In vivo low‐intensity magnetic pulses durably alter neocortical neuron excitability and spontaneous activity

Abstract

Magnetic brain stimulation is a promising treatment for neurological and psychiatric disorders. However, a better understanding of its effects at the individual neuron level is essential to improve its clinical application. We combined focal low‐intensity repetitive transcranial magnetic stimulation (LI‐rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neurons in vivo. Continuous 10 Hz LI‐rTMS reliably evoked firing at ∼4–5 Hz during the stimulation period and induced durable attenuation of synaptic activity and spontaneous firing in cortical neurons, through membrane hyperpolarization and a reduced intrinsic excitability. However, inducing firing in individual neurons by repeated intracellular current injection did not reproduce the effects of LI‐rTMS on neuronal properties. These data provide a novel understanding of mechanisms underlying magnetic brain stimulation showing that, in addition to inducing biochemical plasticity, even weak magnetic fields can activate neurons and enduringly modulate their excitability. Key points Repetitive transcranial magnetic stimulation (rTMS) is a promising technique to alleviate neurological and psychiatric disorders caused by alterations in cortical activity. Our knowledge of the cellular mechanisms underlying rTMS‐based therapies remains limited. We combined in vivo focal application of low‐intensity rTMS (LI‐rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neurons to characterize the effects of weak magnetic fields at single cell level. Ten minutes of LI‐rTMS delivered at 10 Hz reliably evoked action potentials in cortical neurons during the stimulation period, and induced durable attenuation of their intrinsic excitability, synaptic activity and spontaneous firing. These results help us better understand the mechanisms of weak magnetic stimulation and should allow optimizing the effectiveness of stimulation protocols for clinical use.

Low intensity repetitive transcranial magnetic stimulation modulates brain-wide functional connectivity to promote anti-correlated c-Fos expression

“…In the acute stimulation group, cortical regions directly beneath the coil showed prominent increases in c-Fos density compared to sham, suggesting that 10 Hz LI-rTMS excites neurons within the induced e-field. Our interpretation is supported by previous electrophysiological experiments showing that 10 Hz LI-rTMS triggers action potentials and increases neuronal firing in the barrel cortex (S1) during stimulation 36 . However, in the period immediately after stimulation, there is electrophysiological evidence for both increases and decreases in neuronal activity: Boyer et al 36 found a reduced neuronal firing rate 10–20 min post-stimulation in the barrel cortex, decreasing neuronal excitability, while Tang et al 37 found that LI-rTMS lowered action potential thresholds in vitro in motor cortical neurons, increasing neuronal excitability.…”

“…Our interpretation is supported by previous electrophysiological experiments showing that 10 Hz LI-rTMS triggers action potentials and increases neuronal firing in the barrel cortex (S1) during stimulation 36 . However, in the period immediately after stimulation, there is electrophysiological evidence for both increases and decreases in neuronal activity: Boyer et al 36 found a reduced neuronal firing rate 10–20 min post-stimulation in the barrel cortex, decreasing neuronal excitability, while Tang et al 37 found that LI-rTMS lowered action potential thresholds in vitro in motor cortical neurons, increasing neuronal excitability. The different experimental preparations (in vivo vs. in vitro ) make the results hard to compare, and in our study we saw increased c-Fos density in both motor and somatosensory cortices with acute LI-rTMS.…”

“…Our interpretation is supported by previous electrophysiological experiments showing that 10 Hz LI-rTMS triggers action potentials and increases neuronal firing in the barrel cortex (S1) during stimulation 36 . However, in the period immediately after stimulation, there is electrophysiological evidence for both increases and decreases in neuronal activity: Boyer et al 36 found a reduced neuronal firing rate 10-20 min post-stimulation in the barrel Table 1. General direction of change in c-Fos expression following Acute or Chronic LI-rTMS, organised across higher order brain classifications.…”

Magnetic field effects in biology from the perspective of the radical pair mechanism

“…The authors concluded that cryptochrome was required for the magnetosensitivity of the neurons, which was consistent with ROS production by activated cryptochrome [222]. In a recent study, the team showed that LI-rTMS (10 mT and 10 Hz) evoked neuronal firing during the stimulation period and induced durable attenuation of synaptic activity and spontaneous firing in cortical neurons of rats in vivo [223].…”

Interactions between Guidance Cues and Neuronal Activity: Therapeutic Insights from Mouse Models

“…To gain a better understanding of how rTMS affects the brain, custom miniature coils have been developed that deliver focal low-intensity (LI) magnetic stimulation ranging between 1 and 150 mT to the rodent brain [ 85 , 102 , 103 ]. These coils were first used in ephrin-KO mice to attempt to increase neuronal activity and repair abnormal topography [ 104 ].…”