Broad, long-term objectives: To reduce the burdens of illness and disability associated with learned fear responses that are part of post-traumatic stress disorder (PTSD) and phobias. To determine the neural mechanisms that subserve learning, extinction (EXT) and spontaneous recovery (SR) of a defensive reaction to a learned fear conditioned taste aversion (CTA). To explore alternative methods to extinguish a CTA with the goal of reducing, or eliminating, SR of the fear/aversion.
Specific aims : To use an explicitly unpaired (EU) procedure in which a Conditioned Stimulus (CS) and Unconditioned Stimulus (US) are both presented during EXT - but never contingently to extinguish a CTA and characterize this procedure's ability to suppress SR of a CTA. To compare patterns of neural activity (as measured by c-Fos protein expression) in brains of animals that have extinguished a CTA and spontaneously recovered the aversion versus those that have undergone the EU extinction procedure and have extinguished a CTA but have NOT spontaneously recovered the aversion. Background: Significant effort has gone into discovering the means by which the brain remembers new information. However, relatively little work has addressed the processes by which the brain discards or discounts less-useful data. Moreover, very little is known about how the brain controls the re-emergence (SR) of once-discarded/discounted information. Research design and methods: We will create CTAs in rats by pairing the taste of saccharin (SAC; CS) with an i.p. injection of Lithium Chloride (LiCI; US) and then administer EXT trials using 2 different methods. Rats will either have CS-only exposures or (using an explicitly unpaired procedure) be exposed to both CS and US in a way that produces a learned safety. Following EXT and SR tests, brains of experimental subjects and yoked controls will be prepared for C-Fos assays. The objectives of the proposed work include: (1) Identifying brain areas important in the acquisition, extinction, and SR of a CTA; and (2) Documenting differences in neural activity in rats that have spontaneously recovered a CTA versus those that have not. Health relatedness: This project will reveal how the brain either """"""""unlearns"""""""" or differentially encodes new meanings associated with a previously learned defensive reaction to fear. The work may identify more effective ways to reduce or eliminate learned fears and will advance the development of treatments for deficits in EXT (e.g., PTSD, phobias). ? ? ?
|Mickley, G Andrew; Ketchesin, Kyle D; Ramos, Linnet et al. (2013) Stimulation of the dorsal periaqueductal gray enhances spontaneous recovery of a conditioned taste aversion. Brain Res 1493:27-39|
|Mickley, G Andrew; Hoxha, Nita; Luchsinger, Joseph L et al. (2013) Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion. Pharmacol Biochem Behav 106:16-26|
|Mickley, G Andrew; Remus, Jennifer L; Ramos, Linnet et al. (2012) Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion. Physiol Behav 105:417-27|
|Mickley, G Andrew; Wilson, Gina N; Remus, Jennifer L et al. (2011) Periaqueductal gray c-Fos expression varies relative to the method of conditioned taste aversion extinction employed. Brain Res 1423:17-29|
|Disorbo, Anthony; Wilson, Gina N; Bacik, Stephanie et al. (2009) Time-dependent retrograde amnesic effects of muscimol on conditioned taste aversion extinction. Pharmacol Biochem Behav 92:319-26|
|Mickley, G Andrew; Disorbo, Anthony; Wilson, Gina N et al. (2009) Explicit disassociation of a conditioned stimulus and unconditioned stimulus during extinction training reduces both time to asymptotic extinction and spontaneous recovery of a conditioned taste aversion. Learn Motiv 40:209-220|
|Mickley, G Andrew; Hoxha, Zana; Bacik, Stephanie et al. (2007) Spontaneous recovery of a conditioned taste aversion differentially alters extinction-induced changes in c-Fos protein expression in rat amygdala and neocortex. Brain Res 1152:139-57|
|Mickley, G Andrew; Kenmuir, Cynthia L; Yocom, Anna M et al. (2005) A role for prefrontal cortex in the extinction of a conditioned taste aversion. Brain Res 1051:176-82|
|Mickley, G Andrew; Kenmuir, Cynthia L; Dengler-Crish, Christine M et al. (2004) Repeated exposures to gustatory stimuli produce habituation or positive contrast effects in perinatal rats. Dev Psychobiol 44:176-88|
|Mickley, G Andrew; Kenmuir, Cynthia L; McMullen, Colleen A et al. (2004) Dynamic processing of taste aversion extinction in the brain. Brain Res 1016:79-89|