Dynamic regulation of synaptic maturation state by voltage-gated A-type K+ channels in CA1 hippocampal pyramidal...

Neuronal activity is critical for the formation and modification of neural circuits during brain development. In hippocampal CA1 pyramidal dendrites, A-type voltage-gated K(+) currents, formed primarily by Kv4.2 subunits, control excitability. Here we used Kv4.2 knock-out (Kv4.2-KO) mice along with acute in vivo expression of Kv4.2 or its dominant-negative pore mutant to examine the role of Kv4.2 in the development of CA1 synapses. We found that Kv4.2 expression induces synaptic maturation in juvenile WT mice and rescues developmentally delayed synapses in adult Kv4.2-KO mice. In addition, we show that NMDAR subunit composition can be reverted back to the juvenile form in WT adult synapses by functionally downregulating Kv4.2 levels. These results suggest that Kv4.2 regulation of excitability determines synaptic maturation state, which can be bidirectionally adjusted into adulthood.