The self-regulating nature of spontaneous synchronized activity in developing mouse cortical neurones.

Waves of spontaneous electrical activity that are highly synchronized across large populations of neurones occur throughout the developing mammalian central nervous system. The stages at which this activity occurs are tightly regulated to allow activity-dependent developmental programmes to be initiated correctly. What determines the onset and cessation of spontaneous synchronous activity (SSA) in a particular region of the nervous system, however, remains unclear. We have tested the hypothesis that activity itself triggers developmental changes in intrinsic and circuit properties that determine the stages at which SSA occurs. To do this we exposed cultured slices of mouse neocortex to tetrodotoxin (TTX) to block SSA, which normally occurs between embryonic day 17 (E17) and postnatal day 3 (P3). In control cultured slices, SSA rarely occurs after P3. In TTX-treated slices, however, SSA was generated from P3 (the day of TTX removal) until at least P10. This indicates that in the absence of spontaneous activity, the mechanisms that normally determine the timing of SSA are not initiated, and that a compensatory response occurs that shifts the time of SSA occurrence to later developmental stages.

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 14 to postnatal day 17. We targeted cells in the migratory population of the embryonic intermediate zone (IZ) and in deep layers of embryonic and postnatal cortical plate (CP). 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.