Authors:

Aasrita Tulluri

Date Created:

Not specified

Course Title:

Professor:

Not specified

About Paper:

Women are disproportionately vulnerable to developing Post-Traumatic Stress Disorder (PTSD), yet the neurobiological mechanisms. underlying this susceptibility remain poorly understood. A core symptom of PTSD is fear generalization, in which fear learned in a specific context is inappropriately expressed in safe contexts. We propose that fear generalization reflects impaired memory-updating, characterized by a failure to remap trauma-related memory traces in the presence of new information (e.g., safety signals) and their persistent reactivation outside the original trauma context. Memories are stored as hippocampal engrams, providing a tractable framework for examining memory flexibility. Here, we investigated sex and individual differences in fear-related engram remapping within the dorsal dentate gyrus using WT male and female mice from both inbred (C57BL/6) and outbred (Swiss Webster) strains. Fear memory ensembles were tagged using the TetTag system, followed by immunohistochemistry and fluorescent confocal microscopy to quantify engram overlap. Mice were pre-exposed to a neutral context (B), fear conditioned in a distinct context (A) during which the fear engram was tagged and tested 24 hours later in either the conditioned (retrieval) or neutral (generalization) context, followed by testing in the alternate context. Brains were then collected to assess overlap. In parallel, mice were pre-screened using an acoustic startle reflex (ASR) assay to classify individuals as stress-susceptible or resilient prior to fear learning. We predict that fear generalization is associated with impaired engram remapping. We further predict that ASR-based pre-screening reliably predicts both behavioral fear generalization and engram-level remapping deficits.

Source:

Loyola University Chicago

Topics:

No topics listed

Co-authors:

Aasrita Tulluri