Repetitive transcranial magnetic stimulation reverses reduced excitability of rat visual cortex induced by dark rearing during early critical period

Abstract

Early critical period of visual cortex is characterized by enhanced activity-driven neuronal plasticity establishing the specificity of neuronal connections required for optimal processing of sensory signals. Deprivation from visual input by dark rearing (DR) during this period leads to a lasting impairment of visual performance. Previously, we demonstrated that repetitive transcranial magnetic stimulation (rTMS) applied with intermittent theta-burst (iTBS) pattern during the critical period improved the visual performance of the DR rats. In this study, we describe that the excitability of the binocular part of the visual cortex (V1b), as measured in acute brain slices by input-output ratios of field excitatory synaptic potentials (fEPSPs), is lowered in DR rats compared to normal controls. Verum rTMS applied with the iTBS pattern during DR reversed this DR effect, while no rTMS effect was evident in the non-DR (nDR) rats. In addition, verum rTMS reduced the number of neurons expressing the 67 kD isoform of glutamic acid decarboxylase (GAD67), the calcium-binding protein calbindin (CB) and the zinc-finger transcription factor zif268/EGR1, as determined via immunohistochemistry, only in DR rats but not in nDR rats. Moreover, rTMS reduced the number of neurons expressing the calcium-binding protein parvalbumin (PV) only in nDR rats which showed more PV+ neurons compared to DR rats. This study confirms that iTBS-rTMS may be able to prevent or reverse the effects of DR on visual cortex physiology, likely through a modulation of the activity of inhibitory interneurons.