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Abstract
Corticotropin-releasing factor (CRF) is mainly secreted from the hypothalamic paraventricular nuclei and plays a crucial role in stress-related responses. Recent studies have reported that CRF is a neuromodulator in the central nervous system. In the cerebellum, CRF is essential for the induction of long-term depression (LTD) at the parallel fiber-Purkinje cell synapses. Given that LTD is thought to be one of the fundamental mechanisms of motor learning, CRF may affect motor learning. However, the role of CRF in motor learning in vivo remains unclear. In this study, we aimed to examine the role of CRF in motor learning. This was achieved through a series of behavioral experiments involving the in vivo administration of CRF and its antagonists. Rats injected with CRF directly into the cerebellum exhibited superior performance on the rotarod test, especially during initial training phases, compared to control subjects. Conversely, rats receiving a CRF receptor antagonist demonstrated reduced endurance on the rotating rod compared to controls. Notably, CRF mRNA expression levels in the cerebellum did not show significant variance between the CRF-injected and control groups. These findings imply a critical role of endogenous CRF in cerebellar motor learning and suggest that exogenous CRF can augment this process. (199 words)
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1 Tokai University, Institute of Innovative Science and Technology, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); National Center of Neurology and Psychiatry, Department of Molecular Therapy, National Institute of Neuroscience, Kodaira, Japan (GRID:grid.419280.6) (ISNI:0000 0004 1763 8916)
2 Tokai University School of Medicine, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Josai University, Course of Pharmacy, Graduated School of Pharmaceutical Sciences, Sakado, Japan (GRID:grid.411949.0) (ISNI:0000 0004 1770 2033)
3 Tokai University, Institute of Innovative Science and Technology, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Tokai University School of Medicine, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
4 Tokai University School of Medicine, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
5 Tokai University, Institute of Innovative Science and Technology, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Tokai University School of Medicine, Department of Physiology, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)