Toward a cerebello-thalamo-cortical computational model of spinocerebellar ataxia

Kumar, Gajendra; Eddie, Chi Him

doi:10.1016/j.neunet.2023.01.045

Cited by 4 publications

(3 citation statements)

References 98 publications

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“…A detailed mechanism of how cerebellar stimulation improves motor dysfunction remains to be understood. A recent modeling study suggests that cerebellar DBS can restore the reduced inhibitory input resulting from Purkinje neuron degeneration in ataxic mice [ 172 ], indicating cerebellar stimulation has the potential to modulate synaptic activity and downstream neuronal pathways for motor control. Proper synaptic activity at both pre- and postsynaptic levels relies heavily on ion channels [ 173 ].…”

Section: Emerging Therapies For Cerebellar Ataxia Impinge On Ion Chan...mentioning

confidence: 99%

Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia

Huang

Shakkottai

2023

Life

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In degenerative neurological disorders such as Parkinson’s disease, a convergence of widely varying insults results in a loss of dopaminergic neurons and, thus, the motor symptoms of the disease. Dopamine replacement therapy with agents such as levodopa is a mainstay of therapy. Cerebellar ataxias, a heterogeneous group of currently untreatable conditions, have not been identified to have a shared physiology that is a target of therapy. In this review, we propose that perturbations in cerebellar Purkinje neuron intrinsic membrane excitability, a result of ion channel dysregulation, is a common pathophysiologic mechanism that drives motor impairment and vulnerability to degeneration in cerebellar ataxias of widely differing genetic etiologies. We further propose that treatments aimed at restoring Purkinje neuron intrinsic membrane excitability have the potential to be a shared therapy in cerebellar ataxia akin to levodopa for Parkinson’s disease.

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Section: Emerging Therapies For Cerebellar Ataxia Impinge On Ion Chan...mentioning

confidence: 99%

Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia

Huang

Shakkottai

2023

Life

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“…2021; Gallego et al, 2020), thalamic (Sauerbrei et al, 2020;Logiaco et al, 2021;Yu et al, 2022) and cerebellar signals (Kumar and Ma, 2023). Sensory feedback is critical in finely controlled movements, as the MC has to integrate multiple sensory information including proprioception, vision and tactile sensation, to generate precise commands.…”

Section: Introductionmentioning

confidence: 99%

“…Alternatively, there is a growing recognition of the role that external inputs play in shaping motor cortical activity (Figure 1C). Situated within a vast and distributed brain network, the MC integrates various external inputs, such as sensory feedback (Sauerbrei et al, 2020; Kalidindi et al, 2021; Gallego et al, 2020), thalamic (Sauerbrei et al, 2020; Logiaco et al, 2021; Yu et al, 2022) and cerebellar signals (Kumar and Ma, 2023). Sensory feedback is critical in finely controlled movements, as the MC has to integrate multiple sensory information including proprioception, vision and tactile sensation, to generate precise commands.…”

Section: Introductionmentioning

confidence: 99%

Internal Dynamics Interact with Proprioceptive Feedback During Movement Execution in an RNN Model of Motor Cortex

Jiang,

Bu,

Zheng

et al. 2023

Preprint

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Neuronal population responses in motor cortex display low-dimensional rotational patterns, where neural state rotates consistently during movement execution. These patterns are thought to arise from the internal dynamics within motor cortex. However, external inputs such as proprioception also shape motor cortical activity. To investigate the roles of internal dynamics and proprioceptive feedback, we constructed an inhibitory stabilized network, with excitatory recurrence stabilized by inhibition, designed to control an arm model performing delayed reach task. The optimized network generated patterns similar to those observed in motor cortex data, demonstrating our model’s plausibility. We designed a disruption strategy to dissect the contribution of internal dynamics and proprioceptive feedback, and found that disrupting internal dynamics significantly diminished rotational dynamics, whereas disrupting proprioceptive feedback led to ceaseless movement. Thus, internal dynamics dominate, while proprioceptive feedback fine-turns cortical pattern generation. Analysis of the ablation experiment revealed that proprioceptive feedback improved the robustness against noisy initial conditions by decreasing tangling in neural activity. Finally, our network still exhibited rotational dynamics when the arm moved at a constant speed, suggesting that these rotations could be prominent features of motor cortical activity.

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Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke

Au,

Wu,

Kumar

et al. 2024

Brain, Behavior, and Immunity

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Toward a cerebello-thalamo-cortical computational model of spinocerebellar ataxia

Cited by 4 publications

References 98 publications

Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia

Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia

Internal Dynamics Interact with Proprioceptive Feedback During Movement Execution in an RNN Model of Motor Cortex

Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke

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