Ch13 Synaptic Transmission in the nervous system - 版本历史

Comcat：/* 大多数神经元突触在每个动作电位中释放非常少量的递质量子 */

2024-12-03T09:31:08Z

‎大多数神经元突触在每个动作电位中释放非常少量的递质量子

Comcat：/* 大多数神经元突触在每个动作电位中释放非常少量的递质量子 */

2024-12-03T09:30:53Z

‎大多数神经元突触在每个动作电位中释放非常少量的递质量子

Comcat：/* 当多个递质共定位于同一突触时，大囊泡的胞吐作用需要高频刺激 */

2024-12-03T09:27:41Z

‎当多个递质共定位于同一突触时，大囊泡的胞吐作用需要高频刺激

Comcat：/* ACh、血清素、GABA 和甘氨酸的离子型受体属于配体门控/五聚体通道超家族 */

2024-12-03T09:25:47Z

‎ACh、血清素、GABA 和甘氨酸的离子型受体属于配体门控/五聚体通道超家族

Comcat：/* 大脑中的大多数 IPSP 是由 GABAA 受体介导的，GABAA 受体被几类药物激活 */

2024-12-03T09:23:43Z

‎大脑中的大多数 IPSP 是由 GABAA 受体介导的，GABAA 受体被几类药物激活

Comcat：/* 中枢神经系统中快氨基酸介导的突触 */

2024-12-03T09:21:18Z

‎中枢神经系统中快氨基酸介导的突触

Comcat：/* 海马体中的长期增强可能持续数天或数周 */

2024-12-03T09:12:38Z

‎海马体中的长期增强可能持续数天或数周

Comcat：/* 海马体中的长期增强可能持续数天或数周 */

2024-12-03T09:11:55Z

‎海马体中的长期增强可能持续数天或数周

Comcat：/* 短期突触可塑性通常反映突触前变化 */

2024-12-03T09:07:32Z

‎短期突触可塑性通常反映突触前变化

Comcat：/* 突触强度的使用依赖性变化是许多学习形式的基础 */

2024-12-03T09:04:34Z

‎突触强度的使用依赖性变化是许多学习形式的基础

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 通过定量分析探索了中枢突触小效应的基础，并改进了最初应用于神经肌肉接头的方法。在这种方法中，重复刺激单个突触前轴突，同时在 voltageclamp 条件下记录突触后反应。如神经肌肉接头所述，分析兴奋性突触后电流 （EPSC） 振幅的频率分布（参见图 8-12B）。回想一下，根据标准量子理论：
-   m = np (13-1)
+   m = np                               (13-1)
 Here, m is the total number of quanta released, n is the maximal number of releasable quanta (perhaps equivalent to the number of active zones), and p is the average probability of release. Measurement of these parameters is very difficult. Only in rare cases in central neurons is it possible to find amplitude distributions of EPSCs with clearly separate peaks that may correspond to quantal increments of transmitter. In most cases, EPSC distributions are smooth and broad, which makes quantal analysis difficult to interpret. The analysis is hampered because EPSCs are small, it is extremely difficult to identify each small synapse, the dendrites electrically filter the recorded synaptic signals, noise arises from numerous sources (including the ion channels themselves), and synapses exhibit considerable variability. Nevertheless, what is clear is that most synaptic terminals in the CNS release only a small number of transmitter molecules per impulse, often just those contained in a single quantum (e.g., 1000 to 5000 glutamate molecules). Furthermore, the probability of release of that single quantum is often substantially less than 1; in other words, a presynaptic action potential often results in the release of no transmitter at all. When a quantum of transmitter molecules is released, only a limited number of postsynaptic receptors is available for the transmitter to bind to, usually not more than 100. In addition, because not all the receptors open their channels during each response, only 10 to 40 channels contribute current to each postsynaptic response, compared with the thousands of channels opening in concert during each neuromuscular EPSP.

←上一版本		2024年12月3日 (二) 09:30的版本
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	<b style=color:#0ae>Most neuronal synapses release a very small number of transmitter quanta with each action potential</b>		<b style=color:#0ae>Most neuronal synapses release a very small number of transmitter quanta with each action potential</b>

		+	A single neuromuscular junction has ~1000 active zones (see p. 210). A single presynaptic impulse releases 100 to 200 quanta of transmitter molecules (i.e., ACh), which generates an EPSP of >40 mV in the muscle cell. This is excitation with a vengeance, because the total number of quanta is far more than necessary to cause the muscle cell to fire an action potential and generate a brief contraction. Evolution has designed a neuromuscular junction that works every time, with a large margin of excess for safety. Synapses in the brain are quite different. A typical glutamatergic synapse, which has as few as one active zone, generates EPSPs of only 10 to 1000 μV. In most neurons, one EPSP is rarely enough to cause a postsynaptic cell to fire an action potential.
		+
		+	单个神经肌肉接头有 ~1000 个活动区（见第 210 页）。单个突触前冲动释放 100 到 200 量的递质分子（即 ACh），在肌肉细胞中产生 >40 mV 的 EPSP。这是报复性的兴奋，因为量子的总数远远超过导致肌肉细胞激发动作电位并产生短暂收缩所必需的。Evolution 设计了一种每次都能正常工作的神经肌肉接头，为了安全起见，有很大的超额余量。大脑中的突触完全不同。典型的谷氨酸能突触只有一个活动区，产生的 EPSP 仅为 10 至 1000 μV。在大多数神经元中，一个 EPSP 很少足以导致突触后细胞激发动作电位。
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		+	The basis for the small effect of central synapses has been explored by quantal analysis, with refinements of methods originally applied to the neuromuscular junction. In this approach, a single presynaptic axon is stimulated repeatedly while the postsynaptic response is recorded under voltageclamp conditions. The frequency distribution of amplitudes of excitatory postsynaptic currents (EPSCs) is analyzed, as described for the neuromuscular junction (see Fig. 8-12B). Recall that according to standard quantal theory:
		+
		+	通过定量分析探索了中枢突触小效应的基础，并改进了最初应用于神经肌肉接头的方法。在这种方法中，重复刺激单个突触前轴突，同时在 voltageclamp 条件下记录突触后反应。如神经肌肉接头所述，分析兴奋性突触后电流（EPSC）振幅的频率分布（参见图 8-12B）。回想一下，根据标准量子理论：
		+
		+	m = np (13-1)
		+
		+	Here, m is the total number of quanta released, n is the maximal number of releasable quanta (perhaps equivalent to the number of active zones), and p is the average probability of release. Measurement of these parameters is very difficult. Only in rare cases in central neurons is it possible to find amplitude distributions of EPSCs with clearly separate peaks that may correspond to quantal increments of transmitter. In most cases, EPSC distributions are smooth and broad, which makes quantal analysis difficult to interpret. The analysis is hampered because EPSCs are small, it is extremely difficult to identify each small synapse, the dendrites electrically filter the recorded synaptic signals, noise arises from numerous sources (including the ion channels themselves), and synapses exhibit considerable variability. Nevertheless, what is clear is that most synaptic terminals in the CNS release only a small number of transmitter molecules per impulse, often just those contained in a single quantum (e.g., 1000 to 5000 glutamate molecules). Furthermore, the probability of release of that single quantum is often substantially less than 1; in other words, a presynaptic action potential often results in the release of no transmitter at all. When a quantum of transmitter molecules is released, only a limited number of postsynaptic receptors is available for the transmitter to bind to, usually not more than 100. In addition, because not all the receptors open their channels during each response, only 10 to 40 channels contribute current to each postsynaptic response, compared with the thousands of channels opening in concert during each neuromuscular EPSP.
		+
		+	这里，m 是释放的 quanta 的总数，n 是可发布 quanta 的最大数量（可能相当于活动区域的数量），p 是释放的平均概率。测量这些参数非常困难。只有在中枢神经元的极少数情况下，才有可能找到具有明显分离峰值的 EPSCs 振幅分布，这可能对应于递质的量子增量。在大多数情况下，EPSC 分布平滑而广泛，这使得量子分析难以解释。由于 EPSC 很小，识别每个小突触极其困难，树突对记录的突触信号进行电过滤，噪声来自许多来源（包括离子通道本身），并且突触表现出相当大的可变性，因此分析受到阻碍。然而，很明显的是，CNS 中的大多数突触末梢每次冲动只释放少量递质分子，通常只是单个量子中包含的那些分子（例如，1000 到 5000 个谷氨酸分子）。此外，该单个量子释放的概率通常大大小于 1;换句话说，突触前动作电位通常会导致根本没有递质的释放。当释放一定量的递质分子时，只有有限数量的突触后受体可供递质结合，通常不超过 100 个。此外，由于并非所有受体在每次反应期间都打开它们的通道，因此只有 10 到 40 个通道为每个突触后反应贡献电流，而在每个神经肌肉 EPSP 期间有数千个通道同时打开。
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		+	Because most glutamatergic synapses in the brain contribute such a weak excitatory effect, it may require the nearly simultaneous action of many synapses (and the summation of their EPSPs) to bring the postsynaptic membrane potential above the threshold for an action potential. The threshold number of synapses varies greatly among neurons, but it is roughly in the range of 10 to 100.
		+
		+	因为大脑中的大多数谷氨酸能突触对兴奋作用的贡献如此微弱，所以它可能需要许多突触几乎同时作用（以及它们的 EPSP 的总和）才能使突触后膜电位高于动作电位的阈值。神经元之间的突触阈值数差异很大，但大致在 10 到 100 之间。
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		+	Some exceptions to the rule of small synaptic strengths in the CNS may be noted. One of the strongest connections in the CNS is the one between the climbing fibers and Purkinje cells of the cerebellum (see Fig. 13-1B). Climbing fibers are glutamatergic axons arising from cells in the inferior olivary nucleus, and they are a critical input to the cerebellum. Climbing fibers and Purkinje cells have a dedicated, one-toone relationship. The climbing fiber branches extensively and winds intimately around each Purkinje cell, making numerous synaptic contacts. When the climbing fiber fires, it generates a massive EPSP (~40 mV, similar to the neuromuscular EPSP) that evokes a burst of spikes in the Purkinje cell. Like the neuromuscular junction, the climbing fiber–Purkinje cell relationship seems to be designed to deliver a suprathreshold response every time it is activated. It achieves this strength in the standard way: each climbing fiber makes ~200 synaptic contacts with each Purkinje cell.
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		+	可能会注意到 CNS 中小突触强度规则的一些例外。CNS 中最强的连接之一是攀爬纤维和小脑浦肯野细胞之间的连接（见图 13-1B）。攀爬纤维是起源于下橄榄核细胞的谷氨酸能轴突，它们是小脑的关键输入。攀爬纤维和浦肯野细胞具有专门的一对一关系。攀爬纤维广泛分支并紧密缠绕在每个浦肯野细胞周围，形成许多突触接触。当攀爬纤维发射时，它会产生一个巨大的 EPSP（~40 mV，类似于神经肌肉 EPSP），从而在浦肯野细胞中引起一阵尖峰。与神经肌肉接头一样，攀爬纤维-浦肯野细胞关系似乎被设计为在每次激活时提供超阈值反应。它以标准方式实现这种强度：每根攀爬纤维与每个浦肯野细胞进行 ~200 次突触接触。
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		+	<br>

	=== 当多个递质共定位于同一突触时，大囊泡的胞吐作用需要高频刺激 ===		=== 当多个递质共定位于同一突触时，大囊泡的胞吐作用需要高频刺激 ===

@@ 第459行： / 第459行： @@
 === 当多个递质共定位于同一突触时，大囊泡的胞吐作用需要高频刺激 ===
 <b style=color:#0ae>When multiple transmitters colocalize to the same synapse, the exocytosis of large vesicles requires high-frequency stimulation</b>
 <br>

←上一版本		2024年12月3日 (二) 09:25的版本
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	<b style=color:#0ae>The ionotropic receptors for ACh, serotonin, GABA, and glycine belong to the superfamily of ligand-gated/pentameric channels</b>		<b style=color:#0ae>The ionotropic receptors for ACh, serotonin, GABA, and glycine belong to the superfamily of ligand-gated/pentameric channels</b>

		+	We now know the amino-acid sequences of all major ligandgated ion channels in the brain. Even though the receptors for ACh, serotonin, GABA, and glycine are gated by such different ligands and have such different permeabilities, they have the same overall structure: five protein subunits, with each subunit being made up of four membrane-spanning segments (as shown for the GABAA receptor channel in Fig. 13-17E and inset). For example, inhibitory GABAA and glycine receptors have structures very similar to those of excitatory nicotinic ACh receptors, even though the first two are selective for anions and the last is selective for cations. For both the glycine and nicotinic ACh receptors, the transmitters bind only to the α subunits, whereas for the GABAA receptor, the transmitter GABA binds to a site at the interface of the α and β subunits.
		+
		+	我们现在知道大脑中所有主要配体门控离子通道的氨基酸序列。尽管 ACh、血清素、GABA 和甘氨酸的受体由如此不同的配体门控并且具有如此不同的通透性，但它们具有相同的整体结构：五个蛋白质亚基，每个亚基由四个跨膜片段组成（如图 13-17E 和插图中的 GABAA 受体通道所示）。例如，抑制性 GABAA 和甘氨酸受体的结构与兴奋性烟碱 ACh 受体的结构非常相似，尽管前两种对阴离子具有选择性，而后一种对阳离子具有选择性。对于甘氨酸和烟碱 ACh 受体，递质仅与 α 亚基结合，而对于 GABAA 受体，递质 GABA 与 α 和 β 亚基界面处的位点结合。
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		+	The primary structures of the many subunit types are remarkably similar, particularly within the amino-acid sequences of the hydrophobic membrane-spanning segments. One such stretch, called the M2 domain, tends to have repeating sequences of the polar amino acids threonine and serine. Each of the five subunits that constitute a channel contributes one M2 domain, and the set of five combines to form the water-lined pore through which ions can flow (see Fig. 13-17E). For the channels gated by GABA and glycine, selectivity for Cl− may be determined by positively charged arginines and lysines near the mouth of the pore.
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		+	许多亚基类型的一级结构非常相似，尤其是在疏水膜跨段的氨基酸序列内。其中一种称为 M2 结构域的延伸往往具有极性氨基酸苏氨酸和丝氨酸的重复序列。构成一个通道的 5 个亚基中的每一个都贡献了一个 M2 结构域，这 5 个亚基结合形成水衬里孔，离子可以流经该孔（见图 13-17E）。对于由 GABA 和甘氨酸设门的通道，Cl− 的选择性可由孔口附近带正电荷的精氨酸和赖氨酸来确定。
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		+	Not quite all ligand-gated channels belong to the same superfamily. We have already seen that the family of ionotropic glutamate receptors is distinct from the family of ligand-gated/pentameric channels. Extensive evidence also indicates that ATP is a synaptic transmitter between certain neurons and at neuron–smooth-muscle cell synapses, with rapid actions similar to those of glutamate and ACh. One of the purinergic receptors or purinoceptors, called P2X, is an ATP-gated cation channel with relatively high Ca2+ permeability. The sequence of this receptor bears little resemblance to those of either the ionotropic glutamate receptor family or the ligand-gated/pentameric channel superfamily. Instead, each subunit appears to have only two membranespanning segments, and a full channel comprises just three subunits. Functionally, the ATP-gated channel closely resembles the nicotinic ACh receptor; structurally, it is much more akin to the channel superfamily that includes voltage-gated Na+ and K+ channels (see pp. 182–183) and to some mechanosensitive channels. This similarity appears to be a case of convergent evolution among ion channels.
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		+	并非所有配体门控通道都属于同一个超家族。我们已经看到，离子型谷氨酸受体家族与配体门控/五聚体通道家族不同。大量证据还表明，ATP 是某些神经元之间和神经元-平滑肌细胞突触处的突触递质，其快速作用类似于谷氨酸和 ACh。一种嘌呤能受体或嘌呤受体，称为 P2X，是具有相对较高的 Ca2+ 通透性的 ATP 门控阳离子通道。该受体的序列与离子型谷氨酸受体家族或配体门控/五聚体通道超家族的序列几乎没有相似之处。相反，每个亚基似乎只有两个跨膜片段，而一个完整的通道仅包含三个亚基。在功能上，ATP 门控通道与烟碱型 ACh 受体非常相似;在结构上，它更类似于包括电压门控 Na+ 和 K+ 通道（参见第 182-183 页）的通道超家族和一些机械敏感通道。这种相似性似乎是离子通道之间收敛进化的一个情况。
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		+	<br>

	=== 大多数神经元突触在每个动作电位中释放非常少量的递质量子 ===		=== 大多数神经元突触在每个动作电位中释放非常少量的递质量子 ===

←上一版本		2024年12月3日 (二) 09:23的版本
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	<b style=color:#0ae>Most IPSPs in the brain are mediated by the GABAA receptor, which is activated by several classes of drugs</b>		<b style=color:#0ae>Most IPSPs in the brain are mediated by the GABAA receptor, which is activated by several classes of drugs</b>

		+	GABA mediates the bulk of fast synaptic inhibition in the CNS, and glycine mediates most of the rest. Both the GABAA receptor and the glycine receptor are ionotropic receptors that are, in fact, Cl−-selective channels. Note that GABA can also activate the relatively common GABAB receptor, which is a GPCR or metabotropic receptor that is linked to either the opening of K+ channels or the suppression of Ca2+ channels. Finally, GABA can activate the ionotropic GABAC receptor, found primarily in neurons of the retina.
		+
		+	GABA 介导 CNS 中的大部分快速突触抑制，甘氨酸介导其余大部分。GABAA 受体和甘氨酸受体都是离子型受体，实际上是 Cl− 选择性通道。请注意，GABA 还可以激活相对常见的 GABAB 受体，这是一种 GPCR 或代谢受体，与 K+ 通道的开放或 Ca2+ 通道的抑制有关。最后，GABA 可以激活主要存在于视网膜神经元中的离子型 GABAC 受体。
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		+	Synaptic inhibition must be tightly regulated in the brain. Too much inhibition causes sedation, loss of consciousness, and coma, whereas too little leads to anxiety, hyperexcitability, and seizures. The need to control inhibition may explain why the GABAA receptor channel has, in addition to its GABA binding site, several other sites where chemicals can bind and thus dramatically modulate the function of the GABAA receptor channel. For example, two classes of drugs, benzodiazepines (one of which is the tranquilizer diazepam [Valium]) and barbiturates (e.g., the sedative phenobarbital), each bind to their own specific sites on the outside face of the GABAA receptor channel. By themselves, these drugs do very little to the channel’s activity. However, when GABA is around, benzodiazepines increase the frequency of channel opening, whereas barbiturates increase the duration of channel opening. In addition, the benzodiazepines can increase Cl− conductance of the GABAA receptor channel. Figure 13-17A to D shows the effects of barbiturates on both the IPSP and the single-channel currents. The result, for both the benzodiazepines and the barbiturates, is more inhibitory Cl− current, stronger IPSPs, and the behavioral consequences of enhanced inhibition.
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		+	突触抑制必须在大脑中受到严格调节。过多的抑制会导致镇静、意识丧失和昏迷，而过少会导致焦虑、过度兴奋和癫痫发作。控制抑制的需要可以解释为什么 GABAA 受体通道除了其 GABA 结合位点外，还有其他几个化学物质可以结合的位点，从而显着调节 GABAA 受体通道的功能。例如，两类药物，苯二氮卓类药物（其中一种是镇静剂地西泮 [安定]）和巴比妥类药物（例如镇静苯巴比妥），各自与 GABAA 受体通道外表面的自身特定位点结合。就其本身而言，这些药物对通道的活动作用很小。然而，当 GABA 存在时，苯二氮卓类药物会增加通道打开的频率，而巴比妥类药物会增加通道打开的持续时间。此外，苯二氮卓类药物可以增加 GABAA 受体通道的 Cl− 电导。图 13-17A 到 D 显示了巴比妥类药物对 IPSP 和单通道电流的影响。对于苯二氮卓类药物和巴比妥类药物，结果是更具抑制性的 Cl− 电流、更强的 IPSP 以及增强抑制的行为后果。
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		+	Surely, however, the GABAA receptor did not evolve specialized binding sites just for the benefit of our modern drugs. This sort of logic has motivated research to find endogenous ligands, or natural chemicals that bind to the benzodiazepine and barbiturate sites and serve as regulators of inhibition. Figure 13-17E shows some of the binding sites on the GABAA receptor. Among the potential natural modulators of the GABAA receptor may be various metabolites of the steroid hormones progesterone, corticosterone, and testosterone. Some of these hormones increase the lifetime of GABA-activated single-channel currents or the opening frequency of these channels and may thus enhance inhibition. The steroid effect is unlike the usual genomic mechanisms of steroid hormones (see pp. 71–72). Instead, steroids modulate the GABAA receptor in a manner similar to barbiturates— directly, through binding sites that are distinct from the other drug-binding sites on the GABAA receptor. Thus, these steroids are not the natural agonists of the benzodiazepine and barbiturate binding sites. The GABAA receptor is also subject to modulation by the effects of phosphorylation triggered by second-messenger signaling pathways within neurons.
		+
		+	然而，可以肯定的是，GABAA 受体并不是仅仅为了我们的现代药物而进化出专门的结合位点。这种逻辑促使研究寻找内源性配体，或与苯二氮卓类药物和巴比妥酸盐位点结合并作为抑制调节剂的天然化学物质。图 13-17E 显示了 GABAA 受体上的一些结合位点。GABAA 受体的潜在天然调节剂可能包括类固醇激素黄体酮、皮质酮和睾酮的各种代谢物。其中一些激素可延长 GABA 激活的单通道电流的寿命或这些通道的打开频率，从而可能增强抑制。类固醇效应与类固醇激素的通常基因组机制不同（参见第 71-72 页）。相反，类固醇以类似于巴比妥类药物的方式调节 GABAA 受体——直接通过与 GABAA 受体上的其他药物结合位点不同的结合位点。因此，这些类固醇不是苯二氮卓类药物和巴比妥类药物结合位点的天然激动剂。GABAA 受体还受到神经元内第二信使信号通路触发的磷酸化效应的调节。
		+
		+	<br>

	=== ACh、血清素、GABA 和甘氨酸的离子型受体属于配体门控/五聚体通道超家族 ===		=== ACh、血清素、GABA 和甘氨酸的离子型受体属于配体门控/五聚体通道超家族 ===

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 == 中枢神经系统中快氨基酸介导的突触 ==
 <b style=color:#f80>FAST AMINO ACID–MEDIATED SYNAPSES IN THE CNS</b>
 === 大脑中的大多数 EPSP 由两种类型的谷氨酸门控通道介导 ===
 <b style=color:#0ae>Most EPSPs in the brain are mediated by two types of glutamate-gated channels</b>

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	LTP 的归纳有几个有趣的特征，增强了它作为一种记忆机制的候选资格。首先，它是特定于输入的，这意味着只有特定细胞上激活的突触集才会被增强，而同一神经元的未激活突触则保持未增强。其次，LTP 的诱导需要突触前末梢的重合活性以及突触后膜的显着去极化。我们在图 13-20C 中看到了这种效果，它表明诱导 LTP 需要重合突触输入和去极化。由于单个海马突触非常弱，因此需要大量突触后激活意味着 LTP 最好在体内情况下通过协同性诱导——足够的突触前轴突必须配合或巧合地触发，以强烈激活突触后细胞。LTP 的协作特性可用于在突触输入之间形成关联。想象一下，一个单元的两组弱输入本身就太弱而无法诱导 LTP。也许每个都编码了一个物体的某种感官特征：你的宠物猫的视觉（输入 1）和声音（输入 2）。如果两者一起放电的强度足以诱导 LTP，则两组突触输入都将趋于增强，并且它们编码的特征（猫的视觉和声音）将与它们激发突触后细胞的增强能力相关联。相比之下，例如，你的猫的景象和闹钟的声音很少会同时出现，它们的神经等价物也不会关联起来。		LTP 的归纳有几个有趣的特征，增强了它作为一种记忆机制的候选资格。首先，它是特定于输入的，这意味着只有特定细胞上激活的突触集才会被增强，而同一神经元的未激活突触则保持未增强。其次，LTP 的诱导需要突触前末梢的重合活性以及突触后膜的显着去极化。我们在图 13-20C 中看到了这种效果，它表明诱导 LTP 需要重合突触输入和去极化。由于单个海马突触非常弱，因此需要大量突触后激活意味着 LTP 最好在体内情况下通过协同性诱导——足够的突触前轴突必须配合或巧合地触发，以强烈激活突触后细胞。LTP 的协作特性可用于在突触输入之间形成关联。想象一下，一个单元的两组弱输入本身就太弱而无法诱导 LTP。也许每个都编码了一个物体的某种感官特征：你的宠物猫的视觉（输入 1）和声音（输入 2）。如果两者一起放电的强度足以诱导 LTP，则两组突触输入都将趋于增强，并且它们编码的特征（猫的视觉和声音）将与它们激发突触后细胞的增强能力相关联。相比之下，例如，你的猫的景象和闹钟的声音很少会同时出现，它们的神经等价物也不会关联起来。
		+
		+
		+	The molecular mechanisms of one form of LTP in the CA1 region of hippocampus have been partially elucidated. The synapse uses glutamate as its transmitter, and both AMPA and NMDA receptors are activated to generate an EPSP. Induction of this type of LTP depends on an increase in postsynaptic [Ca2+]i levels beyond a critical level and lasting for about 1 to 2 seconds. (Recall that the short-term forms of enhancement required a presynaptic increase in [Ca2+]i; see the preceding section.) Under most conditions, postsynaptic [Ca2+]i levels rise during a tetanic stimulus because of the activation of NMDA receptors, the only type of glutamate-activated channel that is usually permeable to Ca2+ (see Fig. 13-16). Recall also that the NMDA-type glutamate receptor channel is voltage dependent; to open, it requires Vm to be relatively positive. The cooperativity requirement of LTP is really a requirement for the activation of NMDA receptors so that Ca2+ can enter—if the postsynaptic Vm is too negative (as it is when synaptic activation is weak), NMDA channels remain mostly closed. If activation is strong (as it is when multiple inputs cooperate or when tetanus occurs), Vm becomes positive enough to allow NMDA channels to open. The stimulus-induced rise in postsynaptic [Ca2+]i activates at least one essential kinase: CaMKII (see p. 60). Blocking this kinase with drugs prevents induction of LTP. Several other types of kinases are implicated, but the evidence that these mediate—as opposed to modulate—LTP is equivocal.
		+
		+	海马 CA1 区一种形式的 LTP 的分子机制已被部分阐明。突触使用谷氨酸作为其递质，AMPA 和 NMDA 受体都被激活以产生 EPSP。这种类型的 LTP 的诱导取决于突触后 [Ca2+]i 水平的增加超过临界水平并持续约 1 至 2 秒。（回想一下，短期形式的增强需要 [Ca2+]i 的突触前增加;见上一节。在大多数情况下，突触后 [Ca2+]i 水平在强直性刺激期间升高，因为 NMDA 受体被激活，NMDA 受体是唯一一种通常对 Ca2+ 具有渗透性的谷氨酸激活通道（见图 13-16）。还记得 NMDA 型谷氨酸受体通道是电压依赖性的;要打开，它要求 Vm 相对正。LTP 的协同性要求实际上是激活 NMDA 受体的要求，以便 Ca2+ 可以进入——如果突触后 Vm 太负（就像突触激活较弱时一样），NMDA 通道大部分保持闭合。如果激活很强（如当多个输入合作或发生破伤风时），Vm 变得足够正，允许 NMDA 通道打开。刺激诱导的突触后 [Ca2+]i 升高激活至少一种必需激酶：CaMKII（见第 60 页）。用药物阻断这种激酶可防止 LTP 的诱导。涉及其他几种类型的激酶，但这些激酶介导而不是调节 LTP 的证据是模棱两可的。
		+
		+
		+	The molecular pathways leading to the expression and maintenance of LTP are more obscure after the Ca2+-induced activation of CaMKII. Evidence has been presented both for and against postsynaptic and presynaptic changes as explaining the increase in synaptic strength. For the most commonly studied form of LTP described here (i.e., dependent on NMDA receptors), compelling evidence demonstrates a postsynaptic mechanism involving the recruitment of more AMPA receptors to the postsynaptic membrane. Sometimes, postsynaptic AMPA receptors appear to be functionally “silent” until LTP mechanisms activate them or insert them into the membrane. Evidence also suggests a presynaptic mechanism for enhancing transmitter release. This presynaptic hypothesis requires the presence of some unknown, rapidly diffusing retrograde messenger that can carry a signal from the postsynaptic side (where rising [Ca2+]i is clearly a trigger for LTP) back to the presynaptic terminal.
		+
		+	在 Ca2+ 诱导的 CaMKII 激活后，导致 LTP 表达和维持的分子途径更加模糊。已经提出了支持和反对突触后和突触前变化的证据，以解释突触强度的增加。对于此处描述的最常见研究的 LTP 形式（即依赖于 NMDA 受体），令人信服的证据表明突触后机制涉及将更多的 AMPA 受体募集到突触后膜。有时，突触后 AMPA 受体在功能上似乎是“沉默的”，直到 LTP 机制激活它们或将它们插入膜中。证据还表明，一种增强递质释放的突触前机制。这种突触前假说需要存在一些未知的、快速扩散的逆行信使，该信使可以将信号从突触后侧（其中上升的 [Ca2+]i 显然是 LTP 的触发因素）带回突触前末梢。

	<br>		<br>

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 === 海马体中的长期增强可能持续数天或数周 ===
 <b style=color:#0ae>Long-term potentiation in the hippocampus may last for days or weeks</b>
 <br>

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 === 短期突触可塑性通常反映突触前变化 ===
 <b style=color:#0ae>Short-term synaptic plasticity usually reflects presynaptic changes</b>
 <br>

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 === 突触强度的使用依赖性变化是许多学习形式的基础 ===
 <b style=color:#0ae>Use-dependent changes in synaptic strength underlie many forms of learning</b>
 <br>