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De Grazia, M.

Publications and source records attributed to De Grazia, M..

2 recordsLinked to original sources

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

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.

neuroscience↗

Automated derivation of mean field models from spiking neural networks for the simulation of brain dynamics

A mean field model (MFM) is a mesoscopic description of neuronal population dynamics that can reduce the complexity of neural microcircuits into equations preserving key functional properties. The generation of a MFM is a complex mathematical process that starts with the incorporation of single neuron input/output relationships and local connectivity. Once neuron electroresponsiveness and synaptic properties are defined, in principle, the process can be automatized. Here we develop a tool for automatic MFM derivation from biophysically grounded spiking networks (Auto-MFM) by performing micro-to-mesoscale parameter remapping, estimating input/output relationships specific for different neuronal populations (i.e., transfer functions), and optimizing transfer function parameters. Auto-MFM was tested using a spiking cerebellar circuit as a generative model. The cerebellar MFM derived with Auto-MFM accurately reproduced cerebellar population dynamics of the corresponding spiking network, matching mean and time-varying firing rates across a wide range of stimulation patterns. Auto-MFM allowed us to model and explore physiological and pathological circuit variants; indeed, it was used to map ataxia-related structural connectivity alterations of the cerebellar network, in which Purkinje cells with simplified dendritic structure altered the cerebellar connectivity. Furthermore, Auto-MFM was used to create a library of cerebellar MFMs by sweeping the level of the excitatory conductance at mossy fiber - granule cell synapse, which is altered in several neuropathologies. Auto-MFM is thus proving a flexible and powerful tool to generate region-specific MFMs of healthy and pathological brain networks to be embedded in brain digital models.

neuroscience↗