Cerebellum and cognition: Does the rodent cerebellum participate in cognitive functions?

Shipman, Megan L.; Green, John T.

doi:10.1016/j.nlm.2019.02.006

Cited by 34 publications

(20 citation statements)

References 205 publications

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“…Similar to the synchronous activation of cell ensembles that control individual muscles (Welsh et al, 1995), cerebellar firing properties and circuit patterning could also instruct non-motor communication across higher-order brain centers. Our extracellular recordings included cells in lobules VI-VII of the vermis and CrusI and CrusII of the hemispheres, regions known to be involved in motor behaviors, with additional and growing evidence that they contribute to various non-motor behaviors (Koziol et al, 2014;McAfee et al, 2019;Shipman and Green, 2019). Based on the abnormalities we uncovered, we speculate that the function of cerebellar dystrophin complexes could mediate such functions in vivo, during behavior.…”

Section: Discussionmentioning

confidence: 99%

In vivo cerebellar circuit function is disrupted in an mdx mouse model of Duchenne muscular dystrophy

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Miterko

Arancillo

et al. 2019

Disease Models &Amp; Mechanisms

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Duchenne muscular dystrophy (DMD) is a debilitating and ultimately lethal disease involving progressive muscle degeneration and neurological dysfunction. DMD is caused by mutations in the dystrophin gene, which result in extremely low or total loss of dystrophin protein expression. In the brain, dystrophin is heavily localized to cerebellar Purkinje cells, which control motor and nonmotor functions. In vitro experiments in mouse Purkinje cells revealed that loss of dystrophin leads to low firing rates and high spiking variability. However, it is still unclear how the loss of dystrophin affects cerebellar function in the intact brain. Here, we used in vivo electrophysiology to record Purkinje cells and cerebellar nuclear neurons in awake and anesthetized female mdx (also known as Dmd) mice. Purkinje cell simple spike firing rate is significantly lower in mdx mice compared to controls. Although simple spike firing regularity is not affected, complex spike regularity is increased in mdx mutants. Mean firing rate in cerebellar nuclear neurons is not altered in mdx mice, but their local firing pattern is irregular. Based on the relatively wellpreserved cytoarchitecture in the mdx cerebellum, our data suggest that faulty signals across the circuit between Purkinje cells and cerebellar nuclei drive the abnormal firing activity. The in vivo requirements of dystrophin during cerebellar circuit communication could help explain the motor and cognitive anomalies seen in individuals with DMD. This article has an associated First Person interview with the first author of the paper.

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Section: Discussionmentioning

confidence: 99%

In vivo cerebellar circuit function is disrupted in an mdx mouse model of Duchenne muscular dystrophy

Stay

Miterko

Arancillo

et al. 2019

Disease Models &Amp; Mechanisms

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“…Concerning the function of the cerebellum, although behaviour and clinical neurology studies have suggested that the cerebellum contributes to movement 19 , motor control 19 , 20 , and muscular coordination 21 , a growing body of neuroimaging studies have demonstrated that it is also related to cognition and executive functions (e.g. working memory, strategy formation, organising, and cognitive flexibility) 22 , 23 . Task-fMRI and r-fMRI results have suggested that motor representation is related to the activation of the anterior lobules of the cerebellum and lobule VIII 24 , whereas the posterior lobules of the cerebellum, such as lobules VI–Crus I, lobules Crus II–VIIb, and lobule IX 24 , are thought to be crucial for cognition representation.…”

Section: Introductionmentioning

confidence: 99%

The indispensable role of the cerebellum in visual divergent thinking

Gao

Liu

Zhang

et al. 2020

Sci Rep

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Recent research has shown that the cerebellum is involved not only in motor control but also in higher-level activities, which are closely related to creativity. This study aimed to explore the role of the cerebellum in visual divergent thinking based on its intrinsic activity. To this end, we selected the resting-state fMRI data of high- (n = 22) and low-level creativity groups (n = 22), and adopted the voxel-wise, seed-wise, and dynamic functional connectivity to identify the differences between the two groups. Furthermore, the topological properties of the cerebello-cerebral network and their relations with visual divergent thinking were calculated. The voxel-wise functional connectivity results indicated group differences across the cerebellar (e.g. lobules VI, VIIb, Crus I, and Crus II) and cerebral regions (e.g. superior frontal cortex, middle frontal cortex, and inferior parietal gyrus), as well as the cerebellar lobules (e.g. lobules VIIIa, IX, and X) and the cerebral brain regions (the cuneus and precentral gyrus). We found a significant correlation between visual divergent thinking and activities of the left lobules VI, VIIb, Crus I, and Crus II, which are associated with executive functions. Our overall results provide novel insight into the important role of the cerebellum in visual divergent thinking.

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“…Sex-specific differences in circuit coupling resulting from endocannabinoid regulation of neuronal activation may contribute to hypotheses of baseline and stress-effects on behavioral performance differences in cerebellar tasks, like eyeblink conditioning 47,80,81 . Understanding regional specificity within the cerebellum is critical, as extensive work has shown that distinct cerebellar cortical regions exhibit differential functional connectivity with cerebrum in humans and animals 52,82 . Though this study did not investigate www.nature.com/scientificreports www.nature.com/scientificreports/ differences across cortical regions, the question becomes increasingly important as we begin to understand more about how cerebellar signaling projects outwards through the deep nuclei to regulate cerebral signaling (cf.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to eyeblink conditioning, the cerebellum is gaining traction as an important node in cognitive processes. Tasks of spatial navigation, working memory, and cognitive flexibility are most notable (e.g., spontaneous/learned alternation, Morris water maze, set-shifting, discrimination learning, among others) 52 . Specifically, the Crus I area investigated in the current study has been implicated in evidence-accumulation decision making 53 and autism spectrum-related behaviors such as social impairment 54 in mouse models.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Aberrations To Cerebellar Endocannabinoids Induced By Early-Life Stress

Moussa-Tooks

Larson

Gimeno

et al. 2020

Sci Rep

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emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling with studies on stress-induced endocannabinoid dysregulation focusing on cerebral changes that are temporally proximal to stressors. Little is known about temporally distal and sexspecific effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Following limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids, related lipids, and mRNA were assessed, and behavioral performance evaluated. Regional and sex-specific effects were present at baseline and following earlylife stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar interpositus nucleus in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Cerebellar interpositus transcriptomics revealed substantial sex effects, with minimal stress effects. Stress did impair novel object recognition in both sexes and social preference in females. Accordingly, the cerebellar endocannabinoid system exhibits robust sex-specific differences, malleable through early-life stress, suggesting the role of endocannabinoids and stress to sexual differentiation of the brain and cerebellarrelated dysfunctions. In humans, poor prenatal and early postnatal care is a major developmental stressor commonly found in low socioeconomic groups 1,2. Such stress can affect neurodevelopment during critical periods of early life, greatly impacting both cognitive and behavioral outcomes in adulthood 3-8. Many studies have examined the effects of stress on the cerebrum, such as the hippocampus, and found both neural and behavioral aberrations 9. However, compelling evidence shows that the cerebellum, which is bidirectionally interconnected with vast regions of the forebrain 10-14 , is also profoundly affected by stress 15,16. the Stress Response Evidence suggests that developmental impairments in humans and rats are mediated by poor regulation of homeostatic systems as a function of early-life stress 17,18. One such homeostatic mechanism is the stress response. Stress typically results in hypothalamic release of corticotropin releasing hormone (CRH), which stimulates the pituitary gland to secrete adrenocorticotropic hormone (ACTH) and, in turn, prompts the adrenal cortex to release cortisol (or the rat homologue corticosterone; CORT). CORT enters the bloodstream and acts on various nervous system targets, which provides negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis, including the hypothalamus. CORT binds to glucocorticoid receptors in hypothalamic paraventricular nucleus (PVN) neurons, a process that ultimately suppresses the HPA axis by inhibiting the continued release of glutamate. The endocannabino...

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Cerebellum and cognition: Does the rodent cerebellum participate in cognitive functions?

Cited by 34 publications

References 205 publications

In vivo cerebellar circuit function is disrupted in an mdx mouse model of Duchenne muscular dystrophy

In vivo cerebellar circuit function is disrupted in an mdx mouse model of Duchenne muscular dystrophy

The indispensable role of the cerebellum in visual divergent thinking

Long-Term Aberrations To Cerebellar Endocannabinoids Induced By Early-Life Stress

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