“…In principle, this family of in-vitro MEA technologies utilizes different forms of 3D vertical nano-structures (nano-pillars) that pierce the plasma membrane of cultured cells (by electroporation or spontaneously) in a way similar to classical sharp electrodes (Figure 1 and Tian et al, 2010;Angle and Schaefer, 2012;Duan et al, 2012;Gao et al, 2012;Robinson et al, 2012;Angle et al, 2014;Qing et al, 2014;Abbott et al, 2017;Dipalo et al, 2017;Liu et al, 2017;Abbott et al, 2018;Abbott et al, 2019;Mateus et al, 2019;Li et al, 2020;Teixeira et al, 2020;Yoo et al, 2020;Xu et al, 2021;Zhang et al, 2021). At the same time, a number of laboratories have developed the "IN-CELL" recording and stimulation configuration, in which micrometer-sized, extracellular gold mushroom-shaped microelectrodes (gMμEs) record attenuated synaptic and action potentials (Figure 1 and Spira et al, 2007;Hai et al, 2010b;a;Fendyur and Spira, 2012;Spira and Hai, 2013;Rabieh et al, 2016;Shmoel et al, 2016;Weidlich et al, 2017;McGuire et al, 2018;Spira et al, 2018;Mateus et al, 2019;Spira et al, 2019;Jones et al, 2020;Teixeira et al, 2020). Ultrastructural imaging complemented by electrophysiology and model system analysis of the culturedneurons/gMμEs configuration have revealed that the biophysical principles of "IN-CELL" recordings are identical to those of the perforated patch electrode configuration…”