Bidirectional control of fear memories by the cerebellum through the ventrolateral periaqueductal grey

• Published in: bioRxiv
• Main Authors: Frontera, Jimena L, Hind Baba Aïssa, Sala, Romain William, Mailhes-Hamon, Caroline, Georgescu, Ioana Antoaneta, Léna, Clément, Popa, Daniela
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 20.02.2020
• Subjects: Amygdala; Anxiety; Associative learning; Cerebellum; Fear conditioning; Glutamatergic transmission; Parafascicular nucleus; Prefrontal cortex; Thalamus; γ-Aminobutyric acid
• DOI: 10.1101/2020.02.19.956375

Fear conditioning is a form of associative learning that is known to involve 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 memory, indicating a role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. In addition, we found that a FN - thalamic parafascicular nucleus pathway, which may relay cerebellar influence to the amygdala, is involved in anxiety and fear expression but not in fear memory. Our results reveal the contributions to the emotional system of the cerebellum, which exerts a potent control on the strength of the fear memory through excitatory FN-vlPAG projections.