Browsing by Subject "Synapse"

Now showing 1 - 7 of 7
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    A Theoretical Study on Porous-Silicon Based Synapse Design for Neural Hardware
    (IEEE, 2021-12) Sikder, Orthi; Schubert, Peter; Electrical and Computer Engineering, School of Engineering and Technology
    Porous silicon (po-Si) is a form of silicon (Si) with nanopores of tunable sizes and shapes distributed over the bulk structure. Although crystalline Si (c-Si) is already established as one of the most advantageous and promising elements for its technological significance, the additional key aspect of po-Si is its large surface area with respect to its small volume which is beneficial for surface chemistry. In this work, we explore the design of a po-Si based synaptic device and investigate its potential for neuromorphic hardware. First, we analyze several electrical properties of po-Si through density functional theory (Ab Initio/ first principle) calculation. We show that the presence of intra-pore dangling states appears within the bandgap region of po-Si. While the bandgap of the po-Si is well known to be higher than c-Si yielding low carrier density and higher resistance, the appearance of these dangling states can significantly participate in electronic transport through hopping mechanism. Then, we analyze the electric-field driven modulation in the dangling bond through controlled intra-pore Si-H bond dissociation. Such modulation of the dangling state density further allows the tenability of the po-Si conductance. Finally, we theoretically evaluate the current-voltage characteristics of our proposed po-Si based synaptic devices and determine the possible range of obtainable conductivity for different porosity. Our analysis signifies that the integration of such devices in the synaptic fabric can enable significantly denser and energy-efficient neuromorphic hardware.
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    Iron deficiency reduces synapse formation in the Drosophila clock circuit
    (Humana Press, 2019-05) Rudisill, Samuel S.; Martin, Bradley R.; Mankowski, Kevin M.; Tessier, Charles R.; Medical and Molecular Genetics, School of Medicine
    Iron serves as a critical cofactor for proteins involved in a host of biological processes. In most animals, dietary iron is absorbed in enterocytes and then disseminated for use in other tissues in the body. The brain is particularly dependent on iron. Altered iron status correlates with disorders ranging from cognitive dysfunction to disruptions in circadian activity. The exact role iron plays in producing these neurological defects, however, remains unclear. Invertebrates provide an attractive model to study the effects of iron on neuronal development since many of the genes involved in iron metabolism are conserved, and the organisms are amenable to genetic and cytological techniques. We have examined synapse growth specifically under conditions of iron deficiency in the Drosophila circadian clock circuit. We show that projections of the small ventrolateral clock neurons to the protocerebrum of the adult Drosophila brain are significantly reduced upon chelation of iron from the diet. This growth defect persists even when iron is restored to the diet. Genetic neuronal knockdown of ferritin 1 or ferritin 2, critical components of iron storage and transport, does not affect synapse growth in these cells. Together, these data indicate that dietary iron is necessary for central brain synapse formation in the fly and further validate the use of this model to study the function of iron homeostasis on brain development.
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    Loss of F-box only protein 2 (Fbxo2) disrupts levels and localization of select NMDA receptor subunits, and promotes aberrant synaptic connectivity
    (Society for Neuroscience, 2015-04-15) Atkin, Graham; Moore, Shannon; Lu, Yuan; Nelson, Rick F.; Tipper, Nathan; Rajpal, Guatam; Hunt, Jack; Tennant, William; Hell, Johannes W.; Murphy, Geoffrey G.; Paulson, Henry; Department of Otolaryngology -- Head & Neck Surgery, IU School of Medicine
    NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these receptors are highly regulated with respect to their localization, activation, and abundance both within and on the surface of mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models and F-box Only Protein 2 (Fbxo2) knock-out mice, we found that the ubiquitin ligase substrate adaptor protein Fbxo2, previously reported to facilitate the degradation of the NMDAR subunit GluN1 in vitro, also functions to regulate GluN1 and GluN2A subunit levels in the adult mouse brain. In contrast, GluN2B subunit levels are not affected by the loss of Fbxo2. The loss of Fbxo2 results in greater surface localization of GluN1 and GluN2A, together with increases in the synaptic markers PSD-95 and Vglut1. These synaptic changes do not manifest as neurophysiological differences or alterations in dendritic spine density in Fbxo2 knock-out mice, but result instead in increased axo-dendritic shaft synapses. Together, these findings suggest that Fbxo2 controls the abundance and localization of specific NMDAR subunits in the brain and may influence synapse formation and maintenance.
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    Mechanisms of the release of anterogradely transported neurotrophin-3 from axon terminals
    (Society for Neuroscience, 2002-02-01) Wang, XiaoXia; Butowt, Rafal; Vasko, Michael R.; von Bartheld, Christopher S.; Pharmacology and Toxicology, School of Medicine
    Neurotrophins have profound effects on synaptic function and structure. They can be derived from presynaptic, as well as postsynaptic, sites. To date, it has not been possible to measure the release of neurotrophins from axon terminals in intact tissue. We implemented a novel, extremely sensitive assay for the release and transfer of anterogradely transported neurotrophin-3 (NT-3) from a presynaptic to a postsynaptic location that uses synaptosomal fractionation after introduction of radiolabeled NT-3 into the retinotectal projection of chick embryos. Release of the anterogradely transported NT-3 in intact tissue was assessed by measuring the amount remaining in synaptosomal preparations after treatment of whole tecta with pharmacological agents. Use of this assay reveals that release of NT-3 from axon terminals is increased by depolarization, calcium influx via N-type calcium channels, and cAMP analogs, and release is most profoundly increased by excitation with kainic acid or mobilization of calcium from intracellular stores. NT-3 release depends on extracellular sodium, CaM kinase II activity, and requires intact microtubules and microfilaments. Dantrolene inhibits the high potassium-induced release of NT-3, indicating that release of calcium from intracellular stores is required. Tetanus toxin also inhibits NT-3 release, suggesting that intact synaptobrevin or synaptobrevin-like molecules are required for exocytosis. Ultrastructural autoradiography and immunolabel indicate that NT-3 is packaged in presumptive large dense-core vesicles. These data show that release of NT-3 from axon terminals depends on multiple regulatory proteins and ions, including the mobilization of local calcium. The data provide insight in the mechanisms of anterograde neurotrophins as synaptic modulators.
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    Silicon Based Nano-electronic Synaptic Device for Neuromorphic Hardware
    (2024-08) Sikder, Orthi; Schubert, Peter; King, Brian; Rizkalla, Maher; Agarwal, Mangilal
    Porous silicon (po-Si) is a unique form of silicon (Si) that features tunable nanopores distributed throughout its bulk structure. While crystalline Si (c-Si) already boasts technological advantages, po-Si offers an additional key aspect with its large surface area relative to its small volume, making it highly conducive to surface chemistry. In this research, our focus centers on the design of a synaptic device based on po-Si, exploring its potential for neuromorphic hardware applications. To begin, we delve into the analysis of several electrical properties of po-Si using density functional theory (ab initio/first principles) calculations. Notably, we discover the presence of intra-pore dangling states within the bandgap region of po-Si. Although po-Si is known for its higher bandgap compared to c-Si, resulting in low carrier density and increased resistance, the existence of these dangling states significantly impacts its electronic transport. Additionally, we investigate the electric field driven modulation of dangling bonds through controlled intra-pore Si-H bond dissociation. This modulation enables precise control over the density of dangling states, facilitating the tunability of po-Si conductance. Theoretically evaluating the current-voltage characteristics of our proposed po-Si based synaptic devices, we determine the potential range of obtainable conductivity. Finally, we evaluate the performance by integrating porous silicon nanoelectronics devices into neural networks. These devices exhibit superior synaptic plasticity, faster response times, and reduced power consumption compared to other synapses. The research indicates that porous-silicon devices are highly effective in neuromorphic systems, paving the way for more efficient and scalable neural networks. These advancements have significant practical and cost-effective implications for a wide range of applications, including pattern recognition, machine learning, and artificial intelligence. Overall, our analyses reveal that the integration of po-Si based synaptic devices into the neural fabric offers a path towards achieving significantly denser and more energy-efficient neuromorphic hardware. With its tunable properties, large surface area, and potential for controlled conductance, po-Si emerges as a promising candidate for the development of advanced silicon-based nano-electronic devices tailored for neuromorphic computing. As we delve deeper into the potentials of po-Si, the era of cognitive computing, inspired by the elegance of bio-mimetic neural networks, edges closer to becoming a reality.
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    Spinophilin-dependent regulation of GluN2B-containing NMDAR-dependent calcium influx, GluN2B surface expression, and cleaved caspase expression
    (Wiley, 2023) Salek, Asma B.; Claeboe, Emily T.; Bansal, Ruchi; Berbari, Nicolas F.; Baucum, Anthony J., II.; Biology, School of Science
    N-methyl-d-aspartate receptors (NMDARs) are calcium-permeable ion channels that are ubiquitously expressed within the glutamatergic postsynaptic density. Phosphorylation of NMDAR subunits defines receptor conductance and surface localization, two alterations that can modulate overall channel activity. Modulation of NMDAR phosphorylation by kinases and phosphatases regulates the amount of calcium entering the cell and subsequent activation of calcium-dependent processes. The dendritic spine enriched protein, spinophilin, is the major synaptic protein phosphatase 1 (PP1) targeting protein. Depending on the substrate, spinophilin can act as either a PP1 targeting protein, to permit substrate dephosphorylation, or a PP1 inhibitory protein, to enhance substrate phosphorylation. Spinophilin limits NMDAR function in a PP1-dependent manner. Specifically, we have previously shown that spinophilin sequesters PP1 away from the GluN2B subunit of the NMDAR, which results in increased phosphorylation of Ser-1284 on GluN2B. However, how spinophilin modifies NMDAR function is unclear. Herein, we utilize a Neuro2A cell line to detail that Ser-1284 phosphorylation increases calcium influx via GluN2B-containing NMDARs. Moreover, overexpression of spinophilin decreases GluN2B-containing NMDAR activity by decreasing its surface expression, an effect that is independent of Ser-1284 phosphorylation. In hippocampal neurons isolated from spinophilin knockout animals, there is an increase in cleaved caspase-3 levels, a marker of calcium-associated apoptosis, compared with wildtype mice. Taken together, our data demonstrate that spinophilin regulates GluN2B containing NMDAR phosphorylation, channel function, and trafficking and that loss of spinophilin enhances neuronal cleaved caspase-3 expression.
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    Yeast interfering RNA larvicides targeting neural genes induce high rates of Anopheles larval mortality
    (BioMed Central, 2017-11-13) Mysore, Keshava; Hapairai, Limb K.; Sun, Longhua; Harper, Elizabeth I.; Chen, Yingying; Eggleson, Kathleen K.; Realey, Jacob S.; Scheel, Nicholas D.; Severson, David W.; Wei, Na; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    Background Although larviciding can reduce the number of outdoor biting malaria vector mosquitoes, which may help to prevent residual malaria transmission, the current larvicide repertoire is faced with great challenges to sustainability. The identification of new effective, economical, and biorational larvicides could facilitate maintenance and expansion of the practice of larviciding in integrated malaria vector mosquito control programmes. Interfering RNA molecules represent a novel class of larvicides with untapped potential for sustainable mosquito control. This investigation tested the hypothesis that short interfering RNA molecules can be used as mosquito larvicides. Results A small interfering RNA (siRNA) screen for larval lethal genes identified siRNAs corresponding to the Anopheles gambiae suppressor of actin (Sac1), leukocyte receptor complex member (lrc), and offtrack (otk) genes. Saccharomyces cerevisiae (baker’s yeast) was engineered to produce short hairpin RNAs (shRNAs) for silencing of these genes. Feeding larvae with the engineered yeasts resulted in silenced target gene expression, a severe loss of neural synapses in the larval brain, and high levels of larval mortality. The larvicidal activities of yeast interfering RNA larvicides were retained following heat inactivation and drying of the yeast into user-friendly tablet formulations that induced up to 100% larval mortality in laboratory trials. Conclusions Ready-to-use dried inactivated yeast interfering RNA larvicide tablets may someday be an effective and inexpensive addition to malaria mosquito control programmes and a valuable, biorational tool for addressing residual malaria transmission. Electronic supplementary material The online version of this article (10.1186/s12936-017-2112-5) contains supplementary material, which is available to authorized users.