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


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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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).

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