@article{6e76739f430d4965bc7271c7fe52f093,
title = "Anterior thalamic dysfunction underlies cognitive deficits in a subset of neuropsychiatric disease models",
abstract = "Neuropsychiatric disorders are often accompanied by cognitive impairments/intellectual disability (ID). It is not clear whether there are converging mechanisms underlying these debilitating impairments. We found that many autism and schizophrenia risk genes are expressed in the anterodorsal subdivision (AD) of anterior thalamic nuclei, which has reciprocal connectivity with learning and memory structures. CRISPR-Cas9 knockdown of multiple risk genes selectively in AD thalamus led to memory deficits. While the AD is necessary for contextual memory encoding, the neighboring anteroventral subdivision (AV) regulates memory specificity. These distinct functions of AD and AV are mediated through their projections to retrosplenial cortex, using differential mechanisms. Furthermore, knockdown of autism and schizophrenia risk genes PTCHD1, YWHAG, or HERC1 from AD led to neuronal hyperexcitability, and normalization of hyperexcitability rescued memory deficits in these models. This study identifies converging cellular to circuit mechanisms underlying cognitive deficits in a subset of neuropsychiatric disease models.",
keywords = "anterior thalamic nuclei, autism, cognition, memory, neuropsychiatric disorders, retrosplenial, schizophrenia, thalamus",
author = "Roy, {Dheeraj S.} and Ying Zhang and Tomomi Aida and Soonwook Choi and Qian Chen and Yuanyuan Hou and Lea, {Nicholas E.} and Skaggs, {Keith M.} and Quay, {Juliana C.} and Min Liew and Hannah Maisano and Vinh Le and Carter Jones and Jie Xu and Dong Kong and Sullivan, {Heather A.} and Arpiar Saunders and McCarroll, {Steven A.} and Wickersham, {Ian R.} and Guoping Feng",
note = "Funding Information: We thank Z.J. Huang for the IRES-Cre construct; P. Qi and D. Hee for help with mouse generation; E. Hwang for help with LFP analyses; C. Wang for viral packaging; M. Fleishman, B. Clear, J. Kim, H. Zaniewski, and K. Levandowski for technical assistance; and all members of the Feng laboratory for their support. This work was supported by the Stanley Center at the Broad Institute , the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT , the James and Patricia Poitras Center for Psychiatric Disorders Research at MIT , and the NIH BRAIN Initiative (grant U01MH114819 to G.F.). MEXT , CNSI/NINS , the Nakatani Foundation , the SENSHIN Foundation , the Mochida Foundation , the Takeda Foundation , and the Medical Research Institute of TMDU supported T.A. NSF EAGER 2035018 supported Q.C. Funding Information: We thank Z.J. Huang for the IRES-Cre construct; P. Qi and D. Hee for help with mouse generation; E. Hwang for help with LFP analyses; C. Wang for viral packaging; M. Fleishman, B. Clear, J. Kim, H. Zaniewski, and K. Levandowski for technical assistance; and all members of the Feng laboratory for their support. This work was supported by the Stanley Center at the Broad Institute, the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, the James and Patricia Poitras Center for Psychiatric Disorders Research at MIT, and the NIH BRAIN Initiative (grant U01MH114819 to G.F.). MEXT, CNSI/NINS, the Nakatani Foundation, the SENSHIN Foundation, the Mochida Foundation, the Takeda Foundation, and the Medical Research Institute of TMDU supported T.A. NSF EAGER 2035018 supported Q.C. D.S.R. Y.Z. and G.F. contributed to study design. D.S.R. Y.Z. S.C. K.M.S. J.C.Q. M.L. H.M. V.L. and C.J. contributed to data collection and analysis. T.A. generated viral constructs and C1ql2-Cre mice. Q.C. prepared KD viruses. D.S.R. Y.Z. Y.H. and N.E.L. conducted surgeries and histological analyses. J.X. and D.K. developed the Cre-dependent SpCas9 construct. H.A.S. and I.R.W. developed RVs. A.S. and S.A.M. established the DropViz dataset. D.S.R. Y.Z. and G.F. wrote the paper. All authors discussed and commented on the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = aug,
day = "18",
doi = "10.1016/j.neuron.2021.06.005",
language = "English (US)",
volume = "109",
pages = "2590--2603.e13",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "16",
}