Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway
Name
Rei-2015-Basolateral amygdala.pdf
Size
1.43 MB
Format
Adobe PDF
Checksum (MD5)
d5c1a43f7c9f8b6e0306ffe36fc9940e
Author(s)
Rei, Damien
Mason, Xenos
Seo, Jinsoo
Rudenko, Andrii
Wang, Jun
Siegert, Sandra
Cho, Sukhee
Deisseroth, Karl
Tsai, Li-Huei
Graeff, Johannes
Date Issued
June 2015
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Rei, Damien, Xenos Mason, Jinsoo Seo, Johannes Gräff, Andrii Rudenko, Jun Wang, Richard Rueda, et al. “Basolateral Amygdala Bidirectionally Modulates Stress-Induced Hippocampal Learning and Memory Deficits through a p25/Cdk5-Dependent Pathway.” Proc Natl Acad Sci USA 112, no. 23 (May 20, 2015): 7291–7296.
Version
Final published version
Abstract
Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.1415845112
