【神经】复习纲要最终版.doc

神经科学导论
1. 你如何理解特定的脑功能定位于不同的脑区？
不同的功能定位于不同的神经根，那么不同的功能也很有可能定位于不同的脑部位。
这是有很多实验证明的：有人曾通过系统的摧毁闹得特定部位，并检查由此引起的而感觉和运动缺陷（Flourens）；broca遇到的一个病人（左额叶上发现了损伤，自己无法说话，但是能够理解别人的言语）
总结：特定脑功能定位于不同的脑部位→Flourens 否定了Gall 的颅相说，Paul Broca 大脑分区， 建立神经心理学

2. 脑有哪些组织层次？你如何理解神经元是脑的基本功能单元？
神经元，突触，
3.举例说明神经系统结构和功能在进化上的保守性及对环境适应性；
保守性：
1.For example, similar fear reaction for many different species (the same behavioral trait) which evolved from a common ancestor. Advantageous presumably because it facilitated escape from predators.Because behavior reflects the activity of the nervous system, we can infer that the brain mechanisms that underlie this fear reaction may be similar across these species.
2. 抢乌贼巨大轴突，神经电冲动传导，适用于人类
3. 如大鼠有机会重复自我摄取可卡因，也会明显成瘾。
环境适应性：
猴在树梢上跳跃与敏锐视觉，大鼠虽然“鼠目寸光”在洞中穿行与嘴边的触须。

突触传递
1. 电突触的结构和功能特征；无脊椎动物电突触生理功能举例；
结构：
Six connexins form a channel (connexon接合质), and two connexons (one from each cell) form a gap junction channel.

功能特性：
Functional properties of electrical synapses:
Equally pass in both direction
Electrically coupled
Very fast, and if the synapse is large, fail-safe. Thus, an AP in the presynaptic neuron can produce, almost instantaneously, an AP in the postsynaptic neuron.

举例：
In invertebrate species, such as the crayfish小龙虾, electrical synapses are sometimes found between sensory and motor neurons in neural pathways mediating escape reflexes.

2. 化学突触的基本结构：相关结构名词的中英文及其意义；突触囊泡（synaptic vesicle）和分泌颗粒（secretory granule）的比较；突触前后组分的比较；基于结构的突触分类；外周化学突触神经肌接头的结构特征及功能意义；
相关结构名词的中英文与意义：
synaptic cleft突触间隙 (20–50 nm ), filled with a matrix of fibrous
extracellular protein. One function of this matrix is to make the pre- and postsynaptic membranes adhere to each other.
presynaptic element突触前部, is usually an axon terminal.
synaptic vesicles (50 nm in diameter), store neurotransmitter used to communicate with the postsynaptic neuron.
secretory granules (larger vesicles, about 100 nm diameter) contain soluble protein (dark in EM, large dense-core vesicles)
Membrane differentiations膜的分化： on either side of the synaptic cleft
Active zone活性带：looks like pyramid角锥体, the sites of NT release
postsynaptic density 突触后密集区：contains receptors converting signal from intercellular to intracellular
突触囊泡（synaptic vesicle）和分泌颗粒（secretory granule）的比较：
突触囊泡（synaptic vesicle）： synaptic vesicles (50 nm in diameter), store neurotransmitter used to communicate with the postsynaptic neuron. 分泌颗粒（secretory granule）： secretory granules (larger vesicles, about 100 nm diameter) contain soluble protein (dark in EM, large dense-core vesicles)
突触前后组分的比较： Membrane differentiations—— Active zone活性带：looks like pyramid角锥体, the sites of NT release postsynaptic density 突触后密集区：contains receptors converting signal from intercellular to intracellular

基于结构的突触分类：
Two categories of CNS synaptic membrane differentiations.
(a) A Gray’s type I synapse is asymmetrical and usually excitatory.
(b) A Gray’s type II synapse is symmetrical and usually inhibitory.
外周化学突触神经肌接头的结构特征及功能意义：
相同之处：Neuromuscular junctions occur between the axons of motor neurons of the spinal cord and skeletal muscle. NMJ has many of the structural features of chemical synapses in the CNS.
特征
结构：The neuromuscular junction： The postsynaptic membrane, known as the motor endplate, contains junctional folds with numerous neurotransmitter receptors.
功能：Neuromuscular synaptic transmission is fast and reliable. An AP in the motor axon always causes an AP in the muscle cell it innervates (What structural features for this reliability?)

3.化学突触传递的基本原理（要点）
Synthesis and package into vesicles of neurotransmitter (NT); 突触合成
单胺类和氨基酸类：
酶运输到轴突终末，将前提物质合成神经递质
➁ 转运体蛋白浓缩神经递质入突触囊泡并存储.
肽类：
➀ 肽链前提在胞体合成➁ 高尔基体中裂解合成活性肽链
出芽形成分泌囊泡 分泌颗粒运输到轴突终末存储
Release of vesicle NT to cleft in response to a presynaptic AP; 突触前动作电位诱导递质释放
动作电位→突触前膜去极化→ 电压门控钙离子通道激活（[Ca2+]i0.0002 mM → 0.1 mM）→囊泡释放（胞吐）→递质释放入突触间隙
囊泡释放（胞吐）：[Ca2+]i 增加诱发已经锚定的囊泡与突触前膜融合以及储备囊泡从细胞骨架释放并锚定到活性带。突触囊泡借助一系列囊泡膜蛋白和突触膜蛋白的相互作用完成入坞（docking）、启动（priming）、融合（fusion）过程，称作SNARE假说。
补充：SNARE: SNAP Receptor SNAP: Soluble NSF Attach Protein NSF: N-ethylmaleimide-sensitive factor (N-乙基马来酰亚胺敏感的融合因子)
Induction of an electrical or biochemical response to NT in the postsynaptic neuron 突触后面反应
递质门控离子通道→EPSP（Excitatory postsynaptic potential (EPSP)Ach- or Glutamate-gated channels）或IPSP（Inhibitory postsynaptic potential (IPSP)
BABA- or Glycine-gated channels）
G 蛋白耦联受体G-proteins→效应分子“effector” proteins（两种:G-protein-gated ion channels和Enzymes that synthesize second messengers）
Clearance of NT from the synaptic cleft 递质清除
简单扩散（氨基酸类和单胺类递质）、重摄取：突触前膜特殊转运蛋白、降解：酶解

4. 神经递质的类别和化学特征；神经递质在同一神经元的共存；化学和多肽类神经递质的合成和储存的基本特点；转运体概念；
Three chemical categories
Amine, amino acid, peptide
Secretory granules and synaptic vesicles
神经递质在同一神经元的共存：amine + peptide；amino acid + peptide
化学和多肽类神经递质的合成和储存的基本特点：
单胺类和氨基酸类：
酶运输到轴突终末，将前提物质合成神经递质
➁ 转运体蛋白浓缩神经递质入突触囊泡并存储.
肽类：
➀ 肽链前提在胞体合成➁ 高尔基体中裂解合成活性肽链
➂ 出芽形成分泌囊泡➃ 分泌颗粒运输到轴突终末存储
转运体概念：
Transporters, proteins in the vesicle membrane, take up and concentrate the amino acid and amaine neurotransmitters inside the vesicle.

5. 递质释放的电及分子事件；突触囊泡快速释放的关键机制；肽类递质释放的特点；
递质释放的电及分子事件：An action potential in the axon terminal → depolarization of the terminal membrane → voltage-gated calcium channels in the active zones to open （[Ca2+]i 0.0002 mM → ˃0.1 mM）→ vesicles release（exocytosis）→ the contents to spill out into the synaptic cleft
突触囊泡快速释放的关键机制：The exocytosis occurs very rapidly within 0.2 msec of the Ca2+ influx into the terminal. Why?
The mechanism by which [Ca2+] i stimulates exocytosis:
Reserve pool of vesicles bound to the cytoskeleton
Docking of vesicles to active zone
SNARE protein complex, conformation altered by ↑[Ca2+]i
Endocytosis
Recycled vesicle refilled with neurotransmitter
肽类递质释放的特点：Secretory granules also release peptide neurotransmitters by exocytosis：
typically not at the active zones
requires high-frequency trains of AP and more calcium influx.

6. 与递质结合的突触后受体的基本类型和功能特征；EPSC、IPSC概念、相关的主要递质和受体；G蛋白偶联受体的基本结构和功能特征、自身受体；
与递质结合的突触后受体的基本类型和功能特征：基本类型：receptors can be classified into two types: transmitter-gated ion channels and G-protein-coupled receptors； 功能特征： key in a lock, induce conformational changes in the receptor and lead to different functions.
EPSC、IPSC概念、相关的主要递质和受体：见上文
G蛋白偶联受体的基本结构和功能特征功能特征：Fast chemical synaptic transmission is mediated by amino acid and amine neurotransmitters acting on transmitter-gated ion channels. However, all three types of neurotransmitter, acting on GPCR, can also have slower, longer-lasting, and much more diverse postsynaptic actions.
自身受体： 1.found in the presynaptic axon terminal; 2.Sensitive to the neurotransmitter; 3.Typically, autoreceptors are GPCR; 4.The common consequences is inhibition of neurotransmitter release, this allows a presynaptic terminal to regulate itself

7. 神经递质的回收和降解的三个主要途径；神经药理学的基本概念（以乙酰胆碱受体为例）
神经递质的回收和降解的三个主要途径:见上文
神经药理学的基本概念（以乙酰胆碱受体为例）：Each of the steps of synaptic transmission is chemical, and therefore can be affected by specific drugs and toxins.
Inhibitors: e.g. Nerve gases inhibite the enzyme AChE. Inhibitors of neurotransmitter receptors, called receptor antagonists (e.g. Curare, an arrow-tip poison, binds tightly to the ACh receptors)
Receptor agonists： e.g. nicotine, binds to, and activates, the ACh receptors in skeletal muscle and CNS. nicotinic ACh receptors (nAChR).

8. 突触整合的基本原理（要点）；决定EPSP输入是否产生AP的主要因素；
EPSP的整合
树突性质对突触整合的贡献
抑制作用
调制作用
决定EPSP输入是否产生AP的主要因素，包括协同起作用的兴奋性突触数目、突触到峰电位起始区的距离以及树突膜的性质。

9. 神经元信息的输入和输出特征；量子释放的概念；EPSP总和（时间、空间）；树突特征与突触整合；抑制作用（抑制性突触的分布特征、IPSP、分流抑制）；调制（如何实现功能？）
量子释放：神经递质释放的最基本单位是一个突触囊泡的内容物。每个囊泡含有大约相同数目的递质分子。被释放的递质总量就是这个数的整数倍。因此突触后EPSP的幅度就是对一个囊泡内容物反应幅度的整数倍。突触后的EPSP是量子化的，反映了一个突触囊泡的递质分子总数和突触中可用的突触受体的数量。
空间总和：将在树突上不同突触处同时产生的许多EPSPs进行叠加
时间总和：在同一个突触产生的，时间间隔在1~15ms之内的一系列EPSP叠加
分流抑制
抑制性突触后受体结合的神经递质是GABA或Gly，递质门控通道仅允许Cl-通透，驱使Cl-向使膜电位朝氯平衡电位(-65mv)的方向跨膜移动。当递质释放时，如果膜电位低于-65mV，激活这些通道就会导致一个超极化IPSP。
考虑如下情况，在突触远端有一个兴奋性突触，靠近胞体的突触近端有一个抑制性突触。激活兴奋性突触能触发正电荷流入树突，此电流在其流向胞体的过程中使膜去极化。但是在激活的抑制性突触位点，膜电位大约等于-65mV，正电位在该位点流出膜外，迫使Vm为-65mV。这个突触作为一个电分流，防止电流流过胞体到达轴丘，这种抑制称为分流抑制。
调制
许多具有G蛋白偶联神经递质受体的突触都不与离子通道直接关联。这些受体的突触性激活不会直接诱发EPSP和IPSP，而是调节与递质门控通道偶联的突触所产生的EPSP。这种突触传递叫做调制。

递质系统
1. 鉴定神经递质的标准是什么？
Criteria to identify a neurotransmitter:
The molecule must be synthesized and stored in the presynaptic neuron.
The molecule must be released by the presynaptic axon terminal upon stimulation.
The molecule, when experimentally applied, must produce a response in the postsynaptic cell that mimics the response produced by the release of neurotransmitter from the presynaptic neuron.
1.该分子在突触前神经元合成并储存
2.受到刺激时由突触前膜释放
3.将该分子外加于突触与突触前膜，释放该递质的效应一致

2. 有什么方法可以鉴定神经元特定神经递质的存在？
免疫细胞化学immunocytochemistry ；This method uses labeled antibodies
to identify the location of molecules within cells.
原位杂交in situ hybridization； In the method of in situ hybridization, a synthetic probe is constructed containing a sequence of complementary nucleotides that will allow it to stick to the mRNA. If the probe is labeled, the location of cells containing the mRNA will be revealed.

3. 神经递质乙酰胆碱的发现以及从发现吗啡受体到发现内源性吗啡配体，对你有什么启发？
To show that a neurotransmitter candidate is actually released upon stimulation.
Axon stimulation → test biological activity → chemical analysis
(as Loewi and Dale did in identification of ACh as a transmitter at many peripheral synapses)
Ligand-Binding Methods：Selective drugs provide an opportunity to analyze receptors directly, even before the neurotransmitter itself had been identified.

4. 乙酰胆碱能神经元：乙酰胆碱代谢循环要点；抑制乙酰胆碱酯酶的病理联系；
The neurotransmitter at NMJ, synthesized by all the motor neurons in the spinal cord and brain stem. Other cholinergic cells contribute to the functions of specific circuits in the PNS and CNS.
循环：
ACh synthesis needs an enzyme, choline acetyltransferase (ChAT).
Transport of choline into the neuron is the rate-limiting step in ACh synthesis.
抑制乙酰胆碱酯酶的病理联系：
Acetylcholinesterase (AChE) secreted from Cholinergic and noncholinergic neurons to degrades ACh. Inhibition of AChE disrupts transmission at cholinergic synapses on skeletal muscle and heart muscle.

5. 儿茶酚胺能神经元：儿茶酚胺类神经递质有哪些？代谢要点及重要的病理联系（如巴金森病、药物依赖）；
儿茶酚胺类神经递质有哪些？
Include dopamine (DA), norepinephrine (NE), and epinephrine.
代谢要点：
All such neurons contain tyrosine hydroxylase (TH)酪氨酸羟化酶, which catalyzes the first step in catecholamine synthesis, the conversion of tyrosine to a compound called dopa多巴。多巴在轴浆中合成；去甲肾上腺素在囊泡中多巴胺-β羟化酶作用下由多巴胺合成；肾上腺素在轴浆中有苯乙醇胺氮位甲基移位酶作用下有去甲肾上腺素合成。
重要的病理联系:
1.Dopa is converted into the neurotransmitter dopamine by the enzyme dopa decarboxylase. Parkinson’s disease and dopa supplement therapy.
2.The actions of catecholamines in the synaptic cleft are terminated by selective uptake of the neurotransmitters back into the axon terminal via Na+-dependent transporters. This step is sensitive to a number of different drugs. For example, amphetamine and cocaine block catecholamine uptake.

6.5-羟色胺能神经元：代谢要点与抗抑郁症联系
与抗抑郁症联系： Serotonergic neurons are relatively few in number, but they appear to play an important role in the brain systems that regulate mood, emotional behavior, and sleep. 5-HT is removed from the synaptic cleft by the action of a specific transporter, which is sensitive to a number of different drugs. e.g. antidepressant drugs like fluoxetine. Once back in the cytosol, 5-HT is either reloaded to SVs or degraded by MAO.

7. 有哪些氨基酸能神经元？神经元为何能有效利用必需氨基酸作为神经递质？合成GABA的关键酶是什么？

有哪些氨基酸能神经元？Amino acid neurotransmitters Glu, Gly, and GABA serve as neurotransmitters at most CNS synapses
神经元为何能有效利用必需氨基酸作为神经递质？Glutamate and glycine are synthesized from glucose and other precursors by enzymes existing in all cells. Differences among neurons are quantitative rather than qualitative. e.g. the glutamatergic terminals have about 20 mM Glu, only 2-3 times higher than nonglutamatergic cells. Importantly, in glutamatergic terminalss, but not in other’s, the glutamate transporter concentrates Glu in SVs to reach about 50 mM.
合成GABA的关键酶是什么？
The key synthesizing enzyme is glutamic acid decarboxylase (GAD), a good marker for GABAergic neurons. One chemical step to convert the major excitatory into the major inhibitory neurotransmitter in the brain!

8. 嘌呤能神经元：ATP作为递质的要点
1.ATP is concentrated in vesicles , released into the cleft by presynaptic spikes in a Ca2+-dependent manner.
2.ATP is often packaged in vesicles along with another classic transmitter (e.g. catecholamine) which means they are probably co-transmitters.

9. 突触后向突触前逆向信号传递的概念及相关的类神经递质物质
endocannabinoids (大麻酚,endogenous cannabinoids), can be released from postsynaptic neurons and act on presynaptic terminals, called retrograde signaling; thus, endocannabinoids are retrograde messengers, a kind of feedback regulation.
Gaseous molecule, nitric oxide (NO). Carbon monoxide (CO) has also been suggested as a messenger, being extensively studied and hotly debated.
10. 乙酰胆碱受体的亚型及其药理学（哪些内容对其他递质受体具有普适性？）
the nicotinic ACh receptor at NMJ have five subunits arranged like a barrel to form a single pore. Four different subunits α, β, γ, δ are used. There is one ACh binding site on each of the α subunits.
The nicotinic ACh receptor on neurons is also a pentamer, but, unlike the muscle receptor, most of them are comprised of α and β subunits only.

11. 递质门控离子通道结构的基本特征：多亚基组成、亚基具有不同的结构，以乙酰胆碱受体和谷氨酸受体通道说明之。
Similarities in subunit structure for different transmitter-gated ion channels
(a) They have in common the four regions called M1–M4, which are segments where the polypeptides will coil into alpha helices to span the membrane. Kainate receptors are subtypes of glutamate receptors. (b) M1–M4 regions of the ACh subunit, as they are believed to be threaded through the membrane.
The glutamate-gated channels are most likely tetramers structure. The M2 region does not span the membrane, but instead forms a hairpin that both enters and exits from the inside of the membrane, resembling potassium channels.

12. AMPA受体和NMDA受体都是谷氨酸门控的离子通道，但有各自的功能特征，请说明。
AMPA-gated channels are permeable to both Na+ and K +, and most of them are not permeable to Ca2+. The net effect is to admit Na+ ions into the cell, causing a rapid and large depolarization.
NMDA-gated channels differ from AMPA receptors in two very important ways: (1) NMDA-gated channels are permeable to Ca2+, and (2) inward ionic current through NMDA-gated channels is voltage dependent.
It is hard to overstate the importance of intracellular Ca2+ to cell functions. presynaptical and postsynaptical; physiological and pathological. Thus, activation of NMDA receptors can, in principle, cause widespread and lasting changes in the postsynaptic neuron.

13. GABA受体受体的调制及其药理学意义；
Synaptic inhibition must be tightly regulated