In memory overgeneralization, details from negatively-valenced episodic memories become excessively generalized to unrelated neutral situations. This is a key cognitive distortion associated with major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Stress promotes memory generalization, and this process likely relies on stress-induced changes in dorsal hippocampal (DH) memory circuits. To study this, we modeled stress-induced generalization (SIG) in male and female mice using social stress and contextual fear conditioning. Using chemogenetic circuit manipulations, we demonstrate that SIG is mediated by cholinergic DH inputs from medial septum (MS), excitatory DH inputs from the ventral tegmental area (VTA), and excitatory DH outputs to retrosplenial cortex (RSC). Based on known roles of these projections, these results suggest that stress (1) acts upon MS->DH projections to shift memory encoding/retrieval dynamics to promote memory generalization, (2) acts upon VTA->DH projections to prioritize retrieval of negative over neutral memories, and (3) acts on DH->RSC projections to engage circuits that represent remote memories with more general features relative to specific features. Altogether, these findings elucidate circuit mechanisms of SIG that can serve as therapeutic targets for treatment of memory overgeneralization.

Creator

• Ren, Lynn Yi

DOI

• https://doi.org/10.21985/n2-wdcz-jm78

Subject

• Neurosciences

Language

• en

Alternate Identifier

• etdadmin_upload_851720
• http://dissertations.umi.com/northwestern:15800

Date created

• 2021-01-01

Resource type

• Dissertation

Rights statement

• In Copyright