MOLECULAR MECHANISMS OF CONDITIONED TASTE AVERSION

Summary

Principal Investigator: THOMAS HOUPT
Abstract: Conditioned taste aversion (CTA) is a form of associative learning in which an animal avoids and reacts aversively to the taste of a food that has previously been paired with illness. CTA has been described in many species, from invertebrates to humans, and has important implications in drug and radiation therapies. It is also a model for altered responsiveness in ingestive behaviors, as in eating disorders. We have discovered that the induction of the immediate-early gene c-Fos by intraoral infusion of sucrose in the medial intermediate region of the nucleus of the solitary tract (iNTS) and the central nucleus of the amygdala (CeA) in the rat appears to be a specific and quantifiable neuronal correlate of the expression of a CTA previously acquired by pairing intraoral infusions of sucrose with lithium chloride. We hypothesize that cFos expression reveals functionally important brain sites mediating CTA, and that the time course of CTA consolidation and c-Fos expression in some of these sites reveals the time and place of gene expression that mediates CTA learning. We will make fiber-sparing, excitotoxic lesions of brain sites that express c-Fos after CTA acquisition and expression. Alterations in CTA induced by lesions will be measured by quantifying intake, taste reactivity, and c-Fos expression. We will quantify the time course of consolidation of long-term CTA memory, and determine the critical period of gene expression required for consolidation with site-specific injections of protein synthesis inhibitors. We will then use single-cell antisense RNA amplification to identify the neurochemical phenotype and gene expression profile of c- Fos-positive cells in critical brain sites at critical times of consolidation. This proposal presents a novel approach to CTA by correlating the effects of fiber-sparing lesions on behavior with effects on the pattern of c-Fos expression, and by examining molecular correlates of the transition from short-term to long-term memory in CTA learning. These experiments will contribute to an understanding of the neural pathways and molecular mechanisms underlying changes in food preferences that occur in eating disorders such as obesity and anorexia nervosa.
Funding Period: 1996-08-01 - 2006-11-30
more information: NIH RePORT

Top Publications

  1. pmc Mitogen-activated protein kinase in the amygdala plays a critical role in lithium chloride-induced taste aversion learning
    Bumsup Kwon
    Department of Biological Science, Program in Neuroscience, Florida State University, Tallahassee, FL 32306 4295, USA
    Neurobiol Learn Mem 97:132-9. 2012
  2. pmc Area postrema lesions attenuate LiCl-induced c-Fos expression correlated with conditioned taste aversion learning
    Corinne M Spencer
    Department of Biological Science, King Life Sciences Building, The Florida State University, Tallahassee, FL 32306 4295, United States
    Physiol Behav 105:151-60. 2012
  3. pmc Intra-amygdalar okadaic acid enhances conditioned taste aversion learning and CREB phosphorylation in rats
    Denesa L Oberbeck
    Department of Biological Science, Program in Neuroscience, The Florida State University, Tallahassee, FL 32306, USA
    Brain Res 1348:84-94. 2010
  4. pmc c-Fos induction by a 14 T magnetic field in visceral and vestibular relays of the female rat brainstem is modulated by estradiol
    Angie M Cason
    Department of Biological Science, Program in Neuroscience, The Florida State University, Tallahassee, FL 32306 4295, USA
    Brain Res 1347:48-57. 2010
  5. pmc Phospho-acetylation of histone H3 in the amygdala after acute lithium chloride
    Bumsup Kwon
    Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA
    Brain Res 1333:36-47. 2010
  6. pmc Interactions of temperature and taste in conditioned aversions
    Patrick L Smith
    Department of Psychology, Program in Neuroscience, The Florida State University, Tallahassee, FL 32306, USA
    Physiol Behav 99:324-33. 2010
  7. pmc A combined method of laser capture microdissection and X-Gal histology to analyze gene expression in c-Fos-specific neurons
    Bumsup Kwon
    Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA
    J Neurosci Methods 186:155-64. 2010
  8. pmc Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe nuclei of ovariectomized rats
    Heidi M Rivera
    Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306 4301, USA
    Brain Res 1259:51-8. 2009
  9. pmc D-cycloserine enhances short-delay, but not long-delay, conditioned taste aversion learning in rats
    Rachel A Davenport
    Program in Neuroscience, Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA
    Pharmacol Biochem Behav 91:596-603. 2009
  10. pmc Expression of AP-1 family transcription factors in the amygdala during conditioned taste aversion learning: role for Fra-2
    Bumsup Kwon
    Department of Biological Science and Program in Neuroscience, The Florida State University, Tallahassee, FL 32306, USA
    Brain Res 1207:128-41. 2008

Detail Information

Publications12

  1. pmc Mitogen-activated protein kinase in the amygdala plays a critical role in lithium chloride-induced taste aversion learning
    Bumsup Kwon
    Department of Biological Science, Program in Neuroscience, Florida State University, Tallahassee, FL 32306 4295, USA
    Neurobiol Learn Mem 97:132-9. 2012
    ..Our data suggest that the intracellular signaling cascade of the MAPK pathway in the CeA plays a critical role in the processing of visceral information induced by LiCl for CTA learning...
  2. pmc Area postrema lesions attenuate LiCl-induced c-Fos expression correlated with conditioned taste aversion learning
    Corinne M Spencer
    Department of Biological Science, King Life Sciences Building, The Florida State University, Tallahassee, FL 32306 4295, United States
    Physiol Behav 105:151-60. 2012
    ..Because c-Fos induction in several regions was correlated with magnitude of CTA acquisition, these regions are implicated in the central mediation of lithium effects during CTA learning...
  3. pmc Intra-amygdalar okadaic acid enhances conditioned taste aversion learning and CREB phosphorylation in rats
    Denesa L Oberbeck
    Department of Biological Science, Program in Neuroscience, The Florida State University, Tallahassee, FL 32306, USA
    Brain Res 1348:84-94. 2010
    ....
  4. pmc c-Fos induction by a 14 T magnetic field in visceral and vestibular relays of the female rat brainstem is modulated by estradiol
    Angie M Cason
    Department of Biological Science, Program in Neuroscience, The Florida State University, Tallahassee, FL 32306 4295, USA
    Brain Res 1347:48-57. 2010
    ..These results suggest that ovarian steroids may mediate sex differences in the behavioral responses to magnetic field exposure at the level of visceral and vestibular nuclei of the brainstem...
  5. pmc Phospho-acetylation of histone H3 in the amygdala after acute lithium chloride
    Bumsup Kwon
    Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA
    Brain Res 1333:36-47. 2010
    ..Furthermore, the level of phospho-acetylation of histone H3, c-Fos induction, and amygdalar-dependent taste aversion learning is constrained by endogenous histone deacetylase activity...
  6. pmc Interactions of temperature and taste in conditioned aversions
    Patrick L Smith
    Department of Psychology, Program in Neuroscience, The Florida State University, Tallahassee, FL 32306, USA
    Physiol Behav 99:324-33. 2010
    ..These results demonstrate that temperature can serve as a salient cue in conditioned aversions that affect ingestion independent of taste cues or by potentiating taste cues...
  7. pmc A combined method of laser capture microdissection and X-Gal histology to analyze gene expression in c-Fos-specific neurons
    Bumsup Kwon
    Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA
    J Neurosci Methods 186:155-64. 2010
    ..Combining LCM and transgenic reporter genes provides a powerful tool with which to investigate tissue- or cell-specific gene expression...
  8. pmc Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe nuclei of ovariectomized rats
    Heidi M Rivera
    Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306 4301, USA
    Brain Res 1259:51-8. 2009
    ..Further studies are required to determine whether the increased expression of Pet-1 and 5-HTT mRNA plays a causal role in the anorexigenic effect of estradiol...
  9. pmc D-cycloserine enhances short-delay, but not long-delay, conditioned taste aversion learning in rats
    Rachel A Davenport
    Program in Neuroscience, Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA
    Pharmacol Biochem Behav 91:596-603. 2009
    ..These results suggest that DCS enhancement of CTA is dependent on mechanisms underlying gustatory processing during long-delay taste-toxin associations...
  10. pmc Expression of AP-1 family transcription factors in the amygdala during conditioned taste aversion learning: role for Fra-2
    Bumsup Kwon
    Department of Biological Science and Program in Neuroscience, The Florida State University, Tallahassee, FL 32306, USA
    Brain Res 1207:128-41. 2008
    ..Changes in Fra-2 and c-Fos expression in the BLA and CeA at the time of conditioning, together with constitutive expression of c-Jun and JunD, may contribute to CTA learning...
  11. pmc D-Cycloserine enhances conditioned taste aversion learning in rats
    Melissa Nunnink
    Department of Biological Sciences, Program in Neuroscience, BRF 252 MC 4340, The Florida State University, Tallahassee, FL 32306, USA
    Pharmacol Biochem Behav 87:321-30. 2007
    ..These results confirm the participation of NMDA receptor, and specifically the glycine-binding site of NMDA receptor, in CTA learning...
  12. pmc NMDA receptor in conditioned flavor-taste preference learning: blockade by MK-801 and enhancement by D-cycloserine
    Glen J Golden
    Department of Biological Science, Program in Neuroscience, The Florida State University, Tallahassee, FL 32306 4340, USA
    Pharmacol Biochem Behav 86:587-96. 2007
    ..These results demonstrate that NR neurotransmission is critical for CFTP learning. Furthermore, enhancement of CFTP learning by DCS suggests that endogenous levels of glycine or D-serine may be a limiting factor in CFTP learning...