Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

The amygdala modulates prefrontal cortex activity relative to conditioned fear

Abstract

Animals learn that a tone can predict the occurrence of an electric shock through classical conditioning. Mice or rats trained in this manner display fear responses, such as freezing behaviour, when they hear the conditioned tone. Studies using amygdalectomized rats have shown that the amygdala is required for both the acquisition and expression of learned fear responses1,2,3. Freezing to a conditioned tone is enhanced following damage to the dorsal part of the medial prefrontal cortex4, indicating that this area may be involved in fear reduction. Here we show that prefrontal neurons reduce their spontaneous activity in the presence of a conditioned aversive tone as a function of the degree of fear. The depression in prefrontal spontaneous activity is related to amygdala activity but not to the freezing response itself. These data indicate that, in the presence of threatening stimuli, the amygdala controls both fear expression and prefrontal neuronal activity. They suggest that abnormal amygdala-induced modulation of prefrontal neuronal activity may be involved in the pathophysiology of certain forms of anxiety disorder.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Conditioned inhibition: electrophysiology and behaviour.
Figure 2: Effect of amygdala lesion.

Similar content being viewed by others

References

  1. Davis,M. in The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction (ed. Aggleton, J. P.) 255–305 (Wiley-Liss, New York, 1992).

    Google Scholar 

  2. LeDoux,J. E. Emotion: clues from brain. Annu. Rev. Psychol. 46, 209–235 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Maren,S. & Fanselow,M. S. The amygdala and fear conditioning: has the nut been cracked? Neuron 16, 237–240 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Morgan,M. A. & LeDoux,J. E. Differential contribution of dorsal and ventral medial prefrontal cortex to acquisition and extinction of conditioned fear in rats. Behav. Neurosci. 109, 681–688 (1995).

    Article  CAS  PubMed  Google Scholar 

  5. Rescorla,R. A. Pavlovian conditioned inhibition. Psychol. Bull. 72, 77–94 (1969).

    Article  Google Scholar 

  6. Campeau,S. et al. Elicitation and reduction of fear: behavioural and neuroendocrine indices and brain induction of the immediated-early gene c-fos. Neuroscience 78, 1087–1104 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Papini,M. R. & Bitterman,M. E. The two-test strategy in the study of inhibitory conditioning. J. Exp. Psychol. Anim. Behav. Process. 19, 342–352 (1993).

    Article  CAS  PubMed  Google Scholar 

  8. Thomas,E. & Yadin,E. Multiple unit activity in the septum during Pavlovian aversive conditioning: evidence for an inhibitory role for the septum. Exp. Neurol. 69, 50–60 (1980).

    Article  CAS  PubMed  Google Scholar 

  9. McDonald,A. J. Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat. Neuroscience 44, 1–14 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. LaBar,K. S. & LeDoux,J. E. Partial disruption of fear conditioning in rats with unilateral amygdala damage: correspondence with unilateral temporal lobectomy in humans. Behav. Neurosci. 110, 991–997 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Farb,C. R. & LeDoux,J. E. NMDA and AMPA receptors in the lateral nucleus of the amygdala are postsynaptic to auditory thalamic afferents. Synapse 27, 106–121 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. LeDoux,J. E., Farb,C. & Ruggiero,D. A. Topographic organization of neurons in the acoustic thalamus that project to the amygdala. J. Neurosci. 10, 1043–1054 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Turner,B. H. & Herkenham,M. Thalamo-amygdaloid projections in the rat: a test of the amygdala's role in sensory processing. J. Comp. Neurol. 313, 295–325 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Garcia,R., Paquereau,J., Vouimba,R. M. & Jaffard,R. Conditioned fear stress enhances auditory-evoked potentials in the basolateral amygdala of the awake rat. Eur. J. Neurosci. (Suppl.) 9, 194 (1996).

    Google Scholar 

  15. Garcia,R., Paquereau,J., Vouimba,R. M. & Jaffard,R. Footshock stress but not contextual fear conditioning induces long-term enhancement of auditory-evoked potentials in the basolateral amygdala of the freely behaving rat. Eur. J. Neurosci. 10, 457–463 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. Rogan,M. T., Stäubli,U. V. & LeDoux,J. E. Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390, 604–607 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Pérez-Jaranay,J. M. & Vives,F. Electrophysiological study of the response of medial prefrontal cortex neurons to stimulation of the basolateral nucleus of the amygdala in the rat. Brain Res. 564, 97–101 (1991).

    Article  PubMed  Google Scholar 

  18. McDonald,A. J. Organization of amygdaloid projections to the mediodorsal thalamus and prefrontal cortex: a fluorescence retrograde transport study in the rat. J. Comp. Neurol. 262, 46–58 (1987).

    Article  CAS  PubMed  Google Scholar 

  19. Gonzales,C. & Chesselet,M. F. Amygdalo-nigral pathways: an anterograde study in the rat with phaseolus vulgaris leucoagglutinin (PHAL-L). J. Comp. Neurol. 297, 182–200 (1990).

    Article  CAS  PubMed  Google Scholar 

  20. Lindvall,O., Björklund,A., Moore,R. Y. & Stenevi,U. Mesencephalic dopamine neurons projecting to neocortex. Brain Res. 81, 325–331 (1974).

    Article  CAS  PubMed  Google Scholar 

  21. Fuxe,K., Hökfelt,T., Johansson,O., Lidbrink,P. & Ljungdahl,A. The origin of the dopamine nerve terminals in limbic and frontal cortex. Evidence for meso-cortico dopamine neurons. Brain Res. 82, 349–355 (1974).

    Article  CAS  Google Scholar 

  22. Davis,M. et al. Stress-induced activation of prefrontal cortex dopamine turnover: blockade by lesions of the amygdala. Brain Res. 664, 207–210 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Goldstein,L. E., Rasmusson,A. M., Bunney,B. S. & Roth,R. H. Role of the amygdala in the coordination of behavioral, neuroendocrine, and prefrontal cortical monoamine responses to psychological stress in the rat. J. Neurosci. 16, 4787–4798 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ferron,A., Thierry,A. M., Le Douarin,C. & Glowinski,J. Inhibitory influence of the mesocortical dopaminergic system on spontaneous activity or excitatory response induced from the thalamic mediodorsal nucleus in the rat medial prefrontal cortex. Brain Res. 302, 257–265 (1984).

    Article  CAS  PubMed  Google Scholar 

  25. Mantz,J., Milla,C., Glowinsky,J. & Thierry,A. M. Differential effects of ascending neurons containing dopamine and noradrenaline in the control of spontaneous activity and of evoked responses in the rat prefrontal cortex. Neuroscience 27, 517–526 (1988).

    Article  CAS  PubMed  Google Scholar 

  26. Schoenbaum,G., Chiba,A. A. & Gallagher,M. Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning. J. Neurosci. 19, 1876–1884 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bechara,A., Damasio,H., Damasio,A. R. & Lee,G. P. Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making. J. Neurosci. 19, 5473–5481 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Herry,C., Vouimba,R. M. & Garcia,R. Plasticity in the thalamo-prefrontal cortical transmission in behaving mice. J. Neurophysiol. (in the press).

  29. Schoenbaum,G., Chiba,A. A. & Gallagher,M. Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning. Nature Neurosci. 1, 155–159 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Franklin,K. B. J. & Paxinos,G. The Mouse Brain in Stereotaxic Coordinates (Academic, San Diego, 1997).

    Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Fondation Fyssen (R.M.V.) and from NATO (R.G.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to René Garcia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Garcia, R., Vouimba, RM., Baudry, M. et al. The amygdala modulates prefrontal cortex activity relative to conditioned fear. Nature 402, 294–296 (1999). https://doi.org/10.1038/46286

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/46286

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing