Repetitive transcranial magnetic stimulation increases excitability of hippocampal CA1 pyramidal neurons

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is able to induce alteration in cortical activity and excitability that outlast the period of stimulation, which is long-term depre-ssion (LTD) or long-term potentiation (LTP)-like. Accumulating evidence shows that Na+, Ca2+ and K+ channels are important for the regulation of neuronal excitability. To investigate the possible mechanisms of rTMS on regulation of intrinsic excitability in hippocampal neurons, the male or female Sprague-Dawley rats aged 2–3d or 7–8d were treated with 14 or 7-d's low frequency (1Hz) rTMS (400stimuli/d), respectively. After that, the effects of rTMS on ion channels such as Na+-channel, A-type K+-channel and Ca2+-channel in rat hippocampal CA1 pyramidal neurons were performed by standard whole-cell patch-clamp technique. The results showed that the peak amplitude and maximal rise slope of evoked single action potential (AP) were significantly increased after 14-d's rTMS treatment. Meanwhile, the AP threshold was significantly more depolarized in neurons after 14-d's rTMS treatment than neurons in control group that without rTMS treatment. The spontaneous excitatory post-synaptic currents (sEPSCs) frequency and amplitude of CA1 pyramidal neurons in groups with rTMS treatment (both 7d and 14d) were obviously increased compared with the age-matched control group. Furthermore, we found that electrophysiological properties of Na+-channel were markedly changed after rTMS treatment, including negative-shifted activation and inactivation curves, as well as fasten recovery rate. After rTMS application, the IA amplitude of K+-channel was reduced; the activation and inactivation curves of K+-channel were significantly shifted to right. Time constant of recovery from inactivation was also more rapid. Moreover, rTMS induced an obvious increment in the maximal current peak amplitude of Ca2+-channel. At the same time, there was a significant rightward shift in the activation curve and inactivation curves of Ca2+-channel. These data suggest that rTMS can enhance the AP and sEPSCs of hippocampal CA1 neurons. Altered electrophysiological properties of Na+-channel, A-type K+ channels and Ca2+ channels contribute to the underling mechanisms of rTMS-induced up-regulation of neural excitability.