Nano-needle Electrode System for Recording Membrane Potentials in AUTS2-Deficient Neurons.

Investigating spontaneous membrane potentials in neurons harboring Autism Susceptibility Candidate 2 (AUTS2) defects is pivotal for elucidating the pathophysiological mechanisms of neurodevelopmental disorders and for guiding targeted therapeutic strategies. Conventional electrophysiological techniques have substantially advanced understanding of neuronal function. However, they encounter limitations in capturing transient paroxysmal depolarization shifts (PDS) in AUTS2-deficient neurons, primarily owing to ion imbalances and signal attenuation. To address these constraints, we developed a nano-needle electrode system that integrates a nano-needle electrode, a 3D surface profiling device, and a neuro-electrophysiological recording device. This minimally invasive platform enables nondestructive submicron cellular scanning, and electrophysiological recording with a signal-to-noise ratio exceeding 50 dB. Employing this system, we revealed the occurrence of PDS events and a 100-fold enhancement (surpassing 1 kHz) in neuronal firing activity with AUTS2 defects. These findings enhance the understanding of AUTS2's impact on neuronal excitability and highlight our system's potential to guide future therapies for epilepsy and neuropsychiatric disorders.