The Deep Cerebellar Nuclei to Raphe pathway: its function, anatomy and behavioral implications

Diplôme Master The Deep Cerebellar Nuclei to Raphe pathway: its function, anatomy and behavioral implications eng 2026-06-24 2026-06-10 author Brüggimann Cyrus Valric 928531 director Andrianarivelo Njiva Andry 0000-0002-6369-4201 416856 Département de neurosciences fondamentales (NEUFO) director Bellone Camilla 0000-0002-6774-6275 559161 Département de neurosciences fondamentales (NEUFO) 49 The cerebellum is increasingly recognized as a key node in non-motor circuits, yet the behavioral significance of its projections to the midbrain raphe nuclei remains unexplored. We hypothesized that the deep cerebellar nuclei (DCN) regulate affective and cognitive states through a direct monosynaptic pathway to the raphe. In male C57BL/6J mice, monosynaptic retrograde tracing revealed that the dentate nucleus preferentially targets the dorsal raphe nucleus (DRN) and caudal linear nucleus, whereas the fastigial and interposed nuclei innervate the median raphe nucleus, indicating target-specific topographic organization. We then combined chemogenetic silencing, fiber photometry, and optogenetic terminal activation to probe the pathway’s function. Chemogenetic silencing increased anxiety-like avoidance in the elevated plus maze and selectively impaired social novelty discrimination in the three-chamber test, without affecting motor coordination, general locomotion, or basic sociability. Fiber photometry showed elevated DCN-raphe calcium activity durin open-arm occupancy, but not during consummatory, social, or conditioned aversive events. Optogenetic activation of DCN terminals in the DRN produced context-dependent darting behavior in the open arms and increased exploratory approach frequency. These converging findings identify the DCN-raphe pathway as a context-dependent modulator of anxiety-like exploratory behavior and social novelty processing, broadening the functional map of cerebellar non-motor circuits. Dorsal raphe Deep cerebellar nuclei Anatomy Behavior Optogenetics Chemogenetics Fiber photometry Light-sheet microscopy Dewey 616.8 Master of Fundamental Neuroscience 53 Département de neurosciences fondamentales 21A false 973 Les dysfonctions synaptiques du cerveau 971 fc9231d3-d976-43c4-b0da-7252cfb0ccb7 Master thesis Public The_Raphe_to_Deep_Cerebellar_Nuclei.pdf 4146416 application/pdf CC BY-NC-SA-4.0 Main body c8b178ccc4d366e653f06f30d49c580d9fed37cf14bb654dae007e846fb6cee6 2c61605d-257a-4eff-8d9b-3cec407c3a5f Appendix Public Annex1_Statistics_report.pdf 3487364 application/pdf CC BY-NC-SA-4.0 Statistical report 9bb9bdc1e355e367863f20ff3048bc4e107edbdb981ce8c5d32cf85c8d9960b5 c8f0504c-5bc1-449b-ae5b-66a67fcb7e4d Appendix Public Annex2_Individual_datapoints.pdf 6868765 application/pdf CC BY-NC-SA-4.0 All datapoints report b16be276ef231fea550e29c8aa9e48f15eb01e81fbe2a615717790e48785ec6d a96e536c-357e-40ab-adaf-417a34cdc326 Appendix Public Annex4_Sideprojects.pdf 3471469 application/pdf CC BY-NC-SA-4.0 Side projects developed during the master 7327129c64029d5afd36080622f71565eca09a9e0fd4d6016d0001b6b73530aa 3b05967a-6772-45a0-8a7c-6150ed887572 Appendix Public Annex3_Confirmation_histology_annot.pdf 326729513 application/pdf CC BY-NC-SA-4.0 Full resolution microscopy slides 319c14398b0ddd5ac9845d00a4e0001d71e3abc66a2ac4d154cf15d61ca1c0f9 d0daabe8-6e7d-4843-a85f-92410016e89d Appendix Public Annex6_Text_to_speech_accessibility.mp3 19269086 audio/mpeg CC BY-NC-SA-4.0 Text to speech version of the thesis for accessibility purposes, with figures description e502265e1f1e2507b9d3c30f7b9cfaf2326c728e72d7f100319c3131da4798b8 Vignette Public Screenshot_20260712_114632.png 187543 image/png openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Brüggimann, Cyrus Valric

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