Lorivel T, Roy V, Hilber P
Laboratoire de Psychologie et Neurosciences de la Cognition et de l'Affectivité, EA4700, Université de Rouen, LARC Neurosciences Network, Mont-Saint-Aignan Cedex; Institut de Pharmacologie Moléculaire et Cellulaire IPMC, UMR7275 CNRS, Université de Nice - Sophia-Antipolis, Equipe "Développement de stratégies thérapeutiques innovantes pour le traitement de la dépression et de l'AVC", Valbonne; Centre d'Etudes des Transformations des Activités Physiques et Sportives, EA 3832, Université de Rouen, Mont-Saint-Aignan Cedex, France.
Genes Brain Behav. 2014 Nov;13(8):794-801. doi: 10.1111/gbb.12173. Epub 2014 Sep 19.
The Lurcher mutant mice are characterized by massive cerebellar cortex degeneration. Besides their motor and cognitive disturbances, they exhibit both exaggerated blood corticosterone (CORT) level surge and behavioral disinhibition when confronted to anxiogenic conditions (i.e. to a potential threat). In this study, we assessed if such physiological and behavioral hyperactivity was also detectable in a fear-eliciting situation (actual threat). For this purpose, the behaviors and CORT level elevations in Lurcher mice were compared with those of littermate controls in the predator exposure test: mice were exposed either to a rat (exposure) or to a brief wave of the experimenter's hand (sham exposure). While the basal CORT concentrations (24 h before testing) were not significantly different between mice of both genotypes, the post-exposure ones were higher in Lurcher than in control mice whatever the condition of the experimental design (exposure or sham exposure). Predator exposure did not provoke significant increase of CORT levels whatever the genotype. On the contrary, our data clearly showed that fear-related behaviors of cerebellar mutants facing a real threat were exacerbated in comparison to those of control mice. These results suggest that the cerebellar cortex not only participates to fear conditioning and anxiety but also actively contributes to the modulation of the innate fear-related behaviors.
蹒跚突变小鼠的特征是小脑皮质大量退化。除了运动和认知障碍外,当面对焦虑源(即潜在威胁)时,它们还表现出血液皮质酮(CORT)水平的过度激增和行为抑制解除。在本研究中,我们评估了在引发恐惧的情境(实际威胁)中是否也能检测到这种生理和行为亢进。为此,在捕食者暴露试验中,将蹒跚小鼠的行为和CORT水平升高与同窝对照小鼠进行比较:小鼠要么暴露于大鼠(暴露组),要么暴露于实验者手部的短暂挥动(假暴露组)。虽然两种基因型小鼠的基础CORT浓度(测试前24小时)没有显著差异,但无论实验设计条件如何(暴露或假暴露),暴露后蹒跚小鼠的CORT浓度均高于对照小鼠。无论基因型如何,捕食者暴露均未引起CORT水平的显著升高。相反,我们的数据清楚地表明,与对照小鼠相比,面临真正威胁的小脑突变体的恐惧相关行为加剧。这些结果表明,小脑皮质不仅参与恐惧条件反射和焦虑,而且还积极参与对先天性恐惧相关行为的调节。