The specific role of the striatum in interval timing: The Huntington’s disease model

Lunven, Marine; Bapst, Blanche; Langavant, Laurent Cléret de; Gardelle, Vincent de; Bachoud‐Lévi, Anne‐Catherine

doi:10.1016/j.nicl.2021.102865

Cited by 13 publications

(17 citation statements)

References 73 publications

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“…HD (Paulsen et al, 2004;Beste et al, 2007;Cope et al, 2014;Rao et al, 2014;Righi et al, 2016;Agostino et al, 2017) and sometimes pre-HD (Paulsen et al, 2004;Beste et al, 2007;Zimbelman et al, 2007;Rao et al, 2014) patients show impaired temporal processing. Patients with HD tend to have difficulty with relative timing and interval discrimination, as in the current task, which is typically associated with the striatum (Lemoine et al, 2021) in contrast to absolute timing where a learned interval has to be produced which is often associated with the cerebellum (Grahn and McAuley, 2009;Grube et al, 2010;Teki et al, 2011). In recent work, the parameters of the MSN network model employed here were estimated from spiking data from WT and genetically modified HD mice (Ponzi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Ramping activity in the striatum

Ponzi

Wickens

2022

Front. Comput. Neurosci.

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Control of the timing of behavior is thought to require the basal ganglia (BG) and BG pathologies impair performance in timing tasks. Temporal interval discrimination depends on the ramping activity of medium spiny neurons (MSN) in the main BG input structure, the striatum, but the underlying mechanisms driving this activity are unclear. Here, we combine an MSN dynamical network model with an action selection system applied to an interval discrimination task. We find that when network parameters are appropriate for the striatum so that slowly fluctuating marginally stable dynamics are intrinsically generated, up and down ramping populations naturally emerge which enable significantly above chance task performance. We show that emergent population activity is in very good agreement with empirical studies and discuss how MSN network dysfunction in disease may alter temporal perception.

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Section: Discussionmentioning

confidence: 99%

Ramping activity in the striatum

Ponzi

Wickens

2022

Front. Comput. Neurosci.

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“…2-Dysfunctions of the striatum, as a target of dopaminergic pathways and an essential part of the cortico-basal ganglia-thalamic circuits, underlie fully or partially the pathophysiology of these neuro-psychiatric disorders [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76]. 3-A common feature of striatum-related disorders and the seven discussed disorders is a profound decrease in patients' ability to accurately calculate the timing of the initiation and termination of voluntary actions [205][206][207][208][209][210][211][212][213][214][215][216][217][218][219][220]. While time perception deficits have been extensively studied in the PD, SCZ, ADHD, and HD individuals, timing judgment deficits in ASD, OCD, and TS have recently begun to receive attention [205][206][207][208][209][210][211][212][213][214][215][216]<...…”

Section: Implications Of Cilia Dysfunctions In Neuropsychiatric Disor...mentioning

confidence: 99%

“…3-A common feature of striatum-related disorders and the seven discussed disorders is a profound decrease in patients' ability to accurately calculate the timing of the initiation and termination of voluntary actions [205][206][207][208][209][210][211][212][213][214][215][216][217][218][219][220]. While time perception deficits have been extensively studied in the PD, SCZ, ADHD, and HD individuals, timing judgment deficits in ASD, OCD, and TS have recently begun to receive attention [205][206][207][208][209][210][211][212][213][214][215][216][217][218][219][220].…”

Section: Implications Of Cilia Dysfunctions In Neuropsychiatric Disor...mentioning

confidence: 99%

Cilia in the Striatum Mediate Timing-Dependent Functions

Alhassen

Chen

et al. 2022

Mol Neurobiol

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Almost all brain cells contain cilia, antennae-like microtubule-based organelles. Yet, the significance of cilia, once considered vestigial organelles, in the higher-order brain functions is unknown. Cilia act as a hub that senses and transduces environmental sensory stimuli to generate an appropriate cellular response. Similarly, the striatum, a brain structure enriched in cilia, functions as a hub that receives and integrates various types of environmental information to drive appropriate motor response. To understand cilia’s role in the striatum functions, we used loxP/Cre technology to ablate cilia from the dorsal striatum of male mice and monitored the behavioral consequences. Our results revealed an essential role for striatal cilia in the acquisition and brief storage of information, including learning new motor skills, but not in long-term consolidation of information or maintaining habitual/learned motor skills. A fundamental aspect of all disrupted functions was the “time perception/judgment deficit.” Furthermore, the observed behavioral deficits form a cluster pertaining to clinical manifestations overlapping across psychiatric disorders that involve the striatum functions and are known to exhibit timing deficits. Thus, striatal cilia may act as a calibrator of the timing functions of the basal ganglia-cortical circuit by maintaining proper timing perception. Our findings suggest that dysfunctional cilia may contribute to the pathophysiology of neuro-psychiatric disorders, as related to deficits in timing perception.

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“…3-A common feature of striatum-related disorders and the seven discussed disorders is a profound decrease in patients' ability to accurately calculate the timing of the initiation and termination of voluntary actions (194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207)(208)(209). While time perception de cits have been extensively studied in the PD, SCZ, ADHD, and HD individuals, timing judgment de cits in ASD, OCD, TS have recently begun to receive attention (194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207)(208)(209).…”

Section: Implications Of Cilia Dysfunctions In Neuropsychiatric Disor...mentioning

confidence: 99%

Cilia in the Striatum Mediate Timing-Dependent Functions: Implications for Neuro-Psychiatric Disorders

Alhassen

Chen

et al. 2022

Preprint

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Almost all brain cells contain cilia, antennae-like microtubule-based organelles. Yet, the significance of cilia, once considered vestigial organelles, in the higher-order brain functions is unknown. Cilia act as a hub that senses and transduces environmental sensory stimuli to generate an appropriate cellular response. Similarly, the striatum, a brain structure enriched in cilia, functions as a hub that receives and integrates various types of environmental information to drive appropriate motor response. To understand cilia's role in the striatum functions, we used loxP/Cre technology to ablate cilia from the dorsal striatum and monitored the behavioral consequences. Our results revealed an essential role for striatal cilia in the acquisition of and brief storage of information, including learning new motor skills, but not in long-term consolidation of information or maintaining habitual/learned motor skills. A fundamental aspect of all disrupted functions was the "time perception/judgment deficit", indicating a critical role for striatal cilia in brain central "clock" function. Further, the observed behavioral deficits form a set/cluster pertaining to clinical manifestations overlapping across disorders involving the striatum functions and to exhibit timing deficits, including attention-deficit hyperactivity disorder, Huntington's disease, Parkinson's disease, schizophrenia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. Thus, striatal cilia may act as a calibrator of the basal ganglia-cortical circuit "clock" functions by maintaining proper timing perception. Accordingly, dysfunctional cilia might be a unifying factor that contributes to the pathophysiology of neuro-psychiatric disorders, as related to deficits in timing tasks performance, and may serve as therapeutic targets for these disorders.

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The specific role of the striatum in interval timing: The Huntington’s disease model

Cited by 13 publications

References 73 publications

Ramping activity in the striatum

Ramping activity in the striatum

Cilia in the Striatum Mediate Timing-Dependent Functions

Cilia in the Striatum Mediate Timing-Dependent Functions: Implications for Neuro-Psychiatric Disorders

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