Dendritic beading during early brain development impairs signal transmission and synaptic plasticity.

Abstract

Excessive glutamate receptor activation during brain pathologies causes varicose dendritic swelling, also known as "dendritic beading", yet its impact on developing brain circuits is poorly understood. Using field electrophysiology and two-photon imaging in awake, behaving mice and acute brain slices (P11-19), we found that severe and recurrent seizure-like activity (induced by NMDA and 4-aminopyridine) resulted in widespread, long-lasting dendritic beading and spine loss in cortical and hippocampal neurons, with localization patterns distinct from those described in adults. Beads showed persistently high calcium levels and stopped the spread of dendritic calcium signals. Dendritic beads suppressed hippocampal evoked field potentials, followed by only partial recovery, and reduced hippocampal long-term potentiation. Clinically used hyperosmotic treatments (mannitol or hypertonic saline) reduced seizure-induced beading and restored dendritic signal propagation. These findings suggest that seizure-induced dendritic beading disrupts circuit function and synaptic plasticity and may contribute to cognitive deficits after early-life seizures.