Neuronal hyperactivity in neurons derived from individuals with gray matter heterotopia.

ABSTRACT: Periventricular heterotopia (PH), a common form of gray matter heterotopia associated with developmental delay and drug-resistant seizures, poses a challenge in understanding its neurophysiological basis. Human cerebral organoids (hCOs) derived from patients with causative mutations in FAT4 or DCHS1 mimic PH features. However, neuronal activity in these 3D models has not yet been investigated. Here we show that silicon probe recordings reveal exaggerated spontaneous spike activity in FAT4 and DCHS1 hCOs, suggesting functional changes in neuronal networks. Transcriptome and proteome analyses identify changes in neuronal morphology and synaptic function. Furthermore, patch-clamp recordings reveal a decreased spike threshold specifically in DCHS1 neurons, likely due to increased somatic volta

SUBMITTER: Di Matteo F 

PROVIDER: S-EPMC11836124 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature