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Quantitative trait locus analysis of contextual fear conditioning in mice

Nature Genetics volume 17, pages 331–334 (1997)Cite this article

Abstract

Family, twin and adoption studies provide evidence for a substantial genetic component underlying individual differences in general intelligence1, specific cognitive abilities2 and susceptibility to psychopathologies related to fear-inducing events3. Contextual fear conditioning, which is highly conserved across species, can serve as a model for elucidating genes that regulate individual differences in learning and emotion4–. In fear conditioning, an initially neutral stimulus, such as a tone or a particular environment (context), elicits a fear response after it has been paired with an aversive stimulus, such as shock. Two neural circuits have been implicated in fear conditioning. The fear component is regulated by amygdaloid pathways, while the contextual component is, at least in part, dependent on the hippocampus9–14. C57BL/6J (B6) and DBA/2J (D2) mice differ in several types of complex learning15,16, including contextual fear conditioning17. A quantitative trait locus (QTL) analysis of contextual fear conditioning was performed in a B6/D2 F2 intercross population. Two QTLs for contextual conditioning (lod score>4.3) were identified on chromosomes 10 and 16. QTLs for conditioning to the auditory cue (lod score>4.3) were localized to chromosomes 1 and 10. Suggestive QTLs (lod score=2.8–4.1) for contextual conditioning were detected on chromosomes 1,2 and 3.

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References

  1. Bouchard, T.J., Lykken, D.T., McGue, M., Segal, N.L. & Tellegen, A. Sources of human psychological differences: the Minnesota study of twins reared apart. Science 250, 223–228 (1990).

    Article  Google Scholar 

  2. DeFries, J.C. et al. Familial resemblance for specific cognitive abilities. Behav. Genet. 9, 23–43 (1979).

    CAS  PubMed  Google Scholar 

  3. True, W.R. et al. A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Arch. Gen. Psychiatry 50, 257–264 (1993).

    Article  CAS  Google Scholar 

  4. LeDoux, J.E. Brain mechanisms of emotion and emotional learning. Curr. Opin. Neurobiol. 2, 191–197 (1992).

    Article  CAS  Google Scholar 

  5. LeDoux, J.E. Emotion: clues from the brain. Ann. Rev. Psychol. 46, 209–235 (1995).

    Article  CAS  Google Scholar 

  6. Fanselow, M.S. Factors governing one-trial contextual conditioning. Animal Learn. Behav. 18, 264–270 (1990).

    Article  Google Scholar 

  7. Adolphs, R., Tranel, D., Damasio, H. & Damasio, A.R. Fear and the human amygdala. J. Neurosci. 15, 5879–5891 (1995).

    Article  CAS  Google Scholar 

  8. LaBar, K.S., LeDoux, J.E., Spencer, D. & Phelps, E.A. Impaired fear conditioning following unilateral temporal lobectomy in humans. J. Neurosci. 15, 6846–6855 (1995).

    Article  CAS  Google Scholar 

  9. Bechara, A. et al. Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. Science 269, 1115–1118 (1995).

    Article  CAS  Google Scholar 

  10. Scott, S.K. et al. Impaired auditory recognition of fear and anger following bilateral amygdala lesions. Nature 385, 254–257 (1997).

    Article  CAS  Google Scholar 

  11. Phillips, R.G. & LeDoux, J.E. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav. Neurosci. 106, 274–285 (1992).

    Article  CAS  Google Scholar 

  12. Kim, J.J. & Fanselow, M.S. Modality-specific retrograde amnesia of fear. Science 256, 675–677 (1992).

    Article  CAS  Google Scholar 

  13. Phillips, R.G. & LeDoux, J.E. Lesions of the dorsal hippocampal formation interfere with background but not foreground contextual fear conditioning. Learn. Mem. 1, 34–44 (1994).

    CAS  PubMed  Google Scholar 

  14. Logue, S.F., Paylor, R. & Wehner, J.M. Hippocampal lesions cause learning deficits in inbred mice in Morris water maze and conditioned fear tasks. Behav. Neurosci. 111, 104–113 (1997).

    Article  CAS  Google Scholar 

  15. Upchurch, M. & Wehner, J.M. Differences between inbred strains of mice in Morris water maze performance. Behav. Genet. 18, 55–68 (1988).

    Article  CAS  Google Scholar 

  16. Paylor, R., Baskall, L. & Wehner, J.M. Behavioral dissociations between C57BL/6 and DBA/2 mice on learning and memory tasks: A hippocampal-dysfunction hypothesis. Psychobiology 21, 11–26 (1993).

    Google Scholar 

  17. Paylor, R., Tracy, R., Wehner, J.M. & Rudy, J.W. DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning. Behav. Neurosci. 108, 810–817 (1994).

    Article  CAS  Google Scholar 

  18. Blanchard, R.J. & Blanchard, D.C. Crouching as an index of fear. J. Comp. Physiol. Psychol. 67, 370–375 (1969).

    Article  CAS  Google Scholar 

  19. Owen, E.H., Christensen, S.C., Paylor, R. & Wehner, J.M. Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning using BXD recombinant inbred strains. Behav. Neurosci. 111, 292–300 (1997).

    Article  CAS  Google Scholar 

  20. Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 (1995).

    Article  CAS  Google Scholar 

  21. Lander, E.S. et al. MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics 1, 174–181 (1987).

    Article  CAS  Google Scholar 

  22. Flint, J. et al. A simple genetic basis for a complex psychological trait in laboratory mice. Science 269, 1432–1435 (1995).

    Article  CAS  Google Scholar 

  23. Market, P.D., Bennett, B., Beeson, M., Gordon, L. & Johnson, I.E. Mapping of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice. Genome Res. 7, 92–99 (1997).

    Article  Google Scholar 

  24. Gershenfeld, H.K. et al. Mapping quantitative trait loci for open-field behavior in mice. Behav. Genet. 27, 201–210

  25. Buck, K.J., Metten, P., Belknap, J.K. & Crabbe, J.C. Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. J. Neurosci. 17, 3945–3955 (1997).

    Article  Google Scholar 

  26. Ferraro, T.N. et al. Mapping murine loci for seizure response to kainic acid. Mamm. Genome 8, 200–208 (1997).

    Article  CAS  Google Scholar 

  27. Frankel, W.N. et al. New seizure frequency QTL and the complex genetics of epilepsy in EL mice. Mamm. Genome 6, 830–838 (1995).

    Article  CAS  Google Scholar 

  28. Caldarone, B. et al. Quantitative trait loci analysis affecting contextual conditioning in the mouse. Nature Genet. 17, 335–337 (1997).

    Article  CAS  Google Scholar 

  29. Abeliovich, A. et al. PKC-gamma mutant mice exhibit mild deficits in spatial and contextual learning. Cell 75, 1263–1271 (1993).

    Article  CAS  Google Scholar 

  30. Aiba, A. et al. Reduced hippocampal long-term potentiation and context-specific deficit in associative learning in mGluR1 mutant mice. Cell 79, 365–375 (1994).

    Article  CAS  Google Scholar 

  31. Bourtchuladze, R. et al. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 59–68 (1994).

    Article  CAS  Google Scholar 

  32. Chen, C., Rainnie, D.G., Greene, R.W. & Tonegawa, S. Abnormal fear response and aggressive behavior in mutant mice deficient for α-calcium-calmodulin kinase II. Science 266, 291–294 (1994).

    Article  CAS  Google Scholar 

  33. Lu, Y. & Wehner, J.M. Enhancement of contextual fear-conditioning by putative (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators and /V-methyl-D-aspartate (NMDA) receptor antagonists in DBA/2J mice. Brain Res. (in the press).

  34. Sambrook, J., Fritsch, E. & Maniatis, T. Molecular Cloning: A Laboratory Manual, 2nd ed. (Cold Spring Harbor Press, Cold Spring Harbor, New York, 1989).

    Google Scholar 

  35. Dietrich, W.F. et al. A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nature Genet. 7, 220–339 (1994).

    Article  CAS  Google Scholar 

  36. Falconer, D.S. Introduction to Quantitative Genetics,3rd ed. 126 (Longman Scientific & Technical, John Wiley, New York, 1989).

    Google Scholar 

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Authors and Affiliations

  1. Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, 80309, USA

    Jeanne M. Wehner, Richard A. Radcliffe, Shelby T. Rosmann, Steven C. Christensen, Duffy L. Rasmussen, David W. Fulker & Michelle Wiles

  2. School of Pharmacy, University of Colorado, Boulder, Colorado, 80309, USA

    Jeanne M. Wehner

  3. Department of Psychology, University of Colorado, Boulder, Colorado, 80309, USA

    David W. Fulker

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  1. Jeanne M. Wehner
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  2. Richard A. Radcliffe
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Correspondence to Jeanne M. Wehner.

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Wehner, J., Radcliffe, R., Rosmann, S. et al. Quantitative trait locus analysis of contextual fear conditioning in mice. Nat Genet 17, 331–334 (1997). https://doi.org/10.1038/ng1197-331

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