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.
Your institute does not have access to this article
Open Access articles citing this article.
Neuropsychopharmacology Open Access 26 May 2022
Molecular Psychiatry Open Access 03 December 2021
Single cell plasticity and population coding stability in auditory thalamus upon associative learning
Nature Communications Open Access 26 April 2021
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
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).
We thank D. Ringach for software development and M. Hou for histology and help with the surgical preparation of subjects.
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
N-acetylcysteine facilitates extinction of cued fear memory in rats via reestablishing basolateral amygdala glutathione homeostasis
Acta Pharmacologica Sinica (2022)
Molecular Psychiatry (2022)
Nature Reviews Neurology (2022)
The Cerebellum (2022)