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A biologically-grounded cerebellar spiking network model with realistic synaptic transmission captures complex circuit dynamics.

De Grazia, M.; Benozzo, D.; Rodarie, D.; Marchetti, F.; D'Angelo, E.; Casellato, C.

2026-05-14 neuroscience
10.64898/2026.05.12.724100 bioRxiv
Show abstract

Cerebellar neural circuit dynamics rely on a rich repertoire of synaptic and excitability mechanisms, which are thought to determine network computation in physiological and pathological conditions. In this work, we develop and validate a biologically-grounded spiking neural network of the cerebellar cortex, embedding key mechanisms of cellular excitability and synaptic transmission, and assess their impact on signal processing. Neuronal input-output functions, short-term synaptic plasticity, receptor-specific kinetics, and NMDA channel voltage-dependent gating were calibrated against detailed multicompartmental models through automatic tuning procedures. Incorporating these realistic biological properties allowed the network model to simulate key features observed in recordings from acute cerebellar slices. The neuronal discharge and local field potentials elicited by mossy fiber stimulation faithfully reproduced the natural patterns with millisecond precision. Then, selective receptor switch-off revealed the contribution of NMDA, GABA, and AMPA receptors to the frequency-dependent input-output function of the granular layer and Purkinje cells, linking previous empirical findings to specific synaptic mechanisms. This model combines high computational performance with biological realism and offers a computationally efficient framework to investigate neurophysiological phenomena and the neural correlates of behavior in large-scale long-lasting simulations, such as those needed to address the neural underpinnings of learning and of cerebellar pathologies.

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