Biology subjects

Masoli, S.

Publications and source records attributed to Masoli, S..

5 recordsLinked to original sources

bioRxiv2023

Human outperform mouse Purkinje cells in dendritic complexity and computational capacity

Purkinje cells (PC) of the cerebellum are amongst the largest neurons of the brain and have been extensively investigated in rodents. However, their morphological and physiological properties in humans are still poorly understood. Here, we have taken advantage of high-resolution morphological reconstructions and of unique electrophysiological recordings of human PCs ex vivo to generate computational models and estimate computational capacity. An inter-species comparison showed that human PCs had similar fractal structure but were bigger than mouse PCs. Consequently, given a similar spine density (2/m), human PCs hosted about 5 times more dendritic spines. Moreover, human had higher dendritic complexity than mouse PCs and usually emitted 2-3 main dendritic trunks instead than 1. Intrinsic electroresponsiveness was similar in the two species but model simulations revealed that the dendrites generated ~6.5 times (n=51 vs. n=8) more combinations of independent input patterns in human than mouse PCs leading to an exponential 2n increase in Shannon information. Thus, while during evolution human PCs maintained similar patterns of spike discharge as in rodents, they developed more complex dendrites enhancing computational capacity up to the limit of 10 billion times.

neuroscience↗

bioRxiv2021

Scaffold modelling captures the structure-function-dynamics relationship in brain microcircuits

1Modelling brain networks with complex configuration and cellular properties requires a set of neuroinformatic tools and an organized staged workflow. We have therefore developed the Brain Scaffold Builder (BSB), a new modeling framework embedding multiple strategies for cell placement and connectivity and a flexible management of cellular and network mechanisms. With BSB, for the first time, the mouse cerebellar cortex was reconstructed and simulated at cellular resolution, using morphologically realistic multi-compartmental single-neuron models. Embedded connection rules allowed BSB to generate the cerebellar connectome, unifying a collection of scattered experimental data into a coherent construct. Naturalistic background and sensory-burst stimulation were used for functional validation against recordings in vivo, monitoring the impact of subcellular mechanisms on signal propagation and spatio-temporal processing and providing a new ground-truth about circuit organization for the prediction of neural dynamics.

neuroscience↗

bioRxiv2020

Stellate cell computational modelling predicts signal filtering in the molecular layer circuit of cerebellum

The functional properties of cerebellar stellate cells and the way they regulate molecular layer activity are still unclear. We have measured stellate cells electroresponsiveness and their activation by parallel fiber bursts. Stellate cells showed intrinsic pacemaking, along with characteristic responses to depolarization and hyperpolarization, and showed a marked short-term facilitation during repetitive parallel fiber transmission. Spikes were emitted after a lag and only at high frequency, making stellate cells to operate as delay-high-pass filters. A detailed computational model summarizing these physiological properties allowed to explore different functional configurations of the parallel fiber - stellate cell - Purkinje cell circuit. Simulations showed that, following parallel fiber stimulation, Purkinje cells almost linearly increased their response with input frequency but such an increase was inhibited by stellate cells, which leveled the Purkinje cell gain curve to its 4 Hz value. When reciprocal inhibitory connections between stellate cells were activated, the control of stellate cells over Purkinje cell discharge was maintained only at very high frequencies. These simulations thus predict a new role for stellate cells, which could endow the molecular layer with low-pass and band-pass filtering properties regulating Purkinje cell gain and, along with this, also burst delay and the burst-pause responses pattern.

neuroscience↗

bioRxiv2020

Cerebellar Golgi cell models predict dendritic processing and mechanisms of synaptic plasticity

The Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. Although recent works have highlighted the complexity of their dendritic organization and synaptic inputs, the mechanisms through which these neurons integrate complex input patterns remained unknown. Here we have used 8 detailed morphological reconstructions to develop multicompartmental models of Golgi cells, in which Na, Ca, and K channels were distributed along dendrites, soma, axonal initial segment and axon. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons. Basal dendrites turned out to be more tightly electrically coupled to the axon initial segment than apical dendrites. During synaptic transmission, parallel fibers caused slow Ca-dependent depolarizations in apical dendrites that boosted the axon initial segment encoder and Na-spike backpropagation into basal dendrites, while inhibitory synapses effectively shunted backpropagating currents. This oriented dendritic processing set up a coincidence detector controlling voltage-dependent NMDA receptor unblock in basal dendrites, which, by regulating local calcium influx, may provide the basis for spike-timing dependent plasticity anticipated by theory. Author SummaryThe Golgi cells are the main inhibitory interneurons of the cerebellum granular layer and play a fundamental role in controlling cerebellar processing. However, it was unclear how spikes are processed in the dendrites by specific sets of ionic channels and how they might contribute to integrate synaptic inputs and plasticity. Here we have developed detailed multicompartmental models of Golgi cells that faithfully reproduced a large set of experimental findings and revealed the nature of signal interchange between dendrites and axo-somatic compartments. A main prediction of the models is that synaptic activation of apical dendrites can effectively trigger spike generation in the axonal initial segment followed by rapid spike backpropagation into basal dendrites. Here, incoming mossy fiber inputs and backpropagating spikes regulate the voltage-dependent unblock of NMDA channels and the induction of spike timing-dependent plasticity (STDP). STDP, which was predicted by theory, may therefore be controlled by contextual information provided by parallel fibers and integrated in apical dendrites, supporting the view that spike timing is fundamental to control synaptic plasticity at the cerebellar input stage.

neuroscience↗

bioRxiv2019

Parameter tuning differentiates granule cell subtypes enriching the repertoire of retransmission properties at the cerebellum input stage

The cerebellar granule cells (GrCs) form an anatomically homogeneous neuronal population which, in its canonical description, discharges regularly without adaptation. We show here that GrCs in fact generate diverse response patterns to current injection and synaptic activation, ranging from adaptation to acceleration of firing. Adaptation was predicted by parameter optimization in detailed GrC computational models based on the available knowledge on GrC ionic channels. The models also predicted that acceleration required the involvement of additional mechanisms. We found that yet unrecognized TRPM4 currents in accelerating GrCs could specifically account for firing acceleration. Moreover, adapting GrCs were better in transmitting high-frequency mossy fiber (MF) bursts over a background discharge than accelerating GrCs. This implied that different electroresponsive patterns corresponded to specific synaptic properties reflecting different neurotransmitter release probability. The correspondence of pre- and post-synaptic properties generated effective MF-GrC transmission channels, which could enrich the processing of input spike patterns and enhance spatio-temporal recoding at the cerebellar input stage.

neuroscience↗