Behavior Genetics

, Volume 33, Issue 1, pp 43–58 | Cite as

Influence of Shock Training and Explicit Fear-Conditioned Cues on Sleep Architecture in Mice: Strain Comparison

  • Larry D. Sanford
  • Xiangdong Tang
  • Richard J. Ross
  • Adrian R. Morrison


Fear conditioning is thought to model anticipatory anxiety. Inbred mouse strains exhibit different levels of reactivity to aversive environmental stimuli, which may reflect anxiety. We examined the effects of fear conditioning on sleep in mouse strains that differ on behavioral measures of anxiety. Mice (BALB/cJ [C], C57BL/6J [B6], CB6F1/J [CB6], n = 7–10 per strain) were implanted with transmitters for recording sleep by telemetry. Baseline sleep was recorded, and the mice were trained to associate a cue (tone) with footshock (15 cue–shock pairings on 4 consecutive days). Sleep was recorded after shock training and again 4 to 5 days later after presentation of the cue alone. Shock training produced a relatively selective suppression of rapid eye movement sleep (REM) that was greater in the C strain compared to the B6 and CB6 mice. Post-training exposure to the cue alone suppressed REM in all strains. The C strain exhibited a relatively greater immediate suppression of REM, and the CB6 hybrid mice showed the greatest overall suppression of REM. These data demonstrate that stimuli associated with an aversive event can alter sleep and suppress REM in much the same way as exposure to the event itself. Fear conditioning may provide a model for examining genetic and neural mechanisms underlying the influence of anxiety on sleep.

Anxiety conditioning fear mouse strains rapid eye movement sleep sleep 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adrien, J., Dugovic, C., and Martin, P. (1991). Sleep-wakefulness patterns in the helpless rat. Physiol. Behav. 49:257-262.Google Scholar
  2. Ambrosini, M. V., Mariucci, G., Colarieti, L., Bruschelli, G., Carobi, C., and Giuditta, A. (1993). The structure of sleep is related to the learning ability of rats. Eur. J. Neurosci. 5:269-275.Google Scholar
  3. Blanchard, R. J., Blanchard, D. C. (1969). Crouching as an index of fear. J. Comp. Physiol. Psychol. 67:370-375.Google Scholar
  4. Bowker, R. M., and Morrison, A. R. (1976). The startle reflex and PGO spikes. Brain Res. 102:185-190.Google Scholar
  5. Charney, D. S., and Deutch, A. (1996). A functional neuroanatomy of anxiety and fear: Implications for the pathophysiology and treatment of anxiety disorders. Crit. Rev. Neurobiol. 10:419-446.Google Scholar
  6. Crawley, J. N., and Davis, L. G. (1982). Baseline exploratory activity predicts anxiolytic responsiveness to diazepam in five mouse strains. Brain Res. Bull. 8:609-612.Google Scholar
  7. Datta, S. (2000). Avoidance task training potentiates phasic pontinewave density in the rat: A mechanism for sleep-dependent plasticity. J. Neurosci. 20:8607-8613.Google Scholar
  8. Davis, M. (1992a). The role of the amygdala in conditioned fear. In: Aggleton, J. P. (ed.), The Amygdala: Neurobiological Aspects of Emotion, Memory and Mental Dsyfunction, New York: Wiley-Liss, pp. 255-305.Google Scholar
  9. Davis, M. (1992b). The role of the amygdala in fear and anxiety. Ann. Rev. Neurosci. 15:353-375.Google Scholar
  10. Desmedt, A., Garcia, R., and Jaffard, R. (1998). Differential modulation of changes in hippocampal-septal synaptic excitability by the amygdala as a function of either elemental or contextual fear conditioning in mice. J. Neurosci. 18:480-487.Google Scholar
  11. Falls, W. A., Carlson, S., Turner, J. G., and Willott, J. F. (1997). Fear-potentiated startle in two strains of inbred mice. Behav. Neurosci. 111:855-861.Google Scholar
  12. Friedmann, J. K. (1974). A diallel analysis of the genetic underpinnings of mouse sleep. Physiol. Behav. 12:169-175.Google Scholar
  13. Gorman, J. M., Kent, J. M., Sullivan, G. M., and Scoplan, J. D. (2000). Neuroanatomical hypothesis of panic disorder, Revised. Am. J. Psychiatry. 157:493-505.Google Scholar
  14. Hall, C. S. (1934). Emotional behavior in the rat. I. Defecation and urination as measures of individual differences in emotionality. J. Comp. Psychol. 18:385-403.Google Scholar
  15. Hitchcock, J., and Davis, M. (1986). Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm. Behav. Neurosci. 100:11-22.Google Scholar
  16. Hode, Y., Ratomponirina, C., Gobaille, M., Maitre, M., Kopp, C., and Misslin, R. (2000). Hypoexpression of benzodiazepine receptors in the amygdala of neophobic BALB/c mice compared to C57BL/6 mice. Pharmacol. Biochem. Behav. 65:35-38.Google Scholar
  17. Jouvet, M. (1967). Neurophysiology of the states of sleep. Physiol. Rev. 47:117-177.Google Scholar
  18. Logue, S. F., Owen, E. H., Rasmussen, D. L., and Wehner, J. M. (1997). Assessment of locomotor activity, acoustic and tactile startle, and prepulse inhibition of startle in inbred mouse strains and F1 hybrids: Implications of genetic background for single gene and quantitative trait loci analyses. Neuroscience 80:1075-1086.Google Scholar
  19. Louie, K., and Wilson, M. A. (2001). Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron. 29:145-156.Google Scholar
  20. Marks, I. M. (1986). Genetics of fear and anxiety disorders. Br. J. Psychiatr. 149:406-418.Google Scholar
  21. Mathis, C., Paul, S. M., and Crawley, J. N. (1994). Characterization of benzodiazepine-sensitive behaviors in the A/J and C57BL/6J inbred strains of mice. Behav. Genet. 24:171-180.Google Scholar
  22. Meerlo, P., Easton, A., Bergmann, B. M., and Turek, F. W. (2001). Restraint increases prolactin and REM sleep in C57BL/6J mice but not in BALB/cJ mice. Am. J. Physiol. Reg. Int. Comp. Physiol. 281:R846-R854.Google Scholar
  23. Paylor, R., Tracy, R., Wehner, J., and Rudy, J. W. (1994). DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning. Behav. Neurosci. 108:810-817.Google Scholar
  24. Phillips, R. G., and LeDoux, J. E. (1992). Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav. Neurosci. 106:274-285.Google Scholar
  25. Radulovic, J., Kammermeier, J., and Spiess, J. (1998). Relationship between fos production and classical fear conditioning: Effects of novelty, latent inhibition, and unconditioned stimulus pre-exposure. J. Neurosci. 18:7452-7461.Google Scholar
  26. Rogan, M. T., Staubli, U. V., and LeDoux, J. E. (1997). Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390:604-607.Google Scholar
  27. Sanford, L. D., Ball, W. A., Morrison, A. R., Ross, R. J., and Mann, G. L. (1992a. Peripheral and central components of alerting: Habituation of acoustic startle, orienting responses and elicited waveforms. Behav. Neurosci. 106:112-120.Google Scholar
  28. Sanford, L. D., Morrison, A. R., Ball, W. A., Ross, R. J., and Mann, G. L. (1993). The amplitude of elicited PGO waves: A correlate of orienting. Electroenceph. Clin. Neurophysiol. 86:438-445.Google Scholar
  29. Sanford, L. D., Morrison, A. R., Ball, W. A., Ross, and Mann, G. L. (1992b. Varying expressions of alerting mechanisms in wakefulness and across sleep states. Electroenceph. Clin. Neurophysiol. 82:458-468.Google Scholar
  30. Sanford, I. D., Silvestri, A. J., Ross, R. J., and Morrison, A. R. (2001). Influence of fear conditioning on elicited pontogeniculo-occipital waves and rapid eye movement sleep. Arch. Ital. Biol. 139:169-184.Google Scholar
  31. Smith, C. (1985). Sleep states and learning: A review of the animal literature. Neurosci. Biobehav. Rev. 9:157-168.Google Scholar
  32. Smith, C. (1995). Sleep states and memory processes. Behav. Brain Res. 69:137-145.Google Scholar
  33. Tang, X., and Sanford, L. D. (2002). Telemetric recording of sleep and home cage activity in mice. Sleep 25:691-699.Google Scholar
  34. Tang, X., Orchard, S. M., and Sanford, L. D. (2002a. Home cage activity and behavioral performance in inbred and hybrid mice. Behav. Brain Res. (in Press).Google Scholar
  35. Tang, X., Yang, L., and Sanford, L. D. (2002b. Sleep alterations after different levels of conditioned fear training. Sleep 25:282.Google Scholar
  36. Trullas, R., Skolnick, P. (1993). Differences in fear motivated behaviors among inbred mouse strains. Psychopharmacology (Berl) 111:323-331.Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Larry D. Sanford
  • Xiangdong Tang
  • Richard J. Ross
  • Adrian R. Morrison

There are no affiliations available

Personalised recommendations