Biology subjects

De Pitta, M.

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

4 recordsLinked to original sources

bioRxiv2023

The nonlinear meccano of hyperactivity in Alzheimer

The pathophysiological process of Alzheimers disease (AD) is believed to begin many years before the formal diagnosis of AD dementia. This protracted preclinical phase offers a crucial window for potential therapeutic interventions, yet its comprehensive characterization remains elusive. Accumulating evidence suggests that amyloid-{beta} (A{beta}) may mediate neuronal hyperactivity in circuit dysfunction in the early stages of AD. At the same time, neural activity can also facilitate A{beta} accumulation through intricate feed-forward interactions, complicating elucidating the conditions governing A{beta}-dependent hyperactivity and its diagnostic utility. In this study, we use biophysical modeling to shed light on such conditions. Our analysis reveals that the inherently nonlinear nature of the underlying molecular interactions can give rise to various modes of hyperactivity emergence. This diversity in the mechanisms of hyperactivity may ultimately account for a spectrum of AD manifestations.

neuroscience↗

bioRxiv2021

Multiple forms of working memory emerge from synapse-astrocyte interactions

Competing accounts propose that working memory (WM) is subserved either by persistent activity in single neurons, or by time-varying activity across a neural population, or by activity-silent mechanisms carried out by hidden internal states of the neural population. While WM is traditionally regarded to originate exclusively from neuronal interactions, cortical networks also include astrocytes that can modulate neural activity. We propose that different mechanisms of WM can be brought forth by astrocyte-mediated modulations of synaptic transmitter release. In this account, the emergence of different mechanisms depends on the networks spontaneous activity and the geometry of the connections between synapses and astrocytes.

neuroscience↗

bioRxiv2018

Astrocyte networks and intercellular calcium propagation

Astrocytes organize in complex networks through connections by gap junction channels that are regulated by extra- and intracellular signals. Calcium signals generated in individual cells, can propagate across these networks in the form of intercellular calcium waves, mediated by diffusion of second messengers molecules such as inositol 1,4,5-trisphosphate. The mechanisms underpinning the large variety of spatiotemporal patterns of propagation of astrocytic calcium waves however remain a matter of investigation. In the last decade, awareness has grown on the morphological diversity of astrocytes as well as their connections in networks, which seem dependent on the brain area, developmental stage, and the ultrastructure of the associated neuropile. It is speculated that this diversity underpins an equal functional variety but the current experimental techniques are limited in supporting this hypothesis because they do not allow to resolve the exact connectivity of astrocyte networks in the brain. With this aim we present a general framework to model intercellular calcium wave propagation in astrocyte networks and use it to specifically investigate how different network topologies could influence shape, frequency and propagation of these waves.

neuroscience↗

bioRxiv2017

Modeling neuron-glia interactions with the Brian 2 simulator

Despite compelling evidence that glial cells could crucially regulate neural network activity, the vast majority of available neural simulators ignores the possible contribution of glia to neuronal physiology. Here, we show how to model glial physiology and neuron-glia interactions in the Brian 2 simulator. Brian 2 offers facilities to explicitly describe any model in mathematical terms with limited and simple simulator-specific syntax, automatically generating high-performance code from the user-provided descriptions. The flexibility of this approach allows us to model not only networks of neurons, but also individual glial cells, electrical coupling of glial cells, and the interaction between glial cells and synapses. We therefore conclude that Brian 2 provides an ideal platform to efficiently simulate glial physiology, and specifically, the influence of astrocytes on neural activity.

neuroscience↗