Adenosine A1 receptor activation mediates the developmental shift at layer 5 pyramidal cell synapses and is a determinant of mature synaptic strength
Adenosine A1 receptor activation mediates the developmental shift at layer 5 pyramidal cell synapses and is a determinant of mature synaptic strength
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DOI：
10.1113/jphysiol.2012.244392
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发表时间：
2013-07-01
影响因子：
5.5
通讯作者：
Richardson, Magnus J. E.
中科院分区：
文献类型：
--
作者：
Kerr, Michael I.;Wall, Mark J.;Richardson, Magnus J. E.
在出生后的第一个月内，啮齿动物新皮层中的第5层锥体细胞之间的突触能突触从表现出神经递质释放的高概率、大的单位振幅和突触抑制的不成熟状态切换到释放的概率降低、较小的单位振幅和突触易化的成熟状态。利用成对的记录，我们证明了大鼠体感第5层厚簇锥体细胞之间突触释放概率的发育转变是由突触前腺苷A（1）受体的更高和更异质的激活介导的。在对照条件下，未成熟突触的变异系数、失败率和释放概率的分布几乎与A（1）受体阻断条件一致;然而，在对照条件下，成熟突触的分布范围更广，跨越了A（1）受体激动和拮抗条件。未成熟和成熟的突触表达A（1）受体，在功能效力上没有观察到差异，因此在成熟的新皮层中观察到的异质性A（1）受体激活似乎是由于突触之间腺苷浓度增加而引起的。鉴于A（1）受体激活在决定突触振幅和成熟的第5层锥体细胞之间的传递统计中所起的中心作用，腺苷源和汇在突触末端附近的定位可能构成一种新的长期突触可塑性形式。
During the first postnatal month glutamatergic synapses between layer 5 pyramidal cells in the rodent neocortex switch from an immature state exhibiting a high probability of neurotransmitter release, large unitary amplitude and synaptic depression to a mature state with decreased probability of release, smaller unitary amplitude and synaptic facilitation. Using paired recordings, we demonstrate that the developmental shift in release probability at synapses between rat somatosensory layer 5 thick-tufted pyramidal cells is mediated by a higher and more heterogeneous activation of presynaptic adenosine A(1) receptors. Immature synapses under control conditions exhibited distributions of coefficient of variation, failure rate and release probability that were almost coincident with the A(1) receptor blocked condition; however, mature synapses under control conditions exhibited much broader distributions that spanned those of both the A(1) receptor agonized and antagonized conditions. Immature and mature synapses expressed A(1) receptors with no observable difference in functional efficacy and therefore the heterogeneous A(1) receptor activation seen in the mature neocortex appears due to increased adenosine concentrations that vary between synapses. Given the central role demonstrated for A(1) receptor activation in determining synaptic amplitude and the statistics of transmission between mature layer 5 pyramidal cells, the emplacement of adenosine sources and sinks near the synaptic terminal could constitute a novel form of long-term synaptic plasticity.