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Sunday, July 19 • 8:00pm - 9:00pm
P10: Using Adaptive Exponential Integrate-and-Fire neurons to study general principles of patho-topology of cerebellar networks

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Maurizio De Pitta, Jose Angel Ornella Rodrigues, Juan Sustacha, Giulio Bonifazi, Alicia Nieto-Reyes, Sivan Kanner, Miri Goldin, Ari Barzilai, Paolo Bonifazi

(A-T) is an example of a systemic genetic disease impacting the cerebellar circuit’s structure and function. Kanner et al. [1] have shown how the A-T phenotype in mice correlates with severe glial atrophy and increased synaptic markers, resulting in altered cerebellar networks’ dynamics. In particular, experiments in cerebellar cultures showed a disruption of networks’ synchronizations, which were recovered by replacements of A-T glial cells with healthy ones. Notably, the only presence of healthy astrocyte was sufficient to restore the physiological synaptic puncta level between mutated neurons. In the intact cerebellar circuits, glial morphological alterations and an increase in inhibitory synaptic connectivity markers were first reported and correlated (preliminary unpublished results) with an increase in the complex spiking of the Purkinje cells (PCs). In order to understand and model these structural-functional circuits’ alterations, we developed a simplified model of the cerebellar circuit. To this aim, we adopt the adaptive Exponential Integrate-and-Fire (aEIF) neuron model in different parameter configurations, to capture essential functional features of four different cell types: granule cells and excitatory neurons of the inferior olive (IONs); Purkinje cells and inhibitory neurons of the Deep Cerebellar Nuclei (DPNNs). Next, we explore different degrees of connectivity and synaptic weights, the dynamics of the simplified cerebellar circuitry. Our simulations suggest that the concomitant increased number of inhibitory connections from PC to DPNNs, and from DPNNs to IONs, ultimately results in a disinhibited IONs dynamics. As a consequence, IONs provide a higher rate of excitation to PCs within the cerebellar loop, which finally leads to higher complex spiking frequency in PCs. These results provide new insights into the dysfunctional A-T cerebellar dynamics and open a new perspective for targeted pharmacological treatments.

Acknowledgements

We thank the 'Junior Leader' Fellowship Program by 'la Caixa' Banking Foundation (Grant LCF/BQ/LI18/11630006).

References

1. Kanner S, Goldin M, Galron R, et al. Astrocytes restore connectivity and synchronization in dysfunctional cerebellar networks. Proc. Natl. Acad. Sci. USA. 2018,

Speakers
avatar for Maurizio De Pitta

Maurizio De Pitta

Research Fellow, Basque Center for Applied Mathematics
I am part of the Group in Mathematical, Computational, and Experimental Neuroscience at the Basque Center for Applied Mathematics in Bilbao (Spain). My expertise is in the study of neuron-glial interactions in the healthy and diseased brain. I use multi-disciplinary approaches at the cross-roads of Physics and Computer Science, and collaborate with biologists, engineers, and medical doctors, to harness the... Read More →


Sunday July 19, 2020 8:00pm - 9:00pm CEST
Slot 19