Neural Mechanisms fo Extinction and Spontaneous Recovery

Summary

Principal Investigator: G Mickley
Abstract: DESCRIPTION (provided by applicant): 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).
Funding Period: 2001-09-01 - 2010-08-31
more information: NIH RePORT

Top Publications

  1. pmc Stimulation of the dorsal periaqueductal gray enhances spontaneous recovery of a conditioned taste aversion
    G Andrew Mickley
    The Neuroscience Program, Baldwin Wallace University, 275 Eastland Rd, Berea, OH 44017, USA
    Brain Res 1493:27-39. 2013
  2. pmc Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion
    G Andrew Mickley
    The Neuroscience Program, Baldwin Wallace University, 275 Eastland Rd, Berea, OH, 44017, USA
    Pharmacol Biochem Behav 106:16-26. 2013
  3. ncbi A role for prefrontal cortex in the extinction of a conditioned taste aversion
    G Andrew Mickley
    Department of Psychology and the Neuroscience Program, Baldwin Wallace College, 275 Eastland Road, Berea, OH 44017 2088, USA
    Brain Res 1051:176-82. 2005
  4. ncbi Spontaneous recovery of a conditioned taste aversion differentially alters extinction-induced changes in c-Fos protein expression in rat amygdala and neocortex
    G Andrew Mickley
    Neuroscience Program, Baldwin Wallace College, Berea, OH 44017 2088, USA
    Brain Res 1152:139-57. 2007
  5. pmc Time-dependent retrograde amnesic effects of muscimol on conditioned taste aversion extinction
    Anthony DiSorbo
    Department of Psychology, Neuroscience Program, Baldwin Wallace College, 275 Eastland Rd, Berea, OH 44017 2088, USA
    Pharmacol Biochem Behav 92:319-26. 2009
  6. pmc Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion
    G Andrew Mickley
    The Neuroscience Program, Baldwin Wallace College, 275 Eastland Rd, Berea, OH 44017, USA
    Physiol Behav 105:417-27. 2012
  7. pmc Periaqueductal gray c-Fos expression varies relative to the method of conditioned taste aversion extinction employed
    G Andrew Mickley
    The Neuroscience Program, Baldwin Wallace College, 275 Eastland Rd, Berea, OH, 44017, USA
    Brain Res 1423:17-29. 2011

Scientific Experts

Detail Information

Publications8

  1. pmc Stimulation of the dorsal periaqueductal gray enhances spontaneous recovery of a conditioned taste aversion
    G Andrew Mickley
    The Neuroscience Program, Baldwin Wallace University, 275 Eastland Rd, Berea, OH 44017, USA
    Brain Res 1493:27-39. 2013
    ..These data refute a cause-and-effect relationship between enhanced dPAG c-fos expression and a reduction in SR. However, they highlight a role for the dPAG in modulating SR of extinguished CTAs...
  2. pmc Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion
    G Andrew Mickley
    The Neuroscience Program, Baldwin Wallace University, 275 Eastland Rd, Berea, OH, 44017, USA
    Pharmacol Biochem Behav 106:16-26. 2013
    ..Our data suggest that long-term dietary MgT may enhance the consolidation/retention of a CTA, speed extinction, and inhibit SR of this learned aversion...
  3. ncbi A role for prefrontal cortex in the extinction of a conditioned taste aversion
    G Andrew Mickley
    Department of Psychology and the Neuroscience Program, Baldwin Wallace College, 275 Eastland Road, Berea, OH 44017 2088, USA
    Brain Res 1051:176-82. 2005
    ..e., explicitly unpaired CS-US exposures) or animals drinking SAC for the first time. These data indicate a role for mPFC (prelimbic and infralimbic cortex) in the formation of a CTA extinction memory...
  4. ncbi Spontaneous recovery of a conditioned taste aversion differentially alters extinction-induced changes in c-Fos protein expression in rat amygdala and neocortex
    G Andrew Mickley
    Neuroscience Program, Baldwin Wallace College, Berea, OH 44017 2088, USA
    Brain Res 1152:139-57. 2007
    ..The data also suggest that certain sub-nuclei of the AMY may play a relatively minor role in SR of this defensive reaction to a learned fear...
  5. pmc Time-dependent retrograde amnesic effects of muscimol on conditioned taste aversion extinction
    Anthony DiSorbo
    Department of Psychology, Neuroscience Program, Baldwin Wallace College, 275 Eastland Rd, Berea, OH 44017 2088, USA
    Pharmacol Biochem Behav 92:319-26. 2009
    ..Differences between muscimol's effects on CTA conditioning and CTA extinction indicate that fear conditioning and extinction involve, to some degree, different neuronal mechanisms...
  6. pmc Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion
    G Andrew Mickley
    The Neuroscience Program, Baldwin Wallace College, 275 Eastland Rd, Berea, OH 44017, USA
    Physiol Behav 105:417-27. 2012
    ..However, the timing of acute DCS treatments during extinction and the method of extinction employed can interact to affect spontaneous recovery of a CTA...
  7. pmc Periaqueductal gray c-Fos expression varies relative to the method of conditioned taste aversion extinction employed
    G Andrew Mickley
    The Neuroscience Program, Baldwin Wallace College, 275 Eastland Rd, Berea, OH, 44017, USA
    Brain Res 1423:17-29. 2011
    ..The findings are clinically relevant as we seek the development of treatments for deficits in fear extinction (e.g. PTSD, phobias)...