Abstract
Long-term potentiation (LTP) is an experience-dependent form of neural plasticity believed to involve mechanisms that underlie memory formation1,2,3. LTP has been studied most extensively in the hippocampus, but the relation between hippocampal LTP and memory has been difficult to establish4,5,6. Here we explore the relation between LTP and memory in fear conditioning, an amygdala-dependent form of learning in which an innocuous conditioned stimulus (CS) elicits fear responses after being associatively paired with an aversive unconditioned stimulus (US). We have previously shown that LTP induction in pathways that transmit auditory CS information to the lateral nucleus of the amygdala (LA) increases auditory-evoked field potentials in this nucleus7. Now we show that fear conditioning alters auditory CS-evoked responses in LA in the same way as LTP induction. The changes parallel the acquisition of CS-elicited fear behaviour, are enduring, and do not occur if the CS and US remain unpaired. LTP-like associative processes thus occur during fear conditioning, and these may underlie the long-term associative plasticity that constitutes memory of the conditioning experience.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Malenka, R. C. & Nicoll, R. A. NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms. Trends Neurosci. 16, 521–527 (1993).
Bliss, T. V. P. & Collingridge, G. L. Asynaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993).
Brown, T. H. & Chattarji, S. in Models of Neural Networks II (eds Domany, E., Van Hemmen, J. L. & Schulten, K.) 287–314 (Springer-Verlag, New York, (1994)).
Stäubli, U. V. in Brain and Memory: Modulation and Mediation of Neuroplasticity (eds McGaugh, J. L., Weinberger, N. M. & Lynch, G.) 303–318 (Oxford Univ. Press, New York, (1995)).
Barnes, C. A. Involvement of LTP in memory: Are we “searching under the streetlight?”. Neuron 15, 751–754 (1955).
Eichenbaum, H. The LTP–memory connection. Nature 378, 131–132 (1995).
Rogan, M. T. & LeDoux, J. E. LTP is accompanied by commensurate enhancement of auditory-evoked responses in a fear conditioning circuit. Neuron 15, 127–136 (1995).
Phillips, R. G. & LeDoux, J. E. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav. Neurosci. 106, 274–285 (1992).
Rogan, M. T., Stäubli, U. V. & LeDoux, J. E. AMPA-receptor facilitation accelerates fear learning without altering the level of conditioned fear acquired. J. Neurosci. 17, 5928–5935 (1997).
Kim, J. J. & Fanselow, M. S. Modality-specific retrograde amnesia of fear. Science 256, 675–677 (1992).
Moser, E. I., Moser, M.-B. & Andersen, P. Potentiation of dentate synapses initiated by exploratory learning in rats: dissociation from brain temperature, motor activity, and arousal. Learn. Memory 1, 55–73 (1994).
Blanchard, R. J. & Blanchard, D. C. Passive and active reactions to fear-eliciting stimuli. J. Comp. Physiol. Psychol. 68, 129–135 (1969).
Blanchard, R. J. & Blanchard, D. C. Crouching as an index of fear. J. Comp. Physiol. Psychol. 67, 370–375 (1969).
Bouton, M. E. & Bolles, R. C. Conditioned fear assessed by freezing and by the suppression of three different baselines. Anim. Learn. Behav. 8, 429–434 (1980).
Bolles, R. C. & Fanselow, M. S. Aperceptual-defensive-recuperative model of fear and pain. Behav. Brain Sci. 3, 291–323 (1980).
Moser, E., Mathiesen, I. & Anderson, P. Association between brain temperature and dentate field potentials in exploring and swimming rats. Science 259, 1324–1326 (1993).
Winson, J. & Absug, C. Neuronal transmission through hippocampal pathways dependent on behavior. J. Neurophysiol. 41, 716–732 (1978).
Leung, S. Behavior-dependent evoked potentials in the hippocampal CA1 region of the rat. I. Correlation with behavior and EEG. Brain Res. 198, 95–117 (1980).
Buzsaki, G., Grastyan, E., Czopf, J., Kellenyi, L. & Prohaska, O. Changes in neuronal transmission in the rat hippocampus during behavior. Brain Res. 225, 235–247 (1981).
Quirk, G. J., Repa, J. C. & LeDoux, J. E. Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat. Neuron 15, 1029–1039 (1995).
Skelton, R. W., Scarth, A. S., Wilkie, D. M., Miller, J. J. & Philips, G. Long-term increases in dentate granule cell responsivity accompany operant conditioning. J. Neurosci. 7, 3081–3087 (1987).
Deadwyler, S. A., West, M. O., Christian, E., Hampson, R. E. & Foster, T. C. Sequence-related changes in sensory-evoked potentials in the dentate gyrus: as mechanism for item-specific short-term information storage in the hippocampus. Behav. Neural Biol. 44, 201–212 (1985).
Jeffrey, K. J. LTP and spatial learning — where to next? Hippocampus 7, 95–110 (1997).
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).
Li, X., Phillips, R. G. & LeDoux, J. E. NMDA and non-NMDA receptors contribute to synaptic transmission between the medial geniculate body and the lateral nucleus of the amygdala. Exp. Brain Res. 105, 87–100 (1995).
Li, X. F., Stutzmann, G. E. & LeDoux, J. L. Convergent but temporally separated inputs to lateral amygdala neurons from the auditory thalamus and auditory cortex use different postsynaptic receptors: in vivo intracellular and extracellular recordings in fear conditioning pathways. Learn. Memory 3, 229–242 (1996).
Miserendino, M. J. D., Sananes, C. B., Melia, K. R. & Davis, M. Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala. Nature 345, 716–718 (1990).
Maren, S., Aharonov, G., Stote, D. L. & Fanselow, M. S. N-Methyl-d-Aspartate receptors in the basolateral amygdala are required for both acquisition and expression of the conditional fear in rats. Behav. Neurosci. 110, 1365–1374 (1996).
Gewirtz, J. C. & Davis, M. Second-order fear conditioning prevented by blocking NMDA receptors in amygdala. Nature 388, 471–473 (1997).
Rogan, M. T. & LeDoux, J. E. Intra-amygdala infusion of APV blocks both auditory evoked potentials in the lateral amygdala and thalamo-amygdala transmission, but spares cortico-amygdala transmission. Soc. Neurosci. Abstr. 21, 1930 (1995).
Acknowledgements
We thank D. Ringach for software development and M. Hou for histology and help with the surgical preparation of subjects.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rogan, M., Stäubli, U. & LeDoux, J. Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390, 604–607 (1997). https://doi.org/10.1038/37601
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/37601
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.