Brain Machine Interfaces (BMI) provide a communication pathway between the electrical conducting units of the brain (neurons) and external devices. BMI technology may provide improved neurological and physiological functions to patients suffering from disabilities due to damaged nervous systems. Unfortunately, microelectrodes used in Intracortical Neural Interfaces (INI), a subset of the BMI device family, have yet to demonstrate long-term in vivo performance due to material, mechanical and electrical failures. Many state-of-the-art INI devices are constructed using stacks of multiple materials, such as silicon (Si), titanium (Ti), platinum (Pt), parylene C, and polyimide. Not only must each material tolerate the biological environment without exacerbating the inflammatory response, each of the materials used must physically withstand the environment as well as interact well with each other. One approach to address abiotic mechanisms has been optimizing the materials required to fabricate the INI devices. Silicon Carbide (SiC) is a physically robust, hemo and biocompatible, and chemically inert semiconductor. An ‘all-SiC’, or monolithic SiC, device may be the disruptive technology needed in the BMI field to finally achieve long-term and wide-spread use of this technology in humans. The all-SiC device concept is where SiC serves as all device layers: the base (substrate), the conducting traces (electrodes), and the surface conformal insulating layer. The monolithic SiC neural probe is realized by forming high-quality pn junctions of heavily doped SiC on a layer of the opposite polarity. Heavily doped semiconductors display semi-metallic electrical performance, which allow for efficient electrical conduction in the electrode without the deleterious effects of metal ions interacting with the neural environment. The conformal insulator is realized using amorphous-SiC (a-SiC) which can be patterned to open windows to allow electrical conduction to occur between the electrode tips and the brain. Several generations of monolithic SiC devices have been fabricated, tested and are reported in this dissertation. The devices were fabricated utilizing two polytypes of SiC (4H-SiC and 3C-SiC). The monolithic SiC microelectrodes were fabricated utilizing techniques used in the fabrication of Si based microelectrodes. Monolithic SiC devices fabricated include planar single-ended MEAs (with varying lengths and varying active recording area), 60-channel MEAs for in-vitro studies, and 16-electrode Michigan style neural probes for in-vivo studies. Electrical testing of the pn junction demonstrated that the 4H-SiC device can block a forward bias voltage of up to 2.3V and displays reverse bias leakage below 1 nArms well past -20V. Current leakage between adjacent electrodes was ~7.5 nArms over a voltage range of -50V to +50V. Furthermore, electrochemical results show that the 4H-SiC microelectrodes interact with an electrochemical environment primarily through capacitive mechanisms and has an impedance comparable to gold electrodes. Electrode impedance ranged from 675±130 kΩ (GSA = 496 µm2) to 46.5±4.80 kΩ (GSA = 500K µm2). However, the 4H-SiC devices cannot deliver charge as efficiently as other conventionally used microelectrode materials, such as iridium oxide (IrOx), but a larger water window compensates for this since larger stimulation voltages are supported compared to IrOx. All studies and data collected thus far indicate that the monolithic SiC neural device can aid in the advancement of chronic INI use in clinical settings. The all-SiC devices rely on the integration of only robust and highly compatible SiC material, they may offer a promising solution to probe delamination and biological rejection associated with the use of multiple materials used in many current INI devices. Follow-on work is planned to prove this assertion via in vivo studies.

Made available in DSpace on 2015-03-03T15:15:27Z (GMT). No. of bitstreams: 1 TharcisyoSSD_DISSERT.pdf: 3303211 bytes, checksum: cec9a1421d7e1a74109ea2385531baa3 (MD5) Previous issue date: 2012-03-02 / This study proposes an observing program focused on the investigation of the stellar magnetism and dynamo evolution in cool active solar-like stars. More mainly in the solar analogs and twins. Observations of stars of our base were carried out with two spectropolarimeter (ESPaDOnS@CFHT and NARVAL@TBL). The analyse of stars in stage different allows an understanding of the dependence of magnetic activity on basic stellar parameters such as rotation, mass, age and depth of the convection zone. This study provides measures necessary for testing dynamo theories. The 65 targets for this project are solar type stars with mass spanning from 0:9 M=Mfi 1:075 solar masses and at different evolutionary stages. Our two main science objectives were, (i) To determine how the magnetic field evolved from the ZAMS to the TO (turn off) for stars with 0:9 M=Mfi 1:075; (ii) To determine the impact of convective depth and rotation on magnetic of cool stars of solar type. The main result from this study was the characterization of the dependence of magnetic field intensity as function of age, Rossby number and the convective zone deepening. This context, the availability of ESPaDOnS and NARVAL opens an exceptional possibility to study the magnetic properties of Sun-like stars by means of spectropolarimetric observations / Este estudo prop?e um programa observacional focado na investiga??o da evolu??o do magnetismo estelar e do d?namo em estrelas frias, ativas e do tipo-solar. Mais precisamente nas estrelas an?logas e g?meas solares. As observa??es das estrelas da nossa base foram realizadas com dois espectropolar?metros (ESPaDOnS@CFHT e NARVAL@TBL). A an?lise das estrelas em diferentes est?gios permite uma compreens?o da depend?ncia da atividade magn?tica em fun??o de par?metros estelares b?sicos como, por exemplo, a rota??o, a massa, a profundidade da zona convectiva e a idade. Este estudo fornece medidas necess?rias para testar ? teoria do d?namo. Os 65 objetos utilizados nesse trabalho tratam-se de estrelas do tipo solar, com massa no intervalo de 0:9 < M=M < 1:075 e em diferentes est?gios evolutivos. Nossos dois principais objetivos cient?ficos foram, (i) Determinar como o campo magn?tico evoluiu a partir da sequ?ncia principal de idade zero (ZAMS) at? o turn off, num intervalo de massa 0:9<M=M,<1:075; (ii) Determinar o impacto da profundidade da zona convectiva e da rota??o no magnetismo das estrelas frias do tipo solar. O principal resultado deste estudo foi a caracteriza??o da depend?ncia da intensidade do campo magn?tico com a idade, com o n?mero de Rossby e com o aprofundamento da zona convectiva. Neste contexto, a disponibilidade do ESPaDOnS e NARVAL abre uma excepcional possibilidade para estudarmos as propriedades magn?ticas das estrelas do tipo-solar atrav?s das observa??es espectropolarim?tricas.

Made available in DSpace on 2014-12-17T15:37:14Z (GMT). No. of bitstreams: 1 LuaneMSF_DISSERT.pdf: 1389510 bytes, checksum: 8552b7721296822725c28f11de3be41a (MD5) Previous issue date: 2012-07-30 / GABAergic neurotransmission has been implicated in many aspects of learning and memory, as well as mood and anxiety disorders. The amygdala has been one of the major focuses in this area, given its essential role in modulating emotionally relevant memories. However, studies with male subjects are still predominant in the field. Here we investigated the consequences for an aversive memory of enhancing or decreasing GABAergic transmission in the basolateral nucleus of the amygdala (BLA). Wistar female rats were trained in the plus-maze discriminative avoidance task, in which they had to learn to avoid one of the enclosed arms where an aversive stimulus consisting of a bright light and a loud noise was given (day 1). Fifteen minutes before the test session (day 2) animals received 0,2 &#956;L infusions of either saline solution, the GABAergic agonist muscimol (0,05 mg/ml), or the GABAergic antagonist bicuculine (0,025 mg/ml) bilaterally intra-BLA. On the test day, females in proestrous or estrous presented adequate retrieval and did not extinguish the task, while females in metestrous or diestrous presented impaired retrieval. In the first group, muscimol infusion impaired retrieval and bicuculline had no effect, suggesting naturally low levels of GABAergic transmission in the BLA of proestrous and estrous females. In the second group, muscimol infusion had no effect and bicuculline reversed retrieval impairment, suggesting naturally high levels of GABAergic transmission in the BLA of metestrous and diestous females. Additionally, proestrous and estrous females presented higher anxiety levels compared to metestrous and diestrous females, which could explain better performance of this group. On the other hand, BLA GABAergic system did not interfere with the innate fear response because drug infusions had no effect in anxiety. Thus, retrieval alterations caused by the GABAergic drugs were probably related specifically to memory processes / A transmiss?o GABA?rgica est? envolvida em diversos aspectos do aprendizado e da mem?ria, assim com em transtornos de humor e ansiedade. Um dos grandes focos nessa ?rea tem sido a am?gdala, uma estrutura essencial para a modula??o de mem?rias emocionais. Entretanto, os estudos na ?rea s?o majoritariamente feitos em machos. Nesse trabalho foi investigado em ratas as consequ?ncias de uma transmiss?o GABA?rgica aumentada ou reduzida na am?gdala basolateral (BLA) para uma mem?ria aversiva. Ratas Wistar foram treinadas na esquiva discriminativa no labirinto em cruz elevado, aprendendo a evitar um dos bra?os fechados, onde recebiam um est?mulo aversivo consistindo de uma luz forte e um som alto (dia 1). Quinze minutos antes do teste (dia 2) os animais receberam 0,2&#956;L de solu??o salina, do agonista GABA?rgico muscimol (0,05 mg/ml), ou do antagonista GABA?rgico bicuculina (0,025 mg/ml) bilateralmente intra-BLA. F?meas testadas em proestro e estro evocaram adequadamente e n?o extinguiram a tarefa, enquanto f?meas testadas em metaestro e diestro tiveram um d?ficit na evoca??o. No primeiro grupo, a infus?o de muscimol prejudicou a evoca??o e a infus?o de bicuculina n?o teve efeito, indicando n?veis naturalmente baixos de transmiss?o GABA?rgica na BLA de f?meas em proestro e estro. J? no segundo grupo, a infus?o de muscimol n?o teve efeito e a infus?o de bicuculina reverteu o d?ficit na evoca??o, indicando n?veis naturalmente altos de transmiss?o GABA?rgica na BLA de f?meas em metaestro e diestro. F?meas em proestro e estro apresentaram maiores n?veis de ansiedade quando comparadas ?s f?meas em metaestro e diestro, o qu? poderia explicar o melhor desempenho desse grupo. Entretanto, o sistema GABA?rgico da BLA provavelmente n?o interfere com o medo inato, uma vez que os f?rmacos n?o tiveram efeito na ansiedade. Dessa forma, as altera??es na evoca??o causadas por eles parecem estar relacionadas especificamente a processos mnem?nicos

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-03-09T19:50:49Z No. of bitstreams: 1 TharcisyoSaESousaDuarte_TESE.pdf: 4000536 bytes, checksum: 76f14cacb9f32138dca1e02cb150ad3b (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-03-13T19:38:20Z (GMT) No. of bitstreams: 1 TharcisyoSaESousaDuarte_TESE.pdf: 4000536 bytes, checksum: 76f14cacb9f32138dca1e02cb150ad3b (MD5) / Made available in DSpace on 2017-03-13T19:38:21Z (GMT). No. of bitstreams: 1 TharcisyoSaESousaDuarte_TESE.pdf: 4000536 bytes, checksum: 76f14cacb9f32138dca1e02cb150ad3b (MD5) Previous issue date: 2016-05-20 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O estudo das estrelas do tipo-solar inclui naturalmente as estrelas an?logas e g?meas, que s?o estrelas id?nticas ao Sol. Estes objetos desempenham um papel fundamental no ?mbito da astrof?sica moderna, principalmente, na investiga??o da nossa estrela como um objeto comum. Dentre os diversos par?metros f?sicos observ?veis, a atividade magn?tica e cromosf?rica - para um conjunto de estrelas muito similares ao Sol (an?logas e g?meas) - s?o essenciais para compreendermos a evolu??o din?mica da atividade estelar em escalas de tempo da ordem de v?rios bilh?es de anos, isto ? tempo de vida de uma estrela do tipo-solar sobre a sequ?ncia principal. Neste trabalho, entre outros aspectos, investigaremos as rela??es existentes entre o per?odo de rota??o, abund?ncia de l?tio, atividade magn?tica e cromosf?rica, massa e idades destes grupos de estrelas. Analisaremos ainda as determina??es das idades de acordo com a t?cnica da girocronologia. O objetivo principal do nosso trabalho ? investigar a lei de decaimento de cada um dos destes par?metros com base em uma ampla amostra de estrelas classificadas como an?logas e g?meas solares. Nossos resultados deram origem a quatro publica??es em revistas indexadas, dos quais dois j? se encontram em modo ?impress?. Estes resultados mostram que as leis de evolu??o (decaimento da abund?ncia de l?tio, da rota??o e do campo magn?tico) s?o fortemente dependentes do tipo-estelar, mostrando-se mais nitidez para as estrelas an?logas e g?meas. / The interest in studying the objects similar to the Sun, stars labeled as solar-type stars, analogs and solar twins, brings in its essence an attempt to end out another reference star and, furthermore, provides an investigation of evolutionary dynamic of our star as a function of various parameters. For this, we used three distinct samples of observable data, 170 solar-type stars from BCool catalog and observed with spectropolarimeters ESPaDOnS e NARVAL, 88 solar-twin stars of HARPS surveys, and 20 solar-analog stars from Kepler. From these data, we have investigated mainly the correlation among the rotation period, lithium abundance and stellar age. For the BCool stars and solar-twin from HARPS, we have used the rotation period determined through of chromospheric activity, in the case of Kepler solar analogs, the rotation period it is derived from photometric modulation. The lithium abundance for most of the solar-type and solar-twin stars have been collected from literature, while for the solar analogs, the lithium abundance were determined in the LTE regime using Kurucz atmospheric models and the MOOG code. For stellar age, we have used the gyrochronology method, which was calibrated using the Sun and a selection of open clusters, to redetermine them and comparing them with those derived from standard isochronal. Our results indicate that exist a decay law for the rotation period as a function of lithium abundance. This correlation becomes more clear for the solar-analog and solartwin stars, even the rotation period being determined through distinct mechanisms for each case. For stellar ages, measured from standard isochronal and gyrochronology, we realized that they diverge considerably when the stars are older than the Sun. This result has also been investigated by van Saders et al. (2016) and reect our limitation about thestellar evolution and mixing mechanisms. Our work has resulted in five publications in indexed journals, two already in print format, one recently submitted and other in final stage of conclusion.

Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2018-06-04T18:05:30Z No. of bitstreams: 1 NATALIA_PRADELLA_CIGNACHI_TES.pdf: 6840858 bytes, checksum: 8e5f3ae6a98395bf09135b6770903f35 (MD5) / Rejected by Sheila Dias (sheila.dias@pucrs.br), reason: Devolvido devido ? falta da capa institucional no arquivo em PDF. on 2018-06-14T14:34:13Z (GMT) / Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2018-06-19T13:28:41Z No. of bitstreams: 1 NAT?LIA_PREDELLA_CIGNACHI_TES.pdf: 11102267 bytes, checksum: 121fbf4d2b9ae1c4a36e21d23ab3140d (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-06-27T14:32:32Z (GMT) No. of bitstreams: 1 NAT?LIA_PREDELLA_CIGNACHI_TES.pdf: 11102267 bytes, checksum: 121fbf4d2b9ae1c4a36e21d23ab3140d (MD5) / Made available in DSpace on 2018-06-27T14:43:00Z (GMT). No. of bitstreams: 1 NAT?LIA_PREDELLA_CIGNACHI_TES.pdf: 11102267 bytes, checksum: 121fbf4d2b9ae1c4a36e21d23ab3140d (MD5) Previous issue date: 2018-01-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / This thesis encompasses two parts: firstly, we compared the bone healing in female and male mice, after induction of type 1 diabetes (T1D); secondly, the bone regeneration was evaluated in a menopause model induced by bilateral ovariectomy (OVX), with or without T1D induction. For the part I, the animals (female and male) were initially assigned into two groups, namely control or T1D (elicited by streptozotocin; STZ). In the part II, the females were divided into four experimental groups: sham-operated or OVX, with or without STZ T1D induction. After T1D induction, a monocortical femoral defect was created. In either parts of the present study, we evaluated the effects of supplementation with vitamin D3 and/or insulin. In the second part, the effects of estrogen replacement were also analyzed. Following 21 days of bone defect creation, the animals were euthanized; the femurs and blood were collected for posterior analysis. Both T1D females and males presented a reduction in body weight gain, associated with hyperglycemia. There were no changes in the serum levels of the pro-inflammatory cytokines [interleukin-1? (IL-1?), tumor necrosis factor (TNF) and interferon-? (IFN-?)] in all the evaluated groups. T1D mice of both sexes presented a delayed bone regeneration, according to the histological and micro-CT assessment. The supplementation with vitamin D3 restored the bone healing in female and male T1D mice, reaching values close to controls. The insulin therapy improved the bone remodeling in T1D mice of both sexes, but the effects of this hormone were superior in males. The evaluation of osteoclast activity did not reveal significant differences among the experimental groups. Real time PCR revealed slight differences in the mRNA expression of two transcription factors related to osteoblast differentiation, namely runx2 and osterix, as measured in the area into the bone defect. A higher upregulation of both factors was seen in T1D males treated with vitamin D3. Conversely, vitamin D3-treated T1D females displayed an upregulation of insulin-like growth factor 1 (IGF-1), further indication sex-related differences for the treatments. Besides the experimental protocols described for the 12 part I of this thesis, in the part II, we also evaluated some behavioral locomotor parameters and serum levels of calcium and alkaline phosphatase. OVX animals presented increased body weight gain, accompanied by uterus atrophy. Otherwise, T1D induction elicited a reduction of body weight gain, which was more pronounced in OVX-T1D animals. Serum levels of alkaline phosphatase were divergent in the non-diabetic and T1D OVX animals. Calcium or cytokine levels were similar in all the experimental groups. The sham-operated T1D, the non-diabetic OVX and the OVX-T1D groups presented a delayed bone regeneration, as indicated by histological and micro-CT analysis. Estrogen replacement improved the bone healing in all OVX groups. There was a trend toward an upregulation of IGF-1 mRNA in non-diabetic OVX animals, which was not mirrored in OVX-T1D mice. Locomotor parameters remained unaltered, except by a general reduction of rearing numbers in T1D animals. / A presente tese est? dividida em duas partes: na parte I, comparou-se a regenera??o ?ssea em camundongos f?meas e machos, com diabetes do tipo 1 (T1D). Na parte II, foi avaliada a regenera??o ?ssea no modelo de menopausa experimental induzido por ovariectomia (OVX), com ou sem T1D. Na parte I, os animais (machos e f?meas) foram divididos em dois grandes grupos: controle e T1D (induzido por estreptozotocina; STZ). Na parte II, os animais foram divididos em quatro grandes grupos: f?meas falso-operadas e OVX, com ou sem T1D. Ap?s a indu??o do T1D, foi criado um defeito ?sseo monocortical no f?mur. Nas duas partes do trabalho, foram avaliados os efeitos da suplementa??o com vitamina D3 e/ou insulina. Na segunda parte, tamb?m se avaliou o efeito da reposi??o hormonal com estradiol. Decorridos 21 dias do procedimento da cria??o do defeito, os animais foram eutanasiados; o f?mur e o sangue foram coletados para an?lises posteriores. Tanto as f?meas, quanto os machos T1D, apresentaram uma redu??o do ganho de peso corporal, associado ? hiperglicemia. N?o houve altera??es nos n?veis s?ricos das citocinas pr?-inflamat?rias interleucina-1? (IL-1?), fator de necrose tumoral (TNF) ou interferon-? (IFN?). Os animais T1D, de ambos os sexos, apresentaram um comprometimento na regenera??o ?ssea, como demonstrado pelas an?lises histol?gicas e de micro-CT. A suplementa??o com vitamina D3 reestabeleceu a regenera??o ?ssea em f?meas e machos T1D, apresentando valores pr?ximos aos encontrados nos animais do grupo controle. A terapia com insulina melhorou a remodela??o ?ssea nas f?meas e machos T1D; por?m, os efeitos foram mais pronunciados nos machos. A avalia??o da atividade osteocl?stica n?o revelou diferen?as significativas entre os grupos experimentais, ap?s a indu??o de T1D, em machos ou f?meas. Os resultados do PCR em tempo real para runx2 e osterix (dois fatores de transcri??o relacionados aos osteoblastos), no tecido ?sseo, n?o demonstraram nenhuma diferen?a significativa, exceto por um aumento nos n?veis de RNAm dos dois fatores nos camundongos machos T1D, que receberam suplementa??o com vitamina 10 D3. Por outro lado, f?meas T1D que receberam vitamina D3 apresentaram um aumento na express?o dos n?veis de RNAm para o fator de crescimento semelhante ? insulina do tipo 1 (IGF-1), quando comparado com os machos que tiveram o mesmo tratamento, sugerindo assim, diferen?as relacionadas ao sexo. Al?m das an?lises j? mencionadas anteriormente, na parte II da tese, par?metros comportamentais e n?veis s?ricos de c?lcio e fosfatase alcalina tamb?m foram analisados. Os resultados da segunda parte do trabalho demonstraram que os animais submetidos a OVX tiveram um aumento do peso corporal, com atrofia uterina. Em contrapartida, quando foi induzido T1D, houve uma diminui??o do peso corporal mais acentuada no grupo OVX que no grupo falso-operado. Os animais falso-operados e OVX T1D apresentaram hiperglicemia, confirmando o desenvolvimento do diabetes. Os n?veis s?ricos de fosfatase alcalina foram divergentes entre os grupos n?o-diab?ticos OVX e OVX T1D. N?o houve varia??es dos n?veis de c?lcio. Os animais falso-operados T1D, n?o diab?ticos OVX e OVX T1D apresentaram preju?zos similares na regenera??o ?ssea, como observado pelas an?lises histol?gicas e imagens de micro-CT. A reposi??o com estradiol melhorou a cicatriza??o ?ssea nos animais n?o-diab?ticos OVX e OVX T1D. Houve uma tend?ncia ao aumento nos n?veis de RNAm de IGF-1 no grupo OVX, o que n?o foi observado quando da associa??o de T1D e menopausa. N?o foram observadas diferen?as na atividade locomotora dos animais com T1D e/ou OVX, a n?o ser por uma diminui??o no n?mero de rearings no grupo falso-operado T1D, independente do tratamento com vitamina D3, insulina e estradiol, de forma isolada ou em associa??o.

This dissertation presents an investigation of micromachined three-dimensional microelectrode arrays (3-D MEAs) targeted toward in-vitro and in-vivo biomedical applications. Current 3-D MEAs are predominantly silicon-based, fabricated in a planar fashion, and are assembled to achieve a true 3-D form: a technique that cannot be extended to micro-manufacturing. The integrated 3-D MEAs developed in this work are polymer-based and thus offer potential for large-scale, high volume manufacturing. Two different techniques are developed for microfabrication of these MEAs - laser micromachining of a conformally deposited polymer on a non-planar surface to create 3-D molds for metal electrodeposition; and metal transfer micromolding, where functional metal layers are transferred from one polymer to another during the process of micromolding thus eliminating the need for complex and non-repeatable 3-D lithography processes. In-vitro and in-vivo 3-D MEAs are microfabricated using these techniques and are packaged utilizing Printed Circuit Boards (PCB) or other low-cost manufacturing techniques. To demonstrate in-vitro applications, growth of 3-D co-cultures of neurons/astrocytes and tissue-slice electrophysiology with brain tissue of rat pups were implemented. To demonstrate in-vivo application, measurements of nerve conduction were implemented. Microelectrode impedance models, noise models and various process models were evaluated. The results confirmed biocompatibility of the polymers involved, acceptable impedance range and noise of the microelectrodes, and potential to improve upon an archaic clinical diagnostic application utilizing these 3-D MEAs.

Extracellular neuroelectronic interfacing has important applications in the fields of neural prosthetics, biological computation and whole-cell biosensing for drug screening and toxin detection. While the field of neuroelectronic interfacing holds great promise, the recording of high-fidelity signals from extracellular devices has long suffered from the problem of low signal-to-noise ratios and changes in signal shapes due to the presence of highly dispersive dielectric medium in the neuron-microelectrode cleft. This has made it difficult to correlate the extracellularly recorded signals with the intracellular signals recorded using conventional patch-clamp electrophysiology. For bringing about an improvement in the signalto-noise ratio of the signals recorded on the extracellular microelectrodes and to explore strategies for engineering the neuron-electrode interface there exists a need to model, simulate and characterize the cell-sensor interface to better understand the mechanism of signal transduction across the interface. Efforts to date for modeling the neuron-electrode interface have primarily focused on the use of point or area contact linear equivalent circuit models for a description of the interface with an assumption of passive linearity for the dynamics of the interfacial medium in the cell-electrode cleft. In this dissertation, results are presented from a nonlinear dynamic characterization of the neuroelectronic junction based on Volterra-Wiener modeling which showed that the process of signal transduction at the interface may have nonlinear contributions from the interfacial medium. An optimization based study of linear equivalent circuit models for representing signals recorded at the neuron-electrode interface subsequently iv proved conclusively that the process of signal transduction across the interface is indeed nonlinear. Following this a theoretical framework for the extraction of the complex nonlinear material parameters of the interfacial medium like the dielectric permittivity, conductivity and diffusivity tensors based on dynamic nonlinear Volterra-Wiener modeling was developed. Within this framework, the use of Gaussian bandlimited white noise for nonlinear impedance spectroscopy was shown to offer considerable advantages over the use of sinusoidal inputs for nonlinear harmonic analysis currently employed in impedance characterization of nonlinear electrochemical systems. Signal transduction at the neuron-microelectrode interface is mediated by the interfacial medium confined to a thin cleft with thickness on the scale of 20-110 nm giving rise to Knudsen numbers (ratio of mean free path to characteristic system length) in the range of 0.015 and 0.003 for ionic electrodiffusion. At these Knudsen numbers, the continuum assumptions made in the use of Poisson-Nernst-Planck system of equations for modeling ionic electrodiffusion are not valid. Therefore, a lattice Boltzmann method (LBM) based multiphysics solver suitable for modeling ionic electrodiffusion at the mesoscale neuron-microelectrode interface was developed. Additionally, a molecular speed dependent relaxation time was proposed for use in the lattice Boltzmann equation. Such a relaxation time holds promise for enhancing the numerical stability of lattice Boltzmann algorithms as it helped recover a physically correct description of microscopic phenomena related to particle collisions governed by their local density on the lattice. Next, using this multiphysics solver simulations were carried out for the charge relaxation dynamics of an electrolytic nanocapacitor with the intention of ultimately employing it for a simulation of the capacitive coupling between the neuron and the v planar microelectrode on a microelectrode array (MEA). Simulations of the charge relaxation dynamics for a step potential applied at t = 0 to the capacitor electrodes were carried out for varying conditions of electric double layer (EDL) overlap, solvent viscosity, electrode spacing and ratio of cation to anion diffusivity. For a large EDL overlap, an anomalous plasma-like collective behavior of oscillating ions at a frequency much lower than the plasma frequency of the electrolyte was observed and as such it appears to be purely an effect of nanoscale confinement. Results from these simulations are then discussed in the context of the dynamics of the interfacial medium in the neuron-microelectrode cleft. In conclusion, a synergistic approach to engineering the neuron-microelectrode interface is outlined through a use of the nonlinear dynamic modeling, simulation and characterization tools developed as part of this dissertation research.