Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion
Modulation of human cortical excitability by repetitive transcranial magnetic stimulation
(rTMS) appears to be in part related to changed activity of inhibitory systems. Our
own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS
to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons
(FSIs), evident via a strongly reduced PV expression. We further found the iTBS
effect on PV to be age-dependent since no reduction in PV could be induced
before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day
(PD) 30. To elucidate possible iTBS-induced changes in the electrical properties
of FSIs and cortical network activity during cortical critical period, we performed
ex vivo—in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the
current study. FSIs of verum iTBS-treated rats displayed a higher excitability than
sham-treated controls at PD29–38, evident as higher rates of induced action
potential firing at low current injections (100–200 pA) and a more depolarized
resting membrane potential. This effect was absent in younger (PD26–28) and older
animals (PD40–62). Slices of verum iTBS-treated rats further showed higher rates
of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and
previous findings we conclude that FSIs are particularly sensitive to TBS during
early cortical development, when FSIs show an activity-driven step of maturation
which is paralleled by intense growth of the PNNs and subsequent closure of the
cortical critical period. Although to be proven further, rTMS may be a possible
early intervention to compensate for hypo-activity related mal-development of cortical
neuronal circuits