Presynaptic Gating of Postsynaptically Expressed Plasticity at Mature Thalamocortical Synapses
Presynaptic Gating of Postsynaptically Expressed Plasticity at Mature Thalamocortical Synapses
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DOI：
10.1523/jneurosci.3281-11.2011
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发表时间：
2011-11-02
影响因子：
5.3
通讯作者：
Zakharenko, Stanislav S.
中科院分区：
文献类型：
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作者：
Blundon, Jay A.;Bayazitov, Ildar T.;Zakharenko, Stanislav S.
丘脑皮质（TC）投射提供了将感觉信息提升到哺乳动物新皮质的主要途径。这些投射阵列在丘脑接受神经元上形成突触输入，从而有助于感觉皮层中感受野（RF）的形成。 RF 的经验依赖性可塑性在生物体的整个生命周期中持续存在，但在成人中需要激活皮质的胆碱能输入。相比之下，TC 预测的突触可塑性仅限于出生后早期。这种脱节导致人们普遍认为 TC 突触是仅在新生儿感觉皮层中射频可塑性的主要部位，但它们在成熟后会失去这种可塑性。在这里，我们测试了另一种假设，即成熟的 TC 投射不会失去突触可塑性，而是获得阻止突触可塑性诱导的门控机制。通过对包含听觉丘脑和皮层的急性小鼠脑切片中的单个突触进行全细胞记录和突触后和突触前活动的直接测量（分别为 FM 1-43 测定的双光子谷氨酸解笼和双光子成像），我们确定长期抑制 (LTD) 在成熟 TC 突触中持续存在，但在突触前门控。胆碱能激活通过 M-1 毒蕈碱受体释放突触前门控，下调腺苷对通过 A(1) 腺苷受体起作用的神经递质释放的抑制。一旦突触前门控被释放，成熟的 TC 突触可以通过 I 类代谢型谷氨酸受体在突触后表达 LTD。这些结果表明，TC 突触的突触可塑性在整个生命周期中都得到保留，因此可能是新生儿和成熟动物中 RF 可塑性的细胞基质。
Thalamocortical (TC) projections provide the major pathway for ascending sensory information to the mammalian neocortex. Arrays of these projections form synaptic inputs on thalamorecipient neurons, thus contributing to the formation of receptive fields (RFs) in sensory cortices. Experience-dependent plasticity of RFs persists throughout an organism's life span but in adults requires activation of cholinergic inputs to the cortex. In contrast, synaptic plasticity at TC projections is limited to the early postnatal period. This disconnect led to the widespread belief that TC synapses are the principal site of RF plasticity only in neonatal sensory cortices, but that they lose this plasticity upon maturation. Here, we tested an alternative hypothesis that mature TC projections do not lose synaptic plasticity but rather acquire gating mechanisms that prevent the induction of synaptic plasticity. Using whole-cell recordings and direct measures of postsynaptic and presynaptic activity (two-photon glutamate uncaging and two-photon imaging of the FM 1-43 assay, respectively) at individual synapses in acute mouse brain slices that contain the auditory thalamus and cortex, we determined that long-term depression (LTD) persists at mature TC synapses but is gated presynaptically. Cholinergic activation releases presynaptic gating through M-1 muscarinic receptors that downregulate adenosine inhibition of neurotransmitter release acting through A(1) adenosine receptors. Once presynaptic gating is released, mature TC synapses can express LTD postsynaptically through group I metabotropic glutamate receptors. These results indicate that synaptic plasticity at TC synapses is preserved throughout the life span and, therefore, may be a cellular substrate of RF plasticity in both neonate and mature animals.