Reference code: | PT/FB/BL-2018-085.04 |
Location: | BF-GMS
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Title:
| The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity
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Publication year: | 2024
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URL:
| https://doi.org/10.1038/s41380-024-02412-z
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Abstract/Results: | ABSTRACT:
Fear-related pathologies are among the most prevalent psychiatric conditions, having inappropriate learned fear and resistance to extinction as cardinal features. Exposure therapy represents a promising therapeutic approach, the efficiency of which depends on inter-individual variation in fear extinction learning, which neurobiological basis is unknown. We characterized a model of extinction learning, whereby fear-conditioned mice were categorized as extinction (EXT)-success or EXT-failure, according to their inherent ability to extinguish fear. In the lateral amygdala, GluN2A-containing NMDAR are required for LTP and stabilization of fear memories, while GluN2B-containing NMDAR are required for LTD and fear extinction. EXT-success mice showed attenuated LTP, strong LTD and higher levels of synaptic GluN2B, while EXT-failure mice showed strong LTP, no LTD and higher levels of synaptic GluN2A. Neurotrophin 3 (NT3) infusion in the lateral amygdala was sufficient to rescue extinction deficits in EXT-failure mice. Mechanistically, activation of tropomyosin receptor kinase C (TrkC) with NT3 in EXT-failure slices attenuated lateral amygdala LTP, in a GluN2B-dependent manner. Conversely, blocking endogenous NT3-TrkC signaling with TrkC-Fc chimera in EXT-success slices strengthened lateral amygdala LTP. Our data support a key role for the NT3-TrkC system in inter-individual differences in fear extinction in rodents, through modulation of amygdalar NMDAR composition and synaptic plasticity.
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Accessibility: | Document exists in file
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Language:
| eng
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Author:
| Masella, G.
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Secondary author(s):
| Silva, F., Corti, E., Azkona, G., Madeira, M. F., Tomé, Â. R., Ferreira, S. G., Cunha, R. A., Duarte, C. B., Santos, M
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Document type:
| Article
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Number of reproductions:
| 1
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Reference:
| Masella, G., Silva, F., Corti, E., Azkona, G., Madeira, M. F., Tomé, Â. R., Ferreira, S. G., Cunha, R. A., Duarte, C. B., & Santos, M. (2024). The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity. Molecular Psychiatry, 10.1038/s41380-024-02412-z. Advance online publication. https://doi.org/10.1038/s41380-024-02412-z
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2-year Impact Factor: | 11|2022
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Impact factor notes: | Impact factor not available yet for 2024
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Times cited: | 0|2024-02-19
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Indexed document: | Yes
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Quartile: | Q1
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Keywords: | Fear extinction learning / GluN2B-containing NMDAR / amygdala NT3-TrkC
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The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity |