In vivo Longitudinal PET Imaging in Long-Term Extinction Fear Memory in Female and Male Rats
2023 Undergraduate Research Symposium
Mahmoud Teran (neuroscience), Morgan M. Glover
Faculty mentor: Shane Perrine
Abstract
Utilization of In vivo Longitudinal PET Imaging to Assess Class IIa HDAC Activity Following Long-Term Extinction Fear Memory in Female and Male Rats
The development of memories, including those throughout extinction learning, require neuroplasticity for encoding and retrieval to occur. As environmental factors can affect gene expression, epigenetic changes can play a critical role in the development of memory formation and updating and ultimately manifesting in behavioral changes reflective of the learning.
The purpose of the current project is to show the utility of Positron Emission Tomography (PET), a functional, molecular imaging technique that employs radioactive substances to measure specific markers in the brain. As part of our efforts to understand the neurobiological mechanisms of fear learning and the role of epigenetic changes using PET, images of the brains were collected before and after extinction learning of acquired long-term fear (LTF) memories induced by shock tone pairings made every 30 seconds over 38 min.
PET images were collected by injecting the radiotracer [18F]TFAHA, a substrate for class IIa histone deacetylases (HDACs). The resulting accumulation of the breakdown product of [18F]TFAHA could be considered as a proxy for class IIa HDAC expression changes before and after LTF memory. HDAC activity is directly related to gene expression changes through deacetylation of histone lysine residues. This results in a closed chromatin conformation and prevents the binding of RNA polymerase II and ultimate gene transcription and protein synthesis.
This can then be manifested and seen as behavioral change. Our preliminary analysis of PET images results indicate a significant interaction effect between pre-to-post class IIa HDAC expression-activity, sex, and shock condition. Additional PET image analysis is anticipated to show the extent of HDAC activity in both the sexes following LTF.
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Mahmoud Teran: Utilization of In vivo Longitudinal PET Imaging to Assess Class IIa HDAC Activity Following Long-Term Extinction Fear Memory in Female and Male Rats