Physiological Properties of Human Fetal Cortex In Vitro

Emergence of neuronal membrane excitability (e.g., voltage-gated ion conductances) and spontaneous electrical activity (e.g., spontaneous firing of action potentials) is an imperative for the normal development and maturation of brain circuits. Understanding the interplay between electrical activity and normal brain development may prove critical for prevention and therapy of devastating neurological and psychiatric diseases. Due to the limited availability of human fetal tissue, our current understanding of functional (physiological) maturation of the human cerebral cortex has been limited to in vivo and in vitro animal models. Although invaluable for the generation of basic insights into this process, animal models fall short in providing an accurate model of human cortical development. The discrepancy between animal and human models of brain development is largely due to evolutionary changes such as differences in the time course, number of cellular divisions, and cellular composition of cortical layers, making it difficult to ascertain the step by step physiological maturation in human. Here, we provide detailed methodology on how to handle human fetal tissue, generate acute brain slices, and perform whole-cell patch-clamp recordings of biophysical membrane properties in human cortical neurons in their natural surroundings, that is, preserved neighboring neurons, glia, and extracellular matrix.