Corticotropin-releasing factor (CRF) and its type 1 receptor (CRFR1) play an important role in the responses to stressful challenges. Despite the well established expression of CRFR1 in granular cells (GrCs), its role in procedural motor performance and memory formation remains elusive. To investigate the role of CRFR1 expression in cerebellar GrCs, we used a mouse model depleted of CRFR1 in these cells. We detected changes in the cellular learning mechanisms in GrCs depleted of CRFR1 in that they showed changes in intrinsic excitability and long-term synaptic plasticity. Analysis of cerebella transcriptome obtained from KO and control mice detected prominent alterations in the expression of calcium signaling pathways components. Moreover, male mice depleted of CRFR1 specifically in GrCs showed accelerated Pavlovian associative eye-blink conditioning, but no differences in baseline motor performance, locomotion, or fear and anxiety-related behaviors. Our findings shed light on the interplay between stress-related central mechanisms and cerebellar motor conditioning, highlighting the role of the CRF system in regulating particular forms of cerebellar learning.

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Keywords Cerebellum, CRF, CRFR1, Eyeblink conditioning, Granule cells
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Journal The Journal of Neuroscience
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Ezra-Nevo, G. (Gili), Prestori, F, Locatelli, F. (Francesca), Soda, T. (Teresa), ten Brinke, M.M, Engel, M. (Mareen), … Chen, A. (Alon). (2018). Cerebellar learning properties are modulated by the CRF receptor. The Journal of Neuroscience, 38(30), 6751–6765. doi:10.1523/JNEUROSCI.3106-15.2018