Publication

Genetic Perturbation of TIA1 Reveals a Physiological Role in Fear Memory

Citation:
Cell Reports. 2019 Mar 12;26(11):2970-2983.e4. doi: 10.1016/j.celrep.2019.02.048. PMID: 30865887.
Authored By:
Rayman JB, Hijazi J, Li X, Kedersha N, Anderson PJ, Kandel ER
Abstract:
TIA1 is a prion-related RNA-binding protein whose capacity to form various types of intracellular aggregates has been implicated in neurodegenerative disease. However, its role in normal brain function is poorly understood. Here, we show that TIA1 bidirectionally modulates stress-dependent synaptic plasticity in the hippocampus, a brain region involved in fear memory and olfactory discrimination learning. At the behavioral level, conditioned odor avoidance is potentiated by TIA1 deletion, whereas overexpression of TIA1 in the ventral hippocampus inhibits both contextual fear memory and avoidance. However, the latter genetic manipulations have little impact on other hippocampus-dependent tasks. Transcriptional profiling indicates that TIA1 presides over a large network of immune system genes with modulatory roles in synaptic plasticity and long-term memory. Our results uncover a physiological and partly sex-dependent function for TIA1 in fear memory and may provide molecular insight into stress-related psychiatric conditions, such as post-traumatic stress disorder (PTSD) and anxiety.
Published in:
Cell Reports

More Publications

January 29, 2024

Scientific Reports

Differential recruitment of brain circuits during fear extinction in non-stressed compared to stress resilient animals

December 29, 2023

Journal of Law and the Biosciences

Defusing the legal and ethical minefield of epigenetic applications in the military, defense, and security context

August 1, 2023

Journal of Psychopharmacology

Improving Translational Relevance in Preclinical Psychopharmacology (iTRIPP)

July 29, 2023

Frontiers in Neurology

Models and methods: a perspective of the impact of six IMI translational data-centric initiatives for Alzheimer’s disease and other neuropsychiatric disorders

July 6, 2023

Gerontology and Geriatric Medicine

Caring for Dementia Caregivers: Understanding Caregiver Stress During the COVID-19 Pandemic

May 19, 2023

Nature Reviews Neurology

Global synergistic actions to improve brain health for human development