Research ReportRepetitive transcranial magnetic stimulation increases excitability of hippocampal CA1 pyramidal neurons

- Effects of rTMS on properties of several ionic channels were studied.
- rTMS increased the excitability of hippocampal CA1 pyramidal neurons.
- rTMS enhanced the AP and sEPSCs of hippocampal CA1 neurons.
- rTMS effects were more remarkable with 14-d's treatment compared with 7 d.

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 2-3 d or 7-8 d were treated with 14 or 7-d's low frequency (1 Hz) rTMS (400 stimuli/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 7 d and 14 d) 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.