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.

  • Article
  • Published:

Two different lateral amygdala cell populations contribute to the initiation and storage of memory

Abstract

Single-cell activity was recorded in the dorsal subnucleus of the lateral amygdala (LAd) of freely behaving rats during Pavlovian fear conditioning, to determine the relationship between neuronal activity and behavioral learning. Neuronal responses elicited by the conditioned stimulus typically increased before behavioral fear was evident, supporting the hypothesis that neural changes in LAd account for the conditioning of behavior. Furthermore, two types of these rapidly modified cells were found. Some, located in the dorsal tip of LAd, exhibited short-latency responses (<20 ms) that were only transiently changed. A second class of cells, most commonly found in ventral regions of LAd, had longer latency responses, but maintained enhanced responding throughout training and even through extinction. These anatomically distinct cells in LAd may be differentially involved in the initiation of learning and long-term memory storage.

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: Behavioral measures of conditioned fear.
Figure 2: Photomicrograph of a thionin-stained brain section from a representative rat, showing electrode tract and lesion site in LAd.
Figure 3: Neuronal plasticity during early extinction, for all cells.
Figure 4: Neuronal plasticity during conditioning, for all cells.
Figure 5: Latency and time course of neuronal plasticity.
Figure 6: Acquisition of neuronal versus behavioral measures of learning.
Figure 7: Persistence of neuronal plasticity during conditioning.
Figure 8: Breakdown of transiently plastic versus long-lasting plastic cells, by latency of plasticity and anatomical location.

Similar content being viewed by others

References

  1. LeDoux, J. E. Emotion circuits in the brain. Annu. Rev. Neurosci. 23, 155–184 (2000).

    Article  CAS  Google Scholar 

  2. Fendt, M. & Fanselow, M. S. The neuroanatomical and neurochemical basis of conditioned fear. Neurosci. Biobehav. Rev. 23, 743–760 (1999).

    Article  CAS  Google Scholar 

  3. Davis, M. Neurobiology of fear responses: the role of the amygdala. J. Neuropsychiatry Clin. Neurosci. 9, 382–402 (1997).

    Article  CAS  Google Scholar 

  4. Maren, S. Long-term potentiation in the amygdala: a mechanism for emotional learning and memory. Trends Neurosci. 22, 561–567 (1999).

    Article  CAS  Google Scholar 

  5. Fanselow, M. S. & LeDoux, J. E. Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron 23, 229–232 (1999).

    Article  CAS  Google Scholar 

  6. Cahill, L., Weinberger, N. M., Roozendaal, B. & McGaugh, J. L. Is the amygdala a locus of “conditioned fear”? Some questions and caveats. Neuron 23, 227–228 (1999).

    Article  CAS  Google Scholar 

  7. 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).

    Article  CAS  Google Scholar 

  8. Rogan, M., Staubli, U. & LeDoux, J. Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390, 604–607 (1997).

    Article  CAS  Google Scholar 

  9. Pare, D. & Collins, D. R. Neuronal correlates of fear in the lateral amygdala: multiple extracellular recordings in conscious cats. J. Neurosci. 20, 2701–2710 (2000).

    Article  CAS  Google Scholar 

  10. McKernan, M. G. & Shinnick-Gallagher, P. Fear conditioning induces a lasting potentiation of synaptic currents in vitro. Nature 390, 607–611 (1997).

    Article  CAS  Google Scholar 

  11. Maren, S. Auditory fear conditioning increases CS-elicited spike firing in lateral amygdala neurons even after extensive overtraining. Eur. J. Neurosci. 12, 4047–4054 (2000).

    Article  CAS  Google Scholar 

  12. Weisskopf, M. G., Bauer, E. P. & LeDoux, J. E. L-Type voltage-gated calcium channels mediate NMDA-independent associative long-term potentiation at thalamic input synapses to the amygdala. J. Neurosci. 19, 10512–10519 (1999).

    Article  CAS  Google Scholar 

  13. Huang, Y. Y. & Kandel, E. R. Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala. Neuron 21, 169–178 (1998).

    Article  CAS  Google Scholar 

  14. Estes, W. K. & Skinner, B. F. Some quantitative properties of anxiety. J. Exp. Psychol. 29, 390–400 (1941).

    Article  Google Scholar 

  15. 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).

    Article  Google Scholar 

  16. Quirk, G. J., Armony, J. L. & LeDoux, J. E. Fear conditioning enhances different temporal components of toned-evoked spike trains in auditory cortex and lateral amygdala. Neuron 19, 613–624 (1997).

    Article  CAS  Google Scholar 

  17. Buchel, C., Morris, J., Dolan, R. J. & Friston, K. J. Brain systems mediating aversive conditioning: an event-related fMRI study. Neuron 20, 947–957 (1998).

    Article  CAS  Google Scholar 

  18. LaBar, K. S., Gatenby, J. C., Gore, J. C., LeDoux, J. E. & Phelps, E. A. Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study. Neuron 20, 937–945 (1998).

    Article  CAS  Google Scholar 

  19. Amorapanth, P., Nader, K. & LeDoux, J. E. Lesions of the periacqueductal gray dissociate-conditioned stimulus elicited freezing from conditioned suppression behavior in rats. Learn. Mem. 6, 491–499 (1999).

    Article  CAS  Google Scholar 

  20. Fox, S. E. & Ranck, J. B. Jr. Electrophysiological characteristics of hippocampal complex-spike cells and theta cells. Exp. Brain Res. 41, 399–410 (1981).

    CAS  Google Scholar 

  21. Pare, D. & Gaudreau, H. Projection cells and interneurons of the lateral and basolateral amygdala: distinct firing patterns and differential relation to theta and delta rhythms in conscious cats. J. Neurosci. 16, 3334–3350 (1996).

    Article  CAS  Google Scholar 

  22. Hennevin, E., Maho, C. & Hars, B. Neuronal plasticity induced by fear conditioning is expressed during paradoxical sleep: evidence from simultaneous recordings in the lateral amygdala and the medial geniculate in rats. Behav. Neurosci. 112, 839–862 (1998).

    Article  CAS  Google Scholar 

  23. Fitts, P. M. & Posner, M. I. Human Performance (Brooks/Cole, Belmont, California, 1967).

    Google Scholar 

  24. Quirk, G. J., Armony, J. L., Repa, J. C., Li, X. F. & LeDoux, J. E. Emotional memory: a search for sites of plasticity. Cold Spring Harb. Symp. Quant. Biol. 61, 247–257 (1996).

    Article  CAS  Google Scholar 

  25. Doron, N. N. & LeDoux, J. E. Organization of projections to the lateral amygdala from auditory and visual areas of the thalamus in the rat. J. Comp. Neurol. 412, 383–409 (1999) [erratum, J. Comp. Neurol. 417, 385–386, 2000].

    Article  CAS  Google Scholar 

  26. Doron, N. N. & LeDoux, J. E. Cells in the posterior thalamus project to both amygdala and temporal cortex: a quantitative retrograde double-labeling study in the rat. J. Comp. Neurol . 425, 257–274 (2000).

    Article  CAS  Google Scholar 

  27. Bordi, F. & LeDoux, J. Sensory tuning beyond the sensory system: an initial analysis of auditory properties of neurons in the lateral amygdaloid nucleus and overlying areas of the striatum. J. Neurosci. 12, 2493–2503 (1992).

    Article  CAS  Google Scholar 

  28. Romanski, L. M., LeDoux, J. E., Clugnet, M. C. & Bordi, F. Somatosensory and auditory convergence in the lateral nucleus of the amygdala. Behav. Neurosci. 107, 444–450 (1993).

    Article  CAS  Google Scholar 

  29. Schafe, G. E. et al. Activation of ERK/MAP kinase in the amygdala is required for memory consolidation of pavlovian fear conditioning. J. Neurosci. 20, 8177–8187 (2000).

    Article  CAS  Google Scholar 

  30. Wilensky, A. E., Schafe, G. E. & LeDoux, J. E. The amygdala modulates memory consolidation of fear-motivated inhibitory avoidance learning but not classical fear conditioning. J. Neurosci. 20, 7059–7066 (2000).

    Article  CAS  Google Scholar 

  31. Pearce, J. M. & Hall, G. A model for Pavlovian learning: variations in the effectiveness of conditioned but not of unconditioned stimuli. Psychol. Rev. 87, 532–552 (1980).

    Article  CAS  Google Scholar 

  32. LeDoux, J. E., Romanski, L. M. & Xagoraris, A. E. Indelibility of subcortical emotional memories. J. Cogn. Neurosci. 1, 238–243 (1989).

    Article  CAS  Google Scholar 

  33. Edeline, J.-M. & Weinberger, N. M. Associative retuning in the thalamic source of input to the amygdala and auditory cortex: receptive field plasticity in the medial division of the medial geniculate body. Behav. Neurosci. 106, 81–105 (1992).

    Article  CAS  Google Scholar 

  34. McEchron, M. D., McCabe, P. M., Green, E. J., Llabre, M. M. & Schneiderman, N. Simultaneous single unit recording in the medial nucleus of the medial geniculate nucleus and amygdaloid central nucleus throughout habituation, acquisition, and extinction of the rabbit's classically conditioned heart rate. Brain Res. 682, 157–166 (1995).

    Article  CAS  Google Scholar 

  35. Weinberger, N. M. Learning-induced changes of auditory receptive fields. Curr. Opin. Neurobiol. 3, 570–577 (1993).

    Article  CAS  Google Scholar 

  36. McGaugh, J. L. Memory—a century of consolidation. Science 287, 248–251 (2000).

    Article  CAS  Google Scholar 

  37. Armony, J. L., Quirk, G. J. & LeDoux, J. E. Differential effects of amygdala lesions on early and late plastic components of auditory cortex spiketrains during fear conditioning. J. Neurosci. 18, 2592–2601 (1998).

    Article  CAS  Google Scholar 

  38. Poremba, A. & Gabriel, M. Amygdalar efferents initiate auditory thalamic discriminative training-induced neuronal activity. J. Neurosci. 21, 270–278 (2001).

    Article  CAS  Google Scholar 

  39. Bordi, F. & LeDoux, J. E. Response properties of single units in areas of rat auditory thalamus that project to the amygdala. II. Cells receiving convergent auditory and somatosensory inputs and cells antidromically activated by amygdala stimulation. Exp. Brain Res. 98, 275–286 (1994).

    Article  CAS  Google Scholar 

  40. Helmstetter, F. J. & Bellgowan, P. S. Effects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats. Behav. Neurosci. 108, 1005–1009 (1994).

    Article  CAS  Google Scholar 

  41. Muller, J., Corodimas, K. P., Fridel, Z. & LeDoux, J. E. Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit CS and to contextual stimuli. Behav. Neurosci. 111, 683–691 (1997).

    Article  CAS  Google Scholar 

  42. Lee, H. & Kim, J. J. Amygdalar NMDA receptors are critical for new fear learning in previously fear-conditioned rats. J. Neurosci. 18, 8444–8454 (1998).

    Article  CAS  Google Scholar 

  43. 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).

    Article  CAS  Google Scholar 

  44. Schafe, G. E. & LeDoux, J. E. Memory consolidation of auditory pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala. J. Neurosci. 20, RC96 (2000).

    Article  CAS  Google Scholar 

  45. Bailey, D. J., Sun, W., Thompson, R. F., Kim, J. J. & Helmstetter, F. J. Acquisition of fear conditioning in rats requires the synthesis of mRNA in the amygdala. Behav. Neurosci. 113, 276–282 (1999).

    Article  CAS  Google Scholar 

  46. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic, Sydney, Australia, 1986).

    Google Scholar 

  47. Gothard, K. M., Skaggs, W. E., Moore, K. M. & McNaughton, B. L. Binding of hippocampal CA1 neural activity to multiple reference frames in a landmark-based navigation task. J. Neurosci. 16, 823–835 (1996).

    Article  CAS  Google Scholar 

  48. McNaughton, B. L., O'Keefe, J. & Barnes, C. A. The stereotrode: a new technique for simultaneous isolation of several single units in the central nervous system from multiple unit records. J. Neurosci. Methods 8, 391–397 (1983).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported in part by NIH grants RO1 MH46516, KO2 MH00956, R37 MH38774 and F31 MH11659. The work was also supported by a grant from the W.M. Keck Foundation to N.Y.U.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Christopher Repa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Repa, J., Muller, J., Apergis, J. et al. Two different lateral amygdala cell populations contribute to the initiation and storage of memory. Nat Neurosci 4, 724–731 (2001). https://doi.org/10.1038/89512

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/89512

This article is cited by

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