Aging-associated weakening of the action potential in fast-spiking interneurons in the human neocortex

• Published in: Journal of biotechnology Vol. 389; pp. 1 - 12
• Main Authors: Szegedi, Viktor, Tiszlavicz, Ádám, Furdan, Szabina, Douida, Abdennour, Bakos, Emoke, Barzo, Pal, Tamas, Gabor, Szucs, Attila, Lamsa, Karri
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.06.2024
• Subjects: action potentials; Active conductances; biotechnology; capacitance; cognition; Electrophysiology; humans; Input-output transformation; interneurons; neocortex; neurodegenerative diseases; Passive membrane properties; Signal transduction; sodium channels; surgery; Translational; Electrophysiology; Signal transduction; Active conductances; Translational; Passive membrane properties; Input-output transformation
• ISSN: 0168-1656; 1873-4863; 1873-4863
• DOI: 10.1016/j.jbiotec.2024.04.020

Aging is associated with the slowdown of neuronal processing and cognitive performance in the brain; however, the exact cellular mechanisms behind this deterioration in humans are poorly elucidated. Recordings in human acute brain slices prepared from tissue resected during brain surgery enable the investigation of neuronal changes with age. Although neocortical fast-spiking cells are widely implicated in neuronal network activities underlying cognitive processes, they are vulnerable to neurodegeneration. Herein, we analyzed the electrical properties of 147 fast-spiking interneurons in neocortex samples resected in brain surgery from 106 patients aged 11–84 years. By studying the electrophysiological features of action potentials and passive membrane properties, we report that action potential overshoot significantly decreases and spike half-width increases with age. Moreover, the action potential maximum-rise speed (but not the repolarization speed or the afterhyperpolarization amplitude) significantly changed with age, suggesting a particular weakening of the sodium channel current generated in the soma. Cell passive membrane properties measured as the input resistance, membrane time constant, and cell capacitance remained unaffected by senescence. Thus, we conclude that the action potential in fast-spiking interneurons shows a significant weakening in the human neocortex with age. This may contribute to the deterioration of cortical functions by aging. •Recordings in human acute brain slices prepared from tissue resected during brain surgery enable investigating neuronal changes with age.•Action potential in fast-spiking interneurons shows a significant weakening in the human neocortex with age.•Neuron intrinsic excitability, measured as the input resistance, membrane time constant, and cell capacitance remained unaffected by senescence.•These changes in neurons’ electrical activity may contribute to the deterioration of cortical functions with age.