Early development of voltage-gated ion currents and firing properties in neurons of the mouse cerebral cortex

Voltage and current clamp recordings were made from acute slices of mouse cerebral cortex from embryonic day 13 to postnatal day 17. We measured dye coupling, electrical coupling, and voltage-gated currents using whole-cell voltage clamp in three distinct zones of mouse sensorimotor cortex at embryonic day 14 (E14). Cells of the ventricular zone (VZ) were extensively dye coupled, often in clusters of more than 100 cells, but were much less electrically coupled, making measurement of voltage-gated currents accurate. All VZ cells expressed delayed K+ currents (I_K), and 30%, including morphologically identified radial glia, also expressed inward Na+ currents (I_Na). This fraction is consistent with I_Na expression being an early event following cell cycle exit. Intermediate zone (IZ) cells also expressed I_K and I_Na. Cells of the cortical plate (CP) expressed both I_K and I_Na, with I_Na being almost 10-fold larger than in VZ cells. No cell in any zone expressed detectable hyperpolarization-activated currents. Our data suggest that the distribution and density of I_Na may be related to early events of cell cycle exit and migration.; We also targeted cells in the migratory population of the embryonic intermediate zone (IZ) and in deep layers of embryonic and postnatal cortical plate (CP) at various developmental stages. IZ neurons maintain fairly consistent properties through the embryonic period, all expressing high input resistance, inward Na+ currents and outward K+ currents, and none showing any hyperpolarization-activated currents. In CP neurons, several changes in physiological properties occur in the late embryonic and early postnatal period: inward Na+ current density is strongly upregulated while outward K+ current density remains almost unchanged, input resistance drops dramatically, and a hyperpolarization-activated current resembling I_h appears. As a result of these changes, the action potential becomes larger, shorter in duration, and its threshold shifts to more negative potentials. In addition, CP cells become capable of firing repetitively and an increasing fraction show spontaneous action potentials. This coordinated development of ion channel properties may help to time the occurrence of developmentally relevant spontaneous activity in the immature cortex.