039期|成人大脑如何学新而不忘旧(下)
日期:2023-05-11 08:00

(单词翻译:单击)

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To carry out their search for filopodia, the trio used a sensitive microscopy technique called eMAP. They studied 2,234 synapses between cortical nerve cells of a type called pyramidal neurons, which have thousands of synapses each.

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为了寻找丝状伪足,三位研究人员使用了一种名为"电子显微放射自显影法"(eMAP)的灵敏显微镜成像技术%RF.=BaZxT(@x#YQD9EI。一种名为椎体神经元的皮层神经细胞每个都有数千个突触,他们研究了其中的2234个,.s+2W4=.,ZQEZL=)

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Peering through an emap microscope is enough to determine which cellular protrusions are filopodia. But it cannot show which synapses on them are silent. To do that, they needed to test how the filopodia responded to glutamate, the brain's main excitatory neurotransmitter.

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通过eMAP显微镜观察就可以确定哪些细胞突起是丝状伪足,但并不能显示上面的哪些突触处于沉默状态tJgc|.]ND182W。要确定这一点,他们需要测试丝状伪足对谷氨酸的反应,谷氨酸也就是大脑主要的兴奋性神经递质16.2!4|!2W

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First, they had to deliver a 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.

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首先,他们必须向想要测试的特定突触输送一定量的谷氨酸GB.Crq^]H,*G)B。为此,他们在被测试的神经元上倒入"束缚态"的谷氨酸溶液)I2MO2RO4zR1gTWOfeNS。这种状态下的谷氨酸分子是惰性的,在两束激光交汇的能量冲击下才会被激活-DxBBl,rW,hk.#)

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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.

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将激光对准待研究的突触,可以释放出谷氨酸这种神经递质,研究人员通过使用超细电极测量神经元对应部分的电活动,就可以观察突触是否有反应AD5[a67%@V

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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.

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他们发现,接触到谷氨酸时,成熟的锥体神经元突起产生了电活动,与预期一致|oRDjb[UNcT-(Rb9R=,S。但丝状伪足没有活动,证实了其突触的沉默状态BXmM@twK5wHt51

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Silent synapses are, however, useless unless they can be switched on at the appropriate moment. And the researchers confirmed this is possible.

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然而,沉默的突触是没有用的,除非能在适当的时候被激活g]o#4;Y_O[2l^.-i。研究人员已经证实这是可行的RE3z(z1+^Hn[I[

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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.

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他们想办法让一种对释放谷氨酸的模拟在神经元内产生电涌,从而诱导丝状伪足上的沉默突触转化为最成熟、活跃的突触Ae)EbNw~Dx

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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.

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在这种操作的诱导下,沉默突触在几分钟内便开始表现出活跃突触的受体分子特征,同样的操作却没有对成熟突触产生任何作用pw|H*O3[4[

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The researchers thereby show that 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).

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研究人员由此确定,成熟突触的连接强度难以改变(从而满足了两难困境中的稳定性的要求),但要激活沉默突触却很容易(满足了可塑性的要求)5%bM82b;8Lb;6

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The next thing to investigate is how, why and when new filopodia appear.

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下一步要研究的就是新的丝状伪足是如何、为何以及何时出现的KC45)7tl3]0Q+

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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".

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哈尼特博士说,所有这些"求知若渴"的沉默突触和丝状伪足的发现,"为我们提供了一种手段来了解成年人的学习能力、以及如何能够通过某种干预,使其不随衰老或疾病发展而退化"U%oZOzrVBCTI5%Fa97Mb

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