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    Conditioned Taste Aversion

    Kevin Nahler Kevin Nahler

    Tony Norton National Geographic

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    I. Conditioned Taste Aversion (CTA)

    A. Definition

    B. Evolutionary Basis

    II. CTA at the Organ System Level

    A. Brain Stem Activity

    B. Role of the Amygdala

    III. Molecular Processes Behind CTA

    A. CREB

    B. c-FosC.Metabotropic Glutamate Receptors

    IV. Substances that produce CTA

    A. Lithium Chloride

    B. Estrogen

    C. Thiabendazole

    V. Practical Application of CTA

    A. Reduction of Livestock and Crop Losses

    B. Conservation of Endangered Species and Other Wildlife

    C. Drug and Radiation Therapies for Humans

    VI. References

    Tony Norton

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    Conditioned Taste Aversion (CTA) is a form of

    associative learning and classical conditioning

    in which an animal avoids and acts aversivelyto the taste of a food that has previously been

    paired with illness. (Houpt)

    Why would such a phenomenon exist innature?

    University of FloridaKevin Nahler

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    CTA in the Brain Stem (Short Term Memory and Physiological Response)

    Brain stem receives input regarding internalconditions in the body; controls involuntary functions

    such as digestion, respiration, and circulation; food

    preference learning takes place at least partially in the

    brain stem

    The Nucleus of the Solitary Tract in the medulla

    (emetic center) junction of nerves from tongue thatbring taste sensations with the vagus nerve that

    brings sensory impulses from the upper GI tract

    If digestion and absorption results in nutrients being

    replenished in the body, the brain remembers that

    food choice as a good one; if food contains poison of

    some kind, the brain stem receives signals from thedigestive tract and send signals back that result in

    vomiting and other detoxifying processes

    The brain remembers the external cues surrounding

    the food that produced the illness and will not

    tolerate the scent and taste of that food in the future

    (taste-illness pairing also results in association of non-taste cues such as scent or appearance of food)

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    CTA in the Amygdala and Gustatory Cortex

    (Long Term Memory and Behavioral Response)

    The gustatory cortex (in the

    cerebrum) processes and retains

    memory of taste while the amygdala

    plays a crucial role in the integration

    and expression of CTA behavior (i.e.the formation of long term memories

    and patterns of behavior of CTA)

    The memory of CTA produced in the

    brain stem only remains effective if

    certain genes are expressed in theamygdala

    The amygdala has been shown to be

    responsible for many types of aversive

    and emotional learning

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    Molecular Mechanisms of CTA cAMP Response Element-Binding Protein (CREB)

    cAMP = second messenger that regulates ion channels(Ca2+) (among other functions)

    CREB = transcription factor that binds to cAMP responseelements on DNA to increase or decrease transcription

    Genes regulated by cAMP Response Elements (CRE-regulated genes) produce long term changes in theamygdala that enable retention of CTA-relevantinformation

    Must be functioning properly for long term CTA memoryto be produced (does not affect short term memory orretrieval of long term memory once it has been formed)

    c-Fos Proto-oncogene; transcription factor; immediate early

    gene family

    Among other functions, c-Fos controls genes that controlsome immune responses (c-Fos genes are expressed aftersensory stimulation, such as light exposure, food intake, ortoxin intake)

    c-Fos-like immune (c-FLI) proteins were used todemonstrate the relationship between c-Fos and CTA (i.e.ingestion of LiCl resulted in expression of c-Fos)

    c-Fos is found in brain tissue during all CTA responses

    Metabotropic Glutamate Receptors (mGluRs) Affect second messengers and ion channels via G-proteins

    mGluR7 (one of eight subtypes of mGluRs) is expressed inthe amygdala, among other areas of the central nervoussystem (localized at presynaptic axon terminals); plays arole in amygdala-dependent averse responses; coupledwith inhibition of cAMP cascade

    mGluR7 must be functioning properly for CTA to occur

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    Some CTA-inducing CompoundsLithium Chloride (LiCl)Naturally occuring salt

    Produces a strong, long-lasting CTA

    EPA has found some potentially negative environmental

    impacts associated with use in untargeted baits

    Estrogen (estradiol) (C18H24O2)Includes both naturally occurring and synthetic hormones

    Produces the strongest, longest-lasting CTA

    Because it is a hormone, its use may affect development

    and reproduction in some vertebrates

    Thiabendazole (TBZ) (C10H7N3S)Has also been used as an anti-fungal, a preservative food

    additive, and a chelating agent to treat heavy metal

    poisoning

    Produces moderate CTA with minimal side effects

    May be a safe alternative to other compounds but more

    testing is needed

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    Practical Applications of CTA

    Reduction of Livestock and Crop Losses

    Economic impact

    Socio-political impact

    Human health impact

    Conservation of Endangered Species and OtherWildlife

    Reduced depredation and crop destructionresult in greater survival and reproductive ratesfor wildlife (particularly critical for endangeredand threatened species)

    Drug and Radiation Therapies for Humans

    Understanding CTA could lead to improvedtreatments for a variety of diseases whosetreatments currently involve debilitating sideeffects

    Tony Norton

    afssa.fr

    fluofarma.com

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    References "Amygdala." Wikipedia, The Free Encyclopedia. 5 Dec 2008, 08:29 UTC. 10 Dec 2008

    .

    Gill, Elaine L., Anne Whiterow, and David P. Cowan. A Comparative Assessment of Potential Conditioned Taste

    Aversion Agents for Vertebrate Management. Applied Animal Behaviour Science. Volume 67, Issue 3, April 3,

    2000, pp. 229-240.

    Houpt, Thomas A., et al. Increased c-fos Expression in Nucleus of the Solitary Tract Correlated with Conditioned

    Taste Aversion to Sucrose in Rats. Neuroscience Letters. Issue 172, February 18, 1994, pp. 1-5.

    Lamprecht, Raphael, and Yadin Dudai. Transient Expression of c-fos in Rat Amygdala During Training is Required

    for Encoding Conditioned Taste Aversion Memory. Learning Memory. Volume 3, 1996, pp. 31-41.

    Lamprecht, Raphael, Shoshi Hazvi, and Yadin Dudai. cAMP Response Element-Binding Protein in the Amygdala is

    Required for Long- but not Short-Term Conditioned Taste Aversion Memory. The Journal of Neuroscience.

    Volume 17, Number 21, Issue of November 1, 1997, pp. 8443-8450.

    Massei, Giovanna, and David P. Cowan. Strength and Persistence of Conditioned Taste Aversion in Rats:

    Evaluation of 11 Potential Compounds. Applied Animal Behaviour Science. Volume 75, Issue 3, January 23, 2002,

    pp. 249-260.

    Masugi, Miwako, et al. Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Deficit in Fear Response

    and Conditioned Taste Aversion. The Journal of Neuroscience. Volume 19, Number 3, Issue of February 1, 1999,

    pp. 955-963.

    Nicolaus, Lowell. Predation Politics: The Sad Story of Wolves, Conditioned Taste Aversion, and the Wildlife

    Management Hierarchy. [Online] Available http://www.conditionedtasteaversion.net/index.html, March 2008.

    "Solitary nucleus." Wikipedia, The Free Encyclopedia. 20 Aug 2008, 05:25 UTC. 10 Dec 2008

    .

    Ternent, M.A., and D.L. Garshelis. Taste Aversion Conditioning to Reduce Nuisance Activity by Black Bears in a

    Minnesota Military Reservation. Wildlife Society Bulletin. Volume 27, Number 3, 1999, pp. 720-728.

    Images of CTA-inducing compounds and cAMP downloaded from Wikipedia; images of brain found using Google

    image search