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Neuron. 2019 Aug 27. pii: S0896-6273(19)30697-X. doi: 10.1016/j.neuron.2019.08.013. [Epub ahead of print]

Structural and Functional Remodeling of Amygdala GABAergic Synapses in Associative Fear Learning.

Author information

1
Department of Pharmacology, Medical University of Innsbruck, Innsbruck 6020, Austria.
2
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
3
Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, University of Innsbruck, Innsbruck 6020, Austria.
4
Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck 6020, Austria.
5
Center for Brain Research, Department of Molecular Neurosciences, Medical University of Vienna, Vienna 1090, Austria.
6
Department of Pharmacology, Medical University of Innsbruck, Innsbruck 6020, Austria; Center for Brain Research, Department of Molecular Neurosciences, Medical University of Vienna, Vienna 1090, Austria.
7
Institute of Science and Technology Austria, Klosterneuburg 3400, Austria.
8
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland; University of Basel, Basel, Switzerland.
9
Department of Pharmacology, Medical University of Innsbruck, Innsbruck 6020, Austria. Electronic address: francesco.ferraguti@i-med.ac.at.

Abstract

Associative learning is thought to involve different forms of activity-dependent synaptic plasticity. Although previous studies have mostly focused on learning-related changes occurring at excitatory glutamatergic synapses, we found that associative learning, such as fear conditioning, also entails long-lasting functional and structural plasticity of GABAergic synapses onto pyramidal neurons of the murine basal amygdala. Fear conditioning-mediated structural remodeling of GABAergic synapses was associated with a change in mIPSC kinetics and an increase in the fraction of synaptic benzodiazepine-sensitive (BZD) GABAA receptors containing the α2 subunit without altering the intrasynaptic distribution and overall amount of BZD-GABAA receptors. These structural and functional synaptic changes were partly reversed by extinction training. These findings provide evidence that associative learning, such as Pavlovian fear conditioning and extinction, sculpts inhibitory synapses to regulate inhibition of active neuronal networks, a process that may tune amygdala circuit responses to threats.

KEYWORDS:

GABA; GABA(A) receptors; extinction; freeze-fracture; gating kinetics; inhibition; learning; plasticity; synapse

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