生物谷報道：研究人員用小鼠做實驗,，發(fā)現(xiàn)了一個與神經(jīng)元傳遞有關(guān)的變異蛋白質(zhì)，該變異能打亂大腦中突觸放電的平衡,。這個變異在某些患有與自閉癥有關(guān)的紊亂的人身上也有,，變異對小鼠學(xué)習(xí)的微妙影響也許使它們能成為研究某些形式的自閉癥的模式動物。變異的蛋白質(zhì)是neuroligin-3,，是一個突觸細(xì)胞黏合分子,。帶有變異的小鼠的抑制性突觸傳遞增加，從而降低了神經(jīng)元的“放電率”,。Katsuhiko  Tabuchi和同事說,，變異小鼠與它們同籠伙伴的交互有所減少，但它們的空間記憶比沒有變異的小鼠要好。研究人員指出,，這與人類行為和遺傳相類似,，意味著抑制性突觸傳遞的增加也許與某種形式的自閉癥有關(guān)。

原始出處:

Published Online September 6, 2007
Science DOI: 10.1126/science.1146221

Submitted on June 7, 2007
Accepted on August 23, 2007

A Neuroligin-3 Mutation Implicated in Autism Increases Inhibitory Synaptic Transmission in Mice

Katsuhiko Tabuchi 1, Jacqueline Blundell 2, Mark R. Etherton 1, Robert E. Hammer 3, Xinran Liu 1, Craig M. Powell 4, Thomas C. Südhof 5*

1 Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
2 Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
3 Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
4 Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
5 Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

* To whom correspondence should be addressed.
Thomas C. Südhof , E-mail: [email protected]

Autism spectrum disorders (ASDs) are characterized by impairments in social behaviors that are sometimes coupled to specialized cognitive abilities. A small percentage of ASD patients carry mutations in genes encoding neuroligins, which are postsynaptic cell adhesion molecules. Here we introduce one of these mutations into mice – the R451C-substitution in neuroligin-3. R451C-mutant mice showed impaired social interactions but enhanced spatial learning abilities. Unexpectedly, these behavioral changes were accompanied by an increase in inhibitory synaptic transmission, with no apparent effect on excitatory synapses. Deletion of neuroligin-3, in contrast, did not cause such changes, indicating that the R451C-substitution represents a gain-of-function mutation. These data suggest that increased inhibitory synaptic transmission may contribute to human ASDs and that the R451C KI mice may be a useful model for studying autism-related behaviors.