Biology subjects

Scolamiero, M.

Publications and source records attributed to Scolamiero, M..

3 recordsLinked to original sources

bioRxiv2026

Chromatic topological mapping reveals organelle-specific spatial organization within microglia

In branched cells, including neurons and glia, intracellular organelles are distributed across complex cellular arbors where their spatial arrangement supports transport, signaling, and compartmentalized function. Although intracellular organelle organization is increasingly recognized as an important feature of cellular state and function, existing approaches assess organelle abundance or spatial position without accounting for the branching architecture that shapes cellular function. Here, we introduce the chromatic topological morphology descriptor (chromatic TMD), a framework that quantitatively resolves intracellular organization in relation to branching morphology. Applied to reconstructed microglia with annotated lysosomal and mitochondrial compartments across retinal layers and after optic nerve crush injury, chromatic TMD identifies distinct organelle-specific spatial programs: CD68+-endosomal-lysosomes undergo layer-dependent branch-specific redistribution, revealing selective intracellular reorganization after injury, whereas mitochondrial organization remains closely coupled to branching morphology. These findings establish intracellular organization as an additional layer of cellular architecture that can be systematically analyzed across branched neural cells.

neuroscience↗

bioRxiv2023

The impact of Parkinson's disease on striatal network connectivity and cortico-striatal drive: an in-silico study

Striatum, the input stage of the basal ganglia, is important for sensory-motor integration, initiation and selection of behaviour, as well as reward learning. Striatum receives glutamatergic inputs from mainly cortex and thalamus. In rodents, the striatal projection neurons (SPNs), giving rise to the direct and the indirect pathway (dSPNs and iSPNs, respectively), account for 95% of the neurons and the remaining 5% are GABAergic and cholinergic interneurons. Interneuron axon terminals as well as local dSPN and iSPN axon collaterals form an intricate striatal network. Following chronic dopamine depletion as in Parkinsons disease (PD), both morphological and electrophysiological striatal neuronal features have been shown to be altered in rodent models. Our goal with this in-silico study is twofold: a) to predict and quantify how the intrastriatal network connectivity structure becomes altered as a consequence of the morphological changes reported at the single neuron level, and b) to investigate how the effective glutamatergic drive to the SPNs would need to be altered to account for the activity level seen in SPNs during PD. In summary we predict that the richness of the connectivity motifs in the striatal network is significantly decreased during PD, while at the same time a substantial enhancement of the effective glutamatergic drive to striatum is present. AUTHOR SUMMARYThis in-silico study predicts the impact that the single cell neuronal morphological alterations will have on the striatal microcircuit connectivity. We find that the richness in the topological striatal motifs is significantly reduced in Parkinsons disease, highlighting that just measuring the pairwise connectivity between neurons gives an incomplete description of network connectivity. Moreover, we predict how the resulting electrophysiological changes of SPN excitability together with their reduced number of dendritic branches affect their response to the glutamatergic drive from cortex and thalamus. We find that the effective glutamatergic drive is likely significantly increased in PD, in accordance with the hyperglutamatergic hypothesis.

neuroscience↗

bioRxiv2021

Microglial MorphOMICs unravel region- and sex-dependent morphological phenotypes from postnatal development to degeneration

Microglia contribute to tissue homeostasis in physiological conditions with environmental cues influencing their ever-changing morphology. Strategies to identify these changes usually involve user-selected morphometric features, which, however, have proved ineffective in establishing a spectrum of context-dependent morphological phenotypes. Here, we have developed MorphOMICs, a topological data analysis approach to overcome feature-selection-based biases and biological variability. We extracted a spatially heterogeneous and sexually-dimorphic morphological phenotype for seven adult brain regions, with ovariectomized females forming their own distinct cluster. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration models, 5xFAD and CK-p25. Females show an earlier morphological shift in the immediately-affected brain regions. Finally, we demonstrate that both the primary- and the short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs maps microglial morphology into a spectrum of cue-dependent phenotypes in a minimally-biased and semi-automatic way.

neuroscience↗