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Calcium-permeable AMPA receptors mediate long-term potentiation in interneurons in the amygdala

Abstract

Fear conditioning is a paradigm that has been used as a model for emotional learning in animals1. The cellular correlate of fear conditioning is thought to be associative N -methyl-D-aspartate (NMDA) receptor-dependent synaptic plasticity within the amygdala1,2,3. Here we show that glutamatergic synaptic transmission to inhibitory interneurons in the basolateral amygdala is mediated solely by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In contrast to AMPA receptors at inputs to pyramidal neurons, these receptors have an inwardly rectifying current–voltage relationship, indicative of a high permeability to calcium4,5. Tetanic stimulation of inputs to interneurons caused an immediate and sustained increase in the efficacy of these synapses. This potentiation required a rise in postsynaptic calcium, but was independent of NMDA receptor activation. The potentiation of excitatory inputs to interneurons was reflected as an increase in the amplitude of the GABAA-mediated inhibitory synaptic current in pyramidal neurons. These results demonstrate that excitatory synapses onto interneurons within a fear conditioning circuit show NMDA-receptor independent long-term potentiation. This plasticity might underlie the increased synchronization of activity between neurons in the basolateral amygdala after fear conditioning6.

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Figure 1: Properties of pyramidal cells and interneurons in the basolateral amygdala.
Figure 2: Spontaneous EPSCs in pyramidal cells and interneurons are glutamatergic.
Figure 3: Synaptic currents mediated by AMPA receptors in interneurons are inwardly rectifying.
Figure 4: Long-term potentiation in interneurons requires an increase in postsynaptic calcium concentration.
Figure 5: Disynaptic LTP of inhibitory synaptic currents in pyramidal cells.

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References

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

    Article  CAS  Google Scholar 

  2. Davis, M., Rainnie, D. & Cassell, M. Neurotransmission in the rat amygdala related to fear and anxiety. Trends Neurosci. 17, 208–214 (1994).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  4. Washburn, M. S., Numberger, M., Zhang, S. & Dingledine, R. Differential dependence on GluR2 expression of three characteristic features of AMPA receptors. J. Neurosci. 17, 9393–9406 (1997).

    Article  CAS  Google Scholar 

  5. Geiger, J. R. P. et al. Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS. Neuron 15, 193–204 (1995).

    Article  CAS  Google Scholar 

  6. Quirk, G. J., Repa, C. & LeDoux, J. E. Fear conditioning enhances short-latency auditory responses of lateral amygdaloid neurons: parallel recordings in the freely behaving rat. Neuron 15, 1029–1039 (1995).

    Article  CAS  Google Scholar 

  7. Washburn, M. S. & Moises, H. C. Electrophysiological and morphological properties of rat basolateral amygdaloid neurons in vitro . J. Neurosci. 12, 4066–4079 (1992).

    Article  CAS  Google Scholar 

  8. Rainnie, D. G., Asprodini, E. K. & Shinnick-Gallagher, P. Intracellular recordings from morphologically identified neurons of the basolateral amygdala. J. Neurosci. 69, 1350–1362 (1993).

    CAS  Google Scholar 

  9. Connors, B. W. & Gutnick, M. J. Intrinsic firing patterns of diverse neocortical neurons. Trends Neurosci. 13, 99–103 (1990).

    Article  CAS  Google Scholar 

  10. McCormick, D. A., Connors, B. W., Lighthall, J. W. & Prince, D. A. Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J. Neurophysiol. 54, 782–806 (1985).

    Article  CAS  Google Scholar 

  11. Hestrin, S. Different glutamate receptor channels mediate fast excitatory synaptic currents in inhibitory and excitatory cortical neurons. Neuron 11, 1083–1091 (1993).

    Article  CAS  Google Scholar 

  12. Smith, B. N. & Dudek, F. E. Amino acid-mediated regulation of spontaneous synaptic activity patterns in the rat basolateral amygdala. J. Neurophysiol. 76, 1958–1967 (1996).

    Article  CAS  Google Scholar 

  13. Mahanty, N. K. & Sah, P. The physiology of excitatory synapses in the lateral and basolateral amygdala. Soc. Neurosci. Abstr. 22(1996).

  14. Sah, P., Hestrin, S. & Nicoll, R. A. Properties of excitatory postsynaptic currents in interneurones in rat hippocampus in vitro . J. Physiol. (Lond.) 430, 605–616 (1990).

    Article  CAS  Google Scholar 

  15. Geiger, J. R. P., Lubke, J., Roth, A., Frotscher, M. & Jonas, P. Submillisecond AMPA receptor-mediated signalling at a principal neuron–interneuron synapse. Neuron 18, 1009–1023 (1997).

    Article  CAS  Google Scholar 

  16. Farb, C. R., Aoki, C. & LeDoux, J. E. Differential localization of NMDA and AMPA receptor subunits in the lateral and basal nuclei of the amygdala: a light and electron microscopic study. J. Comp. Neurol. 362, 86–108 (1995).

    Article  CAS  Google Scholar 

  17. Hollmann, M. & Heinemann, S. Cloned glutamate receptors. Annu. Rev. Neurosci. 17, 31–108 (1994).

    Article  CAS  Google Scholar 

  18. Jonas, P., Racca, C., Sakmann, B., Seeburg, P. H. & Monyer, H. Differences in Ca2+ permeability of AMPA-type glutamate receptor channels in neocortical neurons caused by differential GluR-B subunit expression. Neuron 12, 1281–1289 (1994).

    Article  CAS  Google Scholar 

  19. Jonas, P. & Burnashev, N. Molecular mechanisms controlling calcium entry through AMPA-type glutamate receptor channels. Neuron 15, 987–990 (1995).

    Article  CAS  Google Scholar 

  20. Racca, C., Catania, M. V., Monyer, H. & Sakmann, B. Expression of AMPA-glutamate receptor B subunit in rat hippocampal neurons. Eur. J. Neurosci. 8, 1580–1590 (1996).

    Article  CAS  Google Scholar 

  21. McBain, C. J. & Dingledine, R. Heterogeneity of synaptic glutamate receptors on CA3 stratum radiatum interneurons of rat hippocampus. J. Physiol. (Lond.) 462, 373–392 (1993).

    Article  CAS  Google Scholar 

  22. Isa, T., Itazawa, S., Iino, M., Tsuzuki, K. & Ozawa, S. Distribution of neurones expressing inwardly rectifying and Ca2+-permeable AMPA receptors in rat hippocampal slices. J. Physiol. (Lond.) 491, 719–733 (1996).

    Article  CAS  Google Scholar 

  23. McDonald, A. J. Localization of AMPA glutamate receptor subunits in subpopulations of non-pyramidal neurons in the rat basolateral amygdala. Neurosci. Lett. 208, 175–178 (1996).

    Article  CAS  Google Scholar 

  24. Malenka, R. C., Kauer, J. A., Perkel, D. J. & Nicoll, R. A. The impact of postsynaptic calcium on synaptic transmission — its role in long term potentiation. Trends Neurosci. 12, 444–450 (1989).

    Article  CAS  Google Scholar 

  25. Rainnie, D. G., Asprodini, E. K. & Schinnick-Gallagher, P. Inhibitory transmission in the basolateral amygdala. J. Neurophysiol. 66, 999–1009 (1991).

    Article  CAS  Google Scholar 

  26. Jia, Z. et al. Enhanced LTP in mice deficient in the AMPA receptor GluR2. Neuron 17, 945–956 (1996).

    Article  CAS  Google Scholar 

  27. Gu, J. G., Albuquerque, C., Lee, C. J. & MacDermott, A. B. Synaptic strengthening through activation of Ca2+-permeable AMPA receptors. Nature 381, 793–796 (1996).

    Article  ADS  CAS  Google Scholar 

  28. 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).

    Article  CAS  Google Scholar 

  29. Cobb, S. R., Buhl, E., Halasy, K., Paulsen, O. & Somogyi, P. Synchronization of neuronal activity in the hippocampus by individual GABAergic interneurons. Nature 378, 75–78 (1995).

    Article  ADS  CAS  Google Scholar 

  30. Blanton, M. G., Lo Turco, J. J. & Kriegstein, A. R. Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex. J. Neurosci. Methods 30, 203–210 (1989).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank John Bekkers, Bob Callister and Troy Margrie for comments on the manuscript, and John Clements for help with analysis software in Axograph. P. Sah is a Charles and Sylvia Viertel Senior Medical Research Fellow. This work was supported by grants from the National Health and Medical Research Council of Australia.

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Correspondence to Pankaj Sah.

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Mahanty, N., Sah, P. Calcium-permeable AMPA receptors mediate long-term potentiation in interneurons in the amygdala. Nature 394, 683–687 (1998). https://doi.org/10.1038/29312

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