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Intensive reading of foreign journals, IROFJ：1.5-Neuroscience

IROFJ：1.5-Neuroscience

【1.5】

Neuroscience

Silent synapses

How adult brains learn the new without forgetting the old

【1】Learning new things is hard. Remembering what has already been learned is harder. Any successful learning system, be it a brain or a piece of artificial-intelligence software, must strike the right balance between stability and flexibility. It must be stable enough to remember important old things yet flexible enough to learn new ones without destroying old memory traces—preferably for as long as it exists.

【2】Learning is a result of changes in the pattern of neural connectivity in the brain. Each connection between nerve cells, called a synapse, is a tiny gap between the ends of branches ramifying from such cells. Messages jump across these gaps in the form of molecules called neurotransmitters. Current estimates suggest there are 600 trillion synapses in a human brain.

【3】How, then, to deal with the stability-plasticity dilemma—particularly as brains age and, as it were, fill up? Research by Dimitra Vardalaki, Kwanghun Chung and Mark Harnett at the Massachusetts Institute of Technology, just published in Nature, suggests one way is to preserve into adulthood a type of memory-forming synapse found in children. These are called silent synapses.

【4】Silent synapses—which, as their name suggests, transmit no signal from one nerve cell to another—are often found on the ends of slender, immature protrusions from nerve cells, called filopodia. Until now, it had been thought that these disappeared as a brain matured. But Drs Vardalaki, Chung and Harnett have shown not only that they are present in adulthood, but also that they are common, at least in mice. Just over a quarter of the connections they sampled in adult mouse visual cortices were silent synapses on filopodia. And murine and human brains are sufficiently alike that something similar almost certainly applies to people.

【5】To carry out their search for filopodia, the trio used a sensitive microscopy technique called eMAP. They studied 2,234 synapses between corticalnerve cells of a type called pyramidal neurons (pictured), which have thousands of synapses each. Peering through an eMAP microscope is enough to determine which cellular protrusions are filopodia. But it cannot show which synapses on them are silent.

【6】To do that, they needed to test how the filopodia responded to glutamate, the brain's main excitatory neurotransmitter. First, they had to delivera controlled flow of glutamate to the particular synapse they wanted to test. To this end, they poured a soup of “caged” glutamate over the neuron under examination. This form of the molecule is inert until hit with energy from the intersection of two laser beams.

【7】Aiming those at the synapse under study enabled them to uncage the neurotransmitter and see, by measuring the electrical activity in that part of the neuron using an ultrafine electrode, whether the synapse responded. They found that mature pyramidal-neuron protrusions generated electrical activity when exposed to glutamate, as expected. filopodia did not, confirming the silence of their synapses.

【8】Silent synapses are, however, useless unless they can be switched on at the appropriate moment. And the researchers confirmed this is possible. They were able to induce the silent versions on filopodia to turn into mature, active synapses by pairing the simulated release of glutamate with a subsequent surge of electricity inside the neuron.

【9】This pairing of events caused silent synapses to start, within minutes, displaying receptor molecules characteristic of active synapses. The same pairing, applied to mature synapses, did nothing. The researchers thereby show it is hard to get a mature synapse to change the strength of its connection (thus satisfying the stability side of the dilemma), but easy to unsilence a silent one (satisfying the plasticity side).

【10】The next thing to investigate is how, why and when new filopodia appear. The discovery of all these eager-to-learn silent synapses and filopodia, Dr Harnett says, “is a lever for us to get into understanding learning in adults and how potentially we can get access to make it not degrade over the course of ageing or disease”.

IROFJ：1.5-Neuroscience IROFJ：1.5-Neurowissenschaften IROFJ：1.5-Neuroscience IROFJ：1.5-Neurociencia IROFJ：1.5-Neurosciences IROFJ：1.5-Neuroscienze IROFJ：1.5-ニューロサイエンス IROFJ：1.5-Neurologija IROFJ：1.5-Neurowetenschappen IROFJ：1.5-Neuroscience IROFJ：1.5-Neurociência IROFJ：1.5-Нейронаука IROFJ：1.5-Nörobilim IROFJ: 1.5 - Неврологія IROFJ：1.5-神经科学

【1.5】

Neuroscience

Silent synapses 沉默的突触

How adult brains learn the new without forgetting the old 成年人的大脑如何在不忘记旧事物的情况下学习新事物

【1】Learning new things is hard. 【1】Learning new things is hard. 【1】学习新事物很难。 Remembering what has already been learned is harder. Težje se je spomniti že naučenega. 记住已经学过的东西更难。 Any successful learning system, be it a brain or a piece of artificial-intelligence software, must strike the right balance between stability and flexibility. Vsak uspešen učni sistem, pa naj gre za možgane ali programsko opremo z umetno inteligenco, mora najti pravo ravnovesje med stabilnostjo in prilagodljivostjo. 任何成功的学习系统，无论是大脑还是人工智能软件，都必须在稳定性和灵活性之间取得适当的平衡。 It must be stable enough to remember important old things yet flexible enough to learn new ones without destroying old memory traces—preferably for as long as it exists. Biti mora dovolj stabilen, da si zapomni pomembne stare stvari, hkrati pa dovolj prilagodljiv, da se lahko nauči novih, ne da bi pri tem uničil stare spominske sledi - po možnosti tako dolgo, dokler obstaja. 它必须足够稳定，能够记住重要的旧事物，同时又必须足够灵活，能够在不破坏旧记忆痕迹的情况下学习新事物——最好是只要它存在就可以。

【2】Learning is a result of changes in the pattern of neural connectivity in the brain. 【2】学习是大脑神经连接模式变化的结果。 Each connection between nerve cells, called a synapse, is a tiny gap between the ends of branches ramifying from such cells. 神经细胞之间的每个连接（称为突触）是从这些细胞发出的分支末端之间的微小间隙。 Messages jump across these gaps in the form of molecules called neurotransmitters. Current estimates suggest there are 600 trillion synapses in a human brain. Po trenutnih ocenah je v človeških možganih 600 bilijonov sinaps. 目前估计表明人脑中有 600 万亿个突触。

【3】How, then, to deal with the stability-plasticity dilemma—particularly as brains age and, as it were, fill up? 【3】Kako torej rešiti dilemo o stabilnosti in plastičnosti, še posebej, ko se možgani starajo in tako rekoč polnijo? 【3】那么，如何应对稳定性与可塑性的困境——尤其是当大脑老化并且大脑充满时？ Research by Dimitra Vardalaki, Kwanghun Chung and Mark Harnett at the Massachusetts Institute of Technology, just published in Nature, suggests one way is to preserve into adulthood a type of memory-forming synapse found in children. Raziskave Dimitre Vardalaki, Kwanghuna Chunga in Marka Harnetta s Tehnološkega inštituta v Massachusettsu, pravkar objavljene v reviji Nature, kažejo, da je eden od načinov ohranitev vrste sinapse, ki tvori spomin in jo najdemo pri otrocih, tudi v odrasli dobi. 麻省理工学院的 Dimitra Vardalaki、Kwanghun Chung 和 Mark Harnett 刚刚在《自然》杂志上发表的研究表明，一种方法是将儿童中发现的一种形成记忆的突触保留到成年。 These are called silent synapses. Te sinapse imenujemo tihe sinapse. 这些被称为沉默突触。

【4】Silent synapses—which, as their name suggests, transmit no signal from one nerve cell to another—are often found on the ends of slender, immature protrusions from nerve cells, called filopodia. 【4】 Tihe sinapse - ki, kot pove že njihovo ime, ne prenašajo signala iz ene živčne celice v drugo - pogosto najdemo na koncih vitkih, nezrelih izrastkov živčnih celic, imenovanih filopodiji. 【4】沉默突触——顾名思义，不会将信号从一个神经细胞传递到另一个神经细胞——通常出现在神经细胞细长、未成熟的突起（称为丝状伪足）的末端。 Until now, it had been thought that these disappeared as a brain matured. Doslej je veljalo, da z dozorevanjem možganov izginejo. 到目前为止，人们一直认为这些随着大脑的成熟而消失。 But Drs Vardalaki, Chung and Harnett have shown not only that they are present in adulthood, but also that they are common, at least in mice. Dr. Vardalaki, Chung in Harnett pa so dokazali, da so prisotne tudi v odrasli dobi in da so pogoste, vsaj pri miših. 但 Vardalaki、Chung 和 Harnett 博士表明，它们不仅存在于成年期，而且很常见，至少在小鼠中是这样。 Just over a quarter of the connections they sampled in adult mouse visual cortices were silent synapses on filopodia. Nekaj več kot četrtina povezav, ki so jih vzorčili v vidnem korteksu odraslih miši, so bile tihe sinapse na filopodijah. 他们在成年小鼠视觉皮层中采样的连接中，只有超过四分之一是丝状伪足上的沉默突触。 And murine and human brains are sufficiently alike that something similar almost certainly applies to people. Mišji in človeški možgani pa so si dovolj podobni, da nekaj podobnega skoraj zagotovo velja tudi za ljudi. 小鼠和人类的大脑非常相似，类似的情况几乎肯定适用于人类。

【5】To carry out their search for filopodia, the trio used a sensitive microscopy technique called eMAP. 【5】 Za iskanje filopodij je trojica uporabila občutljivo mikroskopsko tehniko, imenovano eMAP. 【5】为了寻找丝状伪足，三人组使用了一种名为 eMAP 的灵敏显微镜技术。 They studied 2,234 synapses between corticalnerve cells of a type called pyramidal neurons (pictured), which have thousands of synapses each. Preučili so 2 234 sinaps med kortikalnimi živčnimi celicami vrste, imenovane piramidni nevroni (na sliki), ki imajo vsaka na tisoče sinaps. 他们研究了一种称为锥体神经元（如图）的皮质神经细胞之间的 2,234 个突触，每个神经元都有数千个突触。 Peering through an eMAP microscope is enough to determine which cellular protrusions are filopodia. Z mikroskopom eMAP lahko ugotovimo, katere celične izbokline so filopodiji. 通过 eMAP 显微镜观察足以确定哪些细胞突起是丝状伪足。 But it cannot show which synapses on them are silent. Ne more pa pokazati, katere sinapse na njih so neme. 但它无法显示它们的哪些突触是沉默的。

【6】To do that, they needed to test how the filopodia responded to glutamate, the brain's main excitatory neurotransmitter. 【6】 Za to so morali preveriti, kako se filopodiji odzivajo na glutamat, glavni možganski vzburjevalni nevrotransmiter. 【6】为此，他们需要测试丝状伪足对谷氨酸（大脑主要的兴奋性神经递质）的反应。 First, they had to delivera controlled flow of glutamate to the particular synapse they wanted to test. 首先，他们必须向他们想要测试的特定突触提供受控的谷氨酸流量。 To this end, they poured a soup of “caged” glutamate over the neuron under examination. V ta namen so na preiskovani nevron nalili juho glutamata v "kletki". 为此，他们将“笼中”谷氨酸汤倒在接受检查的神经元上。 This form of the molecule is inert until hit with energy from the intersection of two laser beams. Ta oblika molekule je inertna, dokler je ne zadene energija iz presečišča dveh laserskih žarkov. 这种形式的分子是惰性的，直到被两束激光束相交产生的能量击中。

【7】Aiming those at the synapse under study enabled them to uncage the neurotransmitter and see, by measuring the electrical activity in that part of the neuron using an ultrafine electrode, whether the synapse responded. 【7】 Če so jih usmerili na preučevano sinapso, so lahko sprostili nevrotransmiter in z merjenjem električne aktivnosti v tem delu nevrona z ultrafinimi elektrodami ugotovili, ali se sinapsa odziva. 【7】瞄准所研究的突触，使他们能够解开神经递质，并通过使用超细电极测量神经元该部分的电活动来观察突触是否做出反应。 They found that mature pyramidal-neuron protrusions generated electrical activity when exposed to glutamate, as expected. Ugotovili so, da so zreli izrastki piramidnih nevronov po pričakovanjih ustvarili električno aktivnost, ko so bili izpostavljeni glutamatu. 他们发现，正如预期的那样，成熟的锥体神经元突起在接触谷氨酸时会产生电活动。 filopodia did not, confirming the silence of their synapses. filopodije ne, kar potrjuje tišino njihovih sinaps. 丝状伪足却没有，这证实了它们突触的沉默。

【8】Silent synapses are, however, useless unless they can be switched on at the appropriate moment. 【8】 Tihi sinapsi so neuporabni, če jih ni mogoče vklopiti v ustreznem trenutku. 【8】然而，除非能够在适当的时刻打开，否则沉默的突触是没有用的。 And the researchers confirmed this is possible. Raziskovalci so potrdili, da je to mogoče. They were able to induce the silent versions on filopodia to turn into mature, active synapses by pairing the simulated release of glutamate with a subsequent surge of electricity inside the neuron. Tihe različice na filopodijah so lahko spodbudili, da se spremenijo v zrele, aktivne sinapse, tako da so simulirano sproščanje glutamata povezali s posledičnim električnim valom v nevronu. 通过将谷氨酸的模拟释放与神经元内随后的电流激增相结合，他们能够诱导丝状伪足上的沉默版本转变成成熟、活跃的突触。

【9】This pairing of events caused silent synapses to start, within minutes, displaying receptor molecules characteristic of active synapses. 【9】这对事件导致沉默的突触在几分钟内启动，显示出活跃突触特征的受体分子。 The same pairing, applied to mature synapses, did nothing. 同样的配对应用于成熟的突触，却没有任何作用。 The researchers thereby show it is hard to get a mature synapse to change the strength of its connection (thus satisfying the stability side of the dilemma), but easy to unsilence a silent one (satisfying the plasticity side). Raziskovalci so s tem pokazali, da je težko prisiliti zrelo sinapso, da spremeni moč svoje povezave (s čimer je izpolnjena stran dileme o stabilnosti), vendar je enostavno utišati tiho sinapso (s čimer je izpolnjena stran dileme o plastičnosti). 研究人员因此表明，很难让成熟的突触改变其连接的强度（从而满足困境的稳定性方面），但很容易使沉默的突触恢复沉默（满足可塑性方面）。

【10】The next thing to investigate is how, why and when new filopodia appear. 【10】 Naslednja stvar, ki jo je treba raziskati, je, kako, zakaj in kdaj se pojavijo novi filopodiji. 【10】接下来要调查的是新的丝状伪足如何、为何以及何时出现。 The discovery of all these eager-to-learn silent synapses and filopodia, Dr Harnett says, “is a lever for us to get into understanding learning in adults and how potentially we can get access to make it not degrade over the course of ageing or disease”. Dr. Harnett pravi, da je odkritje vseh teh tihih sinaps in filopodij, ki se želijo učiti, "vzvod za razumevanje učenja pri odraslih in za to, kako bi lahko dostopali do tega, da se ne bi poslabšalo med staranjem ali boleznijo". 哈内特博士说，所有这些渴望学习的沉默突触和丝状伪足的发现，“是我们了解成年人学习能力的一个杠杆，以及我们如何才能使其在衰老或衰老过程中不退化”。疾病”。