Individuals suffering from post-traumatic stress disorder (PTSD) and anxiety disorders show persistent avoidance of activities, places, or people associated with their traumatic event. Persistent avoidance interferes with routine activities and also prevents individuals from overcoming their fears through extinction. Our goal is to understand the neural mechanisms of avoidance, in light of what is known about the neural circuits of fear learning. We will utilize a platform-mediated avoidance task, in which rats avoid tone-signaled shock by stepping onto a nearby platform. Based on our pharmacological data, the prelimbic prefrontal cortex (PL) and ventral striatum (VS) are necessary for platform avoidance. For this proposal, we will first characterize single unit activity in PL during avoidanc expression (Aim 1), and then determine when these responses are necessary for avoidance by optogenetically silencing PL neurons during specific time periods (e.g. tone onset, platform mounting;
Aim 2). This will allow us to test a causal relationship between PL neuronal firing and avoidance expression. We will then determine when VS activity is critical for avoidance by optogenetically silencing VS neurons during the same time periods used for silencing PL neurons in Aim 2 (Aim 3) and reveal how the contribution of VS compares with PL in avoidance expression. These findings will advance our understanding about the differences between the neural circuits of fear and avoidance and their implication for anxiety disorders.

Public Health Relevance

This research will elucidate the neural mechanisms of avoidance expression. Understanding avoidance behavior will provide insight for developing novel treatments and therapies for individuals suffering from post- traumatic stress and other anxiety disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH105185-02
Application #
9094258
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Desmond, Nancy L
Project Start
2015-04-16
Project End
2018-04-15
Budget Start
2016-04-16
Budget End
2017-04-15
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Puerto Rico Med Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
948108063
City
San Juan
State
PR
Country
United States
Zip Code