A Novel Long-term, Multi-Channel and Non-invasive Electrophysiology Platform for Zebrafish.

Zebrafish are a popular vertebrate model for human neurological disorders and drug discovery. Although fecundity, breeding convenience, genetic homology and optical transparency have been key advantages, laborious and invasive procedures are required for electrophysiological studies. Using an electrode-integrated microfluidic system, here we demonstrate a novel multichannel electrophysiology unit to record multiple zebrafish. This platform allows spontaneous alignment of zebrafish and maintains, over days, close contact between head and multiple surface electrodes, enabling non-invasive long-term electroencephalographic recording. First, we demonstrate that electrographic seizure events, induced by pentylenetetrazole, can be reliably distinguished from eye or tail movement artifacts, and quantifiably identified with our unique algorithm. Second, we show long-term monitoring during epileptogenic progression in a scn1lab mutant recapitulating human Dravet syndrome. Third, we provide an example of cross-over pharmacology antiepileptic drug testing. Such promising features of this integrated microfluidic platform will greatly facilitate high-throughput drug screening and electrophysiological characterization of epileptic zebrafish

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 309)

This bibliography lists 136 reports, articles and other documents introduced into the NASA scientific and technical information system in February, 1988

SYNTHESIS AND EVALUATION OF ANTIMICROBIAL ACTIVITY OF PHENYL AND FURAN-2-YL[1,2,4] TRIAZOLO[4,3-a]QUINOXALIN-4(5H)-ONE AND THEIR HYDRAZONE PRECURSORS

A variety of 1-(s-phenyl)-[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one (3a-3h) and 1-(s-furan-2-yl)-[1,2,4]triazolo[4,3- a]quinoxalin-4(5H)-one (5a-d) were synthesized from thermal annelation of corresponding hydrazones (2a-h) and (4a-d) respectively in the presence of ethylene glycol which is a high boiling solvent. The structures of the compounds prepared were confirmed by analytical and spectral data. Also, the newly synthesized compounds were evaluated for possible antimicrobial activity. 3-(2-(4-hydroxylbenzylidene)hydrazinyl)quinoxalin-2(1H)-one (2e) was the most active antibacterial agent while 1-(5-Chlorofuran-2-yl)-[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one (5c) stood out as the most potent antifungal agent

Depth-specific optogenetic control in vivo with a scalable, high density µLED neural probe

Controlling neural circuits is a powerful approach to uncover a causal link between neural activity and behaviour. Optogenetics has been widely adopted by the neuroscience community as it offers cell-type-specific perturbation with millisecond precision. However, these studies require light delivery in complex patterns with cellular-scale resolution, while covering a large volume of tissue at depth in vivo. Here we describe a novel high-density silicon-based microscale light-emitting diode (µLED) array, consisting of up to ninety-six 25 µm-diameter µLEDs emitting at a wavelength of 450 nm with a peak irradiance of 400 mW/mm2. A width of 100 µm, tapering to a 1 µm point, and a 40 µm thickness help minimise tissue damage during insertion. Thermal properties permit a set of optogenetic operating regimes, with ~0.5°C average temperature increase. We demonstrate depth-dependent activation of mouse neocortical neurons in vivo, offering an inexpensive novel tool for the precise manipulation of neural activity

Central nervous system microstimulation: Towards selective micro-neuromodulation

Electrical stimulation technologies capable of modulating neural activity are well established for neuroscientific research and neurotherapeutics. Recent micro-neuromodulation experimental results continue to explain neural processing complexity and suggest the potential for assistive technologies capable of restoring or repairing of basic function. Nonetheless, performance is dependent upon the specificity of the stimulation. Increasingly specific stimulation is hypothesized to be achieved by progressively smaller interfaces. Miniaturization is a current focus of neural implants due to improvements in mitigation of the body's foreign body response. It is likely that these exciting technologies will offer the promise to provide large-scale micro-neuromodulation in the future. Here, we highlight recent successes of assistive technologies through bidirectional neuroprostheses currently being used to repair or restore basic brain functionality. Furthermore, we introduce recent neuromodulation technologies that might improve the effectiveness of these neuroprosthetic interfaces by increasing their chronic stability and microstimulation specificity. We suggest a vision where the natural progression of innovative technologies and scientific knowledge enables the ability to selectively micro-neuromodulate every neuron in the brain

Aerospace Medicine and Biology: Cumulative index, 1979

This publication is a cumulative index to the abstracts contained in the Supplements 190 through 201 of 'Aerospace Medicine and Biology: A Continuing Bibliography.' It includes three indexes-subject, personal author, and corporate source

Human iPSC derived neural cells as models of brain development and as tools in pharmaceutical drug discovery

Human brain evolution has resulted in a cognitive superiority compared to all other animals. Unique cortical structures and expanding progenitor populations have been associated with the possibility for developing a highly folded neocortex and expanded surface area, which is linked to cognitive function. Alongside the development of the neuronal population there has been a remarkable evolution of a second population of brain cells called astrocytes. Astrocytes, which historically have been viewed as the glue of the brain, are now considered as a major regulator of brain homeostasis and neuron communication. Hypothesized to meet the increased complexity of neuronal sub-populations astrocytes have become highly diversified. Specific astrocytes can only be observed in higher primates and generally comprises a more advance form and structure enabling a single astrocyte to support a higher number of neurons. Additionally, it has been shown that human astrocytes can improve cognitive function in mice, an observation signifying the importance of astrocytes in human brain evolution. However, increased complexity is accompanied by biological errors resulting in human specific diseases. Disease mechanisms linked to human biological traits poses challenges when trying to uncover and develop treatments against its pathological conditions using animal models. With decreasing drug developmental programs in the pharmaceutical industry targeting neurological and psychiatric diseases there is a need to improve and accelerate drug discovery in this area. Studying cellular functions of the human brain is challenging partly due to limited accessibility of brain tissue. Historically, the main source of cells was derived from healthy tissue following surgical procedures as well as post-mortem and fetal tissue. However, since the discovery of induced pluripotent stem cells, having the potential to generate any cell type in the body, accessibility to neural like cells has changed dramatically. Common strategies for acquiring neurons and astrocytes from pluripotent stem cells are to try and mimic the naturally occurring embryonic development. However, this requires the establishment of defined and detailed protocols instructing the cells how to develop and becoming the cell type of interest. Neurons follow a step-wise development program which have been uncovered and in great parts mimicked in the lab. However, whether this step-wise developmental progression holds true for astrocytes is yet to be defined. The aim of this thesis was to develop a protocol to derive astrocytes from human induced pluripotent stem cells (hiPSC) and benchmark them against current models available for the pharmaceutical industry. Moreover, the project aimed to establish hiPSC derived neuronal and astrocyte models in a pharmaceutical setting to investigate their potential contribution in drug development. The characterization of four astrocytic models in comparison to a neural stem cell and nonneural model showed expected astrocyte specific characteristics. However, large differences in gene expression and astrocyte associated functions indicated a large heterogeneity among models which was also demonstrated in drug response stimulations. This clearly implies that discovery of new chemical compounds for further drug development will be context dependent, having identification bias towards the model of choice. Moreover, thorough characterization and diverse applications demonstrated a very robust and reproducible protocol for the generation of hiPSC derived astrocytes, a feature naturally critical if utilized in pharmaceutical assays. Finally, in addition to improved functionality compared to conventional models, hiPSC derived astrocytes show developmental traits linked to embryonic development increasing translability and model relevance. Furthermore, in a proof of principle study hiPSC derived neurons were shown to be able to predict unwanted side effect of a drug used to prevent excessive blood loss from major trauma or surgery. The drug is believed to affect specific neurons resulting in involuntary seizures. Besides demonstrating receptor activity of the drug, human iPSC derived neurons were shown to be applicable in the development of new drugs lacking this side effect. Finally, this was performed using a label-free and simple method which is highly applicable for drug screening. In conclusion this thesis presents a protocol for the derivation of an astrocytic model having translatability to the embryonic development and possesses several cellular functions observed by astrocytes in vivo. The application of hiPSC derived neurons and astrocytes in a pharmaceutical setting demonstrate that they can make a significant contribution in drug discovery

Implantable Low-Noise Fiberless Optoelectrodes for Optogenetic Control of Distinct Neural Populations

The mammalian brain is often compared to an electrical circuit, and its dynamics and function are governed by communication across different types neurons. To treat neurological disorders like Alzheimer’s and Parkinson’s, which are characterized by inhibition or amplification of neural activity in a particular region or lack of communication between different regions of the brain, there is a need to understand troubleshoot neural networks at cellular or local circuit level. In this work, we introduce a novel implantable optoelectrode that can manipulate more than one neuron type at a single site, independently and simultaneously. By delivering multi-color light using a scalable optical waveguide mixer, we demonstrate manipulation of multiple neuron types at precise spatial locations in vivo for the first time. We report design, micro-fabrication and optoelectronic packaging of a fiber-less, multicolor optoelectrode. The compact optoelectrode design consists of a 7 μm x 30 μm dielectric optical waveguide mixer and eight electrical recording sites monolithically integrated on each shank of a 22 μm-thick four-shank silicon neural probe. The waveguide mixers are coupled to eight side-emitting injection laser diodes (ILDs) via gradient-index (GRIN) lenses assembled on the probe backend. GRIN-based optoelectrode enables efficient optical coupling with large alignment tolerance to provide wide optical power range (10 to 3000 mW/mm2 irradiance) at stimulation ports. It also keeps thermal dissipation and electromagnetic interference generated by light sources sufficiently far from the sensitive neural signals, allowing thermal and electrical noise management on a multilayer printed circuit board. We demonstrated device verification and validation in CA1 pyramidal layer of mice hippocampus in both anesthetized and awake animals. The packaged devices were used to manipulate variety of multi-opsin preparations in vivo expressing different combinations of Channelrhodopsin-2, Archaerhodopsin and ChrimsonR in pyramidal and parvalbumin interneuron cells. We show effective stimulation, inhibition and recording of neural spikes at precise spatial locations with less than 100 μV stimulation-locked transients on the recording channels, demonstrating novel use of this technology in the functional dissection of neural circuits.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/137171/1/kkomal_1.pd

STEM Undergraduate Research Symposium 2016 Full Program

Full Program of the 2016 LSSF STEM Undergraduate Research Conference