Cerebellar learning properties are modulated by the CRF receptor

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.