Neurons differentiate magnitude and location of mechanical stimuli

Abstract

Neuronal activity can be modulated by mechanical stimuli. To study this phenomenon quantitatively, we mechanically stimulated rat cortical neurons by shear stress and local indentation. Neurons show 2 distinct responses, classified as transient and sustained. Transient responses display fast kinetics, similar to spontaneous neuronal activity, whereas sustained responses last several minutes before returning to baseline. Local soma stimulations with micrometer-sized beads evoke transient responses at low forces of ∼220 nN and pressures of ∼5.6 kPa and sustained responses at higher forces of ∼360 nN and pressures of ∼9.2 kPa. Among the neuronal compartments, axons are highly susceptible to mechanical stimulation and predominantly show sustained responses, whereas the less susceptible dendrites predominantly respond transiently. Chemical perturbation experiments suggest that mechanically evoked responses require the influx of extracellular calcium through ion channels. We propose that subtraumatic forces/pressures applied to neurons evoke neuronal responses via nonspecific gating of ion channels.

Piezo2, A Pressure Sensitive Channel Is Expressed in Select Neurons of the Mouse Brain: a Putative Mechanism for Synchronizing Neural Networks by Transducing Intracranial Pressure Pulses

“…These results are consistent with earlier and more recent studies of Piezo2 expression rodent and human brains [26,27,34,35,40,41]. Although Piezo2 is well established as a pressure sensitive channel in peripheral neurons [5,[17][18][19][20][21][22][23][24][25] further functional studies, using patch clamp [43] and/or single cell Ca 2+ imaging [44] are required to con rm that Piezo2 is functionally active in these different neuron types. Interestingly, the rst patch clamp study demonstrating single pressure-activated single channel currents in NC and HC pyramidal neurons in mouse brain slices, indicated a low frequency channel activity in the absence of applied pressure that increased in frequency with increasing steady state pressure [43].…”

Ultrasound neuromodulation depends on pulse repetition frequency and can modulate inhibitory effects of TTX

“…Voltage-gated Na 2+ channel conductance has been shown to increase with mechanical deformation 45 , providing a potential mechanism for US ion channel interaction. Gaub et al found that mechanical deformation of neurons with pressures greater than 6 kPa resulted in increased calcium signaling in cultured cortical and hippocampal mouse cells expressing GCaMP6s and suggest sub-traumatic pressures applied to neurons evoke neuronal responses via gating of ion channels 46 . Unique to our results, a concentration of 0.5 µM TTX suppressed the baseline level of calcium signaling, but US still induced calcium mobilization.…”

Displacement Imaging for Focused Ultrasound Peripheral Nerve Neuromodulation

“…The parametric study revealed that CMAPs were observed at the whole range of pulse durations given a sufficiently high pressure. This may indicate that the physical stretch of the nerve from FUS may trigger CMAP events, especially given evidence of established links between mechanical forces and neural function and activity [47], [49]- [51]. Regarding the safety of our technique, H&E stains in Fig.…”