Static magnetic field stimulation enhances shunting inhibition via a SLC26 family Cl−channel, inducing intrinsic plasticity

Abstract

Magnetic fields are being used for detailed anatomical and functional examination of the human brain. In addition, evidences for their efficacy in treatment of brain dysfunctions is accumulating. Transcranial static magnetic field stimulation (tSMS) is a recently developed technique for non-invasively modifying brain functions. In tSMS, a strong and small magnet when placed over the skull can temporarily suppress brain functions. Its modulatory effects persist beyond the time of stimulation. However, the neurophysiological mechanisms underlying tSMS-induced plasticity remain unclear. Here, using acute motor cortical slice preparation obtained from male C57BL/6N mice, we show that tSMS alters the intrinsic electrical properties of neurons by altering the activity of chloride (Cl−) channels in neurons. Exposure of mouse pyramidal neurons to a static magnetic field (SMF) at a strength similar to human tSMS, temporarily decreased their excitability and induced transient neuronal swelling. The effects of SMF were blocked by DIDS and GlyH-101, but not by NPPB, consistent with the pharmacological profile of SLC26A11, a transporter protein with Cl−channel activity. Whole-cell voltage-clamp recordings of the GlyH-101-sensitive Cl−current component showed significant enhancement of the component at both subthreshold and depolarized membrane potentials after SMF application, resulting in shunting inhibition and reduced repetitive action potential (AP) firing at the respective potentials. Thus, this study provides the first neurophysiological evidence for the inhibitory effect of tSMS on neuronal activity and advances our mechanistic understanding of non-invasive human neuromodulation.Significance StatementTranscranial static magnetic field stimulation (tSMS) is a recently developed non-invasive brain stimulation technique. In tSMS, a strong, small magnet placed over the skull temporarily suppresses brain functions, and its modulatory effects persist beyond the stimulation time. To elucidate the neurophysiological mechanisms of tSMS, we evaluated the excitability of mouse pyramidal neurons exposed to a static magnetic field at a strength similar to that of human tSMS using whole-cell patch-clamp experiments. We demonstrated that the static magnetic field temporarily decreased neuronal excitability by increasing the activity of a specific type of Cl−channel in the plasma membrane, and it also induced transient neuronal swelling. This study reveals for the first time the neurophysiological mechanism of tSMS-induced suppression of brain functions.