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小脑回路中谷氨酸能突触多样性的机制及功能作用

Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit.

作者信息

Zampini Valeria, Liu Jian K, Diana Marco A, Maldonado Paloma P, Brunel Nicolas, Dieudonné Stéphane

机构信息

Institut de Biologie de l'ENS, Ecole Normale Supérieure, Paris, France.

Inserm, U1024, Paris, France.

出版信息

Elife. 2016 Sep 19;5:e15872. doi: 10.7554/eLife.15872.

DOI:10.7554/eLife.15872
PMID:27642013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5074806/
Abstract

Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying vestibular inputs to the cerebellar cortex. We show that UBCs respond to sinusoidal modulations of their sensory input with heterogeneous amplitudes and phase shifts. Experiments and modeling indicate that this variability results both from the kinetics of synaptic glutamate transients and from the diversity of postsynaptic receptors. While phase inversion is produced by an mGluR2-activated outward conductance in OFF-UBCs, the phase delay of ON UBCs is caused by a late rebound current resulting from AMPAR recovery from desensitization. Granular layer network modeling indicates that phase dispersion of UBC responses generates diverse phase coding in the granule cell population, allowing climbing-fiber-driven Purkinje cell learning at arbitrary phases of the vestibular input.

摘要

突触电流在其时间特性上表现出很大程度的异质性,但其功能作用仍不清楚。我们在大鼠小脑切片中研究了单极刷状细胞(UBC)的突触电流,这些细胞产生将前庭输入传递到小脑皮质的固有苔藓纤维。我们发现,UBC对其感觉输入的正弦调制以异质幅度和相位偏移做出反应。实验和建模表明,这种变异性既源于突触谷氨酸瞬变的动力学,也源于突触后受体的多样性。虽然在OFF-UBC中,mGluR2激活的外向电导产生了相位反转,但ON UBC的相位延迟是由AMPA受体脱敏恢复产生的晚期反弹电流引起的。颗粒层网络建模表明,UBC反应的相位分散在颗粒细胞群体中产生了不同的相位编码,从而允许攀缘纤维驱动的浦肯野细胞在前庭输入的任意相位进行学习。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/253ae188c472/elife-15872-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/036001614f1b/elife-15872-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/986be641e0ae/elife-15872-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/ac4065d13d4b/elife-15872-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/8775825b91d5/elife-15872-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/ca4eda6c9b8f/elife-15872-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/253ae188c472/elife-15872-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/036001614f1b/elife-15872-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/986be641e0ae/elife-15872-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/ac4065d13d4b/elife-15872-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/8775825b91d5/elife-15872-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/ca4eda6c9b8f/elife-15872-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/5074806/253ae188c472/elife-15872-fig7.jpg

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Nat Neurosci. 2015 May;18(5):718-27. doi: 10.1038/nn.3974. Epub 2015 Mar 30.
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ON and OFF unipolar brush cells transform multisensory inputs to the auditory system.
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Balance performance in aged mice is dependent on unipolar brush cells.老年小鼠的平衡能力取决于单极刷状细胞。
bioRxiv. 2024 Oct 12:2024.10.10.617602. doi: 10.1101/2024.10.10.617602.
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