Network Variability Across Human Tissue Samples In Vitro: The Problem and a Solution

Abstract

Slices prepared from cortical tissue that is surgically removed from patients to treat their epilepsy provide an opportunity to directly study the mechanisms underlying ictal activity. However, human in vitro studies have several limitations. One problem that may severely compromise investigations of network properties in these slices relates to how difficult it is to cut the tissue at angles that optimally preserve columnar connectivity. To address this problem, the authors investigated the degree of network variability in human tissue across samples and, within a single tissue sample, across slices cut at different angles using a novel form of optical imaging based on flavoprotein autofluorescence. The authors found a high degree of variability in the spatial extent, degree, and patterning of activation in slices from different samples. They also found variability across the slices cut from a single tissue sample at different angles. Indeed, these results suggest that human tissue samples have disparate degrees of network activity and that abnormal tissue may be confined to clusters of synchronously oscillating domains. Assessing circuit connectivity in a slice a priori will allow investigators to control for the overall degree of slice connectivity and selectively target active (or inactive) areas, making for better-informed comparisons of data.