Static magnetic stimulation induces structural plasticity at the axon initial segment of inhibitory cortical neurons

Abstract

Static magnetic stimulation (SMS) is a form of non-invasive brain stimulation that alters neural activity and induces neural plasticity that outlasts the period of stimulation. This can modify corticospinal excitability or motor behaviours, suggesting that SMS may alter the intrinsic excitability of neurons. In mammalian neurons, the axon initial segment (AIS) is the site of action potential initiation and undergoes structural plasticity (changes in length and position from the soma) as a homeostatic mechanism to counteract chronic changes in neuronal activity. We investigated whether the chronic application of SMS (6 and 48 h, 0.5 T) induces structural AIS plasticity in postnatally derived primary cortical neurons. Following 6 h of SMS, we observed a shortening in mean AIS length compared to control, that persisted 24 h post stimulation. In contrast, 48 h of SMS induced an immediate distal shift that persisted 24 h post-stimulation. Pharmacological blockade of voltage gated L/T-type calcium channels during stimulation did not prevent SMS-induced AIS structural plasticity. Our findings provide the foundation to expand the use of chronic SMS as a non-invasive method to promote AIS plasticity.

Opportunities and obstacles in non-invasive brain stimulation

“…Interestingly, stimulation itself can also change structural components of the brain. For instance, subthreshold rTMS alters the dendritic spine structure in pyramidal neurons in mice (Tang et al, 2021 ) and static magnetic stimulation through the use of a permanent magnet has been shown to decrease the length of the axon initial segment in cell cultures (Beros et al, 2022 ). In the development of stimulation configurations, modeling current flow allows for a comprehensive understanding of the interplay between stimulation montage, E-field, and neural orientation (Lee et al, 2021 ).…”