Bidirectional control of fear memories by cerebellar neurons projecting to the ventrolateral periaqueductal grey

• Published in: Nature communications Vol. 11; no. 1; p. 5207
• Main Authors: Frontera, Jimena Laura, Baba Aissa, Hind, Sala, Romain William, Mailhes-Hamon, Caroline, Georgescu, Ioana Antoaneta, Léna, Clément, Popa, Daniela
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.10.2020; Nature Portfolio
• Subjects: 13/1; 13/51; 14/19; 14/35; 14/63; 631/378/1457; 631/378/3920; 64/60; 9/30; Humanities and Social Sciences; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18953-0

Fear conditioning is a form of associative learning that is known to involve different brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memories, indicating an important role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. Moreover, FN-vlPAG projections also modulate extinction learning. We also found a FN-parafascicular thalamus pathway, which may relay cerebellar influence to the amygdala and modulates anxiety behaviors. Overall, our results reveal multiple contributions of the cerebellum to the emotional system. The cerebellum has a role in motor control, but may also contribute to other functions. Here the authors demonstrate a role for the cerebellar fastigial nucleus projection onto ventrolateral periaqueductal grey neurons during fear acquisition.