Transport-Related Effects on Intrinsic and Synaptic Properties of Human Cortical Neurons: A Comparative Study

Abstract

Transporting human brain tissue from the operating theater to an off-site laboratory may affect sample integrity for electrophysiological studies. This study investigated how a 30-40 minute transport influenced the intrinsic, synaptic, and morphological properties of human cortical neurons. Electrophysiological recordings were performed on Layer 2/3 (L2/3 pyramidal cells and fast-spiking (FS) interneurons from human cortical slices (n = 200 neurons from 32 surgeries), comparing on-site recordings at RWTH Aachen University Hospital and off-site at Research Centre Juelich. Action potential firing patterns remained largely preserved across both recording sites, but several differences were observed. Off-site recorded pyramidal cells showed a slightly depolarized resting membrane potential and a significantly lower rheobase current. In off-site recorded FS interneurons, we found a narrower action potential half-width and an increased amplitude, suggesting altered ion channel kinetics and/or neuromodulatory environment. Additionally, a significant reduction in large rhythmic depolarizations (LRDs) and the amplitudes of excitatory postsynaptic potentials (EPSPs) in off-site recorded FS interneurons indicated an impaired synaptic efficacy. The dendritic spine densities in apical oblique and apical tuft dendrites of off-site recorded pyramidal cells were also reduced. These findings emphasize the need for optimized transport conditions to preserve synaptic integrity, network properties, and neuronal morphology. Standardized protocols are crucial for ensuring reliable and reproducible results in studies of human cortical microcircuits. Significance StatementThis study demonstrates that transporting live human brain tissue for neuronal recordings significantly impacts the intrinsic, synaptic, and network properties of cortical neurons. By comparing on-site and off-site recordings, we found that even a brief transportation (30-40 minutes) induces increased neuronal excitability, reduced synaptic efficacy, and diminished network events such as LRDs. These alterations are likely due to the mechanical stress and washout of critical neuromodulators, which compromise tissue integrity and neuronal function. The findings underscore the necessity for optimizing transport protocols to preserve synaptic and network integrity, ensuring reliable and reproducible results in human brain research. Ultimately, this work advances our understanding of cortical microcircuitry and informs best practices for handling human brain tissue in experimental settings.