Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Although much progress has been made in uncovering the neural basis of fear learning through studies of Pavlovian conditioning, little is known about how to reduce or eliminate traumatic memories in pathological cases, which is of great clinical concern. We have recently devised a novel behavioral paradigm that attenuates and prevents the return of fear memories. Our results indicate that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias. In parallel, a new computational model developed in our collaborator's lab (Dr. Yael Niv, at Princeton University) provides a principled explanation for our results, and will help generate testable predictions to refine our protocol, and better understand the mechanisms that underlie the persistent updating of fear memories. In the proposed studies, we will first refine our protocol using computationally-derived predictions. Next, we will test the limits of this optimized protocol, and examine whether it may be used to target stronger, older, and more complex fear memories, with the hopes that it may eventually be employed to attenuate traumatic memories in clinical populations.

Public Health Relevance

Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory setting to reduce acquired fear;however, the clinical efficacy of these techniques has been limited. We have recently presented a novel behavioral paradigm that attenuates and prevents the return of fear memories by combining reconsolidation and extinction principles (Ret+Ext). Our findings suggest that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias. Here, we propose to extend these findings to isolate the neural mechanisms that underlie our fear-reducing treatment, and to closely examine the strengths, weaknesses, and possible consequences of using this Ret+Ext paradigm.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH091147-03
Application #
8389682
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Vicentic, Aleksandra
Project Start
2010-12-06
Project End
2015-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
3
Fiscal Year
2013
Total Cost
$360,198
Indirect Cost
$120,198
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Jones, Carolyn E; Monfils, Marie-H (2016) Dominance status predicts social fear transmission in laboratory rats. Anim Cogn 19:1051-1069
Meyza, K Z; Bartal, I Ben-Ami; Monfils, M H et al. (2016) The roots of empathy: Through the lens of rodent models. Neurosci Biobehav Rev :
Jones, Carolyn E; Monfils, Marie-H (2016) Post-retrieval extinction in adolescence prevents return of juvenile fear. Learn Mem 23:567-75
Lee, Hongjoo J; Haberman, Rebecca P; Roquet, Rheall F et al. (2015) Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats. Front Behav Neurosci 9:369
Jones, Carolyn E; Riha, Penny D; Gore, Andrea C et al. (2014) Social transmission of Pavlovian fear: fear-conditioning by-proxy in related female rats. Anim Cogn 17:827-34
Shumake, Jason; Furgeson-Moreira, Sergio; Monfils, Marie H (2014) Predictability and heritability of individual differences in fear learning. Anim Cogn 17:1207-21
Tedesco, Vincenzo; Roquet, Rheall F; DeMis, John et al. (2014) Extinction, applied after retrieval of auditory fear memory, selectively increases zinc-finger protein 268 and phosphorylated ribosomal protein S6 expression in prefrontal cortex and lateral amygdala. Neurobiol Learn Mem 115:78-85
Jones, Carolyn E; Ringuet, Stephanie; Monfils, Marie-H (2013) Learned together, extinguished apart: reducing fear to complex stimuli. Learn Mem 20:674-85
Schiller, Daniela; Kanen, Jonathan W; LeDoux, Joseph E et al. (2013) Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement. Proc Natl Acad Sci U S A 110:20040-5
Auber, Alessia; Tedesco, Vincenzo; Jones, Carolyn E et al. (2013) Post-retrieval extinction as reconsolidation interference: methodological issues or boundary conditions? Psychopharmacology (Berl) 226:631-47

Showing the most recent 10 out of 12 publications