Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway
Author(s)
Rei, Damien; Mason, Xenos; Seo, Jinsoo; Rudenko, Andrii; Wang, Jun; Siegert, Sandra; Cho, Sukhee; Deisseroth, Karl; Tsai, Li-Huei; Graeff, Johannes; Rueda IV, Richard; Canter, Rebecca Gail; Mungenast, Alison; ... Show more Show less
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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.
Date issued
2015-06Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and MemoryJournal
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
ISSN
0027-8424
1091-6490