ELECTRICAL PROPERTIES OF IMMATURE HUMAN PROJECTION NEURONS AND ITS ROLE IN NEURONAL MIGRATION

The human neocortex is the largest and most evolutionarily advanced structure of the brain, which controls higher cognitive functions. Its development requires a highly orchestrated process in which millions of neurons are generated and subsequently migrate to their final destinations. A fundamental step in this process, which shapes the architecture of the neocortex, is neuronal migration, and impairments in this process are thought to contribute to human neurodevelopmental disorders.
Accumulated evidences obtained in mouse models indicate that distinct forms and levels of membrane electrical activity play a critical role in regulation of neuronal migration. The significant differences between mouse and human models underscore the need to study these processes in human-specific systems. Here, we link electrical activity of immature projection neurons and their neuronal migration using human fetal brain tissue. To elucidate the cellular and molecular mechanisms underlying it we investigated how intrinsic electrical membrane properties of excitatory projection neurons modulate their migration during human neocortical development. For this purpose, we focused on passive membrane parameters and early voltage-dependent conductance that precede action potential firing. Our preliminary results show that human excitatory projection neurons exhibit a more hyperpolarized resting membrane potential than the mouse ones. Although both species display sodium and potassium currents, these currents are weaker in human neurons. This work will provide key insights into the mechanisms controlling cortical formation and clarify the contribution of intrinsic electrical properties to the migration of projection neurons into the human cerebral cortex.