Micro-connectomics: probing the organization of neuronal networks at the cellular scale.

Defining the organizational principles of neuronal networks at the cellular scale, or micro-connectomics, is a key challenge of modern neuroscience. In this Review, we focus on graph theoretical parameters of micro-connectome topology, often informed by economical principles that conceptually originated with Ramón y Cajal's conservation laws. First, we summarize results from studies in intact small organisms and in samples from larger nervous systems. We then evaluate the evidence for an economical trade-off between biological cost and functional value in the organization of neuronal networks. Various results suggest that many aspects of neuronal network organization are indeed the outcome of competition between these two fundamental selection pressures.This work was supported by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Nature Publishing Group

Neurospheres on Patterned PEDOT:PSS Microelectrode Arrays Enhance Electrophysiology Recordings

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Microelectrode arrays (MEAs) are a versatile diagnostic tool to study neural networks. Culture of primary neurons on these platforms allows for extracellular recordings of action potentials. Despite many advances made in the technology to improve such recordings, the recording yield on MEAs remains sparse. Here, enhanced recording yield is shown induced by varying cell densities on poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)-coated MEAs. It is demonstrated that high cell densities (900 cells mm−2) of primary cortical cells increase the number of recording electrodes by 53.1% ± 11.3%, compared with low cell densities (500 cells mm−2) with 6.3% ± 1.4%. To further improve performance, 3D clusters known as neurospheres are cultured on the MEAs, significantly increasing single unit activity recordings. Extensive spike sorting is performed to analyze the unit activity recording multiple neurons with a single microelectrode. Finally, patterning of polyethylene glycol diacrylate through laser ablation is demonstrated, as a means to more precisely confine neurospheres on top of the electrodes. The possibility of recording single neurons with multiple neighboring electrodes is shown. Overall, a total recording yield of 21.4% is achieved, with more than 90% obtained from electrodes with neurospheres, maximizing the functionality of these planar MEAs as effective tools to study pharmacology-based effects on neural networks

A bilayered PVA/PLGA-bioresorbable shuttle to improve the implantation of flexible neural probes.

OBJECTIVE: Neural electrophysiology is often conducted with traditional, rigid depth probes. The mechanical mismatch between these probes and soft brain tissue is unfavorable for tissue interfacing. Making probes compliant can improve biocompatibility, but as a consequence, they become more difficult to insert into the brain. Therefore, new methods for inserting compliant neural probes must be developed. APPROACH: Here, we present a new bioresorbable shuttle based on the hydrolytically degradable poly(vinyl alcohol) (PVA) and poly(lactic-co-glycolic acid) (PLGA). We show how to fabricate the PVA/PLGA shuttles on flexible and thin parylene probes. The method consists of PDMS molding used to fabricate a PVA shuttle aligned with the probe and to also impart a sharp tip necessary for piercing brain tissue. The PVA shuttle is then dip-coated with PLGA to create a bi-layered shuttle. MAIN RESULTS: While single layered PVA shuttles are able to penetrate agarose brain models, only limited depths were achieved and repositioning was not possible due to the fast degradation. We demonstrate that a bilayered approach incorporating a slower dissolving PLGA layer prolongs degradation and enables facile insertion for at least several millimeters depth. Impedances of electrodes before and after shuttle preparation were characterized and showed that careful deposition of PLGA is required to maintain low impedance. Facilitated by the shuttles, compliant parylene probes were also successfully implanted into anaesthetized mice and enabled the recording of high quality local field potentials. SIGNIFICANCE: This work thereby presents a solution towards addressing a key challenge of implanting compliant neural probes using a two polymer system. PVA and PLGA are polymers with properties ideal for translation: commercially available, biocompatible with FDA-approved uses and bioresorbable. By presenting new ways to implant compliant neural probes, we can begin to fully evaluate their chronic biocompatibility and performance compared to traditional, rigid electronics