Critical period is a time of heightened plasticity during development when the brain becomes sensitive to environmental cues which can influence structure and function. As this period is important in stabilizing neuronal projections, any negative environmental influence during this time can lead to abnormal brain organization which has been linked to several neurodevelopmental disorders. Therefore, enhancing, or prolonging plasticity during critical neurodevelopmental periods can be of therapeutic importance.

We investigated the impact of low-intensity repetitive transcranial magnetic stimulation (LI-rTMS) on markers of critical period plasticity. We delivered LI-rTMS to the primary visual cortex (V1) in young ephrin-A2/A5^+/- mice (sham: n=6, treatment: n=5), which have disorganised visual system projections, and in wildtype mice (sham: n=7, treatment: n=7), daily for two-weeks starting at postnatal day 28 (peak of critical period in V1). Following the treatment mice were euthanised, perfused and brains were cryosectioned. Sections containing V1 were immunostained for parvalbumin (PV)-expressing interneurons and their surrounding perineuronal nets (PNN) which are important determinants of the critical period.

Although following LI-rTMS there was no significant change in the density of PV-expressing interneurons or PNNs, we observed changes in the intensity of the nets surrounding PV-expressing interneurons. Following TMS, there were more low intensity nets compared to high intensity nets in the ephrin-A2/A5^+/- mice, suggesting that TMS might delay or prevent the maturation of these nets. As PNNs play an important role in closing the critical period, our findings suggest TMS might prolong critical period plasticity when abnormal brain wiring is present.