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

Jimena L. Frontera, Romain W. Sala, Ioana A. Georgescu, Hind Baba Aissa, Marion N. d’Almeida, Daniela Popa and Clément Léna ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36943-w

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