Synaptic Self

关于记忆，最重要的一点：

It's a reconstruction of facts and experiences on the basis of the way they were stored, not as they actually occured.

接着从1904年一个德国科学家寻找engram，到Lashley，再到H.M引出的海马，简单的梳理了下对记忆的探索。

......engram to refer to the neural representation of a memory.

It seemed that the memory loss was related more to the size of the lesion than to its placement in the cortex.

He used a behavioral task that could be solved in different ways.

As the lesions got bigger, more processes were distrupted, leaving the animal with fewer options for solving the problem.

H.M could recall many of the events of his earlier life, especially those that occured up to several years before the surgery, he was unable to form memories for experiences that occured after the surgery, hewas unable to form memories for a few seconds (he had short-term memories), but he couldn't convert this information into long-term memories. He failed to recognize himself in a mirror, for example, but did recognize himself from old pictures.

Paul MacLean, the originator of the limbic system concept, conceived of the hippocampus as the seat of the Freudian id, a place in the brain where ideas could be mixed together and confused.

p101.开始介绍H.M.可以完成的一些任务。然后关于记忆系统就有了新的认识。

Procedual memory was therefore later renamed with more neutral designation: nondeclaractive memory. The term explicit and implicit memory, suggested by Dan Schacter, essentially refer to the same memory processes as declarative and nondeclarative memory.

Outputs of each of the cortical areas then converge in the rhinal cortical areas, also known as the parahippocampal region, which integrates information from different sensory modalities before shipping it to the hippocampus proper.

接着提到海马与新皮层之间的连接是相互的。

In this way, cortical areas involved in processing a stimulus can, as we will soon see, also participate in the long term storage of memories about that stimulus.

Convergence zones also allow mental representations to go beyond perceptions and to become conceptions - they make possible abstract representation s that are independent of the concrete stimulus.

这种聚合区就像新皮层，在灵长类最多，哺乳动物次之。接着区分了一下顺行性遗忘和逆行性遗忘。

There are basically two kinds of amnesia: one is an inability to remember things that happenred before the surgery or brain injury (called retrograge amnesia), and the other is an inability to form new memories (called anterograde amnesia). While we' ve focused so far on anterograde amnesia, both forms are present in patient with damage to the temporal lobe. Interestingly, the degree of retrograde amnesia is graded over time - memory is worse for events right before the surgery than for earlier ones.

The graded effect of retrograde amnesia is now believed to occur because the role of hippocampus changes over time - the hippocampus is needed for memory storage initially, butits role decreases as time goes by.

对此有一种基于connectionist modeling的解释。

So-called interleaved learning prevents new information from interfering with old memories.

举了个例子区别了rapid 和 interleaved learning 对大脑形成表征的不同影响。

But with the interleaved learning, where the reoresentaion is built up slowly over many repetitions, the network gradually refines the representation......

p107.接着关于记忆从海马参与到逐渐皮层独立的可能做了讨论。

Each reinstatement changes cortical synapses a little. Because the reinstatement depend on the hippocampus, damage to the hippocampus affects recent memories, but not old ones that have already been consolidated in the cortex.

接着提到了关于睡眠期间大脑活动的研究。

Subsequently, when the rats went to sleep, the neural patterns seemed to be repeated in the hippocampus, as if the rats were dreaming about the places they had explored.

目前这方面证据还不充分，只是猜想。然后提到关于新记忆受损比老记忆严重的另外一种可能的解释。

However, with time, the memory trace comes to involve more and more brain regions, especially cortical regions, so that damage to one area, like hippocampus, fails to produce a deficit, since the other areas compensate.

With time, hippocampal activity decreased and came to be unrelated to memory performance, while cortical activity increased and came to be related to the memory performance.

这里提到了图尔文关于记忆的划分。

He argued that episodic memories are about personal experiences (things happened to you at a particular time and place), while semantic memories are about facts (things you come to know, but have not necessarily experienced)......Tulving suggested that episodic memory, which requires conscious recollection of the time and place of some personal experience, is particular characteristic of humans, whereas semantic memories, being the single storage of a fact rather than a personal experience, is within tha capacity of many animals.

接着介绍一个基于这种分类的研究，被试通过脑成像被认为是只有海马受损的孩子，通过在学校学习后关于记忆的测量发现了情境和语义记忆的分离。但有人提出几点质疑：

One is that episodic memory, while poor, is still present in the children, and that even a littlespisodic memory capacity may be sufficient to support a gooddeal of semantic knowledge......but episodic deficit may be more readily detect.

第二是脑成像没有解剖可靠。p110.受到H.M启发，研究者开始在动物身上做实验。

If conscious retrieval was required, the hippocampus tended to be involved.

介绍了Delayed nonmatch to sample，注意是选没出现过的那个。

It turned out, though, that the effects of the lesions were not due to damage to the amygdala or hippocampus, but to damage of surrounding parahippocampal region.

H.M.的这块也受损了。

In sum it seems that the parahippocampal areas and hippocampus make unique contributions, and the delayed nonmatch to sample task reflects the parahippocampal more than the hippocampal contribution.

接着就介绍了去年诺奖获得者的的研究成果，不知道是不是因此得奖的，听新闻上的描述至少也是类似的实验。

......different cells in the hippocampus are active at different locations.

One of the few tasks that hippocampal leision seemed to impair with any consistency was maze learning, a task that is often solved by spatial cues.

然后就介绍了莫里斯水迷宫实验（Morris water maze）。

Damage to the hippocampus in the primates does produce deficits in spatial memory, along with deficit in nonspatial memory.

关于海马还有一种认为其与declarative memory 关系密切。

Specifically, declarative memories are relational. Thus, activation of a declarative memories can be activated independent of the context in which they were established, and by stimuli other than those that were initially involved in the learning.

Conjunction theory则认为海马将各通道的信息混合在一起，成为一个整体了。

In this theory, the original elements, though, are lost, having been formed into conjunctions, while in the relational theory, the elements remain discrete and the hippocampus links them together.

还有一种改进版的configural theory。

The hippocampus learns conjunctions naturally and rapidly. When the hippocampus is damaged, the neocortex can be forced, through extensive training, to also learn conjunctions, but normally it does not do so.

接着开始讲内隐记忆。

The systems that engage in implicit learning are not strictly speaking memory systems. They were designed to perform specific functions......plasticity (the ability to change as a result of experience) is simply a feature of the neuronal infrstructure of these systems that facilitated their operation.

In this sense, explicit memory is, in Stephen Jay Gould's term, an exaptation.

p118.这里介绍了经典条件反射和操作性条件反射。

The subject is passive involved in classical conditioning (the food comes when the stimulus occurs, regardless of what the subject is doing) but in operant conditioning, the subject responds in a certain way.

去损伤脑找寻记忆的痕迹犹如大海捞针，后来就有了cellular-connection approch。

The emphasis was on conditoning as a tool for sutdying bahavioral relevant neural changes rather than as a direct model of human memory.

2000年诺奖得主Kandel也是这种研究角度。接着有一个关于杏仁核的很好的总结。

It had been known that the amygdala plays an important role in fear responses and even learning to fear new stimuli.

The lateral nucleus of the amygdala (lateral amygdala) serves as the input zone. It receives information from the various senses, allowing the outside world to be monitored for threatening information.

When the lateral nucleus detects some threatening stimulus, the central nucleus initiates the expression of defensive behaviors.

The lateral amygdala gets inputs about the stimuli from two sources. It receives a crude but fast representation from subcortical area (the sensory thalamus) and a slower but more complete representation from cortical sensory areas.

这里就是一般的high road 和low road了。两条通路通向同一神经元。

The inputs reach the neurons...... As a result, the cells are then more capable of charging ahead if the cortical information condirms the threat, or of putting on the brakes if the cortical information establishes that no danger is present.

作者这里还做了特别的提醒：

It should not be assumed that high road is aconscious route to the amygdala...... The amygdala engages in implicit processing, including implicit larning, regardless of which pathway provides it with sensory information. As with any other stimulus, we become consciously aware of an emotional stimulus only when that stimulus is processed by networks involved in something called working memory.

接着讲了lateral nucleus的可塑性。

If an animal is lucky enough to survive one dangerous encounter, its brain should store as much about the experience as possible.

p126.这里讨论了条件反射所必须的脑区。

It was disovered that removal of entire neocortex had no effect on the ability of rabbits to be conditioned. In fact, eye blink conditioningcould occur following removal of the most forebrain, icluding the amygdala, hippocampus, and other areas.

These researcher showed that leisions of a certain areas of the cerebellum prevented conditioning, and that activity of neurons in thses areas changed during the course of conditioning.

这些实验关注的不是眨不眨眼，而是接受外部刺激以及控制动作。

Control of precise movements at just the right time is a fundamental aspect of mauy of acquired brhavioral skill.

接着开始讲味觉。

An infant will spit out spit bitter foods on the first encouter. Infants born with massive parts of the forebrain missing, and rats with lesions of all of the forebarin and midbrain still exhibit taste preferneces, suggest that taste mediated by the hindbrain.

提到了关于taste aversion的条件反射（CTA）。

The taste path way from the tongue goes to a region of the hindbrain called nucleus of the solitary tract, which is involved in taste preferences. The same general region of the hindbrain receives fibers from the gut, telling the brain about nausea and other gastrointestinal conditions...... The two parts of the nucleus of the solitary tract do project onto a common area in the middle brain called parabrachial nucleus.

Removal of the forebrain, which leaves only the brain stem to run the show, disrupts the acquisition of CTA, in spite of the fact that the same procedure leaves taste prefenrences undisturbed. The parabrachial nucleus thus does not work alone in the mediation of CTA and instead depends on the forebrain areas.

p129.提了下实验中两种条件反射的联系。

But the first step is that the rat has to learn, through classical conditioning, that the tone predicts the shock.

然后回到了有意识的记忆和无意识的记忆。

Hippocampal damage does not distrupt normal conscious awareness.

介绍了一个实验，讲被试的注意集中在任务上，一部分被试还会在听到声音后立即被吹下眼睛，另一部分被试会在听到声音后一段间隔后被吹下眼睛（trace conditioning）。

The patients with hippocampal damage did not condition in the trace task.

而正常被试当中：

Whether they conditioned was closely related to whether they reported, after the experiment, having noticed a relation between the tone and the puff...... This suggested that the trace conditioning requires awareness, and that the hippocampus mekes this awareness possible.

接着介绍了另外一个实验，在一堆字母L（背景）中找字母T（目标），操作了L的样式。

The normals but not the amnesics benefited from the repetition of the background pattern: they were better at finding the T in the repeated pattern than novel ones......The hippocampus, in other words, was required to process and learn about the unattended background stimuli.

作者这里没注明，我的猜测是即使是同样的背景，T出现的地方也不一样。最后介绍了关于条件反射的情境，比如箱子，也被海马编码的可能性。

Hippocampus......is able to put together many things at once, to relate or configure them into a context.

The key function of the hippocampus is probably processing relations.

介绍了一下《记忆的七宗罪》这本书。

Even in the face of severe memory problems, its sufferers initially remain much the same person they always were —— they walk and talk the same, and have the same basic habits and traits. As the disease spreads widely to other brain areas, those that function implicitly, personality begins to break down.

Brain development is the major battlefield of nature-nurture conflict.

It is less common, but no less appropriate, to think of genes as also influencing us in the form of memory. In this case, though, the synaptic memory comes about as a resultif ancestral rather than personal history.

从胚胎阶段整个发育就有环境因素的参与。

The chemical environment of the embryo is, by necessity, in direct contact with the body chemistry of the mother.

In the neural tube, nonneural precusor cells divide and give rise to neurons.

It's important to make a distinction here between neurogenesis——the birth of new neurons——and synaptogenesis——the creation of new synapses between existing neurons.

目前越来越多的证据显示成年哺乳动物在特定的脑区依然产生新的神经元，但具体的作用还不清楚。有了神经元，神经元还要到他们该去的地方。

Segregation is under the direct control of a special set of genes called homeotic genes.

Segregated cells eventually differentiate, which means that they on different shapes and sizes, and end up with different transmitters and modulators.

这里发现化学环境对神经元最后的功能影响还是大的，特别是未分化的神经元。

As development proceeds, the neural tube expands and bends, eventually assuming a shape that begins to resemble the brain.

这里对于这些神经元的“命运”还是很有争论的。

One possibility is that the function of a cell is specified genetically, so that it is destined to end up in specific areas devoted to a specific function before it leaves the neural tube. Another possibility is that cells learn what to do from the context in which they end up.

这里作者依然强调突触比神经元本身对回路功能的贡献更大。

Once neurons reach their destinations, they begin to sprout axons.

这里有一些蛋白质作为attractant和repellent引导这个过程。p72.

We probably don't have enough genes to account for the wiring of each of the brains's trillions of synaptic conncetions.

这样就产生了火热的争论：instruction 和 selection。

The exact role of neural activity, though, is heatedly debated, with the main issue of contention being whether activity, especially activity initiated by environmental stimulation, helps creat the mature connections or just selects from the initial set of intrinsically established connections those that will be retained.

Selectionists also assume that there's a good deal of randomness involved.

神经元会在发展过程中会死亡目前基本是确定的。

The key issue is not whether synapses are eliminated during development (they clear are) but instead whether the decreases that do occur provide conclusive support for strong version of selectionism - the version that claims that activity only prevents the elimination of synapses.

p76.这里介绍了悲惨的独眼小猫。

Hubel and Wiesel concluded that the development of synapticconnections is a competitive proccess, one in which the connections that are used are kept and those that go unused are elimnated.

当然，实际情况比这个复杂。

They found that as development proceeded, mauy axons did indeed retract (consistent with a selectionist view), but that the remaining axons also increased in complexity (consistent with an instructional view).

接着提到了那些失去某些感觉通道（盲人，失聪人士）的人大脑发生的一些变化。以及灵长类大脑内在出生前的一系列自发性神经冲动。

It is probably best to think of instruction and selection as two complementary meas by which circuits can be constructed rather than as mutually exclusive theories of brain development.

同样重要的是这种折衷并不是坏事，尤其在科研当中，一开始时都希望自己能创造某个独特，颠覆的理论，但其实事实却很少那么极端。

It has taken tremendous amount of work to demonstrate that activity both instructs the formation of new connections and selects used ones from a preexisting pool.

p79.赫布大神出场

In 1949, Donald Hebb, a Canadian psychologist, proposed that if two neurons are active ar the same time, and one is presynaptic to the other, then the connection between them will be strengthened.

这一章讲的比较简单，书的接下来还有大量篇幅涉及具体的机制。

Hebbian plasticity involves the released tranmitter to two kinds of postsynaptic receptors. One of these receptors records that the post cell was active, and the other records which presynaptic terminals contracting the postsynaptic cell were active at the same time.

NMDA receptors, appear to be particular important in that they are able to detect the match between activity in the presynaptic and post synaptic neuron.

Another important set of molecules are neurotrophins, special tonic that promote the survival and growth of neurons.

这种物质是从postsynaptic cell释放然后被presynaptic cell吸收的。

Cell death is prevented if a presynaptic terminal receives a life-sustaining shot of neurotrophins from postsynaptic partner.

The surviving terminals (those that were active) also begin to spout new connections.

p82.开始讨论“先天”。

One is the idea that genes make us all the same, giving us trait that we share with other members of our species. The other is that genes make us unique.

第一种取向介绍了动物行为学。

The classic method used by ethologists to test innateness was to show that a behavior was present at birth or shortly thereafter, or, mre generally, that it merged in the absence of an opportunity for the organism to have learned from environmental stimulation.

接着介绍了对于反驳行为主义的几个经典证据，让你恶心的东西更容易和食物建立联系。

The language may be innate is supported by studies of pidgin language, a simple, crude form of verbal communication among people who speak different languages but live together and have to communicate with one another. Pidgin lacks grammer when it is initially pieced together, but by the second generation, it begins to take on a grammatical structure.

It has been proposed that humans have innate knowledge about numbers, physics, and even about how other human mind work.

之后又提了下对于进化心理学的反驳。其中比较重要的一个反驳是：

As Gould's exaptation argument points out, something can be innate (passed on genetically) even if the role it plays today is not the one form which it evolved.

从物种间的差异来看，基因的确有很大的作用。但在微观层面（神经元级别），学习似乎又有某种相似性。最有趣的是基因建造了回路，但这些回路却注定被经验慢慢改变。p87.

Constructivists accept the principle that genes build the overall structure, and the regressive events like synaptic selection take place, but they argue that epigenetic prewiring and selection alone cannot explain cognition.

举了娃娃损伤与语言有关的脑区比成年人损伤相关区域带来的影响要小。接着作者谈了下constructivist的一些不足，主要涉及noncortical，subcortical，cortex的可能的一些联系和区别。最后给了个总结。p90.开始讨论先天的第二方面，个体独特性。介绍了个关于同属一个物种但分别生活在两种自然环境的蛇的饮食习惯的研究。（是不是应该称为亚种？）

Together, these findings lead to the conclusion that genes help in the explanation of the behavioral difference between group but not within groups, at least in this case.

Genes may play a role in placing a function in the brain of every human, and at the same time make a relatively small contribution to differences in the way that function is wired in individuals.

然后介绍了同卵双胞胎的研究及其结论的局限性，从孕前期共享环境，收养家庭的选择，以及外部环境对类似事物的反应的相似性，以及环境对先天倾向的强化都让结果的解读有很多不确定的地方。后来又很多微观的研究，

An seldom is any brain function as complex as those involved in behavioral or mental process under the control of one gene.

接着介绍了关键期，敏感期对学习的影响。

Language learning is more flexible in children than in adults, as anyone who has tried to learn a second language after puberty knows.

Whether math or music learning has acritical period of synaptic development is not known.

这里有一个很有趣的观点：

the early years are crucial not because the window of opportunity closes but because what is learned at this time becomes the foundation of subsequent learning.

Following the cognitive revolution, though, motivations, like emotions, were overlooked by many psychologists and brain scientists.

Whether all motivated actions are necessarily based on emotional activity is debatable. But that emotions are powerful motivation.

然后从Hull的驱力理论（drive theory）讲起。

That is, what we do today in a certain situation is function of what we did in the past what was successful in reducing drives in similar way.

这里再次提到了两种条件反射的区别。

Instrumental conditioning contrasts with Pavlovian or classical conditioning, where the rewarding or punishing stimulus occurs regardless of what the animal does.

从某些驱力理论解释不了的现象有引出了诱因理论（incentive theory）。

I believe that all we need to acceot is that in the presence of conditioned (learned) or unconditioned (innate) incentives, emotion systems are activated, placing the brain in a state where an instrumental response becomes a highly probable outcome.

把实验分为两个阶段，第一个阶段形成的反应，在第二个阶段也能保持。

The shock, by the way, was never presented in the new chamber. The tone had become a negative secondary incentive, and behaviours that eliminated this simuluswere reinforced and learned as a habit.

用恐惧的好处是作者对杏仁核很熟，通过人工损毁发现了分离。

Damage to the lateral nucleus prevented the learning of the escape response, but central nucleus leision had no effect.

...... the central nucleus was found to be involved in fear reaction but not fear action, and the basal nucleus in the fear action but not reaction.

p244.开始讲快乐中枢的发现（pleasure center）。

The reason these sites were so effective wa not because the hypothalamus is the reward center of the brain, but because a major nerve pathway passes through the hypothalamus.

从这个实验来看。

This is a motivational version of my notion that emotional beahaviors are not necessarily caused by emotional feelings.

找到的这个回路（medial forebrain bundle）主要和多巴胺（dopamine）有关。

Although there are rewarding conditions that do not depend on dopamine , much of what we know about rewards centers around the role of dopamine.

通过阻断多巴胺。

......the animals still "like" the reward when they consuming it, but they are no longer motivated to work for it. Dopamie is thus more involved in anticipatory behaviors (looking for food or drink or a sexual partner) than in cosummatory responses (eating, drinking, having sex).

接着提到了伏隔核。

......the nucleus accumbens, a region of sriatum located in front of the amygdala near the bottom of the forebrain.

...... nucleus accumbens sits ar the crossroads of emotion and movement, and that dopamine release in this region plays crucial role in motivated or goal directed behavior.

这里列了几条理由，主要是通过解剖结构分析，以及注射安非他命和可卡因来实验。接着比较细致的讲了整个回路是如何工作的，其中突出伏隔核的中枢作用：一方面接受杏仁核处理过的外界信息，另一方面讲信号传到运动系统。这里的学习过程和记忆系统类似。

Once an emotional habit is well learned, the brain systems involved in expressing it become simpler. The amygdala, for example, drops out of the circuit...... The accumbens likewise drops out once the response is learned.......

p252.开始提到情绪在行为选择中的作用。达马西奥的研究是必须出现的。

He and his collegues have shown that patient with damage to the orbital prefrontal region have poor judgement and often make decisions that lead to socially in appropriate courses of action....... to use emotional information to guide action.

在实验室中一般倾向如去定位特定的区域和功能。

......in more natural setting, where decisions involve the integration of cognitive and emotional information, it is likely that interaction rather than dissociations between the areas will be commonplace.

接着提到一个人用经济学的群体的思路研究一群神经元处理信息的想法。至此，这些研究都建立在动物身上，作者认为这些对于我们理解人类的动机是远远不够的。又讲回了宏观理论去，从认知失调，到工作自我（working self），再到McClelland's need-achievement theory。这里还区分了一下：内隐的生物动机和外显的心理动机。并且提到了工作记忆和长时记忆在动机行为中的作用。这里专门提了下前扣带回（anterior cingulate)在当中的作用。

介绍了一些早期的神经元与记忆的关系猜想，重点是赫布。

When an axon of cell A is near enough to excite cell B or repeatedly and consistently takes part firing it, some growth process or metabolic changes take place in one or both cells such that A's efficiency, as one of the cells firing B is increased.

两个刺激之间能有联系，则

This means that there has to be some neuron (or a set of neurons) that receives information about both stimuli.

接着就介绍了一些早期的研究。

Repetitive stimulation of nerves going to the spinal cord led to an increase in size of the electrical response elicited in post synaptic nrurons in the spinal cord.

但是这种情况维持的时间很短。又介绍了一个关于猫的habituation的实验。

Habituation is a form of learning in which repeated presentation of a stimulus leads to a weakening of response.

Thompson and Spencer ruled out changes in the ability of the input and output nerves to transmit signals, and concluded that the plastic changes must have crucially involved the interneurons.

目前比较成功的研究是在无脊椎动物身上进行的，因为构造简单。但哺乳动物的演技与这些结果也是一致的。p139.开始介绍在哺乳动物身上进行的研究。

He noticed that a brief burst of electrical stimuli delivered ot fibers headed for the hippocampus in the rabbit led to a dramatic and long-lasting increase in transmission at synapse in the hippocampus.

这个就是长时程增强（LTP）。

The key finding was that, following the potentiating pulses, the synaptic response got bigger, relative to the baseline response, and remained bigger for hours.

接着提了下海马为什么利于这个发现，之前在spinal cord的实验结果维持却很短。后来随着可以把海马切片后单独做实验，这个领域开始热闹起来。

Rapid acquisition, persistence, specificity, and associativity are all features one would expect of a memory mechanism.

Giving potentiating inputs to one pathway, therefore, does not automatically change all of the synapses on the postsynaptic neurons; it only changes those synapses that were stimulated.

两条通路。

When each was stimulated in succession with weak stimuli, no LTP resulted. But if the two pathways were stimulated simultaneously with the weak stimuli, the stimuli could combine (cooperate) to produce LTP in both pathways.

这里有一副比较简单易懂的长时程增强的图。后来通过人工激活突触后神经元，

When a weak presynaptic input arrived during this induced activity, synapses over which it was transmitted to the postsynaptic cell was strengtherned.

p144.这里介绍了glutamate receptor和钙离子对LTP的影响。

The two findings actually complement each other, since it is the special glutamate receptor that allows calcium to rise in the postsynaptic cell when an action potential occurs.

这里简单提了下AMPA和NMDA受体。

Once glutamate has activated the postsynaptic cell (caused it to fire an action potential) by binding to AMPA receptors, the block on the NMDA receptors is removed, and glutamate can open the receptor channel and allow calcium to enter the cell. LTP is the result.

For NMDA receptors to pass calcium, both presynaptic and postsynaptic cell must be active. This is the basic requirement for Hebbian plasticity.

The rise in calium inside the post synaptic cell then leads to the activation of kinases that travel to the cell nucleus where addttional molecular processes occur, including gene activation, which in turn lads to the synthesis of new protein that contribute to the strengthing the synapses.

When synaptic activity in the strong pathway activated the postsynaptic cell, the block on NMDA receptors will be removed, even at weak synapses.

NMDA receptors ...... they are able to register that presynaptic and postsynaptic neurons were active at the same time.

这部分很重要哦，在之后还会从各种角度和研究来讨论。p146.LTP有根据持续时间分为两种：early LTP，late LTP。

It has been known for several decades that if animals are given drugs that prevent the brain from making new proteins, they are able to learn normally but are unable to form long-lasting memories.

这里有个定义，第二信使：

Their job is to initiate chemical recation within the cell on the basis of information provided from outsaide the cell during neurotransmission by first messengers.

这里介绍了启动kinases 对于AMPA受体的作用。

As a result, after the induction of LTP, the same amount of glutamate released from the presynaptic cell by an action potential will have more AMPA receptors to bind to.

关于突触前神经元在这个过程中是否发生改变目前还有争议。

One possible way this could happen is by the means of retrograde messengers, substances released by the postsynaptic cell after LTP is induced and taken up by the presynaptic terminal, which cause changes in the case of glutamate release here.

p150.介绍了传统的用药物阻断某个过程和新的通过培育某种功能缺失的老鼠两种研究方法。接着讲了从细胞核回到树突的过程。

When the new proteins are subsequently made in the cell body, they are then shipped out to essentially all possible synapses in the cell, but only synapses that were tagged during the initial stimulation are able to use the new proteins to stabilized the connection with the presynaptic terminal.

Weak HFS leads to a short-lasting form of LTP (early LTP) that does not require gene expression and protein synthesis. However, it does creat the tag.

除了树突自己的变化。

The other part of the explanation is related to the actual growth of new synapses.

Recent studies demonstrate that proteins can be synthesized in denderites.

再接着介绍了阻断NMDA受体的小鼠进行水迷宫实验的情况。

Particular difficult to ascertain has been the issue of whether NMDA blockade produces a specific effect on learning itself, or instead changes other less specific capacities, such as the ability to preceive a given stimulus or the ability of desire to perform the appropriate response.

除了阻断NMDA受体，还可以增强，这里贴了个实验。关于这个领域目前证据比较多，但实际情况依然比较复杂。

In some studies, hippocampal-dependent learning is unaffected by treatments that block LTP. This type of result, though, has been fairly rare, and centainly is not compelling enough to undermine the whole field. Futher, we now know that there are variety of different forms of LTP, some involving NMDA receptors and some not......

这里说了这么多，但都没有直接证明外显的学习与LTP的关系。

Rogan instead started with a circuit known to be involved in fear conditioning and then asked whether LTP occured in that circuit. The reversal of the strategy (starting with a learning circuit and looking for plasticity in it, rather then starting with a form of plasticiy and asking how it might related to learning) turned out to be very advantageous.

他用声音做条件刺激，电击做无条件刺激。在成功配对后，单独呈现声音也在杏仁核的相关区域引起LTP。

Indeed, Rogan's results showed that fear conditioning and LTP induction produced very similar changes in the electrical responses of amygdala cells to sound stimuli.

In spatial learning, a rat is free to learn about any of the may stimuli present in the environment, making it difficult to determine, in Hebbian terms, precisely what's being asspciated with what. INcontrast, fear conditioning is a straightforward form of associative learning that is easy to define in terms of Hebbian plasticity, where strong (foot shock) and weak (sound) stimuli interact at synapses on the same cells.

......disruption in the lateral amygdala of protein syntheisis or of some of the same kinases that prevent the induction of late LTP in the hipppcampus interferes with the formation of long-term memory for fear conditioning without affecting short-term memory.

Fear conditioning and lateral amygdala LTP thus seem to require the same mix of molecules that has been implicited in synaptic plasiticy and memory in the hippocampus.

最后总结了下这些研究更广泛的意义，以及一些未解决的问题。

Also unsolved is the locus of memory storage - plasticity in the lateral amygdala is clearly involved, but whether this is the only site of change that is maitiained over time remains to be determined.

接着介绍了一种消除创伤后记忆的可能办法，穿越虫洞上也提到过。

That is, if you take a memory out of storage you have to make new proteins (you have to store, or reconsolidate it) in order for the memory to remain a memory.

p162.用无脊椎动物中海兔属的的实验来当做例子，介绍这个领域的研究。

The gill withdrawal reflex exhibits several forms of learning, including habituation: the gill retracts less if the mantle is touched repeatedly...... Habituation can reversed rapidly by giving a strong stimulus, such as an electric shock, to some other part of the mollusk's body, like the tail. Touch of the mantle after a shock results in a big response. This is an independent form of nonassociative learning called sensitization.

Associative learning - namely, classical defense or fear conditioning - also occurs in the gill withdrawal reflex.

Conditioning and sensitzation are similar in that a strong stimulus changes the response to a weak one. But they differ in specificity: in associative conditioning, the amplified response only occurs in the reaction to a stimulus that was paired with the shock, whereas in sensitization the response to stimuli that have no relation to the shock is bigger.

p167.这里介绍了突触前神经元的一些变化与习惯化的关系，以及短时和长时敏感化在神经元层面的异同。

The serotonin binds to serotonin receptors located on the presynaptic axon terminal, and leads to the activation of protein kinase A (PKA), whichi results in a greater amount of glutamate release and thus a bigger postsynaptic response.

Because the increase in the efficiency of transmission between the sensory and motor neuron is due entirely to alteration in the sensory seuron terminal, it is refered to as presynaptic facilitation. Because the state of the activity of the postsynaptic neuron is irrelevant sensitization by dedinition is a form of non-Hebbian plasticity.

The two effects (persistent of PKA and formation of new connections) combine to produce long-lasting increase in transmission between the sensory and motor neurons, and stronger reflex responses.

接着提到了经典条件反射由于突触前神经元的变化，也被认为不是赫布可塑性的例子。后来又有研究表明经典条件反射是赫布学习的例子。

One way of understanding this is that nonassociative (non-Hebbian) presynaptic facilitation functions as the presynaptic component of associative (Hebbian) plasticity.

Also the possibility that fear conditioning, amygdala LTP, and several forms of hippocampal plasticity might, like plasticity in Aplysia, involve presynaptic as well as postsynaptic changes futher strengthens the notion similar mechanisms are used to make memories in diverse species.

最后讲了变种果蝇的研究。

When given the choice between going into a chamber that contained an odor associated with the shock and a chamber that held a different oder, the flies oftern avoided the former chamber.

It is important to keep in mind that a mutant animal goes through its entire life with the genetic alteration, sometimes making it difficult to distinguish effects on learning and memory from other more general consequences of having grown up without certain proteins and their and products.

In each of this mutants, learning actually did take place to come extent, but then decayed rapidly after training.

通过集中学习和分散学习间的差距来测量记忆的效果。

......increase the level of gene transcription factor CREB available in flies at the time just before training...... with extra CREB, a single training trail could accomplish what required multiple trails in normal flies - creat a memory that lasts for days.

稍微提了下这些研究对增强记忆的药物的启发。