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SIGNIFICANCE STATEMENT Although it is known that the corticotropin-releasing factor type 1 receptor (CRFR 1) is highly expressed in the cerebellum, little attention has been given to its role in cerebellar functions in the behaving animal. 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. Moreover, male mice depleted of CRFR 1 specifically in GrCs showed accelerated Pavlovian associative eye-blink conditioning, but no differences in baseline motor performance, locomotion, or fear and anxiety-related behaviors. Analysis of cerebella transcriptome obtained from KO and control mice detected prominent alterations in the expression of calcium signaling pathways components. We detected changes in the cellular learning mechanisms in GrCs depleted of CRFR 1 in that they showed changes in intrinsic excitability and long-term synaptic plasticity.
To investigate the role of CRFR 1 expression in cerebellar GrCs, we used a mouse model depleted of CRFR 1 in these cells.
Despite the well established expression of CRFR 1 in granular cells (GrCs), its role in procedural motor performance and memory formation remains elusive.
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Download Figure 2-2, TIF fileĬorticotropin-releasing factor (CRF) and its type 1 receptor (CRFR 1) play an important role in the responses to stressful challenges. (e) Analysis of percentage of cells expressing GFP (CRFR 1) that co-express tdTomato (Δα6- Cre) signal in extra-cerebellar structures reveals low co-localization in extra-cereballar structures (N= 2 CRFR 1-GFP+tdTomato: yellow, CRFR 1-GFP not co-localized with tdTomato: green). (d) Representative images of the cortex, hippocampus, DCN, pontine and thalamus of the CRFR 1 GFP x α6-tdTomato reporter mouse line. (c) Since granular cells are too crowded to allow for cell by cell count, Mander’s coefficient was used to assess overlap of GFP signal with tdTomato signal Mander’s coefficient reveals that nearly all GFP positive pixels are co-stained with tdTomato, indicating CRFR 1 expressing GrCs (GFP) also express the α6 subunit (tdTomato, n = 9 images/slices, N= 2). (b) Co-localization of tdTomato and GFP expressing cells in the granular layer reveals an almost complete overlap between the α6 subunit (tdTomato red) and CRFR 1 (GFP) indicating CRFR 1 is expressed in the vast majority of GrCs and that the penetrance of α6- Cre will allow for a complete ablation of CRFR 1 from GrCs. (a) Reporter mouse line expressing GFP under the CRFR 1 promoter and tdTomato in Δα6- Cre expressing cells was generated by cross-breeding CRFR 1 GFP with Δα6- Cre and floxed stop tdTomato mice. But this time you are about to prepare a cutting-edge farming system, with top technology and a much larger production.Evaluation of CRFR 1 cKO mouse model. Of course the old kind of knowledge is still important, especially if you have the hand of it.
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