Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection
dc.contributor.author | Zhou, Wenjun | |
dc.contributor.author | He, Yanlin | |
dc.contributor.author | Rehman, Atteeq U. | |
dc.contributor.author | Kong, Yan | |
dc.contributor.author | Hong, Sungguan | |
dc.contributor.author | Ding, Guolian | |
dc.contributor.author | Yalamanchili, Hari Krishna | |
dc.contributor.author | Wan, Ying-Wooi | |
dc.contributor.author | Paul, Basil | |
dc.contributor.author | Wang, Chuhan | |
dc.contributor.author | Gong, Yingyun | |
dc.contributor.author | Zhou, Wenxian | |
dc.contributor.author | Liu, Hao | |
dc.contributor.author | Dean, John | |
dc.contributor.author | Scalais, Emmanuel | |
dc.contributor.author | O’Driscoll, Mary | |
dc.contributor.author | Morton, Jenny E.V. | |
dc.contributor.author | Hou, Xinguo | |
dc.contributor.author | Wu, Qi | |
dc.contributor.author | Tong, Qingchun | |
dc.contributor.author | Liu, Zhandong | |
dc.contributor.author | Liu, Pengfei | |
dc.contributor.author | Xu, Yong | |
dc.contributor.author | Sun, Zheng | |
dc.contributor.department | Biostatistics, IU School of Medicine | en_US |
dc.date.accessioned | 2019-09-05T16:42:29Z | |
dc.date.available | 2019-09-05T16:42:29Z | |
dc.date.issued | 2019-02 | |
dc.description.abstract | Nuclear receptor corepressor 1 (NCOR1) and NCOR2 (also known as SMRT) regulate gene expression by activating histone deacetylase 3 through their deacetylase activation domain (DAD). We show that mice with DAD knock-in mutations have memory deficits, reduced anxiety levels, and reduced social interactions. Mice with NCOR1 and NORC2 depletion specifically in GABAergic neurons (NS-V mice) recapitulated the memory deficits and had reduced GABAA receptor subunit α2 (GABRA2) expression in lateral hypothalamus GABAergic (LHGABA) neurons. This was associated with LHGABA neuron hyperexcitability and impaired hippocampal long-term potentiation, through a monosynaptic LHGABA to CA3GABA projection. Optogenetic activation of this projection caused memory deficits, whereas targeted manipulation of LHGABA or CA3GABA neuron activity reversed memory deficits in NS-V mice. We describe de novo variants in NCOR1, NCOR2 or HDAC3 in patients with intellectual disability or neurodevelopmental disorders. These findings identify a hypothalamus-hippocampus projection that may link endocrine signals with synaptic plasticity through NCOR-mediated regulation of GABA signaling. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Zhou, W., He, Y., Rehman, A. U., Kong, Y., Hong, S., Ding, G., … Sun, Z. (2019). Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection. Nature neuroscience, 22(2), 205–217. doi:10.1038/s41593-018-0311-1 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/20801 | |
dc.language.iso | en_US | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.isversionof | 10.1038/s41593-018-0311-1 | en_US |
dc.relation.journal | Nature Neuroscience | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | CA3 Region, Hippocampal | en_US |
dc.subject | Excitatory Postsynaptic Potentials | en_US |
dc.subject | Intellectual Disability | en_US |
dc.subject | Memory Disorders | en_US |
dc.subject | Nuclear Receptor Co-Repressor 1 | en_US |
dc.subject | Receptors, GABA-A | en_US |
dc.title | Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection | en_US |
dc.type | Article | en_US |