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The cerebellum regulates fear extinction through thalamo-prefrontal cortex interactions in male mice

Author

Listed:
  • Jimena L. Frontera

    (PSL Research University)

  • Romain W. Sala

    (PSL Research University)

  • Ioana A. Georgescu

    (PSL Research University)

  • Hind Baba Aissa

    (PSL Research University)

  • Marion N. d’Almeida

    (PSL Research University)

  • Daniela Popa

    (PSL Research University)

  • Clément Léna

    (PSL Research University)

Abstract

Fear extinction is a form of inhibitory learning that suppresses the expression of aversive memories and plays a key role in the recovery of anxiety and trauma-related disorders. Here, using male mice, we identify a cerebello-thalamo-cortical pathway regulating fear extinction. The cerebellar fastigial nucleus (FN) projects to the lateral subregion of the mediodorsal thalamic nucleus (MD), which is reciprocally connected with the dorsomedial prefrontal cortex (dmPFC). The inhibition of FN inputs to MD in male mice impairs fear extinction in animals with high fear responses and increases the bursting of MD neurons, a firing pattern known to prevent extinction learning. Indeed, this MD bursting is followed by high levels of the dmPFC 4 Hz oscillations causally associated with fear responses during fear extinction, and the inhibition of FN-MD neurons increases the coherence of MD bursts and oscillations with dmPFC 4 Hz oscillations. Overall, these findings reveal a regulation of fear-related thalamo-cortical dynamics by the cerebellum and its contribution to fear extinction.

Suggested Citation

  • Jimena L. Frontera & Romain W. Sala & Ioana A. Georgescu & Hind Baba Aissa & Marion N. d’Almeida & Daniela Popa & Clément Léna, 2023. "The cerebellum regulates fear extinction through thalamo-prefrontal cortex interactions in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36943-w
    DOI: 10.1038/s41467-023-36943-w
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    1. Kenta M. Hagihara & Olena Bukalo & Martin Zeller & Ayla Aksoy-Aksel & Nikolaos Karalis & Aaron Limoges & Tanner Rigg & Tiffany Campbell & Adriana Mendez & Chase Weinholtz & Mathias Mahn & Larry S. Zwe, 2021. "Intercalated amygdala clusters orchestrate a switch in fear state," Nature, Nature, vol. 594(7863), pages 403-407, June.
    2. Ed S. Lein & Michael J. Hawrylycz & Nancy Ao & Mikael Ayres & Amy Bensinger & Amy Bernard & Andrew F. Boe & Mark S. Boguski & Kevin S. Brockway & Emi J. Byrnes & Lin Chen & Li Chen & Tsuey-Ming Chen &, 2007. "Genome-wide atlas of gene expression in the adult mouse brain," Nature, Nature, vol. 445(7124), pages 168-176, January.
    3. Cyril Dejean & Julien Courtin & Nikolaos Karalis & Fabrice Chaudun & Hélène Wurtz & Thomas C. M. Bienvenu & Cyril Herry, 2016. "Prefrontal neuronal assemblies temporally control fear behaviour," Nature, Nature, vol. 535(7612), pages 420-424, July.
    4. Jimena Laura Frontera & Hind Baba Aissa & Romain William Sala & Caroline Mailhes-Hamon & Ioana Antoaneta Georgescu & Clément Léna & Daniela Popa, 2020. "Bidirectional control of fear memories by cerebellar neurons projecting to the ventrolateral periaqueductal grey," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    5. Minagi Ozawa & Patrick Davis & Jianguang Ni & Jamie Maguire & Thomas Papouin & Leon Reijmers, 2020. "Experience-dependent resonance in amygdalo-cortical circuits supports fear memory retrieval following extinction," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    6. Sophie Bagur & Julie M. Lefort & Marie M. Lacroix & Gaëtan Lavilléon & Cyril Herry & Mathilde Chouvaeff & Clara Billand & Hélène Geoffroy & Karim Benchenane, 2021. "Breathing-driven prefrontal oscillations regulate maintenance of conditioned-fear evoked freezing independently of initiation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
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