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Prestori, F.

Publications and source records attributed to Prestori, F..

2 recordsLinked to original sources

Complex dynamics in simplified neuronal models: reproducing Golgi cell electroresponsiveness

Brain neurons exhibit complex electroresponsive properties - including intrinsic subthreshold oscillations and pacemaking, resonance and phase-reset - which are thought to play a critical role in controlling neural network dynamics. Although these properties emerge from detailed representations of molecular-level mechanisms in \"realistic\" models, they cannot usually be generated by simplified neuronal models (although these may show spike-frequency adaptation and bursting). We report here that this whole set of properties can be generated by the extended generalized leaky integrate-and-fire (E-GLIF) neuron model. E-GLIF derives from the GLIF model family and is therefore mono-compartmental, keeps the limited computational load typical of a linear low-dimensional system, admits analytical solutions and can be tuned through gradient-descent algorithms. Importantly, E-GLIF is designed to maintain a correspondence between model parameters and neuronal membrane mechanisms through a minimum set of equations. In order to test its potential, E-GLIF was used to model a specific neuron showing rich and complex electroresponsiveness, the cerebellar Golgi cell, and was validated against experimental electrophysiological data recorded from Golgi cells in acute cerebellar slices. During simulations, E-GLIF was activated by stimulus patterns, including current steps and synaptic inputs, identical to those used for the experiments. The results demonstrate that E-GLIF can reproduce the whole set of complex neuronal dynamics typical of these neurons - including intensity-frequency curves, spike-frequency adaptation, depolarization-induced and post-inhibitory rebound bursting, spontaneous subthreshold oscillations, resonance and phase-reset, - providing a new effective tool to investigate brain dynamics in large-scale simulations.

neuroscience

Hyper-excitability and hyper-plasticity disrupt cerebellar signal transfer in the IB2 KO mouse model of autism

Autism spectrum disorders (ASD) are pervasive neurodevelopmental conditions that often involve mutations affecting synaptic mechanisms. Recently, the involvement of cerebellum in ASD has been suggested but the underlying functional alterations remained obscure. We investigated single-neuron and microcircuit properties in IB2 KO mice, which present a cerebellar phenotype associated with ASD. Granule cells showed a larger NMDA receptor-mediated current and enhanced intrinsic excitability raising the excitatory/inhibitory balance. Furthermore, the spatial organization of granular layer responses to mossy fibers shifted from a Mexican hat to stovepipe hat profile, with stronger excitation in the core and weaker inhibition in the surround. Finally, the size and extension of long-term synaptic plasticity was remarkably increased. These results show for the first time that hyper-excitability and hyper-plasticity disrupt signal transfer in the granular layer of IB2 KO mice supporting cerebellar involvement in the pathogenesis of ASD.

neuroscience