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Barboni, M.

Publications and source records attributed to Barboni, M..

2 recordsLinked to original sources
bioRxiv2025

Nanoscale dendritic shaft constrictions shape synaptic integration in fine caliber principal neuron dendrites

Traditionally, theoretical studies typically described dendritic morphology as optimized for efficient synaptic voltage transfer from spines to the soma, implemented as a tubular design respecting Ralls 3/2 rule for impedance matching at branch points. Here, we reveal that this view is an oversimplification. Using three high-resolution imaging techniques, we demonstrate that dendrites in cortical and hippocampal neurons contain nanoscale constrictions, comparable in diameter to spine necks. We provide theoretical and experimental evidence that these constrictions partition the dendrite into distinct electrical compartments, significantly shaping dendritic integration of synaptic potentials.

neuroscience↗
bioRxiv2025

Early postnatal CA3 hyperexcitability drives hippocampal development and epileptogenesis in SCN2A developmental and epileptic encephalopathy

Developmental and epileptic encephalopathies caused by pathogenic variants in SCN2A (SCN2A-DEE), encoding the voltage-gated sodium channel Nav1.2, present with early-life seizures, developmental delay, and increased mortality. Using a novel Scn2a p.A263V gain-of-function (GOF) mouse model, we demonstrate gene-dose and background-dependent phenotypes ranging from self-limited neonatal seizures to chronic epilepsy with high mortality. In vivo electrophysiology revealed hippocampal seizures as early as postnatal day 2.5, with CA3-driven gamma oscillations preceding seizure onset. CA3 and CA1 pyramidal neurons exhibited transient hyperexcitability during early postnatal development, resolving by P24-30. Single-cell RNA sequencing uncovered gene dose-dependent accelerated maturation of hippocampal networks, peaking at P7, alongside widespread transcriptional changes in excitatory and inhibitory neurons. In adulthood, persistent hippocampal network alterations emerged, marked by reduced mid-gamma oscillations and theta-gamma coupling. Our findings establish hippocampal CA3 hyperexcitability as an early driver of epileptogenesis in SCN2A-DEE and highlight it as a potential therapeutic target to mitigate disease progression.

neuroscience↗