Roles of glutamate and GABA receptors in setting the developmental timing of spontaneous synchronized activity in the...

Spontaneous, synchronized electrical activity (SSA) plays important roles in nervous system development, but it is not clear what causes it to start and stop at the appropriate times. In previous work, we showed that when SSA in neonatal mouse cortex is blocked by TTX in cultured slices during its normal time of occurrence (E17-P3), it fails to stop at P3 as it does in control cultured slices, but instead persists through at least P10. This indicates that SSA is self-extinguishing. Here we use whole-cell recordings and [Ca2+]i imaging to compare control and TTX-treated slices to isolate the factors that normally extinguish SSA on schedule. In TTX-treated slices, SSA bursts average 4 s in duration, and have two components. The first, lasting about 1 s, is mediated by AMPA receptors; the second, which extends the burst to 4 s and is responsible for most of the action potential generation during the burst, is mediated by NMDA receptors. In later stage (P5-P9) control slices, after SSA has declined to about 4% of its peak frequency, bursts lack this long NMDA component. Blocking this NMDA component in P5-P9 TTX-treated slices reduces SSA frequency, but not to the low values found in control slices, implying that additional factors help extinguish SSA. GABA(A) inhibitors restore SSA in control slices, indicating that the emergence of GABA(A)-mediated inhibition is another major factor that helps terminate SSA.