A multi-layer mean-field model of the cerebellum embedding microstructure and population-specific dynamics

PLoS Comput Biol. 2023 Sep 1;19(9):e1011434. doi: 10.1371/journal.pcbi.1011434. eCollection 2023 Sep.

Abstract

Mean-field (MF) models are computational formalism used to summarize in a few statistical parameters the salient biophysical properties of an inter-wired neuronal network. Their formalism normally incorporates different types of neurons and synapses along with their topological organization. MFs are crucial to efficiently implement the computational modules of large-scale models of brain function, maintaining the specificity of local cortical microcircuits. While MFs have been generated for the isocortex, they are still missing for other parts of the brain. Here we have designed and simulated a multi-layer MF of the cerebellar microcircuit (including Granule Cells, Golgi Cells, Molecular Layer Interneurons, and Purkinje Cells) and validated it against experimental data and the corresponding spiking neural network (SNN) microcircuit model. The cerebellar MF was built using a system of equations, where properties of neuronal populations and topological parameters are embedded in inter-dependent transfer functions. The model time constant was optimised using local field potentials recorded experimentally from acute mouse cerebellar slices as a template. The MF reproduced the average dynamics of different neuronal populations in response to various input patterns and predicted the modulation of the Purkinje Cells firing depending on cortical plasticity, which drives learning in associative tasks, and the level of feedforward inhibition. The cerebellar MF provides a computationally efficient tool for future investigations of the causal relationship between microscopic neuronal properties and ensemble brain activity in virtual brain models addressing both physiological and pathological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysics
  • Cerebellum*
  • Mice
  • Neocortex*
  • Neurons
  • Purkinje Cells

Grants and funding

This research 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) to ED, CGWK, FP and AD, and under the Marie Sklodowska-Curie grant agreement No. 892175 to YZ. CGWK received funding from BRC (#BRC704/CAP/CGW), MRC (#MR/S026088/1), Ataxia UK, MS Society (#77), Wings for Life (#169111). This research has also received funding from Centro Fermi project “Local Neuronal Microcircuits” to ED. Special acknowledgement to EBRAINS and FENIX for informatic support and infrastructure. RL, and AG have been supported by Human Brain Project SGA3. This work was also supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022) to ED, CGWK, and CC, and Project EBRAINS-Italy (IR00011) - (M4C2 Line 3.1 of the PNRR, Action 3.1.1 - CUP B51E22000150006) to ED and CC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.