Biomechanical Stresses Due to Tissue Micromotion at the Neural Interface Modulate Intracellular Membrane Potentials

Micromotion in brain tissue at a neural interface can arise from respiration and vascular pulsation besides behavioral perturbations. We have reported 2-4 µm of brain tissue displacements in rodents due to vascular pulsation and 10-30 µm due to respiration. It has been hypothesized that the periodic membrane potential (MP) changes observed in neuronal intracellular recordings correlated to tissue micromotion were an artifact. In this study, using penetrating microelectrodes for intracellular recordings in an Aplysia californica abdominal ganglion, we show that the membrane potentials and firing rates change due to periodic cell compression. We show that these membrane potential changes are modulated by calcium, potassium, and mechanosensitive channel blockers. There were no membrane potential changes in response to periodic stresses <1.5 kPa in n=5 cells. Increases in amplitude of periodic stresses resulted in a linear increase in MP fluctuations; action potentials were generated in response to stresses >3 kPa for n=2 silent neurons suggesting the role of mechanosensitive receptors. Neurons that were already firing changed their firing rate in n=3 cells indicating that MP fluctuations are physiological and not artifacts. Application of 5-HT to the ganglion cell, resulted in decreased firing rate indicating that MP fluctuations are potentially modulated by mechanosensitive SK-channels in Aplysia. Preliminary in vivo rodent experiments show that periodic, intracellular membrane potentials fluctuate in the order of 10-30 mV. Using a custom double barrel pipette to (1) record neural activity and (2) to deliver drugs locally, these periodic membrane potential changes due to breathing and heart rate are inhibited by the mechanosensitive ion channel blocker gadolinium chloride. Results of this study suggest that cells at the electrode-brain tissue interface could be potentially undergoing chronic sub-threshold neuromodulation that could impact its long-term functionality and viability.