A Model with Dopamine Depletion in Basal Ganglia and Cerebellum Predicts Changes in Thalamocortical Beta Oscillations.
Benedetta GambosiFrancesco Jamal SheibanMarco BiasizzoAlberto AntoniettiEgidio D'AngeloAlberto MazzoniAlessandra Laura Giulia PedrocchiPublished in: International journal of neural systems (2024)
Parkinsonism is presented as a motor syndrome characterized by rigidity, tremors, and bradykinesia, with Parkinson's disease (PD) being the predominant cause. The discovery that those motor symptoms result from the death of dopaminergic cells in the substantia nigra led to focus most of parkinsonism research on the basal ganglia (BG). However, recent findings point to an active involvement of the cerebellum in this motor syndrome. Here, we have developed a multiscale computational model of the rodent brain's BG-cerebellar network. Simulations showed that a direct effect of dopamine depletion on the cerebellum must be taken into account to reproduce the alterations of neural activity in parkinsonism, particularly the increased beta oscillations widely reported in PD patients. Moreover, dopamine depletion indirectly impacted spike-time-dependent plasticity at the parallel fiber-Purkinje cell synapses, degrading associative motor learning as observed in parkinsonism. Overall, these results suggest a relevant involvement of cerebellum in parkinsonism associative motor symptoms.
Keyphrases
- parkinson disease
- drug induced
- uric acid
- end stage renal disease
- working memory
- ejection fraction
- induced apoptosis
- prognostic factors
- newly diagnosed
- metabolic syndrome
- peritoneal dialysis
- single cell
- deep brain stimulation
- case report
- white matter
- sleep quality
- resting state
- cell therapy
- oxidative stress
- mesenchymal stem cells
- blood brain barrier
- patient reported outcomes
- functional connectivity
- endoplasmic reticulum stress
- cerebral ischemia