Transparent carbon nanotubes promote the outgrowth of enthorino-dentate projections in lesioned organ slice cultures

The increasing engineering of carbon-based nanomaterials as components of neuro-regenerative interfaces is motivated by their dimensional compatibility with subcellular compartments of excitable cells, such as axons and synapses. In neuroscience applications, carbon nanotubes (CNTs) have been used to improve electronic device performance by exploiting their physical properties. Besides, when manufactured to interface neuronal networks formation in vitro, CNT carpets have shown their unique ability to potentiate synaptic networks formation and function. Due to the low optical transparency of CNTs films, further developments of these materials in neural prosthesis fabrication or in implementing interfacing devices to be paired with in vivo imaging or in vitro optogenetic approaches are currently limited. In the present work, we exploit a new method to fabricate CNTs by growing them on a fused silica surface, which results in a transparent CNT-based substrate (tCNTs). We show that tCNTs favour dissociated primary neurons network formation and function, an effect comparable to the one observed for their dark counterparts. We further adopt tCNTs to support the growth of intact or lesioned Entorhinal-Hippocampal Complex organotypic cultures (EHCs). Through immunocytochemistry and electrophysiological field potential recordings, we show here that tCNTs platforms are suitable substrates for the growth of EHCs and we unmask their ability to significantly increase the signal synchronization and fibre sprouting between the cortex and the hippocampus with respect to Controls. tCNTs transparency and ability to enhance recovery of lesioned brain cultures, make them optimal candidates to implement implantable devices in regenerative medicine and tissue engineering. This article is protected by copyright. All rights reserved

Interfacing neurons with nanostructured electrodes modulates synaptic circuit features

Understanding neural physiopathology requires advances in nanotechnology-based interfaces, engineered to monitor the functional state of mammalian nervous cells. Such interfaces typically contain nanometer-size features for stimulation and recording as in cell-non-invasive extracellular microelectrode arrays. In such devices, it turns crucial to understand specific interactions of neural cells with physicochemical features of electrodes, which could be designed to optimize performance. Herein, versatile flexible nanostructured electrodes covered by arrays of metallic nanowires are fabricated and used to investigate the role of chemical composition and nanotopography on rat brain cells in vitro. By using Au and Ni as exemplary materials, nanostructure and chemical composition are demonstrated to play major roles in the interaction of neural cells with electrodes. Nanostructured devices are interfaced to rat embryonic cortical cells and postnatal hippocampal neurons forming synaptic circuits. It is shown that Au-based electrodes behave similarly to controls. Contrarily, Ni-based nanostructured electrodes increase cell survival, boost neuronal differentiation, and reduce glial cells with respect to flat counterparts. Nonetheless, Au-based electrodes perform superiorly compared to Ni-based ones. Under electrical stimulation, Au-based nanostructured substrates evoke intracellular calcium dynamics compatible with neural networks activation. These studies highlight the opportunity for these electrodes to excite a silent neural network by direct neuronal membranes depolarizatio

Polystyrene nanopillars with inbuilt carbon nanotubes enable synaptic modulation and stimulation in interfaced neuronal networks

The use of nanostructured materials and nanosized-topographies has the potential to impact the performance of implantable biodevices, including neural interfaces, enhancing their sensitivity and selectivity, while reducing tissue reactivity. As a result, current trends in biosensor technology require the effective ability to improve devices with controlled nanostructures. Nanoimprint lithography to pattern surfaces with high-density and high aspect ratio nanopillars (NPs) made of polystyrene (PS-NP, insulating), or of a polystyrene/carbon-nanotube nanocomposite (PS-CNT-NP, electrically conductive) are exploited. Both substrates are challenged with cultured primary neurons. They are demonstrated to support the development of suspended synaptic networks at the NPs' interfaces characterized by a reduction in proliferating neuroglia, and a boost in neuronal emergent electrical activity when compared to flat controls. The authors successfully exploit their conductive PS-CNT-NPs to stimulate cultured cells electrically. The ability of both nanostructured surfaces to interface tissue explants isolated from the mouse spinal cord is then tested. The integration of the neuronal circuits with the NP topology, the suspended nature of the cultured networks, the reduced neuroglia formation, and the higher network activity together with the ability to deliver electrical stimuli via PS-CNT-NP reveal such platforms as promising designs to implement on neuro-prosthetic or neurostimulation devices

New generation of nanostructured sensors and electrodes to bypass CNS lesions

Since the dawn of neurobiology research, neural activity recording and stimulation have experienced a dramatic evolution. Such a process encouraged not only the conception of new technologies to improve our ability to study neurophysiology at the laboratory level, but also the formulation of new solutions to defeat neurological disorder. Among these, neuroprosthetics and neuroelectronic interfaces represent an intriguing panacea to resolve pathological states where conventional methods failed. This arduous challenge requires the collaboration of various subfields in neurobiology research to produce more efficient and highly physiological central nervous system interfacing. In this context, nanotechnologies seem to date eligible candidates to fulfill the needs for the design of next generation implantable neural prosthesis. Size-dependent chemical, topographical or electrical cues can be exploited to mimic biological environments and to faithfully reproduce physiological cells behavior. To safely improve our scientific knowledge about nanotechnologies applicability in biomedicine and more specifically in the context of neuroprosthetics design, a multidisciplinary approach is compulsory. The mutual support between neurobiology and nanoscience has resulted in a large amount of novel neurotechnologies, whose pertinence must be validated by conventional investigation methods in neurobiology to prove their safety and applicability. In particular, in vitro cells and tissue cultures and ex vivo preparations are interrogated by electrophysiology, live imaging, as well as various microscopy and nanoscopy methods, enabling neuroscientists to dissect cell physiology, mechanics and biophysics as a consequence of the interaction with the nanoworld. The purpose of my thesis is to explore the perspective of nanomaterials in the context of neuroprosthetics formulation

Near-Infrared Carbon Nanotube Tracking Reveals the Nanoscale Extracellular Space around Synapses

We provide evidence of a local synaptic nanoenvironment in the brain extracellular space (ECS) lying within 500 nm of postsynaptic densities. To reveal this brain compartment, we developed a correlative imaging approach dedicated to thick brain tissue based on single-particle tracking of individual fluorescent single wall carbon nanotubes (SWCNTs) in living samples and on speckle-based HiLo microscopy of synaptic labels. We show that the extracellular space around synapses bears specific properties in terms of morphology at the nanoscale and inner diffusivity. We finally show that the ECS juxta-synaptic region changes its diffusion parameters in response to neuronal activity, indicating that this nanoenvironment might play a role in the regulation of brain activity

Nanoscale and functional heterogeneity of the hippocampal extracellular space

Summary: The extracellular space (ECS) and its constituents play a crucial role in brain development, plasticity, circadian rhythm, and behavior, as well as brain diseases. Yet, since this compartment has an intricate geometry and nanoscale dimensions, its detailed exploration in live tissue has remained an unmet challenge. Here, we used a combination of single-nanoparticle tracking and super-resolution microscopy approaches to map the nanoscale dimensions of the ECS across the rodent hippocampus. We report that these dimensions are heterogeneous between hippocampal areas. Notably, stratum radiatum CA1 and CA3 ECS differ in several characteristics, a difference that gets abolished after digestion of the extracellular matrix. The dynamics of extracellular immunoglobulins vary within these areas, consistent with their distinct ECS characteristics. Altogether, we demonstrate that ECS nanoscale anatomy and diffusion properties are widely heterogeneous across hippocampal areas, impacting the dynamics and distribution of extracellular molecules

Magnetic detection of neural activity in spinal cord slices

International audienc

Interfacing Neurons with Nanostructured Electrodes Modulates Synaptic Circuit Features

Understanding neural physiopathology requires advances in nanotechnology-based interfaces, engineered to monitor the functional state of mammalian nervous cells. Such interfaces typically contain nanometer-size features for stimulation and recording as in cell-non-invasive extracellular microelectrode arrays. In such devices, it turns crucial to understand specific interactions of neural cells with physicochemical features of electrodes, which could be designed to optimize performance. Herein, versatile flexible nanostructured electrodes covered by arrays of metallic nanowires are fabricated and used to investigate the role of chemical composition and nanotopography on rat brain cells in vitro. By using Au and Ni as exemplary materials, nanostructure and chemical composition are demonstrated to play major roles in the interaction of neural cells with electrodes. Nanostructured devices are interfaced to rat embryonic cortical cells and postnatal hippocampal neurons forming synaptic circuits. It is shown that Au-based electrodes behave similarly to controls. Contrarily, Ni-based nanostructured electrodes increase cell survival, boost neuronal differentiation, and reduce glial cells with respect to flat counterparts. Nonetheless, Au-based electrodes perform superiorly compared to Ni-based ones. Under electrical stimulation, Au-based nanostructured substrates evoke intracellular calcium dynamics compatible with neural networks activation. These studies highlight the opportunity for these electrodes to excite a silent neural network by direct neuronal membranes depolarizatio

High-Performance Implantable Sensors based on Anisotropic Magnetoresistive La 0.67 Sr 0.33 MnO 3 for Biomedical Applications

International audienceWe present the design, fabrication, and characterization of an implantable neural interface based on anisotropic magnetoresistive (AMR) magnetic-field sensors that combine reduced size and high performance at body temperature. The sensors are based on La 0.67 Sr 0.33 MnO 3 (LSMO) as a ferromagnetic material, whose epitaxial growth has been suitably engineered to get uniaxial anisotropy and large AMR output together with low noise even at low frequencies. The performance of LSMO sensors of different film thickness and at different temperatures close to 37 °C has to be explored to find an optimum sensitivity of ∼400%/T (with typical detectivity values of 2 nT•Hz −1/2 at a frequency of 1 Hz and 0.3 nT•Hz −1/2 at 1 kHz), fitted for the detection of low magnetic signals coming from neural activity. Biocompatibility tests of devices consisting of submillimeter-size LSMO sensors coated by a thin poly(dimethyl siloxane) polymeric layer, both in vitro and in vivo, support their high suitability as implantable detectors of low-frequency biological magnetic signals emerging from heterogeneous electrically active tissues