Speaker
Description
Research on parkinsonism underscored the central roles of basal ganglia alterations and dopamine level reductions in symptom emergence [7]. Recent studies, however, hint at cerebellar involvement in altered parkinsonian brain activity [8, 2]. To unravel the role of this region in parkinsonism, we developed an innovative multiscale, multiarea brain model, aiming to investigate neural dynamics in both healthy and parkinsonian states. This model integrates microcircuits of the BG [4] and cerebellum [3], employing spiking neural networks (SNN), which also simulate dopamine depletion mechanisms, and includes a three-equation mass model of the cortex, thalamus and reticular nucleus, reproducing the loops these areas engage in [9]. After validation with respect to the stand-alone SNN circuits, [3, 4], we tested the model first in a generic motor state. We found that the resemblance between our simulations and experimental data [5, 6], as indicated by matching population firing rates and enhanced beta band oscillations, was notably more pronounced when dopamine-depletion effects occurred in both the cerebellum and BG (compared to BG alone), emphasizing a more direct involvement of the cerebellum in parkinsonism. Lastly, we simulated a behavior protocol, eyeblink classical conditioning, incorporating plastic mechanisms at the cerebellar level [1] under both physiological and pathological conditions. Results indicate that despite altered cellular structure, the cerebellum exhibits adaptive capabilities, albeit with reduced effectiveness compared to the physiological state. In summary, our findings stress the significance of recognizing the cerebellum’s role in parkinsonism to fully grasp the intricate neural mechanisms underlying the related disorders.
References
[1] Antonietti et al. In: IEEE Transactions on Biomedical Engineering 63.1 (2015), pp. 210–219.
[2] Bostan and Strick. In: Nature Reviews Neuroscience 19.6 (2018), pp. 338–350.
[3] Geminiani et al. In: Frontiers in computational neuroscience (2019), p. 68.
[4] Lindahl and Kotaleski. In: Eneuro 3.6 (2016).
[5] Mallet et al. In: Journal of neuroscience 28.52 (2008), pp. 14245–14258.
[6] Menardy et al. In: Cerebral Cortex 29.4 (2019), pp. 1752–1766.
[7] Obeso et al. In: Trends in Neurosciences 23 (Oct. 2000), S8–S19.
[8] Wu and Hallett. In: Brain 136.3 (2013), pp. 696–709.
[9] Yousif et al. In: Frontiers in Human Neuroscience 14 (2020), p. 55
Acknowledgements
This project has received funding from the European Union’s Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3) and Horizon Europe Program for Research and Innovation under the Grant Agreement No. 101147319 (EBRAINS 2.0). AA is funded by the Project “EBRAINS-Italy (European Brain ReseArch INfrastructureS-Italy),” granted by European Union – NextGenerationEU (Italian PNRR, Mission 4, “Education and Research” - Component 2, “From research to Business” Investment 3.1 - Call for tender No. 3264 of Dec 28, 2021, of Italian Ministry of University and Research), Project code IR0000011, Concession Decree No. 117 of June 21, 2022, adopted by the Italian Ministry of University and Research, CUP B51E22000150006).
| Preferred form of presentation | Talk (& optional poster) |
|---|---|
| Topic area | Models and applications |
| Keywords | Parkinsonism, Cerebellum, Basal Ganglia |
| Speaker time zone | UTC+1 |
| I agree to the copyright and license terms | Yes |
| I agree to the declaration of honor | Yes |
