Common symptoms of PTSD include panic attacks and persistent avoidance of stimuli associated with the trauma. To understand the underlying mechanisms of panic, researchers have used the model of Pavlovian fear conditioning in rodents. In contrast to fear conditioning, little is known about the circuits of avoidance. Persistent avoidance can severely decrease patients' quality of life by interfering with goal- attainment and reward (cost). In this proposal, we will investigate the neural mechanisms of avoidance in rats, using a platform avoidance task, in which rats exposed to a tone paired with a shock can avoid the shock by stepping onto a platform. Because the platform is located away from the food bar, avoidance deprives rats of access to food (cost), thereby modeling an important aspect of clinical avoidance.
In Aim 1, we will test whether the prefrontal subregions prelimbic and infralimbic cortex are necessary for avoidance. We will also test whether the amygdala and striatum, which are prefrontal targets, are also critical for platform avoidance.
In Aim 2, we will characterize the responses of prelimbic and striatal neurons during expression of avoidance, and the extent to which avoidance responses in striatum depend upon prelimbic input. Understanding the neural circuits of active avoidance will help guide treatment for persistent avoidance in PTSD.

Public Health Relevance

Post-traumatic stress disorder is characterized by panic attacks and persistent avoidance. Conditioned freezing has been studied to understand how the brain processes panic responses. However, very little is known about how the brain processes avoidance. Understanding the neural mechanisms of avoidance could help understand and treat PTSD.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Dissertation Award (R36)
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Special Emphasis Panel (ZMH1-ERB-K (01))
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Rosemond, Erica K
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University of Puerto Rico Med Sciences
San Juan
United States
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Diehl, Maria M; Bravo-Rivera, Christian; Rodriguez-Romaguera, Jose et al. (2018) Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex. Elife 7:
Bravo-Rivera, Christian; Roman-Ortiz, Ciorana; Montesinos-Cartagena, Marlian et al. (2015) Persistent active avoidance correlates with activity in prelimbic cortex and ventral striatum. Front Behav Neurosci 9:184
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Bravo-Rivera, Christian; Diehl, Maria M; Roman-Ortiz, Ciorana et al. (2015) Long-range GABAergic neurons in the prefrontal cortex modulate behavior. J Neurophysiol 114:1357-9
Bravo-Rivera, Christian; Roman-Ortiz, Ciorana; Brignoni-Perez, Edith et al. (2014) Neural structures mediating expression and extinction of platform-mediated avoidance. J Neurosci 34:9736-42