located in a ganglion) is mediated by acetylcholine (ACh) acting on nicotinic receptors (Fig. 14-8). Nicotinic receptors are ligand-gated channels (i.e., ionotropic receptors) with a pentameric structure (see pp. 212–213). Table 14-2 summarizes some of the properties of nicotinic receptors. The nicotinic receptors on postganglionic autonomic neurons are of a molecular subtype (N2) different from that found at the neuromuscular junction (N1). Both are ligand-gated ion channels activated by ACh or nicotine. However, whereas the N1 receptors at the neuromuscular junction (see p. 212) are stimulated by decamethonium and preferentially blocked by d-tubocurarine, N8-2 the autonomic N2 receptors are stimulated by tetramethylammonium but resistant to d-tubocurarine. When activated, N1 and N2 receptors are both permeable to Na+ and K+. Thus, nicotinic transmission triggered by stimulation of preganglionic neurons leads to rapid depolarization of postganglionic neurons.

在节后神经元和靶细胞之间的突触处，ANS 的两个主要分支使用不同的神经递质和受体（表 14-1）。然而，在交感神经和副交感神经分支中，节前神经元和节后神经元之间的突触传递（称为神经节传递，因为突触位于神经节中）是由作用于烟碱受体的乙酰胆碱 （ACh） 介导的（图 14-8）。烟碱受体是具有五聚体结构的配体门控通道（即离子型受体）（参见第 212-213 页）。表 14-2 总结了烟碱受体的一些特性。节后自主神经神经元上的烟碱受体属于与神经肌肉接头 （N1） 处发现的分子亚型 （N2） 不同。两者都是由 ACh 或尼古丁激活的配体门控离子通道。然而，神经肌肉接头处的 N1 受体（见第 212 页）受十甲铵刺激并优先被 d-tubocurarine 阻断，而自主神经 N2 受体受四甲基铵刺激，但对 d-tubocurarine 耐药。激活后，N1 和 N2 受体均能渗透 Na+ 和 K+。因此，由节前神经元刺激触发的烟碱传递导致节后神经元的快速去极化。

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=== 所有节后副交感神经元都释放 ACh 并刺激内脏靶标上的毒蕈碱受体 ===
<b style=color:#0ae>All postganglionic parasympathetic neurons release ACh and stimulate muscarinic receptors on visceral targets</b>

All postganglionic parasympathetic neurons act through muscarinic ACh receptors on the postsynaptic target (see Fig. 14-8). Activation of this receptor can either stimulate or inhibit function of the target cell. Cellular responses induced by muscarinic receptor stimulation are more varied than are those induced by nicotinic receptors. Muscarinic receptors are G protein–coupled receptors (GPCRs; see pp. 51–66)— also known as metabotropic receptors—that (1) stimulate the hydrolysis of phosphoinositide and thus increase [Ca2+]i and activate protein kinase C, (2) inhibit adenylyl cyclase and thus decrease cAMP levels, or (3) directly modulate K+ channels through the G-protein βγ complex (see pp. 197–198 and 542). Because they are mediated by second messengers, muscarinic responses, unlike the rapid responses evoked by nicotine receptors, are slow and prolonged.

所有节后副交感神经元都通过突触后靶标上的毒蕈碱 ACh 受体起作用（见图 14-8）。该受体的激活可以刺激或抑制靶细胞的功能。毒蕈碱受体刺激诱导的细胞反应比烟碱受体诱导的细胞反应更多样化。毒蕈碱受体是 G 蛋白偶联受体 （GPCR;见第 51-66 页）— 也称为代谢受体— （1） 刺激磷酸肌醇的水解，从而增加 [Ca2+]i 并激活蛋白激酶 C，（2） 抑制腺苷酸环化酶，从而降低 cAMP 水平，或 （3） 通过 G 蛋白 βγ 复合物直接调节 K+ 通道（参见第 197-198 页和第 542 页）。因为它们是由第二信使介导的，所以毒蕈碱反应与尼古丁受体诱发的快速反应不同，是缓慢而持久的。


Muscarinic receptors exist in five different pharmacological subtypes (M1 to M5) that are encoded by five different genes. All five subtypes are highly homologous to each other but very different from the nicotinic receptors, which are ligand-gated ion channels. Subtypes M1 through M5 are each stimulated by ACh and muscarine and are blocked by atropine. These muscarinic subtypes have a heterogeneous distribution among tissues, and in many cases a given cell may express more than one subtype. N14-3 Although a wide variety of antagonists inhibit the muscarinic receptors, none is completely selective for a specific subtype. However, it is possible to classify a receptor on the basis of its affinity profile for a battery of antagonists. Selective agonists for the different isoforms have not been available.

毒蕈碱受体存在于 5 种不同的药理学亚型 （M1 至 M5） 中，由 5 个不同的基因编码。所有五种亚型彼此高度同源，但与烟碱受体非常不同，烟碱受体是配体门控离子通道。M1 至 M5 亚型分别受到 ACh 和毒蕈碱的刺激，并被阿托品阻断。这些毒蕈碱亚型在组织之间具有异质性分布，在许多情况下，给定的细胞可能表达不止一种亚型。N14-3 尽管多种拮抗剂抑制毒蕈碱受体，但没有一种对特定亚型具有完全选择性。然而，可以根据受体对一组拮抗剂的亲和力特征对受体进行分类。目前还没有针对不同亚型的选择性激动剂。


A molecular characteristic of the muscarinic receptors is that the third cytoplasmic loop (i.e., between the fifth and sixth membrane-spanning segments) is different in M1, M3, and M5 on the one hand and M2 and M4 on the other. This loop appears to play a role in coupling of the receptor to the G protein downstream in the signal-transduction cascade. In general M1, M3, and M5 preferentially couple to Gαq and then to phospholipase C, with release of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (see p. 58). On the other hand M2 and M4 preferentially couple to Gαi or Gαo to inhibit adenylyl cyclase and thus decrease [cAMP]i (see p. 53).

毒蕈碱受体的分子特征是第三个细胞质环（即，在第五和第六跨膜段之间）一方面在 M1、M3 和 M5 上不同，另一方面在 M2 和 M4 上不同。该环似乎在信号转导级联反应中受体与下游 G 蛋白的偶联中发挥作用。通常，M1、M3 和 M5 优先与 Gαq 偶联，然后与磷脂酶 C 偶联，释放肌醇 1,4,5-三磷酸 （IP3） 和甘油二酯（见第 58 页）。另一方面，M2 和 M4 优先与 Gαi 或 Gαo 偶联以抑制腺苷酸环化酶，从而降低 [cAMP]i（见第 53 页）。

<br>

=== 大多数节后交感神经元将去甲肾上腺素释放到内脏靶标上 ===
<b style=color:#0ae>Most postganglionic sympathetic neurons release norepinephrine onto visceral targets</b>

Most postganglionic sympathetic neurons release norepinephrine (see Fig. 15-8), which acts on target cells through adrenergic receptors. The sympathetic innervation of sweat glands is an exception to this rule. N14-4 Sweat glands are innervated by sympathetic neurons that release ACh and act via muscarinic receptors (see p. 571). The adrenergic receptors are all GPCRs and are highly homologous to the muscarinic receptors (see p. 341). Two major types of adrenergic receptors are recognized, α and β, each of which exists in multiple subtypes (e.g., α1, α2, β1, β2, and β3). In addition, there are heterogeneous α1 and α2 receptors, with three cloned subtypes of each. Table 14-2 lists the signaling pathways that are generally linked to these receptors. For example, β1 receptors in the heart activate the Gs heterotrimeric G protein and stimulate adenylyl cyclase, which antagonizes the effects of muscarinic receptors.

大多数节后交感神经元释放去甲肾上腺素（见图 15-8），它通过肾上腺素能受体作用于靶细胞。汗腺的交感神经支配是这个规则的一个例外[N14-4]。汗腺由交感神经元支配，交感神经元释放 ACh 并通过毒蕈碱受体发挥作用（见第 571 页）。肾上腺素能受体都是 GPCR，与毒蕈碱受体高度同源（见第 341 页）。肾上腺素能受体有两种主要类型，α 和 β，每种受体都存在于多个亚型中（例如，α1、α2、β1、β2 和 β3）。此外，还有异质性 α1 和 α2 受体，每种受体都有三个克隆亚型。表 14-2 列出了通常与这些受体相关的信号转导通路。例如，心脏中的 β1 受体激活 Gs 异源三聚体 G 蛋白并刺激腺苷酸环化酶，从而拮抗毒蕈碱受体的作用。


Adrenergic receptor subtypes have a tissue-specific distribution. α1 receptors predominate on blood vessels, α2 on presynaptic terminals, β1 in the heart, β2 in high concentration in the bronchial muscle of the lungs, and β3 in fat cells. This distribution has permitted the development of many clinically useful agents that are selective for different subtypes and tissues. For example, α1 agonists are effective as nasal decongestants, and α2 antagonists have been used to treat impotence. β1 agonists increase cardiac output in congestive heart failure, whereas β1 antagonists are useful antihypertensive agents. β2 agonists are used as bronchodilators in patients with asthma and chronic lung disease.

肾上腺素能受体亚型具有组织特异性分布。α1 受体在血管中占主导地位，α2 在突触前末梢，β1 在心脏中，β2 在肺支气管肌中高浓度，β3 在脂肪细胞中。这种分布允许开发许多临床上有用的药物，这些药物对不同的亚型和组织具有选择性。例如，α1 激动剂作为鼻减充血剂有效，α2 拮抗剂已用于治疗阳痿。β1 受体激动剂可增加充血性心力衰竭患者的心输出量，而 β1 受体拮抗剂是有用的降压药。β2 激动剂用作哮喘和慢性肺病患者的支气管扩张剂。


The adrenal medulla (see pp. 1030–1034) is a special adaptation of the sympathetic division, homologous to a postganglionic sympathetic neuron (see Fig. 14-8). It is innervated by preganglionic sympathetic neurons, and the postsynaptic target cells, which are called chromaffin cells, have nicotinic ACh receptors. However, rather than possessing axons that release norepinephrine onto a specific target organ, the chromaffin cells reside near blood vessels and release epinephrine into the bloodstream. This neuroendocrine component of sympathetic output enhances the ability of the sympathetic division to broadcast its output throughout the body. Norepinephrine and epinephrine both activate all five subtypes of adrenergic receptor, but with different affinities (see Table 14-2). In general, the α receptors have a greater affinity for norepinephrine, whereas the β receptors have a greater affinity for epinephrine.

肾上腺髓质（见第 1030-1034 页）是交感神经的特殊适应，与节后交感神经神经元同源（见图 14-8）。它由节前交感神经元支配，突触后靶细胞（称为嗜铬细胞）具有烟碱 ACh 受体。然而，嗜铬细胞并不具有将去甲肾上腺素释放到特定靶器官上的轴突，而是位于血管附近并将肾上腺素释放到血液中。交感神经输出的这种神经内分泌成分增强了交感神经部门将其输出广播到全身的能力。去甲肾上腺素和肾上腺素都激活肾上腺素能受体的所有五种亚型，但亲和力不同（见表 14-2）。一般来说，α 受体对去甲肾上腺素具有更大的亲和力，而 β 受体对肾上腺素的亲和力更大。

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=== 节后交感神经和副交感神经神经元通常具有毒蕈碱受体和烟碱受体 ===
<b style=color:#0ae>Postganglionic sympathetic and parasympathetic neurons often have muscarinic as well as nicotinic receptors</b>

The simplified scheme described in the preceding discussion is very useful for understanding the function of the ANS. However, two additional layers of complexity are superimposed on this scheme. First, some postganglionic neurons, both sympathetic and parasympathetic, have muscarinic in addition to nicotinic receptors. Second, at all levels of the ANS, certain neurotransmitters and postsynaptic receptors are neither cholinergic nor adrenergic. We discuss the first exception in this section and the second in the following section.

前面讨论中描述的简化方案对于理解 ANS 的功能非常有用。但是，此方案上还叠加了另外两层复杂性。首先，一些节后神经元，包括交感神经和副交感神经，除了烟碱受体外，还含有毒蕈碱。其次，在 ANS 的所有水平上，某些神经递质和突触后受体既不是胆碱能的，也不是肾上腺素能的。我们将在本节中讨论第一个异常，在下一节中讨论第二个异常。


If we stimulate the release of ACh from preganglionic neurons or apply ACh to an autonomic ganglion, many postganglionic neurons exhibit both nicotinic and muscarinic responses. Because nicotinic receptors (N2) are ligand-gated ion channels, nicotinic neurotransmission causes a fast, monophasic excitatory postsynaptic potential (EPSP). In contrast, because muscarinic receptors are GPCRs, neurotransmission by this route leads to a slower electrical response that can be either inhibitory or excitatory. Thus, depending on the ganglion, the result is a multiphasic postsynaptic response that can be a combination of a fast EPSP through a nicotinic receptor plus either a slow EPSP or a slow inhibitory postsynaptic potential (IPSP) through a muscarinic receptor. Figure 14-9A shows a fast EPSP followed by a slow EPSP.

如果我们刺激节前神经元释放 ACh 或将 ACh 应用于自主神经节，许多节后神经元会同时表现出烟碱和毒蕈碱反应。因为烟碱受体 （N2） 是配体门控离子通道，所以烟碱神经传递会导致快速、单相兴奋性突触后电位 （EPSP）。相反，由于毒蕈碱受体是 GPCR，因此通过这种途径进行的神经传递会导致较慢的电反应，这可能是抑制性的或兴奋性的。因此，根据神经节的不同，结果是多相突触后反应，可以是通过烟碱受体的快速 EPSP 加上通过毒蕈碱受体的慢速 EPSP 或慢速抑制性突触后电位 （IPSP） 的组合。图 14-9A 显示了一个快速 EPSP 后跟一个慢速 EPSP。


A well-characterized effect of muscarinic neurotransmission in autonomic ganglia is inhibition of a specific K+ current called the M current. The M current is widely distributed in visceral end organs, autonomic ganglia, and the CNS. In the baseline state, the K+ channel that underlies the M current is active and thereby produces slight hyperpolarization. In the example shown in Figure 14-9B, with the stabilizing M current present, electrical stimulation of the neuron causes only a single spike. If we now add muscarine to the neuron, activation of the muscarinic receptor turns off the hyperpolarizing M current and thus leads to a small depolarization. If we repeat the electrical stimulation in the continued presence of muscarine (see Fig. 14-9C), repetitive spikes appear because loss of the stabilizing influence of the M current increases the excitability of the neuron. The slow, modulatory effects of muscarinic responses greatly enhance the ability of the ANS to control visceral activity beyond what could be accomplished with only fast nicotinic EPSPs.

毒蕈碱神经传递在自主神经节中的一个明确特征的作用是抑制称为 M 电流的特定 K+ 电流。M 电流广泛分布于内脏终末器官、自主神经节和 CNS。在基线状态下，作为 M 电流基础的 K+ 通道是有效的，因此会产生轻微的超极化。在图 14-9B 所示的示例中，在存在稳定 M 电流的情况下，神经元的电刺激仅引起单个尖峰。如果我们现在将毒蕈碱添加到神经元中，毒蕈碱受体的激活会关闭超极化的 M 电流，从而导致小的去极化。如果我们在持续存在毒蕈碱的情况下重复电刺激（见图 14-9C），则会出现重复的尖峰，因为 M 电流稳定作用的丧失增加了神经元的兴奋性。毒蕈碱反应的缓慢调节作用大大增强了 ANS 控制内脏活动的能力，超出了仅使用快速烟碱 EPSP 所能完成的能力。

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=== 非经典发射机可以在 ANS 的每个级别释放 ===
<b style=color:#0ae>Nonclassic transmitters can be released at each level of the ANS</b>

In the 1930s, Sir Henry Dale N14-5 first proposed that sympathetic nerves release a transmitter similar to epinephrine (now known to be norepinephrine) and parasympathetic nerves release ACh. For many years, attention was focused on these two neurotransmitters, primarily because they mediate large and fast postsynaptic responses that can be easily studied. In addition, a variety of antagonists are available to block cholinergic and adrenergic receptors and thereby permit clear characterization of the roles of these receptors in the control of visceral function. More recently, it has become evident that some neurotransmission in the ANS involves neither adrenergic nor cholinergic pathways. Moreover, many neuronal synapses use more than a single neurotransmitter. Such cotransmission is now known to be common in the ANS. As many as eight different neurotransmitters may be found within some neurons, a phenomenon known as colocalization (see Table 13-1). Thus, ACh and norepinephrine play important but not exclusive roles in autonomic control.

在 1930 年代，亨利·戴尔爵士[N14-5] 首次提出交感神经释放类似于肾上腺素的递质（现在已知是去甲肾上腺素），副交感神经释放 ACh。多年来，人们的注意力都集中在这两种神经递质上，主要是因为它们介导了易于研究的大而快速的突触后反应。此外，有多种拮抗剂可用于阻断胆碱能和肾上腺素能受体，从而可以清楚地表征这些受体在控制内脏功能中的作用。最近，很明显 ANS 中的一些神经传递既不涉及肾上腺素能通路，也不涉及胆碱能通路。此外，许多神经元突触使用不止一种神经递质。现在已知这种共传在 ANS 中很常见。在某些神经元中可能发现多达 8 种不同的神经递质，这种现象称为共定位（见表 13-1）。因此，ACh 和去甲肾上腺素在自主神经控制中起着重要但并非排他性的作用。


The distribution and function of nonadrenergic, noncholinergic (NANC) transmitters are only partially understood. However, these transmitters are found at every level of autonomic control (Table 14-3), where they can cause a wide range of postsynaptic responses. These nonclassic transmitters may cause slow synaptic potentials or may modulate the response to other inputs (as in the case of the M current) without having obvious direct effects. In other cases, nonclassic transmitters have no known effects and may be acting in ways that have not yet been determined.

非肾上腺素能、非胆碱能 （NANC） 递质的分布和功能仅部分了解。然而，这些递质存在于自主神经控制的每个水平（表 14-3），它们可以引起广泛的突触后反应。这些非经典发射器可能会导致突触电位缓慢，或者可能会调制对其他输入的响应（如 M 电流的情况），而不会产生明显的直接影响。在其他情况下，非经典递质没有已知的影响，并且可能以尚未确定的方式发挥作用。

Although colocalization of neurotransmitters is recognized as a common property of neurons, it is not clear what controls the release of each of the many neurotransmitters. In some cases, the proportion of neurotransmitters released depends on the level of neuronal activity (see pp. 327–328). For example, medullary raphé neurons project to the intermediolateral cell column in the spinal cord, where they co-release serotonin, thyrotropin-releasing hormone, and substance P onto sympathetic preganglionic neurons. The proportions of released neurotransmitters are controlled by neuronal firing frequency: at low firing rates, serotonin is released alone; at intermediate firing rates, thyrotropin-releasing hormone is also released; and at high firing rates, all three neurotransmitters are released. This frequency-dependent modulation of synaptic transmission provides a mechanism for enhancing the versatility of the ANS.

尽管神经递质的共定位被认为是神经元的共同特性，但尚不清楚是什么控制了许多神经递质中每一种的释放。在某些情况下，释放的神经递质的比例取决于神经元活动的水平（参见第 327-328 页）。例如，髓质 raphé 神经元投射到脊髓的中间外侧细胞柱，在那里它们共同释放血清素、促甲状腺激素释放激素和 P 物质到交感神经节前神经元上。释放的神经递质的比例受神经元放电频率控制：在低放电速率下，血清素单独释放;在中等放电速率下，也会释放促甲状腺激素释放激素;在高放电速率下，所有三种神经递质都被释放。这种突触传递的频率依赖性调制提供了一种增强 ANS 多功能性的机制。

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=== 两种最不常见的非经典神经递质 ATP 和一氧化氮首先在 ANS 中被发现 ===
<b style=color:#0ae>Two of the most unusual nonclassic neurotransmitters, ATP and nitric oxide, were first identified in the ANS</b>

It was not until the 1970s that a nonadrenergic, noncholinergic class of sympathetic or parasympathetic neurons was first proposed by Geoffrey Burnstock and colleagues, who suggested that ATP might act as the neurotransmitter. This idea, that a molecule used as an intracellular energy substrate could also be a synaptic transmitter, was initially difficult to prove. However, it is now clear that neurons use a variety of classes of molecules for intercellular communication (see pp. 314–322). Two of the most surprising examples of nonclassic transmitters, nitric oxide (NO) and ATP, were first identified and studied as neurotransmitters in the ANS, but they are now known to be more widely used throughout the nervous system.

直到 1970 年代，Geoffrey Burnstock 及其同事才首次提出了一类非肾上腺素能、非胆碱能的交感神经或副交感神经神经元，他们认为 ATP 可能充当神经递质。这个想法，即用作细胞内能量基质的分子也可以是突触递质，最初很难证明。然而，现在很明显，神经元使用各种类别的分子进行细胞间通讯（参见第 314-322 页）。非经典递质的两个最令人惊讶的例子，一氧化氮 （NO） 和 ATP，首先在 ANS 中被确定和研究为神经递质，但现在已知它们在整个神经系统中得到更广泛的应用。


<b style=color:#0ae>ATP</b> ATP is colocalized with norepinephrine in postganglionic sympathetic vasoconstrictor neurons. It is contained in synaptic vesicles, is released on electrical stimulation, and induces vascular constriction when it is applied directly to vascular smooth muscle. The effect of ATP results from activation of P2 purinoceptors on smooth muscle, which include ligand-gated ion channels (P2X) and GPCRs (P2Y and P2U). P2X receptors are present on autonomic neurons and smooth-muscle cells of blood vessels, the urinary bladder, and other visceral targets. P2X receptor channels have a relatively high Ca2+ permeability (see p. 327). In smooth muscle, ATP-induced depolarization can also activate voltage-gated Ca2+ channels (see pp. 189–190) and thus lead to an elevation in [Ca2+]i and a rapid phase of contraction (Fig. 14-10).

<b style=color:#0ae>ATP</b> ATP 与去甲肾上腺素共定位于节后交感神经血管收缩神经元中。它包含在突触囊泡中，在电刺激下释放，当它直接应用于血管平滑肌时会诱导血管收缩。ATP 的影响是由于 P2 嘌呤受体对平滑肌的激活而产生的，平滑肌包括配体门控离子通道 （P2X） 和 GPCR （P2Y 和 P2U）。P2X 受体存在于自主神经元和血管、膀胱和其他内脏靶标的平滑肌细胞上。P2X 受体通道具有相对较高的 Ca2+ 通透性（参见第 327 页）。在平滑肌中，ATP 诱导的去极化还可以激活电压门控的 Ca2+ 通道（参见第 189-190 页），从而导致 [Ca2+]i 升高和快速收缩阶段（图 14-10）。


Norepinephrine, by binding to α1 adrenergic receptors, acts through a heterotrimeric G protein (see pp. 51–66) to facilitate the release of Ca2+ from intracellular stores and thereby produce a slower phase of contraction. Finally, the release of neuropeptide Y may, after prolonged and intense stimulation, elicit a third component of contraction.

去甲肾上腺素通过与 α1 肾上腺素能受体结合，通过异源三聚体 G 蛋白起作用（参见第 51-66 页），以促进 Ca2+ 从细胞内储存中释放，从而产生较慢的收缩阶段。最后，神经肽 Y 的释放，经过长时间和强烈的刺激，可能会引发收缩的第三个组成部分。

<b style=color:#0ae>Nitric Oxide</b> In the 1970s, it was also discovered that the vascular endothelium produces a substance that induces relaxation of vascular smooth muscle. First called endothelium-derived relaxation factor, it was identified as the free radical NO in 1987. NO is an unusual molecule for intercellular communication because it is a short-lived gas. It is produced locally from L-arginine by the enzyme nitric oxide synthase (NOS; see pp. 66–67). The NO then diffuses a short distance to a neighboring cell, where its effects are primarily mediated by the activation of guanylyl cyclase. NOS is found in the preganglionic and postganglionic neurons of both the sympathetic and parasympathetic divisions as well as in vascular endothelial cells. It is not specific for any type of neuron inasmuch as it is found in both norepinephrine- and ACh-containing cells as well as neurons containing a variety of neuropeptides. Figure 14-11 shows how a parasympathetic neuron may simultaneously release NO, ACh, and vasoactive intestinal peptide, each acting in concert to lower [Ca2+]i and relax vascular smooth muscle.

<b style=color:#0ae>NO</b> 在 1970 年代，还发现血管内皮产生一种诱导血管平滑肌松弛的物质。它最初被称为内皮衍生的松弛因子，于 1987 年被确定为自由基 NO。NO 是一种不常见的细胞间通讯分子，因为它是一种短寿命气体。它是通过一氧化氮合酶 （NOS;见第 66-67 页） 从 L-精氨酸局部产生的。然后，NO 会扩散到邻近细胞，在那里其作用主要由鸟苷酸环化酶的激活介导。NOS 存在于交感神经和副交感神经分支的节前和节后神经元以及血管内皮细胞中。它对任何类型的神经元都没有特异性，因为它存在于含有去甲肾上腺素和 ACh 的细胞以及含有多种神经肽的神经元中。图 14-11 显示了副交感神经元如何同时释放 NO、ACh 和血管活性肠肽，每一种都协同作用以降低 [Ca2+]i 并放松血管平滑肌。

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== 内脏的中枢神经系统控制 ==
<b style=color:#f80>CENTRAL NERVOUS SYSTEM CONTROL OF THE VISCERA</b>

=== 交感神经输出可以是大量和非特异性的，如战斗或逃跑反应，或对特定靶器官有选择性 ===
<b style=color:#0ae>Sympathetic output can be massive and nonspecific, as in the fight-or-flight response, or selective for specific target organs</b>

In 1915, Walter Cannon N14-6 proposed that the entire sympathetic division is activated together and has a uniform effect on all target organs. In response to fear, exercise, and other types of stress, the sympathetic division produces a massive and coordinated output to all end organs simultaneously, and parasympathetic output ceases. This type of sympathetic output is used to ready the body for life-threatening situations—the so-called fight-or-flight response. Thus, when a person is presented with a fearful or menacing stimulus, the sympathetic division coordinates all body functions to respond appropriately to the stressful situation. This response includes increases in heart rate, cardiac contractility, blood pressure, and ventilation of the lungs; bronchial dilatation; sweating; piloerection; liberation of glucose into the blood; inhibition of insulin secretion; reduction in blood clotting time; mobilization of blood cells by contraction of the spleen; and decreased GI activity. This mass response is a primitive mechanism for survival. In some people, such a response can be triggered spontaneously or with minimal provocation; each individual episode is then called a panic attack.

1915 年，Walter Cannon[N14-6] 提出整个交感神经系统一起被激活，对所有靶器官产生统一的作用。为了应对恐惧、运动和其他类型的压力，交感神经系统同时向所有末梢器官产生大量且协调的输出，副交感神经输出相反作用。这种类型的交感神经输出用于让身体为危及生命的情况做好准备 —— 所谓的战斗或逃跑反应。因此，当一个人受到恐惧或威胁性的刺激时，交感神经部门会协调所有身体功能，以适当地应对压力情况。这种反应包括心率、心脏收缩力、血压和肺通气量的增加、支气管扩张、出汗、竖毛、将葡萄糖释放到血液中、抑制胰岛素分泌、减少血液凝固时间、通过脾脏收缩动员血细胞、和 GI 活性降低。这种大量反应是一种原始的生存机制。在一些人中，这种反应可以自发触发，也可以在最小程度的挑衅下触发；每个单独的发作都称为恐惧袭击。


The fight-or-flight response is an important mechanism for survival, but under normal nonstressful conditions, output of the sympathetic division can also be more discrete and organ specific. In contrast to Cannon’s original proposal, the sympathetic division does not actually produce uniform effects on all visceral targets. Different postganglionic sympathetic neurons have different electrophysiological properties and release other neurotransmitters in addition to norepinephrine. This specific distribution of neuroactive chemicals among neurons is called chemical coding. For example, depolarization of guinea pig postganglionic sympathetic neurons in the lumbar sympathetic chain ganglia causes a brief burst of action potentials in 95% of the neurons and release of norepinephrine together with ATP and neuropeptide Y. These neurons are thought to innervate arteries and to induce vasoconstriction (see Fig. 14-10). In contrast, depolarization of postganglionic sympathetic neurons in the inferior mesenteric ganglion causes sustained firing in 80% of the neurons and release of norepinephrine together with somatostatin. These neurons appear to control gut motility and secretion. Thus, sympathetic neurons have cellular properties that are substantially variable. This variability permits the sympathetic division to produce different effects on targets with different functions.

战斗或逃跑反应是生存的重要机制，但在正常的非应激条件下，交感神经部门的输出也可能更加离散和器官特异性。与 Cannon 最初的提议相反，交感神经划分实际上并没有对所有本能目标产生一致的影响。不同的节后交感神经神经元具有不同的电生理特性，除去甲肾上腺素外 (NA)，还释放其他神经递质。神经活性化学物质在神经元中的这种特定分布称为化学编码。例如，腰交感神经节中豚鼠节后交感神经元的去极化导致 95% 的神经元动作电位短暂爆发，并释放去甲肾上腺素以及 ATP 和神经肽 Y。这些神经元被认为支配动脉并诱导血管收缩（见图 14-10）。相比之下，肠系膜下神经节中节后交感神经元的去极化导致 80% 的神经元持续放电，并释放去甲肾上腺素和生长抑素。这些神经元似乎控制着肠道的运动和分泌。因此，交感神经元具有基本可变的细胞特性。这种可变性允许交感神经分裂对具有不同功能的目标产生不同的影响。

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=== 副交感神经元参与许多简单的不自主反射 ===
<b style=color:#0ae>Parasympathetic neurons participate in many simple involuntary reflexes</b>

As opposed to neurons in the sympathetic division, neurons in the parasympathetic division function only in a discrete, organ-specific, and reflexive manner. Together with specific visceral afferents and a small number of interneurons, parasympathetic neurons mediate simple reflexes involving target organs. For example, the output of the baroreceptor reflex (see pp. 537–539) is mediated by preganglionic parasympathetic neurons in the dorsal motor nucleus of the vagus. Other examples include urination in response to bladder distention (see pp. 736–737); salivation in response to the sight or smell of food (see p. 895); vagovagal reflexes (see p. 857) in the GI tract, such as contraction of the colon in response to food in the stomach; and bronchoconstriction in response to activation of receptors in the lungs (see pp. 717– 718). The pupillary light reflex is an example of an involuntary parasympathetic reflex that can be tested at the bedside (see p. 362).

与交感神经部的神经元相反，副交感神经部的神经元仅以离散的、器官特异性和反射性的方式发挥作用。副交感神经元与特定的内脏传入神经和少量中间神经元一起介导涉及靶器官的简单反射。例如，压力感受器反射的输出（见第 537-539 页）是由迷走神经背侧运动核中的节前副交感神经元介导的。其他例子包括对膀胱膨胀的反应排尿（见第 736-737 页）；对食物的视觉或气味产生流涎（见第 895 页）；胃肠道中的阴道反射（见第 857 页），例如结肠对胃中食物的反应收缩和响应肺部受体激活的支气管收缩（见第 717-718 页）。瞳孔对光反射是可以在床边测试的非自主副交感神经反射的一个例子（见第 362 页）。

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=== 各种脑干核提供对 ANS 的基本控制 ===
<b style=color:#0ae>A variety of brainstem nuclei provide basic control of the ANS</b>

In addition to nuclei that contain parasympathetic preganglionic neurons (see Fig. 14-5), a variety of other brainstem structures are also involved in visceral control. These structures include the nucleus tractus solitarii, area postrema, ventrolateral medulla, medullary raphé, reticular formation, locus coeruleus, and parabrachial nucleus. These nuclei within the lower part of the brainstem mediate autonomic reflexes, control specific autonomic functions, or modulate the general level of autonomic tone. In some cases, these nuclei play a well-defined role in one specific autonomic function. For example, stimulation of a group of neurons in the rostral portion of the ventrolateral medulla increases sympathetic output to the cardiovascular system—without affecting respiration or sympathetic output to other targets. In other cases, these nuclei are linked to more than one autonomic function. For example, the medullary raphé contains serotonergic neurons that project to cardiovascular, respiratory, and GI neurons, the reticular activating system, and pain pathways. Therefore, these neurons can affect the background level of autonomic tone. The specific functions of some nuclei are not known, and their involvement in autonomic control is inferred from their anatomical connections, a correlation between neuron activity and activity in autonomic nerves, or the effect of lesions.

除了包含副交感神经节前神经元的细胞核（见图 14-5）外，各种其他脑干结构也参与内脏控制。这些结构包括孤束核、极后区、腹外侧延髓、髓质、网状结构、蓝斑和臂旁核。这些位于脑干下部的细胞核介导自主神经反射，控制特定的自主神经功能，或调节自主神经张力的一般水平。在某些情况下，这些细胞核在一种特定的自主神经功能中发挥着明确的作用。例如，刺激腹外侧延髓喙部的一组神经元会增加心血管系统的交感神经输出，而不会影响呼吸或对其他靶标的交感神经输出。在其他情况下，这些细胞核与多个自主神经功能有关。例如，髓质包含血清素能神经元，这些神经元投射到心血管、呼吸和胃肠道神经元、网状激活系统和疼痛通路。因此，这些神经元可以影响自主神经音调的背景水平。一些细胞核的具体功能尚不清楚，它们参与自主神经控制的参与是从它们的解剖学联系、神经元活动与自主神经活动之间的相关性或病变的影响中推断出来的。


One of the most important lower brainstem structures is the nucleus tractus solitarii (NTS) in the medulla. The NTS contains second-order sensory neurons that receive all input from peripheral chemoreceptors (see pp. 710–713) and baroreceptors input (see p. 537), as well as non-nociceptive afferent input from every organ of the thorax and abdomen. Visceral afferents from the vagus nerve make their first synapse within the NTS, where they combine with other visceral (largely unconscious) afferent impulses derived from the glossopharyngeal (CN IX), facial (CN VII), and trigeminal (CN V) nerves. These visceral afferents form a large bundle of nerve fibers—the tractus solitarius—that the NTS surrounds. Afferent input is distributed to the NTS in a viscerotopic manner, with major subnuclei devoted to respiratory, cardiovascular, gustatory, and GI input. The NTS also receives input and sends output to many other CNS regions (Table 14-4), including the brainstem nuclei described above as well as the hypothalamus and the forebrain. These widespread interconnections allow the NTS to influence and to be influenced by a wide variety of CNS functions. Thus, the NTS is the major lower brainstem command center for visceral control. It integrates multiple inputs from visceral afferents and exerts control over autonomic output, thereby participating in autonomic reflexes that maintain the homeostasis of many basic visceral functions.

最重要的下脑干结构之一是延髓中的孤束核 （NTS）。NTS 包含二阶感觉神经元，它们接收来自外周化学感受器（见第 710-713 页）和压力感受器输入（见第 537 页）的所有输入，以及来自胸部和腹部每个器官的非伤害性传入输入。来自迷走神经的内脏传入神经在 NTS 内形成第一个突触，在那里它们与来自舌咽神经 （CN IX）、面部 （CN VII） 和三叉神经 （CN V） 的其他内脏（大部分是无意识的）传入冲动结合。这些内脏传入神经形成一大束神经纤维——孤立束——NTS 围绕着它。传入输入以内脏定向方式分布到 NTS，主要亚核专门用于呼吸、心血管、味觉和 GI 输入。NTS 还接收输入并将输出发送到许多其他 CNS 区域（表 14-4），包括上述脑干核以及下丘脑和前脑。这些广泛的互连使 NTS 能够影响各种 CNS 功能并受其影响。因此，NTS 是内脏控制的主要下脑干指挥中心。它整合了来自内脏传入神经的多个输入，并控制自主神经输出，从而参与维持许多基本内脏功能的稳态的自主神经反射。

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=== 前脑可以调节自主神经输出，反过来，整合在脑干中的本能感觉输入可以影响甚至压倒前脑 ===
<b style=color:#0ae>The forebrain can modulate autonomic output, and reciprocally, visceral sensory input integrated in the brainstem can influence or even overwhelm the forebrain</b>

Only a subset of the nervous system is necessary to maintain autonomic body homeostasis under most conditions. The necessary structures include (1) the brainstem nuclei discussed in the preceding section, (2) the brainstem nuclei that contain the parasympathetic preganglionic neurons, (3) the spinal cord, and (4) the peripheral ANS. These components are capable of acting autonomously, even without input from higher (i.e., rostral) forebrain regions. However, forebrain regions do play a role in coordinating and modulating activity in the lower centers. Many rostral CNS centers influence autonomic output; these centers include the hypothalamus, amygdala, prefrontal cortex, entorhinal cortex, insula, and other forebrain nuclei.

在大多数情况下，维持自主体稳态只需要神经系统的一个子集。必要的结构包括 （1） 上一节中讨论的脑干核，（2） 包含副交感神经节前神经元的脑干核，（3） 脊髓，以及 （4） 外周 ANS。这些组件能够自主行动，即使没有来自高级（即嘴部）前脑区域的输入。然而，前脑区域确实在协调和调节下部中心的活动中发挥作用。许多喙部 CNS 中心影响自主神经输出;这些中枢包括下丘脑、杏仁核、前额叶皮层、内嗅皮层、岛叶和其他前脑核。


The hypothalamus, especially the paraventricular nucleus, is the most important brain region for coordination of autonomic output. The hypothalamus projects to the parabrachial nucleus, medullary raphé, NTS, central gray matter, locus coeruleus, dorsal motor nucleus of the vagus, nucleus ambiguus, and intermediolateral cell column of the spinal cord. Thus, the hypothalamus can initiate and coordinate an integrated response to the body’s needs, including modulation of autonomic output as well as control of neuroendocrine function by the pituitary gland (see p. 978). The hypothalamus coordinates autonomic function with feeding, thermoregulation, circadian rhythms, water balance, emotions, sexual drive, reproduction, motivation, and other brain functions and thus plays a dominant role in the integration of higher cortical and limbic systems with autonomic control. The hypothalamus can also initiate the fight-orflight response[N14-7].

下丘脑，尤其是脑室旁核，是协调自主神经输出的最重要大脑区域。下丘脑投射到臂旁核、髓质、NTS、中央灰质、蓝斑、迷走神经背运动核、模糊核和脊髓中间外侧细胞柱。因此，下丘脑可以启动和协调对身体需求的综合反应，包括自主神经输出的调节以及垂体对神经内分泌功能的控制（见第 978 页）。下丘脑将自主神经功能与进食、体温调节、昼夜节律、水平衡、情绪、性驱动、生殖、动机和其他大脑功能协调起来，因此在高级皮质和边缘系统与自主神经控制的整合中起主导作用。下丘脑也可以启动战斗或逃跑反应[N14-7]。


The hypothalamus often mediates interactions between the forebrain and the brainstem. However, a number of forebrain regions also have direct connections to brainstem nuclei involved in autonomic control. Most of these forebrain regions are part of the limbic system rather than the neocortex. The paucity of direct neocortical connections probably explains why individuals trained to control autonomic output by biofeedback can generally produce only relatively minor effects on overall autonomic activity rather than regulate output to specific organs. Most individuals are incapable of even limited cortical control over the ANS. However, even though we may have only minimal conscious control of autonomic output, cortical processes can strongly modulate the ANS. Emotions, mood, anxiety, stress, and fear can all alter autonomic output (Table 14-5, top section). The pathways for these effects are unknown, but they could be mediated by direct connections or through the hypothalamus.

下丘脑通常介导前脑和脑干之间的相互作用。然而，许多前脑区域也与参与自主神经控制的脑干核有直接联系。这些前脑区域中的大多数是边缘系统的一部分，而不是新皮层的一部分。缺乏直接的新皮层连接可能解释了为什么受过生物反馈控制自主神经输出训练的个体通常只能对整体自主神经活动产生相对较小的影响，而不是调节对特定器官的输出。大多数人甚至无法对 ANS 进行有限的皮层控制。然而，即使我们对自主神经输出的意识控制可能很小，皮层过程也可以强烈调节 ANS。情绪、情绪、焦虑、压力和恐惧都会改变自主神经输出（表 14-5，顶部）。这些影响的途径尚不清楚，但它们可能通过直接连接或通过下丘脑介导。


Not only does forebrain function influence the ANS, visceral activity also influences forebrain function. Visceral afferents reach the neocortex. However, because these afferents are not represented viscerotopically, they cannot be well localized. Nevertheless, visceral afferents can have profound effects on cortical function. Visceral input can modulate the excitability of cortical neurons (Box 14-2) and, in some cases, can result in such overpowering sensory stimuli that it is not possible to focus cortical activity on anything else (see Table 14-5, bottom section).

不仅前脑功能会影响 ANS，内脏活动也会影响前脑功能。内脏传入神经到达新皮层。然而，由于这些传入神经没有在内脏位上表示，因此无法很好地定位。然而，内脏传入神经会对皮质功能产生深远的影响。本能输入可以调节皮层神经元的兴奋性（框 14-2），并且在某些情况下，会导致如此强大的感觉刺激，以至于不可能将皮层活动集中在其他任何东西上（见表 14-5，下半部分）。

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=== CNS 控制中心监督本能反馈回路并协调前馈响应以满足预期需求 ===
<b style=color:#0ae>CNS control centers oversee visceral feedback loops and orchestrate a feed-forward response to meet anticipated needs</b>

The ANS maintains physiological parameters within an optimal range by means of feedback loops made up of sensors, afferent fibers, central autonomic control centers (discussed in the preceding section), and effector systems. These feedback loops achieve homeostasis by monitoring input from visceral receptors and adjusting the output of both the sympathetic and parasympathetic divisions to specific organs so that they maintain activity at a set-point determined by involuntary CNS control centers. As we have already noted, the sympathetic and parasympathetic divisions usually act in opposite ways to make these adjustments. Blood pressure control is an example of a visceral feedback loop in which the CNS monitors current blood pressure through afferents from baroreceptors, compares it with an internally determined set-point, and appropriately adjusts output to the heart, blood vessels, adrenal gland, and other targets. An increase in blood pressure (see pp. 537–539) causes a reflex decrease in sympathetic output to the heart and an increase in parasympathetic output.

ANS 通过由传感器、传入纤维、中枢自主神经控制中心（在上一节中讨论）和效应系统组成的反馈回路将生理参数保持在最佳范围内。这些反馈回路通过监测来自内脏受体的输入并调整交感神经和副交感神经对特定器官的输出来实现体内平衡，以便它们将活动维持在由非自愿 CNS 控制中心确定的设定点。正如我们已经指出的，交感神经和副交感神经的划分通常以相反的方式进行这些调整。血压控制是本能反馈回路的一个例子，其中 CNS 通过压力感受器的传入神经监测当前血压，将其与内部确定的设定点进行比较，并适当调整到心脏、血管、肾上腺和其他目标的输出。血压升高（见第 537-539 页）导致心脏交感神经输出的反射性减少和副交感神经输出增加。


Instead of merely responding through feedback loops, the ANS also anticipates the future needs of the individual. For example, when a person begins to exercise, sympathetic output increases before the increase in metabolic need to prevent an exercise debt from occurring (see p. 1214). Because of this anticipatory response, alveolar ventilation rises to such an extent that blood levels of CO2 (a byproduct of exercise) actually drop at the onset of exercise. This response is the opposite of what would be expected if the ANS worked purely through feedback loops, in which case an obligatory increase in CO2 levels would have preceded the increase in respiratory output (see pp. 716–717). Similarly, a trained athlete’s heart rate begins to increase several seconds before the starting gun fires to signal the beginning of a 100-m dash. This anticipation of future activity, or feedforward stimulation prior to (and during) exercise, is a key component of the regulation of homeostasis during stress because it prevents large changes in physiological parameters that could be detrimental to optimal function. This type of response probably resulted in an evolutionary advantage that permitted the body to respond rapidly and more efficiently to a threat of danger. A system relying solely on feedback could produce a response that is delayed or out of phase with respect to the stimulus. The central neuronal pathways responsible for this anticipatory or feed-forward response are not known.

ANS 不仅通过反馈循环做出响应，还预测个人的未来需求。例如，当一个人开始锻炼时，交感神经输出在防止运动债务发生的新陈代谢需求增加之前增加（见第 1214 页）。由于这种预期反应，肺泡通气量上升到如此程度，以至于血液中的 CO2（运动的副产品）水平实际上在运动开始时下降。这种反应与 ANS 纯粹通过反馈回路工作时的预期相反，在这种情况下，CO2 水平的强制性增加会在呼吸输出增加之前（见第 716-717 页）。同样，训练有素的运动员的心率在发令枪响前几秒钟开始增加，以发出 100 米冲刺的开始。这种对未来活动的预期，或在运动前（和运动中）的前馈刺激，是压力期间调节体内平衡的关键组成部分，因为它可以防止可能对最佳功能有害的生理参数发生巨大变化。这种类型的反应可能导致一种进化优势，使身体能够快速、更有效地对危险的威胁做出反应。仅依赖反馈的系统可能会产生与刺激有关的延迟或异相响应。负责这种预期或前馈反应的中枢神经元通路尚不清楚。

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=== ANS 具有多级反射环 ===
<b style=color:#0ae>The ANS has multiple levels of reflex loops</b>

The human nervous system is built in a hierarchy that mirrors phylogenetic evolution (see pp. 269–274). Each of the successively more primitive components is capable of independent, organized, and adaptive behavior. In turn, the activity of each of the more primitive levels is modulated by rostral, more phylogenetically advanced components. N14-8

人类神经系统建立在反映系统发育进化的层次结构中（参见第 269-274 页）。每个连续的更原始的组件都能够实现独立、有组织和自适应的行为。反过来，每个更原始的水平的活动都受到喙部、系统发育更高级的成分的调节 [N14-8]。

The enteric nervous system of humans is homologous to the most primitive nervous system, the neural net of jellyfish. In both cases, the component neurons control motility and nutrient absorption and respond appropriately to external stimuli.

人类的肠道神经系统与最原始的神经系统，即水母的神经网络同源。在这两种情况下，组成神经元都控制运动和营养吸收，并对外部刺激做出适当的反应。


The autonomic ganglia are homologous to ganglionic nervous systems, such as those of annelid worms. Autonomic ganglia were previously considered a simple relay station for signals from the CNS to the periphery, but it is now clear that they integrate afferent input from the viscera and have substantial independent control mechanisms. The largest of the sympathetic ganglia, the superior cervical ganglion, contains about 1 million neurons. In addition to postganglionic cell bodies, autonomic ganglia also contain interneurons. Axons from interneurons, sensory receptors located in the end organs, and preganglionic neurons converge with postganglionic neuron dendrites to form a dense network of nerve fibers, or a neuropil, within the ganglion. This neuropil confers considerable computational capability on the ganglia. Whereas feedback from skeletal muscle occurs only in the CNS, the peripheral synapses of visceral afferents result in substantial integration of autonomic activity at peripheral sites. This integration is enhanced by the variety of neurotransmitters released, for example, by interneurons in autonomic ganglia (see Table 14-3). Thus, although fast neurotransmission from preganglionic neurons to postganglionic neurons is an important role of the autonomic ganglia, the ganglia are not simply relays.

自主神经节与神经节神经系统同源，例如环节动物蠕虫的神经系统。自主神经节以前被认为是从 CNS 到外周信号的简单中继站，但现在很明显，它们整合了来自内脏的传入输入，并具有大量独立的控制机制。最大的交感神经节是颈上神经节，包含约 100 万个神经元。除了节后细胞体外，自主神经节还包含中间神经元。来自中间神经元的轴突、位于终末器官的感觉受体和节前神经元与节后神经元树突会聚，在神经节内形成致密的神经纤维网络或神经细胞。这种神经细胞赋予神经节相当大的计算能力。虽然骨骼肌的反馈仅发生在 CNS 中，但内脏传入神经的外周突触导致外周部位自主神经活动的大量整合。这种整合通过释放的各种神经递质得到增强，例如，自主神经节中的中间神经元（见表 14-3）。因此，尽管从节前神经元到节后神经元的快速神经传递是自主神经节的重要作用，但神经节不仅仅是中继。


The spinal cord, which coordinates activity among different root levels, first appeared with the evolution of chordates. The CNS of amphioxus, a primitive chordate, is essentially just a spinal cord. In humans who experience transection of the low cervical spinal cord—and in whom the outflow of the respiratory system is spared (see Chapter 32)—the caudal spinal cord and lower autonomic ganglia can still continue to maintain homeostasis. However, these individuals are incapable of more complex responses that require reflexes mediated by the cranial nerve afferents and cranial parasympathetic outflow. In many patients, this situation can lead to maladaptive reflexes such as autonomic hyper-reflexia, in which a full bladder results in hypertension and sweating (Boxes 14-3 and 14-4).

协调不同根水平之间活动的脊髓首先随着脊索动物的进化而出现。两栖动物的 CNS 是一种原始的脊索动物，本质上只是一条脊髓。在经历颈低位脊髓横断的人类中，呼吸系统流出幸免于难（见第 32 章），尾部脊髓和下自主神经节仍然可以继续维持体内平衡。然而，这些个体无法产生更复杂的反应，这些反应需要由颅神经传入神经和颅副交感神经流出介导的反射。在许多患者中，这种情况会导致适应不良反射，例如自主神经反射亢进，其中膀胱充盈会导致高血压和出汗（框 14-3 和 14-4）。


All vertebrates have a brain that is segmented into three parts (see p. 261): the prosencephalon, mesencephalon, and rhombencephalon. With evolution, the more rostral parts took on a more dominant role. The brain of the ammocoete larva of the lamprey is dominated by the medulla, which is also the most vital part of the human brain; in contrast to destruction of more rostral structures, destruction of the medulla leads to instant death in the absence of life support. The medulla coordinates all visceral control and optimizes it for survival. In humans, normal body homeostasis can continue indefinitely with only a medulla, spinal cord, and peripheral ANS.

所有脊椎动物都有一个分为三个部分的大脑（见第 261 页）：前脑、中脑和菱脑。随着进化，更多的喙部占据了更主导的角色。七鳃鳗的 ammocoete 幼虫的大脑以髓质为主，髓质也是人脑中最重要的部分;与破坏更多的喙部结构相反，髓质的破坏会导致在没有生命支持的情况下立即死亡。延髓协调所有内脏控制并对其进行优化以求生存。在人类中，正常的身体稳态可以无限期地持续，只有髓质、脊髓和外周 ANS。


In fish, the midbrain became the dominant CNS structure in response to the increasing importance of vision. The brain of primitive reptiles is only a brainstem and paleocortex, without a neocortex; the corpus striatum is the dominant structure. Thus, the brainstem is sometimes referred to as the reptilian brain. Finally, the neocortex appeared in mammals and became dominant. The phylogenetically advanced portions of the CNS rostral to the medulla— including the hypothalamus, limbic system, and cortex— coordinate activity of the ANS with complex behaviors, motivations, and desires, but they are not required for normal homeostasis.

在鱼类中，中脑成为占主导地位的 CNS 结构，以应对视觉的重要性日益增加。原始爬行动物的大脑只是脑干和古皮层，没有新皮层;纹状体是主要结构。因此，脑干有时被称为爬行动物的大脑。最后，新皮层出现在哺乳动物中并成为主导。中枢神经系统喙部到延髓的系统发育高级部分——包括下丘脑、边缘系统和皮层——将 ANS 的活动与复杂的行为、动机和欲望协调起来，但它们不是正常体内平衡所必需的。

As a result of this hierarchy, impulses from most visceral afferents never reach the cortex, and we are not usually conscious of them. Instead, they make synapses within the enteric plexuses, autonomic ganglia, spinal cord, and brainstem, and they close reflex loops that regulate visceral output at each of these levels.

由于这种等级制度，来自大多数内脏传入神经的冲动永远不会到达皮层，我们通常不会意识到它们。相反，它们在肠丛、自主神经节、脊髓和脑干内形成突触，并关闭调节每个水平内脏输出的反射回路。

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== Reference ==

* [[Physiology]]
* [[Pharmacology]]
* [[Addiction]]
* [[BBB]] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080800/ 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

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