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Kainate receptor-mediated heterosynaptic facilitation in the amygdala

Abstract

Prolonged low-frequency stimulation of excitatory afferents to basolateral amygdala neurons results in enduring enhancement of excitatory synaptic responses. The induction of this form of synaptic plasticity is eliminated by selective antagonists of GluR5 kainate receptors and can be mimicked by the GluR5 agonist ATPA. Kainate receptor-mediated synaptic facilitation generalizes to include inactive afferent synapses on the target neurons, and therefore contrasts with other types of activity-dependent enduring synaptic facilitation that are input-pathway specific. Such heterosynaptic spread of synaptic facilitation could account for adaptive and pathological expansion in the set of critical internal and external stimuli that trigger amygdala-dependent behavioral responses.

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Figure 1: Low-frequency EC stimulation induces long-term facilitation of the excitatory synaptic response in basolateral amygdala (BLA) neurons.
Figure 2: Effects of low-frequency train stimulation on the initial slope of EC-evoked synaptic responses and on cell firing in response to injected current.
Figure 3: GluR5, GluR6 and KA-2 kainate receptor mRNA expression by in situ hybridization histochemistry in rat brain sections at the level of the BLA.
Figure 4: GluR5 receptor-mediated component of the EC-evoked excitatory synaptic response.
Figure 5: ATPA, but not AMPA, induces persistent synaptic facilitation that is eliminated by LY382884 and perfusion with Ca2+-free solution.
Figure 6: Low-frequency train-induced heterosynaptic facilitation of NMDA receptor-mediated synaptic responses.
Figure 7: Heterosynaptic facilitation is not associated with a change in membrane properties of the postsynaptic neuron.
Figure 8: Editing of GluR5 mRNA extracted from microdissections of amygdala and hippocampus.
Figure 9: Role of Ca2+ in low-frequency train-induced heterosynaptic facilitation.

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Acknowledgements

H.L. and G.X. acknowledge the support of the Stanley Foundation Bipolar Network of the NAMI Research Institute. This work was supported in part by DAMD grant 17-00-1-0110 and USUHS RO88DG grant to H.L.

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Correspondence to Michael A. Rogawski.

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Li, H., Chen, A., Xing, G. et al. Kainate receptor-mediated heterosynaptic facilitation in the amygdala. Nat Neurosci 4, 612–620 (2001). https://doi.org/10.1038/88432

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