title: Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway.
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.
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Damien
authors.initials: D
authors.lastname: Rei
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Xenos
authors.initials: X
authors.lastname: Mason
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Seo
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Johannes
authors.initials: J
authors.lastname: Gräff
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Andrii
authors.initials: A
authors.lastname: Rudenko
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Richard
authors.initials: R
authors.lastname: Rueda
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Sandra
authors.initials: S
authors.lastname: Siegert
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Sukhee
authors.initials: S
authors.lastname: Cho
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Canter
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mungenast
authors.affiliation: Department of Bioengineering and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 and lhtsai@mit.edu.
authors.forename: Li-Huei
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000503:physiopathology* / Q000528:radiation effects; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D006624:Hippocampus / Q000503:physiopathology* / Q000528:radiation effects; D007859:Learning Disabilities / Q000503:physiopathology*; D008027:Light; D008569:Memory Disorders / Q000503:physiopathology*; D051379:Mice; D013312:Stress, Physiological
chemical_list: D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse
keywords: HDAC2; basolateral amygdala; behavioral stress; cognitive dysfunction; p25/Cdk5