title: Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro.
abstract: Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity.
authors: Experimental and Regenerative Neurosciences, School of Animal Biology, University of Western Australia, Perth, Australia. Electronic address: Alexander.Tang@research.uwa.edu.au.
authors: Alexander D
authors: AD
authors: Tang
authors: School of Veterinary and Life Sciences, Murdoch University, Perth, Australia.
authors: Ivan
authors: I
authors: Hong
authors: Brain Health Research Centre and Brain Research NZ Centre of Research Excellence, New Zealand; Department of Anatomy, University of Otago, Dunedin, New Zealand.
authors: Laura J
authors: LJ
authors: Boddington
authors: Experimental and Regenerative Neurosciences, School of Animal Biology, University of Western Australia, Perth, Australia.
authors: Andrew R
authors: AR
authors: Garrett
authors: School of Veterinary and Life Sciences, Murdoch University, Perth, Australia.
authors: Sarah
authors: S
authors: Etherington
authors: Brain Health Research Centre and Brain Research NZ Centre of Research Excellence, New Zealand; Department of Anatomy, University of Otago, Dunedin, New Zealand.
authors: John N J
authors: JN
authors: Reynolds
authors: Experimental and Regenerative Neurosciences, School of Animal Biology, University of Western Australia, Perth, Australia. Electronic address: jennifer.rodger@uwa.edu.au.
authors: Jennifer
authors: J
authors: Rodger
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D008564:Membrane Potentials / Q000502:physiology; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods
keywords: Intermittent Theta Burst Stimulation; action potential threshold; low-intensity rMS; spike firing frequency