scholarly journals Development of Optically-Controlled “Living Electrodes” with Long-Projecting Axon Tracts for a Synaptic Brain-Machine Interface

2018 ◽  
Author(s):  
Dayo O. Adewole ◽  
Laura A. Struzyna ◽  
James P. Harris ◽  
Ashley D. Nemes ◽  
Justin C. Burrell ◽  
...  

AbstractAchievements in intracortical neural interfaces are compromised by limitations in specificity and long-term performance. A biological intermediary between devices and the brain may offer improved specificity and longevity through natural synaptic integration with deep neural circuitry, while being accessible on the brain surface for optical read-out/control. Accordingly, we have developed the first “living electrodes” comprised of implantable axonal tracts protected within soft hydrogel cylinders for the biologically-mediated monitoring/modulation of brain activity. Here we demonstrate the controlled fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of neuronal activity within these engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex in vivo as a proof-of-concept for this neural interface paradigm. The creation and functional validation of these preformed, axon-based “living electrodes” is a critical step towards developing a new class of biohybrid neural interfaces to probe and modulate native circuitry.

2021 ◽  
Vol 7 (4) ◽  
pp. eaay5347
Author(s):  
Dayo O. Adewole ◽  
Laura A. Struzyna ◽  
Justin C. Burrell ◽  
James P. Harris ◽  
Ashley D. Nemes ◽  
...  

For implantable neural interfaces, functional/clinical outcomes are challenged by limitations in specificity and stability of inorganic microelectrodes. A biological intermediary between microelectrical devices and the brain may improve specificity and longevity through (i) natural synaptic integration with deep neural circuitry, (ii) accessibility on the brain surface, and (iii) optogenetic manipulation for targeted, light-based readout/control. Accordingly, we have developed implantable “living electrodes,” living cortical neurons, and axonal tracts protected within soft hydrogel cylinders, for optobiological monitoring/modulation of brain activity. Here, we demonstrate fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of these tissue engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex as an in vivo proof of concept for this neural interface paradigm. The creation and characterization of these functional, optically controllable living electrodes are critical steps in developing a new class of optobiological tools for neural interfacing.


2016 ◽  
Vol 102 ◽  
pp. 68-76 ◽  
Author(s):  
Maria Vomero ◽  
Elisa Castagnola ◽  
Emma Maggiolini ◽  
Francesca Ciarpella ◽  
Irene Rembado ◽  
...  

For neural applications, materials able to interface with the brain without harming it while recording high-fidelity signals over long-term implants are still sought after. Glassy Carbon (GC) and Poly (3,4-ethylenedioxythiophene)-poly (styrenesulfonate) (PEDOT-PSS) have proved to be promising materials for neural interfaces as they show – compared to conventional metal electrodes - higher conductivity, better electrochemical stability, very good mechanical properties and therefore seem to be very promising for in vivo applications. We present here, for the first time, a direct comparison between GC and PEDOT-PSS microelectrodes in terms of biocompatibility, electrical and electrochemical properties as well as in vivo recording capabilities, using electrocorticography microelectrode arrays located on flexible polyimide substrate. The GC microelectrodes were fabricated using a traditional negative lithography processes followed by pyrolysis. PEDOT-PSS was selectively electrodeposited on the desired electrodes. Electrochemical performance of the two materials was evaluated through electrochemical impedance spectroscopy and cyclic voltammetry. Biocompatibility was assessed through in-vitro studies evaluating cultured cells viability. The in vivo performance of the GC and PEDOT-PSS electrodes was directly compared by simultaneously recording neuronal activity during somatosensory stimulation in Long-Evans rats. We found that both GC and PEDOT-PSS electrodes outperform metals in terms of electrochemical performance and allow to obtain excellent recordings of somatosensory evoked potentials from the rat brain surface. Furthermore, we found that both GC and PEDOT-PSS substrates are highly biocompatible, confirming that they are safe for neural interface applications.


1995 ◽  
Vol 14 (2) ◽  
pp. 180-186 ◽  
Author(s):  
J. Y. Reginster ◽  
R. Deroisy ◽  
B. Zegels ◽  
I. Jupsin ◽  
A. Albert ◽  
...  

2017 ◽  
Author(s):  
Jackson T. Del Bonis-O’Donnell ◽  
Ami Thakrar ◽  
Jeremy Wain Hirschberg ◽  
Daniel Vong ◽  
Bridget N. Queenan ◽  
...  

ABSTRACTNeurotransmitters are small molecules that orchestrate complex patterns of brain activity. Unfortunately, there exist few sensors capable of directly detecting individual neurotransmitters. Those sensors that do exist are either unspecific or fail to capture the temporal or spatial dynamics of neurotransmitter release. DNA-stabilized silver nanoclusters (DNA-AgNCs) are a new class of biocompatible, fluorescent nanostructures that have recently been demonstrated to offer promise as biosensors. In this work, we identify two different DNA sequences which form dopamine-sensitive nanoclusters. We demonstrate that each sequence supports two distinct DNA-AgNCs capable of providing specific, ratiometric fluorescent sensing of dopamine concentration in vitro. DNA-Ag nanoclusters therefore offer a novel, low-cost approach to quantification of dopamine, creating the potential for real-time monitoring in vivo.


2020 ◽  
Vol 574 ◽  
pp. 118870 ◽  
Author(s):  
Moran Haim Zada ◽  
Awanish Kumar ◽  
Omar Elmalak ◽  
Elana Markovitz ◽  
Ruthy Icekson ◽  
...  

2015 ◽  
Vol 69 (1-2) ◽  
pp. 21-29
Author(s):  
Ljiljana Martac

We used animal model of neurotoxicity in rats, which provided the possibility of studying biological pathophysiological phenomena in vivo and afterwards in vitro conditions. The analysis of electrocortical brain activity using mathematical methods can describe the changes induced by aluminum intoxication in rat as an animal model. In physiological and pathophysiological conditions, on experimental models, mechanisms related to changes in behavior, plasticity and accumulation of aluminum in nervous tissue of the rat brain were observed. Animal models of rats used in the experiments described changes in the group of neuronal activity in the brain of rats in different modes of intoxication aluminum. This study describes ECoG activity in the brain of rats under anesthesia in both the control and aluminum treated animals. Fractal and spectral analysis was used to present qualitative and quantitative changes in the conditions of neurotoxicity. Changes in neurotransmission, as well as the structure and function of the neural network are connected to the molecular-physiological mechanisms of neurotoxicity. Aluminium toxicity was monitored through changes in glutamatergic activity and calcium channel activity. By spectrum analysis neurotoxicity was described through changes in spectral power in the corresponding frequency ranges. By comparing the FD of intoxicated and control individuals there was obtained the range of the change in correlation with the corresponding pathophysiological conditions of intoxication. The shange in FD might be an indication of neurotoxicity.


Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.


Author(s):  
V. A. Maksimenko ◽  
A. A. Harchenko ◽  
A. Lüttjohann

Introduction: Now the great interest in studying the brain activity based on detection of oscillatory patterns on the recorded data of electrical neuronal activity (electroencephalograms) is associated with the possibility of developing brain-computer interfaces. Braincomputer interfaces are based on the real-time detection of characteristic patterns on electroencephalograms and their transformation  into commands for controlling external devices. One of the important areas of the brain-computer interfaces application is the control of the pathological activity of the brain. This is in demand for epilepsy patients, who do not respond to drug treatment.Purpose: A technique for detecting the characteristic patterns of neural activity preceding the occurrence of epileptic seizures.Results:Using multi-channel electroencephalograms, we consider the dynamics of thalamo-cortical brain network, preceded the occurrence of an epileptic seizure. We have developed technique which allows to predict the occurrence of an epileptic seizure. The technique has been implemented in a brain-computer interface, which has been tested in-vivo on the animal model of absence epilepsy.Practical relevance:The results of our study demonstrate the possibility of epileptic seizures prediction based on multichannel electroencephalograms. The obtained results can be used in the development of neurointerfaces for the prediction and prevention of seizures of various types of epilepsy in humans. 


2019 ◽  
Vol 26 (30) ◽  
pp. 5609-5624
Author(s):  
Dijana Saftić ◽  
Željka Ban ◽  
Josipa Matić ◽  
Lidija-Marija Tumirv ◽  
Ivo Piantanida

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.


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