Behavioral effects of neonatal lesions on the cerebellar system

Lalonde, Robert; Strazielle, C.

doi:10.1016/j.ijdevneu.2015.04.007

Cited by 14 publications

(10 citation statements)

References 126 publications

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“…For example, early cerebellar damage has been associated with a reduction in the modulation of dopamine release in the medial prefrontal cortex as well as the reorganization of cerebello-cortical loops (Rogers et al, 2011, 2013). In rodent models, compensatory responses and changes in the activity of brain-related regions have been found to be much greater when cerebellar injuries occurred within the neonatal period (Lalonde and Strazielle, 2015). In children, prenatal and neonatal lesions of the cerebellum generate motor dysfunction (Stoodley and Limperopoulos, 2016) but also cognitive and emotional deficits such as increased anxiety and aggressive behavior (Watson et al, 2018); autistic-like symptomatology in language and social behavior as well as selective attention deficits (Steinlin et al, 2003; Schmahmann et al, 2007).…”

Section: The Cerebellum: Too Many Neurons Just To Not Walk Like a Robotmentioning

confidence: 99%

A Working Hypothesis for the Role of the Cerebellum in Impulsivity and Compulsivity

Miquel

Nicola

Gil‐Miravet

et al. 2019

Front. Behav. Neurosci.

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Growing evidence associates cerebellar abnormalities with several neuropsychiatric disorders in which compulsive symptomatology and impulsivity are part of the disease pattern. Symptomatology of autism, addiction, obsessive-compulsive (OCD), and attention deficit/hyperactivity (ADHD) disorders transcends the sphere of motor dysfunction and essentially entails integrative processes under control of prefrontal-thalamic-cerebellar loops. Patients with brain lesions affecting the cortico-striatum thalamic circuitry and the cerebellum indeed exhibit compulsive symptoms. Specifically, lesions of the posterior cerebellar vermis cause affective dysregulation and deficits in executive function. These deficits may be due to impairment of one of the main functions of the cerebellum, implementation of forward internal models of the environment. Actions that are independent of internal models may not be guided by predictive relationships or a mental representation of the goal. In this review article, we explain how this deficit might affect executive functions. Additionally, regionalized cerebellar lesions have been demonstrated to impair other brain functions such as the emergence of habits and behavioral inhibition, which are also altered in compulsive disorders. Similar to the infralimbic cortex, clinical studies and research in animal models suggest that the cerebellum is not required for learning goal-directed behaviors, but it is critical for habit formation. Despite this accumulating data, the role of the cerebellum in compulsive symptomatology and impulsivity is still a matter of discussion. Overall, findings point to a modulatory function of the cerebellum in terminating or initiating actions through regulation of the prefrontal cortices. Specifically, the cerebellum may be crucial for restraining ongoing actions when environmental conditions change by adjusting prefrontal activity in response to the new external and internal stimuli, thereby promoting flexible behavioral control. We elaborate on this explanatory framework and propose a working hypothesis for the involvement of the cerebellum in compulsive and impulsive endophenotypes.

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Section: The Cerebellum: Too Many Neurons Just To Not Walk Like a Robotmentioning

confidence: 99%

A Working Hypothesis for the Role of the Cerebellum in Impulsivity and Compulsivity

Miquel

Nicola

Gil‐Miravet

et al. 2019

Front. Behav. Neurosci.

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“…Purkinje cells send projections to the cerebellar nuclei, which consists of both excitatory and inhibitory neurons, as well as some direct projections to the vestibular nuclei ( Sillitoe and Joyner, 2007 ). These circuits are important for motor coordination and balance as well as social behaviors including ultrasonic vocalization (USV) in neonatal pups ( Fujita et al, 2008 ; Lalonde and Strazielle, 2015 ). Interestingly, the contribution of the cerebellum to these behaviors is initiated before circuit rewiring is completed ( Lalonde and Strazielle, 2015 ).…”

Section: Resultsmentioning

confidence: 99%

Maturation of Purkinje cell firing properties relies on neurogenesis of excitatory neurons

Heijden

Lackey

Perez

et al. 2021

eLife

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Preterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty. Excitatory granule cells, the most numerous neuron type in the brain, are especially vulnerable and likely instigate disease by impairing the function of their targets, the Purkinje cells. Here, we use regional genetic manipulations and in vivo electrophysiology to test whether excitatory neurons establish the firing properties of Purkinje cells during postnatal mouse development. We generated mutant mice that lack the majority of excitatory cerebellar neurons and tracked the structural and functional consequences on Purkinje cells. We reveal that Purkinje cells fail to acquire their typical morphology and connectivity, and that the concomitant transformation of Purkinje cell firing activity does not occur either. We also show that our mutant pups have impaired motor behaviors and vocal skills. These data argue that excitatory cerebellar neurons define the maturation time-window for postnatal Purkinje cell functions and refine cerebellar-dependent behaviors.

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“… 98 Mutations in Rora have been associated with impaired in motor functions and motor coordination. 99 …”

Section: Resultsmentioning

confidence: 99%

Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum

Goncalves

Southey

Rodriguez-Zas

2018

Bioinform Biol Insights

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The psychostimulant amphetamine can be prescribed to ameliorate the symptoms of narcolepsy, attention-deficit hyperactivity disorder and to facilitate weight loss. This stimulant can also have negative effects including toxicity and addiction risk. The impact of amphetamine on gene networks is partially understood and this study addresses this gap in consideration of the physical activity. The striata of mice exposed to either amphetamine or saline treatment were compared in a mouse line selected for home cage physical overactivity, a phenotype that can be mitigated with amphetamine, and in a contemporary control line using RNA-seq. Genes presenting opposite expression patterns between treatments across lines included a pseudogene of coiled-coil-helix-coiled-coil-helix domain containing 2 gene (Chchd2), ribonuclease P RNA component H1 (Rpph1), short stature homeobox 2 (Shox2), transient receptor potential melastatin 6 (Trpm6), and tumor necrosis factor receptor superfamily, member 9 (Tnfrsf9). Genes presenting consistent treatment patterns across lines, albeit at different levels of significance included cholecystokinin (Cck), vasoactive intestinal polypeptide (Vip), arginine vasopressin (Avp), oxytocin/neurophysin (Oxt), thyrotropin releasing hormone (Trh), neurotensin (Nts), angiotensinogen (Agt), galanin (Gal), prolactin receptor (Prlr), and calcitonin receptor (Calcr). Potassium inwardly rectifying channel, subfamily J, member 6 (Kcnj6), and retinoic acid-related (RAR)-related orphan receptor alpha (Rora) were similarly differentially expressed between treatments across lines. Functional categories enriched among the genes presenting line-dependent amphetamine effect included genes coding for neuropeptides and associated with memory and neuroplasticity and synaptic signaling, energy, and redox processes. A line-dependent association between amphetamine exposure and the synaptic signaling genes neurogranin (Nrgn) and synaptic membrane exocytosis 1(Rims1) was highlighted in the gene networks. Our findings advance the understanding of molecular players and networks affected by amphetamine in support of the development of activity-targeted therapies that may capitalize on the benefits of this psychostimulant.

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Behavioral effects of neonatal lesions on the cerebellar system

Cited by 14 publications

References 126 publications

A Working Hypothesis for the Role of the Cerebellum in Impulsivity and Compulsivity

A Working Hypothesis for the Role of the Cerebellum in Impulsivity and Compulsivity

Maturation of Purkinje cell firing properties relies on neurogenesis of excitatory neurons

Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum

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