The impact of early environmental interventions on structural plasticity of the axon initial segment in neocortex

Plasticity of the axon initial segment (AIS) is a newly discovered type of structural plasticity that regulates cell excitability. AIS plasticity has been reported to happen during normal development of neocortex and also in a few pathological conditions involving disruption of the inhibition/excitation balance. Here we report on the impact of early environmental interventions on structural plasticity of AIS in the mouse neocortex. C57BL/6 mice were raised in standard or enriched environment (EE) from birth up to the time of experiments and were injected with saline or MK-801 [N-Methyl-D-Aspartate (NMDA) receptor antagonist, 1 mg/kg] on postnatal days (P) 6-10. We used Ankyrin G immunoreactivity to mark the AIS of cortical neurons in two sub-regions of frontal cortex (frontal association area, FrA and secondary motor cortex, M2) and in the secondary visual cortex (V2). In 1-month-old mice, the mean AIS length differed between three areas, with the shortest AISs being observed in V2. Postnatal MK-801 or EE led to shortening of AIS only in the frontal areas. However, exposure to EE restored AIS shortening induced by MK-801. Chronic postnatal MK-801 results in structural plasticity of AIS exclusive to the frontal cortex. EE may modify underlying neuronal mechanisms resulting in restoration of AIS length.