There is a compelling need for the development of new sensory and neural prosthetic devices which are capable of more precise point stimulation. Current prosthetic devices suffer from the limitation of low spatial resolution due to the non-specific stimulation characteristics of electrical stimulation, i.e., the spread of electric fields generated. We present a visible light stimulation method for modulating the firing patterns of electrically-excitable cells using surface plasmon resonance phenomena. In in-vitro studies using gold (Au) nanoparticle-coated nanoelectrodes, we show that this method (substrate coated with nanoparticles) has potential for incorporating the technology into neural stimulation prosthetics, such as cochlear implants, with arbitrarily high spatial resolution. Au nanoparticles (NPs) were coated on micropipettes using aminosilane linkers; and these micropipettes were used for stimulating and inhibiting the action potential firing patterns of SH-SY5Y human neuroblastoma cells and neonatal cardiomyocytes. Our findings pave the way for development of biomedical implants and neural testing devices using nanoelectrodes capable of temporally and spatially precise excitation and inhibition of electrically-excitable cellular activity.

Parkinson’s Disease (PD) is a neurodegenerative disorder, within this categoryof diseases it is among the most prevalent worldwide. The etiology of PD isbased in progressive deterioration of neural tissue in the basal ganglia (neuronalnuclei located at the base of the cerebrum) and their related structures. Current research is focusing on treatment approaches to either enhance or replaceexisting pharmaceutical treatment approaches, such as dopamine replacementtherapy. In this project, the focus was on finding correlates between movementdata and neurological signals to provide insight into potential biomarkers forcomplex motor symptoms of PD. This will in turn provide a starting point forspecifically targeted closed-loop neural stimulation that alleviates these symptoms. Although the data available at the time of this thesis did not providesufficient insight to derive a conclusion on the neural correlates, a pipeline wasdeveloped, which analyzes and synchronizes kinematic and neural data and willenable further exploration as additional data is obtained.

It would be of great value to have a precise and non-damaging neuromodulation technique in the field of basic neuroscience research and for clinical treatment of neurological diseases. Infrared neural modulation (INM) is a new modulation modality developed in the last decade, which uses pulsed or continues infrared (IR) light with a wavelength of 1200 to 2200 nm to directly alter neural signals. INM includes both infrared neural stimulation (INS) and infrared neural inhibition (INI). INM is widely investigated for use on peripheral nerves, cochlear nerve fibers, cardiac cells, and the central nervous system. This technique holds the advantages of contact-free and high spatiotemporal precision compared to the traditional electrical stimulation. It does not depend on genetic modification and exogenous absorbers as other optical techniques, such as the optogenetic technique and the enhanced near-infrared neural stimulation (e-NIR). These advantages make INM a viable technique for research and clinical applications. The primary mechanism of the INM is believed to be a photothermal effect, where the IR laser energy absorbed by water leads to a rapid local temperature change. However, so far the details of the mechanism of action potential (AP) generation and inhibition remain elusive. Another issueis that the cells may be endangeredbythe heat exposure, consequently triggering a physiologicalmalfunction or even permanent damage.These concernshave hindered the transfer of the INM technique to the clinical therapy.Therefore, the general aim of this study was to improve the understanding of the details of how INM affects the cells. Laser parameters for safe and efficient stimulation were investigated on the basis of being useful for clinical applications. A tailored heating model and in vitro INM experiments on cortex neurons were used to reach this goal.The first paper was a feasibility study. A 1550nm laser with a beam spot diameter of around 6 mm was used to irradiate the rat cortex neurons, which were seeded on multi-electrode arrays (MEA) and formed well-connected networks. A heating model based on an estimated laser beam (standard Gaussian distribution) was used to simulate temperaturechanges. The damage signal ratio (DSR),based on the temperature,was calculated to predict the heat damage. The average spike rate of all the working electrodes from two MEAs was used to evaluate the degree of theinhibition of the neural networks. Results IVshowed that it is possible to use the 1550 nm laser to safely inhibit the neural network activity and that the degree of the INI is dependent on the power of the laser.The second paper wasan application and mechanism study. The aim of this study was to investigate the safety, efficiency, and cellular mechanism of INI. The same laser as in paper Iwas used in this study. A 20 X objective was used to decrease the beam spot diameteraround 240 μm. The measured laser profile (high order Gaussian beam) was used in the heating model to predict the temperature. The model was verified by local temperature measurements viamicropipette. The action potential rates, measured by the MEA electrodes, were quantified for different temperatures. Bicuculline was added to the cortex neuron cultures to induce hyperexcitation of the neural network. The results showed that the INI is temperature dependent and that the temperature needs to be less than 46 °C at 30 s laser irradiation for safe inhibition. The IR laser couldalso be used to inhibit the hyperexcitedactivity. The degree of inhibition, for the assessed subpopulation of neurons, was better correlated with the action potential amplitude than the width of it and INIcan be accomplished without inhibitory synapses / <p>QC 20180920</p><p></p>