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Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition

Abstract

Fear conditioning involves the induction of long-term potentiation (LTP) of excitatory synaptic transmission in the lateral amygdala, a brain structure which is tightly controlled by GABAergic inhibition. Here we show that dopamine gates the induction of LTP in the mouse lateral amygdala by suppressing feedforward inhibition from local interneurons. Our findings provide a cellular mechanism for the dopaminergic modulation of fear conditioning and indicate that suppression of feedforward inhibition represents a key mechanism for the induction of associative synaptic plasticity in the lateral amygdala.

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Figure 1: Inhibitory synaptic transmission prevents the induction of LTP.
Figure 2: Dopamine enables the induction of LTP in the absence of picrotoxin.
Figure 3: Dopamine depresses feedforward inhibition.
Figure 4: Dopamine decreases inhibition onto projection neurons.
Figure 5: Dopamine increases inhibition onto interneurons.
Figure 6: Two proposed mechanisms, based on the present results, by which dopamine might modulate feedforward inhibitory circuits gating LTP induction in the LA.

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Acknowledgements

We are grateful to B. Gähwiler, M. Scanziani and E. Seifritz for helpful discussions and comments on the manuscript. Supported by the Borderline Personality Disorder Research Foundation and the Swiss National Science Foundation (3100-067749.02).

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Correspondence to Andreas Lüthi.

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Bissière, S., Humeau, Y. & Lüthi, A. Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. Nat Neurosci 6, 587–592 (2003). https://doi.org/10.1038/nn1058

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