Immediate Effects of Magnetic Stimulation on Dentate Gyrus Glutamatergic and GABAergic Neuron Excitability

Background/Objectives: To investigate the immediate regulatory effects of magnetic stimulation with different parameters on the excitability of glutamatergic neurons and GABAergic neurons in the mouse hippocampal dentate gyrus (DG), and to analyze the underlying mechanisms using the Hodgkin-Huxley (HH) model. Methods: Whole-cell patch-clamp recordings were performed on acute brain slices to measure changes in resting membrane potential (RMP), the number of action potentials (APs) evoked by 500-ms long-duration stimulation, as well as AP threshold, peak, half-width, maximum rising slope, and maximum falling slope under magnetic stimulation at various frequencies (1, 10, 20 Hz) and intensities (50, 75 mT). An improved HH model was established based on experimental data to analyze the dynamic changes in gating variables under magnetic stimulation. Results: High-frequency magnetic stimulation (10-20 Hz) significantly increased the number of APs in both neuron types. In glutamatergic neurons, the number of APs increased from 10.12 ± 0.52 in the control group to 15.62 ± 0.84 in the 20 Hz-75 mT group; in GABAergic neurons, it increased from 7.88 ± 0.40 to 12.62 ± 0.53. Magnetic stimulation also depolarized RMP and significantly altered multiple AP waveform parameters in both neuron types. Glutamatergic neurons showed a more distinct frequency dependence, whereas GABAergic neurons were more sensitive to changes in both frequency and intensity in terms of RMP and multiple waveform parameters. Simulation results showed that the 1 Hz conditions produced negligible changes in AP firing, gating-variable dynamics, and steady-state ion-channel parameters compared with the Control condition. In contrast, high-frequency stimulation enhanced the dynamic changes of sodium and potassium channel gating variables and altered their voltage-dependent steady-state properties. Specifically, sodium channel activation shifted toward more negative potentials, whereas sodium channel inactivation and potassium channel activation shifted toward more depolarized potentials. Conclusions: Under the experimental conditions of this study, magnetic stimulation immediately enhanced the excitability of glutamatergic and GABAergic neurons in the hippocampal dentate gyrus of male mice in a frequency-dependent manner. The modified HH model reproduced both the weak effects under low-frequency stimulation and the enhanced excitability under high-frequency stimulation, suggesting that these immediate effects may be related to frequency-dependent changes in the gating kinetics and voltage-dependent properties of sodium and potassium channels.