Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

Abstract

Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

A <inline-formula><tex-math>$\mu$</tex-math></inline-formula>m-Scale Computational Model of Magnetic Neural Stimulation in Multifascicular Peripheral Nerves

“…Previously, the understanding of the magnetic field's interaction with biological tissue had been based on in vitro experiments performed in peripheral [10], [11] and central [12]- [14] nervous systems. To study the effect of stimulation parameters (magnitude and pulse width of coil current), many studies used frog sciatic nerve in in vitro experiments, [11], [15], [16].…”

Assessment and modulation of cortical inhibition using transcranial magnetic stimulation

“…Meanwhile 'contact-free' functional microscopy techniques, e.g. via calcium-or voltagesensitive dyes (Kozyrev et al, 2014;Murphy et al, 2016), indicate that a low stimulation intensity mainly activates inhibitory interneurons, whereas projection neurons will be recruited with higher intensities [see (Pashut et al, 2014)]. Hence, these studies convey a plausible explanation for the already described SICI double-pulse protocol, where the subthreshold conditioning TMS pulse results in a GABA A receptor-dependent inhibition of the test MEP response.…”

“…These fields impede electrophysiological recordings, i.e. single-cell recording of neural activity, despite a few studies, which were performed with a low field strength and adequate position of the recording electrodes (Moliadze et al, 2005;Mueller et al, 2014;Pashut et al, 2014). Meanwhile 'contact-free' functional microscopy techniques, e.g.…”

Untersuchung und Modulation kortikaler Inhibition mittels transkranieller Magnetstimulation

“…Die meisten Annahmen in diesem Bereich beruhen auf computerbasierten Modellen (Esser et al 2005;Rusu et al 2014 (Moliadze et al 2005;Mueller et al 2014;Pashut et al 2014). Der Einsatz "kontaktfreier" funktioneller Mikroskopieverfahren, z.…”

“…Der Einsatz "kontaktfreier" funktioneller Mikroskopieverfahren, z. B. mittels kalzium-oder spannungssensitiver Farbstoffe (Kozyrev et al 2014;Murphy et al 2016), deutet darauf hin, dass bei geringer Stimulationsintensität vornehmlich inhibitorische Interneurone aktiviert werden, während Projektionsneurone erst bei höheren Intensitä-ten rekrutiert werden (siehe auch Pashut et al 2014). Somit bieten diese Studien einen plausiblen Erklärungsansatz für das bereits beschriebene SICI-Doppelpulsprotokoll, bei dem der unterschwellige konditionierende TMS-Puls zu einer GABA A -abhängigen Inhibition der durch den TMS Test-Puls induzierten MEP-Antwort führt.…”