In-Cell Nanoelectronics: Opening the Door to Intracellular Electrophysiology

Establishing a reliable electrophysiological recording platform is crucial for cardiology and neuroscience research. Noninvasive and label-free planar multitransistors and multielectrode arrays are conducive to perform the large-scale cellular electrical activity recordings, but the signal attenuation limits these extracellular devices to record subthreshold activities. In recent decade, in-cell nanoelectronics have been rapidly developed to open the door to intracellular electrophysiology. With the unique three-dimensional nanotopography and advanced penetration strategies, high-throughput and high-fidelity action potential like signal recordings is expected to be realized. This review summarizes in-cell nanoelectronics from versatile nano-biointerfaces, penetration strategies, active/passive nanodevices, systematically analyses the applications in electrogenic cells and especially evaluates the influence of nanodevices on the high-quality intracellular electrophysiological signals. Further, the opportunities, challenges and broad prospects of in-cell nanoelectronics are prospected, expecting to promote the development of in-cell electrophysiological platforms to meet the demand of theoretical investigation and clinical application."Image missing"

A simple device to immobilize protists for electrophysiology and microinjection

ABSTRACTWe present a simple device to mechanically immobilize motile cells such as ciliates and flagellates. It can be used in particular for intracellular electrophysiology and microinjection. A transparent filter with holes smaller than the specimen is stretched over an outlet. A flow is induced by either a peristaltic pump or a depressurized tank, mechanically entraining cells to the bottom, where they immobilize against the filter. The cells swim again freely as soon as the flow is stopped. We demonstrate the device by recording action potentials in Paramecium and injecting a fluorescent dye in the cytosol.

Robotic navigation to subcortical neural tissue for intracellular electrophysiology in vivo

This work represents an automated method for accessing subcortical neural tissue for intracellular electrophysiology in vivo. We have implemented a novel algorithm to detect obstructions during regional pipette localization and move around them while minimizing lateral displacement within brain tissue. This approach leverages computer control of pressure, manipulator position, and impedance measurements to create a closed-loop platform for pipette navigation in vivo. This technique enables whole cell patching studies to be performed throughout the living brain.

Transcriptomic correlates of neuron electrophysiological diversity

How neuronal diversity emerges from complex patterns of gene expression remains poorly understood. Here we present an approach to understand electrophysiological diversity through gene expression by integrating transcriptomics with intracellular electrophysiology. Using a brain-wide dataset of 34 neuron types, we identified 420 genes whose expression levels significantly correlated with variability in one or more of 11 electrophysiological parameters. The majority of these correlations were consistent in an independent sample of 12 visual cortex cell types. Many associations reported here have the potential to provide new insights into how neurons generate functional diversity, and correlations of ion channel genes like Gabrd and Scn1a (Nav1.1) with resting potential and spiking frequency are consistent with known causal mechanisms. These results suggest that despite the complexity linking gene expression to electrophysiology, there are likely some general principles that govern how individual genes establish phenotypic diversity across very different cell types.

Three spectrally distinct photoreceptors in diurnal and nocturnal Australian ants

Ants are thought to be special among Hymenopterans in having only dichromatic colour vision based on two spectrally distinct photoreceptors. Many ants are highly visual animals, however, and use vision extensively for navigation. We show here that two congeneric day- and night-active Australian ants have three spectrally distinct photoreceptor types, potentially supporting trichromatic colour vision. Electroretinogram recordings show the presence of three spectral sensitivities with peaks ( λ max ) at 370, 450 and 550 nm in the night-active Myrmecia vindex and peaks at 370, 470 and 510 nm in the day-active Myrmecia croslandi . Intracellular electrophysiology on individual photoreceptors confirmed that the night-active M. vindex has three spectral sensitivities with peaks ( λ max ) at 370, 430 and 550 nm. A large number of the intracellular recordings in the night-active M. vindex show unusually broad-band spectral sensitivities, suggesting that photoreceptors may be coupled. Spectral measurements at different temporal frequencies revealed that the ultraviolet receptors are comparatively slow. We discuss the adaptive significance and the probability of trichromacy in Myrmecia ants in the context of dim light vision and visual navigation.

5-HT is present in nerves of guinea pig sphincter of Oddi and depolarizes sphincter of Oddi neurons

This study involved immunohistochemistry and intracellular electrophysiology to investigate serotonergic neurotransmission in the sphincter of Oddi (SO). 5-Hydroxytryptamine (HT)-positive neurons (14 cells/preparation) and nerve fibers were observed in the ganglionated plexus. Serotonergic nerve fibers, which persisted under 2- to 6-day organ culture, were densely distributed, with varicose endings encircling some SO neurons. When 5-HT was applied to SO neurons, it elicited three different responses: 1) a fast depolarization to 5-HT in 31 of 62 cells was mimicked by 2-methyl-5-HT and blocked by LY-278584 (1 μM); 2) a prolonged depolarization to 5-HT in 21 of 62 cells evoked an increase in input resistance and was attenuated by the 5-HT1P antagonist renzapride (1 μM) but not by the 5-HT4antagonist SDZ-205557 (0.1–10 μM); and 3) an indirect depolarization blocked by TTX or atropine was observed in 32 of 62 cells. 5-HT superfusion elicited a dose-dependent monophasic depolarization (EC50 = 2 μM, n=14). In conclusion, 5-HT is present in nerves of the SO and elicits both 5-HT3 and 5-HT1P receptor-mediated depolarizations, supporting the concept that 5-HT plays a role in SO regulation.