Insulin-like growth factor 1 regulates excitatory synaptic transmission in pyramidal neurons from adult prefrontal cortex.
Insulin-like growth factor 1 regulates excitatory synaptic transmission in pyramidal neurons from adult prefrontal cortex.
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胰岛素样生长因子1调节成年人前额叶皮质锥体神经元兴奋性突触传递。
DOI：
10.1016/j.neuropharm.2022.109204
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发表时间：
2022-10-01
影响因子：
4.7
通讯作者：
Wang, Zi-Jun
中科院分区：
文献类型：
--
作者：
Yue, Shuwen;Wang, Yunwanbin;Wang, Zi-Jun
关键词：
胰岛素样生长因子1（IGF 1）除了在大脑发育和衰老中发挥作用外，还影响突触功能。虽然IGF 1和IGF 1受体（IGF 1 R）的表达水平在发育过程中达到峰值，并随着年龄的增长而下降，但成人大脑中有丰富的IGF 1或IGF 1 R表达。研究表明，IGF 1调节幼年动物神经元的突触传递。然而，IGF 1对成人大脑神经元的作用仍不清楚。在这里，我们使用成年小鼠（~8周龄）的前额叶皮层（PFC）切片来表征IGF 1对锥体神经元兴奋性突触传递的作用及其潜在的分子机制。我们首先使用翻译核糖体亲和纯化分析验证了锥体神经元中IGF 1 R的表达。然后，采用全细胞膜片钳技术，我们发现IGF 1可使诱发兴奋性突触后电流（EPSC）的幅度衰减，而对微型EPSC的频率和幅度无影响。此外，这种兴奋性神经传递的减少被阻断的药理学抑制IGF 1 R或条件性敲低的IGF 1 R在PFC锥体神经元。此外，我们确定IGF 1诱导的EPSC幅度降低是由于突触后效应（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体[AMPAR]的内化），而不是突触前谷氨酸释放。最后，我们发现，代谢型谷氨酸受体亚型-1（mGluR 1）的抑制取消IGF 1诱导的EPSC诱发振幅的衰减和突触膜AMPAR表达的减少，表明mGluR 1介导的AMPAR内吞参与。总之，这些数据提供了第一个证据，IGF 1调节兴奋性突触传递在成人PFC通过IGF 1 R依赖的信号通路和mGluR 1介导的AMPAR内吞作用之间的相互作用。
Insulin-like growth factor 1 (IGF1) influences synaptic function in addition to its role in brain development and aging. Although the expression levels of IGF1 and IGF1 receptor (IGF1R) peak during development and decline with age, the adult brain has abundant IGF1 or IGF1R expression. Studies reveal that IGF1 regulates the synaptic transmission in neurons from young animals. However, the action of IGF1 on neurons in the adult brain is still unclear. Here, we used prefrontal cortical (PFC) slices from adult mice (~8 weeks old) to characterize the role of IGF1 on excitatory synaptic transmission in pyramidal neurons and the underlying molecular mechanisms. We first validated IGF1R expression in pyramidal neurons using translating ribosomal affinity purification assay. Then, using whole-cell patch-clamp recording, we found that IGF1 attenuated the amplitude of evoked excitatory postsynaptic current (EPSC) without affecting the frequency and amplitude of miniature EPSC. Furthermore, this decrease in excitatory neurotransmission was blocked by pharmacological inhibition of IGF1R or conditional knockdown of IGF1R in PFC pyramidal neurons. In addition, we determined that IGF1-induced decrease of EPSC amplitude was due to postsynaptic effect (internalization of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors [AMPAR]) rather than presynaptic glutamate release. Finally, we found that inhibition of metabotropic glutamate receptor subtype-1 (mGluR1) abolished IGF1-induced attenuation of evoked EPSC amplitude and decrease of AMPAR expression at synaptic membrane, suggesting mGluR1-mediated endocytosis of AMPAR was involved. Taken together, these data provide the first evidence that IGF1 regulates excitatory synaptic transmission in adult PFC via the interaction between IGF1R-dependent signaling pathway and mGluR1-mediated AMPAR endocytosis.
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影响因子：
64.5
作者：
Cao P;Maximov A;Südhof TC
通讯作者：
Südhof TC
影响因子：
4.2
作者：
BARONVANEVERCOOREN, A;OLICHONBERTHE, C;VANOBBERGHEN, E
通讯作者：
VANOBBERGHEN, E
影响因子：
2.5
作者：
BECKSTEAD, RM
通讯作者：
BECKSTEAD, RM
影响因子：
4.8
作者：
CLEMMONS, DR;DEHOFF, ML;CASCIERI, MA
通讯作者：
CASCIERI, MA
影响因子：
5.3
作者：
Carr, DB;Sesack, SR
通讯作者：
Sesack, SR