Afferent convergence to a shared population of interneuron AMPA receptors.

Afferent convergence to a shared population of interneuron AMPA receptors.
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DOI:
10.1038/s41467-023-38854-2
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发表时间:
2023-05-30
影响因子:
16.6
通讯作者:
Wadiche, Jacques I.
Wadiche, Jacques I.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pennock, Reagan L.;Coddington, Luke T.;Yan, Xiaohui;Overstreet-Wadiche, Linda;Wadiche, Jacques I.

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突触前和突触后元素的精确排列优化了兴奋性突触中谷氨酸受体的激活。尽管如此,从突触间隙扩散出来的谷氨酸可以对远处的受体产生作用,这种传递方式被称为溢出。为了揭示谷氨酸的突触外作用,我们定位了介导攀登纤维和小脑皮层分子层中间神经元之间溢出传递的AMPA受体(ampar)。我们发现攀爬纤维溢出产生钙瞬态,由平行纤维突触上的Ca2+渗透性ampar介导。溢出阻断平行的纤维突触电流,表明分离的、独立调节的传入通路汇聚到一个共同的ampar池中。综上所述,这些发现证明了一个电路基序,其中谷氨酸从一个未连接的传入通路“溢出”,协同突触受体,即使在典型谷氨酸释放被抑制时,也允许激活突触后ampar。从突触间隙扩散出来的谷氨酸可以对远处的受体产生作用,这种传递方式被称为溢出。作者发现,在小脑皮层中,来自攀爬纤维的谷氨酸溢出激活了分子层中间神经元的突触AMPA受体,允许来自非连接通路的谷氨酸参与突触后受体。
Precise alignment of pre- and postsynaptic elements optimizes the activation of glutamate receptors at excitatory synapses. Nonetheless, glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. To uncover the extrasynaptic actions of glutamate, we localized AMPA receptors (AMPARs) mediating spillover transmission between climbing fibers and molecular layer interneurons in the cerebellar cortex. We found that climbing fiber spillover generates calcium transients mediated by Ca2+-permeable AMPARs at parallel fiber synapses. Spillover occludes parallel fiber synaptic currents, indicating that separate, independently regulated afferent pathways converge onto a common pool of AMPARs. Together these findings demonstrate a circuit motif wherein glutamate ‘spill-in’ from an unconnected afferent pathway co-opts synaptic receptors, allowing activation of postsynaptic AMPARs even when canonical glutamate release is suppressed. Glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. Here, the authors find in the cerebellar cortex that glutamate spillover from climbing fibers activates synaptic AMPA receptors of molecular layer interneurons, allowing glutamate from an unconnected pathway to co-opt postsynaptic receptors.
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