A limited cerebellar contribution to suprasecond timing across differing task demands.

Heslin, Kelsey A.; Purnell, Jessica R.; Corte, Benjamin J. De; Parker, Krystal L.

doi:10.1037/bne0000531

Cited by 4 publications

(5 citation statements)

References 54 publications

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“…This may be essential as abnormal function of the cerebrocerebellar pathway is implicated in a myriad of neuropsychiatric illnesses like schizophrenia. During interval timing, previous work from our lab has reported inconsistent results from inactivation of the lateral cerebellar nucleus with muscimol (Heslin et al, 2022;Parker et al, 2017). Given the role for the cerebellum in learning, studies investigating cerebellar involvement in Prickle2 −/− mice on the interval timing task may still be warranted at developmental timepoints, or with altered temporal durations, cues, or expected responses timing.…”

Section: Discussionmentioning

confidence: 80%

Disruption of the non-canonical wnt gene PRICKLE2 leads to cerebellar Purkinje cell abnormalities while cerebellar-mediated behaviors remain intact.

Abbott

Hardie

Walsh

et al. 2023

Preprint

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Autism spectrum disorders (ASD) involve brain wide abnormalities that contribute to a constellation of symptoms including behavioral inflexibility, cognitive dysfunction, learning impairments, altered social interactions, and perceptive time difficulties. Although a single genetic variation does not cause ASD, genetic variations such as one involving a non-canonical Wnt signaling gene, Prickle2, has been found in individuals with ASD. Previous work looking into phenotypes of Prickle2 knock-out (Prickle2−/−) and heterozygous mice (Prickle2−/+) suggest patterns of behavior similar to individuals with ASD including altered social interaction and behavioral inflexibility. Growing evidence implicates the cerebellum in ASD. As Prickle2 is expressed in the cerebellum, this animal model presents a unique opportunity to investigate the cerebellar contribution to autism-like phenotypes. Here, we explore cerebellar structural and physiological abnormalities in animals with Prickle2 disruption using immunohistochemistry, whole-cell patch clamp electrophysiology, and several cerebellar-associated motor and timing tasks, including interval timing and eyeblink conditioning. Histologically, Prickle2−/− mice have significantly more empty spaces or gaps between Purkinje cells in the posterior lobules and a decreased propensity for Purkinje Cells to fire action potentials. These structural cerebellar abnormalities did not impair cerebellar-associated behaviors as eyeblink conditioning and interval timing remained intact. Therefore, although Prickle−/− mice show classic phenotypes of ASD, they do not recapitulate the involvement of the adult cerebellum and may not represent the pathophysiological heterogeneity of the disorder.

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Section: Discussionmentioning

confidence: 80%

Disruption of the non-canonical wnt gene PRICKLE2 leads to cerebellar Purkinje cell abnormalities while cerebellar-mediated behaviors remain intact.

Abbott

Hardie

Walsh

et al. 2023

Preprint

Self Cite

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“…Whereas the above computational work proposes a role for how the cerebellum affects cerebral areas during learning across sub- and supra-second timescales, recent experimental work shows that pharmacological inactivation of the lateral cerebellum does not impair supra-second peak-interval timing tasks in rats ( Heslin et al, 2022 ). Using a nose-poke task to earn a water reward, the rats were trained to estimate a target interval.…”

Section: Models Of Cerebro-cerebellar Circuitsmentioning

confidence: 99%

“…Using a nose-poke task to earn a water reward, the rats were trained to estimate a target interval. Heslin et al (2022) tested the rats’ ability to learn a new supra-second target duration by introducing a longer interval once the animals had already been trained on a shorter interval. No deficit was observed in the animals to estimate the new target interval.…”

Section: Models Of Cerebro-cerebellar Circuitsmentioning

confidence: 99%

“…No deficit was observed in the animals to estimate the new target interval. One could argue that while the computational model by Boven et al (2023) tests the acquisition of a novel task, the experimental work by Heslin et al (2022) tests the generalisation of an already learned behaviour to a novel interval. Additionally, a requirement of the peak interval task is that the rate of nose pokes peaks around the target interval time.…”

Section: Models Of Cerebro-cerebellar Circuitsmentioning

confidence: 99%

“…The use of stereotyped behaviours such as grooming in rodents has been shown to contribute to the ability to facilitate timing accuracy ( Gouvea et al, 2014 ; Safaie et al, 2020 ). This suggests that the absence of impairment in the task by Heslin et al (2022) could be due to stereotyped behaviours being performed during the target interval, or because the nose poke movement was not stereotyped and therefore not cerebellar dependent. Moreover, research in humans has identified differences in projections coming from dorsal vs. ventral dentate nucleus, with the latter being implicated in cognitive behaviours ( Shipman and Green, 2020 ).…”

Section: Models Of Cerebro-cerebellar Circuitsmentioning

confidence: 99%

See 2 more Smart Citations

Cerebellar contributions across behavioural timescales: a review from the perspective of cerebro-cerebellar interactions

Boven,

Cerminara

2023

Front. Syst. Neurosci.

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Performing successful adaptive behaviour relies on our ability to process a wide range of temporal intervals with certain precision. Studies on the role of the cerebellum in temporal information processing have adopted the dogma that the cerebellum is involved in sub-second processing. However, emerging evidence shows that the cerebellum might be involved in suprasecond temporal processing as well. Here we review the reciprocal loops between cerebellum and cerebral cortex and provide a theoretical account of cerebro-cerebellar interactions with a focus on how cerebellar output can modulate cerebral processing during learning of complex sequences. Finally, we propose that while the ability of the cerebellum to support millisecond timescales might be intrinsic to cerebellar circuitry, the ability to support supra-second timescales might result from cerebellar interactions with other brain regions, such as the prefrontal cortex.

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Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact

Abbott,

Hardie,

Walsh

et al. 2024

Cerebellum

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A limited cerebellar contribution to suprasecond timing across differing task demands.

Cited by 4 publications

References 54 publications

Disruption of the non-canonical wnt gene PRICKLE2 leads to cerebellar Purkinje cell abnormalities while cerebellar-mediated behaviors remain intact.

Disruption of the non-canonical wnt gene PRICKLE2 leads to cerebellar Purkinje cell abnormalities while cerebellar-mediated behaviors remain intact.

Cerebellar contributions across behavioural timescales: a review from the perspective of cerebro-cerebellar interactions

Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact

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