Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection
- Authors
- Zhou, Wenjun; He, Yanlin; Rehman, Atteeq U.; Kong, Yan; Hong, Sungguan; Ding, Guolian; Yalamanchili, Hari Krishna; Wan, Ying-Wooi; Paul, Basil; Wang, Chuhan; Gong, Yingyun; Zhou, Wenxian; Liu, Hao; Deans, John; Scalais, Emmanuel; O'Driscoll, Mary; Morton, Jenny E., V; Akawi, Nadia; Al-Turki, Saeed; Ambridge, Kirsty; Barrett, Jeffrey; Barrett, Daniel; Bayzetinova, Tanya; Carter, Nigel; Clayton, Stephen; Coomber, Eve; Firth, Helen; Fitzgerald, Tomas; FitzPatrick, David; Gerety, Sebastian; Gribble, Susan; Hurles, Matthew; Jones, Philip; Jones, Wendy; King, Daniel; Krishnappa, Netravathi; Mason, Laura; McRae, Jeremy; Michael, Parker; Middleton, Anna; Miller, Ray; Morley, Katherine; Parthiban, Vijaya; Prigmore, Elena; Rajan, Diana; Sifrim, Alejandro; Singh, Tarjinder; Tivery, Adrian; van Kogelenberg, Margriet; Wright, Caroline; Hou, Xinguo; Wu, Qi; Tong, Qingchun; Liu, Zhandong; Liu, Pengfei; Xu, Yong; Sun, Zheng
- Issue Date
- Feb-2019
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE NEUROSCIENCE, v.22, no.2, pp 205 - +
- Journal Title
- NATURE NEUROSCIENCE
- Volume
- 22
- Number
- 2
- Start Page
- 205
- End Page
- +
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/18266
- DOI
- 10.1038/s41593-018-0311-1
- ISSN
- 1097-6256
1546-1726
- 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 GABA(A) receptor subunit alpha 2 (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 CA3(GABA) projection. Optogenetic activation of this projection caused memory deficits, whereas targeted manipulation of LHGABA or CA3(GABA) 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 neuro-developmental disorders. These findings identify a hypothalamus-hippocampus projection that may link endocrine signals with synaptic plasticity through NCOR-mediated regulation of GABA signaling.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Natural Sciences > Department of Chemistry > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.