Joseph J. Pancrazio

PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology. MEA data show that the PIEZO1 agonist Yoda1 transiently enhances the mean firing rate (MFR) of single units, while the PIEZO1 antagonist GsMTx4 inhibits both spontaneous activity and Yoda1-induced increase in MFR in cortical networks. Furthermore, calcium imaging experiments revealed that Yoda1 significantly increased the frequency of calcium transients in cortical cells. Additionally, in voltage clamp experiments, Yoda1 exposure shifted the cellular reversal potential towards depolarized potentials consistent with the behavior of PIEZO1 as a non-specific cation-permeable channel. Our work demonstrates that murine frontal cortical neurons express functional PIEZO1 channels and quantifies the electrophysiological effects of channel activation in vitro. By quantifying the electrophysiological effects of PIEZO1 activation in vitro, our study establishes a foundation for future investigations into the role of PIEZO1 in neurological processes and potential therapeutic applications targeting mechanosensitive channels in various physiological contexts.

Implantable microelectrode arrays (MEAs) enable the recording of electrical activity of cortical neurons, allowing the development of brain-machine interfaces. However, MEAs show reduced recording capabilities under chronic conditions, prompting the development of novel MEAs that can improve long-term performance. Conventional planar, silicon-based devices and ultra-thin amorphous silicon carbide (a-SiC) MEAs were implanted in the motor cortex of female Sprague–Dawley rats, and weekly anesthetized recordings were made for 16 weeks after implantation. The spectral density and bandpower between 1 and 500 Hz of recordings were compared over the implantation period for both device types. Initially, the bandpower of the a-SiC devices and standard MEAs was comparable. However, the standard MEAs showed a consistent decline in both bandpower and power spectral density throughout the 16 weeks post-implantation, whereas the a-SiC MEAs showed substantially more stable performance. These differences in bandpower and spectral density between standard and a-SiC MEAs were statistically significant from week 6 post-implantation until the end of the study at 16 weeks. These results support the use of ultra-thin a-SiC MEAs to develop chronic, reliable brain-machine interfaces.