Impaired synaptic plasticity in an animal model of autism exhibiting early hippocampal GABAergic-BDNF/TrkB signaling alterations

被引：19

作者：

Sgritta, Martina ^{[1
]}

Vignoli, Beatrice ^{[2
]}

Pimpinella, Domenico ^{[1
]}

Griguoli, Marilena ^{[1
,3
]}

Santi, Spartaco ^{[4
]}

Bialowas, Andrzej ^{[5
]}

Wiera, Grzegorz ^{[5
]}

Zacchi, Paola ^{[6
]}

Malerba, Francesca

Marchetti, Cristina ^{[1
,3
]}

Canossa, Marco ^{[7
]}

Cherubini, Enrico ^{[1
,5
]}

机构：

[1] European Brain Res Inst EBRI, I-00161 Rome, Italy

[2] Univ Trento, Dept Phys, I-38123 Povo, TN, Italy

[3] CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy

[4] Inst Mol Genet Cavalli Sforza, Natl Res Council, Ist Ortoped Rizzoli, IRCCS, I-40136 Bologna, Italy

[5] Int Sch Adv Studies SISSA, Dept Neurosci, I-34136 Trieste, Italy

[6] Univ Trieste, Dept Life Sci, I-34128 Trieste, Italy

[7] Univ Trento, Dept Cellular Computat & Integrat Biol CIBIO, I-38123 Povo, TN, Italy

来源：

ISCIENCE | 2023年 / 26卷 / 01期

基金：

欧洲研究理事会; 欧盟地平线“2020”;

关键词：

TIMING-DEPENDENT PLASTICITY; CA3 PYRAMIDAL CELLS; NEUROTROPHIC FACTOR; GABA; BDNF; MUTATIONS; DENTATE; NETWORK; TRKB; POTENTIALS;

D O I：

10.1016/j.isci.2022.105728

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In Neurodevelopmental Disorders, alterations of synaptic plasticity may trigger structural changes in neuronal circuits involved in cognitive functions. This hypothesis was tested in mice carrying the human R451C mutation of Nlgn3 gene (NLG3R451C KI), found in some families with autistic children. To this aim, the spike time dependent plasticity (STDP) protocol was applied to immature GABAergic Mossy Fibers (MF)-CA3 connections in hippocampal slices from NLG3R451C KI mice. These animals failed to exhibit STD-LTP, an effect that persisted in adulthood when these synapses became glutamatergic. Similar results were obtained in mice lacking the Nlgn3 gene (NLG3 KO mice), suggesting a loss of function. The loss of STD-LTP was associated with a premature shift of GABA from the depolarizing to the hyperpolarizing direction, a reduced BDNF availability and TrkB phosphorylation at potentiated synapses. These effects may constitute a general mechanism underlying cognitive deficits in those forms of Autism caused by synaptic dysfunctions.

引用

页数：20

共 78 条

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