Molosh, Andrei I.Johnson, Philip L.Spence, John P.Arendt, DavidFederici, Lauren M.Bernabe, CristianJanasik, Steven P.Segu, Zaneer M.Khanna, RajeshGoswami, ChirayuZhu, WeiguoPark, Su-JungLi, LangMechref, Yehia S.Clapp, D. WadeShekhar, Anantha2016-03-142016-03-142014-11Molosh, A. I., Johnson, P. L., Spence, J. P., Arendt, D., Federici, L. M., Bernabe, C., … Shekhar, A. (2014). Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase. Nature Neuroscience, 17(11), 1583–1590. http://doi.org/10.1038/nn.38221097-6256https://hdl.handle.net/1805/8840Children with Neurofibromatosis type 1 (NF1) are increasingly recognized to have high prevalence of social difficulties and autism spectrum disorders (ASD). We demonstrated selective social learning deficit in mice with deletion of a single Nf1 gene (Nf1+/−), along with greater activation of mitogen activated protein kinase pathway in neurons from amygdala and frontal cortex, structures relevant to social behaviors. The Nf1+/− mice showed aberrant amygdala glutamate/GABA neurotransmissiondeficits in long-term potentiationand specific disruptions in expression of two proteins associated with glutamate and GABA neurotransmission: a disintegrin and metalloprotease domain 22 (ADAM22) and heat shock protein 70 (HSP70), respectively. All of these amygdala disruptions were normalized by co-deletion of p21 protein-activated kinase (Pak1) gene. We also rescued the social behavior deficits in Nf1+/− mice with pharmacological blockade of Pak1 directly in the amygdala. These findings provide novel insights and therapeutic targets for NF1 and ASD patients.en-USPublisher PolicyAmygdalametabolismHippocampusphysiologyLearningNeurofibromin 1Social Behaviorp21-Activated KinasesArticle