Dissertations / Theses on the topic 'Neurons Models'
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Boatin, William. "Characterization of neuron models." Thesis, Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-04182005-181732/.
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Thesis (M. S.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2006.Dr. Robert H. Lee, Committee Member ; Dr. Kurt Wiesenfeld, Committee Member ; Dr Robert J. Butera, Committee Member.
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Dobbins, Allan C. (Allan Charles). "Difference models of visual cortical neurons." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39539.
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Difference operations are ubiquitous in the visual cortex. The central hypothesis in this thesis is that a nonlinear difference model can account for the functional properties of three different classes of visual cortical neurons. Abstractly each of the different neurons can be understood in terms of the same difference model although the computations they perform can be entirely different.Endstopped neurons respond to short or highly curved oriented patterns. Their behaviour results from the difference in activation of their classical receptive field and inhibitory endzones. Two models of endstopped neurons are evaluated mathematically and by computer simulation. It is concluded that a model with displaced complex cell-like endzones is both more computationally robust and more consistent with the physiological evidence.
Other visual cortical neurons have inhibitory zones which are displaced normally rather than tangentially with respect to the neuron's receptive field orientation. These sidestopped cells are selective for narrow patterns. In other visual cortical neurons the side inhibition is derived from a different eye than the classical receptive field. Because of the geometry of projection these are referred to as binocular Near and Far cells. A difference model of sidestopped and Near and Far neurons is developed which captures their principal features.
Neurons in visual cortical area MT of primates have been shown to exhibit a velocity-specific antagonism between the receptive field and a surrounding region. It is argued that center-surround antagonism is an attempt to resolve competing constraints. Signal reliability increases with spatial averaging, but the variation of the flow field invariably increases with area. A unifying perspective is that difference models provide a means of estimating the range over which a visual quantity is constant or linear. Varieties of these models exist with a more refined property--selectivity for sign of contour curvature or, under certain circumstances, the sign of convexity of the surface generating a binocular disparity or motion field.
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戚大衛 and Tai-wai David Chik. "A numerical study of Hodgkin-Huxley neurons." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31224210.
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Quadroni, Reto. "Realistic models of medial vestibular nuclei neurons /." [S.l.] : [s.n.], 1993. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10255.
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Huss, Mikael. "Computational models of lamprey locomotor network neurons." Licentiate thesis, Stockholm : KTH Numerical Analysis and Computer Science, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-304.
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Shepardson, Dylan. "Algorithms for inverting Hodgkin-Huxley type neuron models." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/31686.
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Thesis (Ph.D)--Algorithms, Combinatorics, and Optimization, Georgia Institute of Technology, 2010.Committee Chair: Tovey, Craig; Committee Member: Butera, Rob; Committee Member: Nemirovski, Arkadi; Committee Member: Prinz, Astrid; Committee Member: Sokol, Joel. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Shaw, Ivan Ting-kun. "Cell death in motor neurons, two complementary models." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0028/NQ50259.pdf.
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Shaw, Ivan Ting-kun 1966. "Cell death in motor neurons : two complementary models." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=35486.
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Target-dependent cell death is an important embryogenic mechanism for regulating and sculpting the developing motor system. Efficient characterization of apoptosis has been more difficult in the nervous system than in other systems due to the use of several different primary culture systems as well as with heterogeneity of neuronal cell populations. We have developed a simple in vitro model of apoptosis with the motor neuron hybrid NSC34, a cell line which expresses much of the motor neuron phenotype (Cashman et al. 1992). Serum-deprived NSC 34 cells in bulk culture undergo cell death, likely from the withdrawal of the growth factors and/or hormones present in fetal calf serum medium supplements. This cell death is accompanied by fragmentation of chromatin into nucleosome multimers, heterochromatization of the nucleus, and other ultrastructural changes reminiscent of apoptotic death. Cell death is inhibitable by addition of agents which block new gene expression ( e.g. cycloheximide) or inhibit endonuclease activity (e.g. aurintricarboxylic acid).We report similar findings with primary embryonic rat motor neurons identified by surface immunoreactivity for p75 LA NGFR, the low-affinity neurotrophin receptor (Bloch-Gallego et al. 1991; Camu and Henderson 1992; Chao and Hempstead 1995). The p75+ motor neuron population could be maintained for more than 48 hours in mixed suspension cultures supplemented with 10% fetal calf serum. However, the p75+ cell population was rapidly depleted in serum-deprived cultures, a phenomenon accompanied by the appearance of oligonucleosomal ladders. Serum-deprived p75+ cells were supported by the motor neuron-relevant factors BDNF, CNTF, GDNF and IGF-1, but not the non-relevant factor NGF. Serum-deprived p75 + cells were also protected by cycloheximide, suggesting a role for apoptosis in the cell death.
We have investigated the role of reactive oxygen species in acquired and genetic motor neuron diseases. Interestingly, a rapid burst of reactive oxygen species is observable within one hour of serum deprivation in both NSC34 and rat motor neuron systems. This burst precedes measurable cell death by at least one day, indicating that oxygen species generation may be an initial hallmark of target-dependent death. The amplitude and temporal nature of this burst may be altered by manipulating various cellular ROS defence mechanisms. Such manipulations also alter cell death progression, suggesting that the apoptotic cascade may be dependent upon this early ROS burst. The identity, source and activity of the relevant ROS may provide insight into the etiology and treatment of human motor neuron diseases.
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Clay, Robert Christopher. "Computer models to simulate ion flow in neurons." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/42951/.
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In this thesis the Drift Diffusion enhanced Hodgkin Huxley model is developed. This model uses the Drift Diffusion equations to model the bulk solutions both within a neuron and in the surrounding extracellular media. The Hodgkin Huxley ion channel behaviour is incorporated into the membrane regions through the use of an altered diffusion coefficient. Firstly the model is applied to the case of intracellular and extracellular media separated by a single membrane. Secondly the model is applied to a cell within a restricted extracellular space. This takes a slice through a cell and is therefore termed a double membrane model, since there are two membrane layers. Finally the model is used to determine whether there is any charge and field buildup on a gold surface located 100 nm from the cell. The results from this could then be used in future to model Surface Plasmon Resonance experiments which may form the basis of novel neuronal activity detectors.
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Mo, Mimi Shin Ning. "Neural vulnerability in models of Parkinson's disease." Thesis, University of Oxford, 2007. http://ora.ox.ac.uk/objects/uuid:ac82e1c1-5d9f-473f-97ac-fcb70b2587ca.
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Parkinson's disease (PD) is a neurodegenerative disorder with no known cure. This thesis explores the degenerative process in two neurotoxin-based models, the 6-hydroxydopamine and the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)/probenecid mouse models, to yield important information about the pathogenesis of PD. Neuronal survival patterns in Parkinsonian patients and animals are heterogeneous. More dopaminergic neurons are lost from the ventral tier of the substantia nigra (SN) than from the dorsal tier or the adjacent ventral tegmental area, possibly due to differential expression of the calcium-binding protein, calbindin D28K. Brain sections were processed for tyrosine hydroxylase (TH) and calbindin (CB) immunocytochemistry to distinguish the dopaminergic subpopulations. I show that more TH+/CB- and TH-/CB+ than TH+/CB+ neurons are lost in both models, suggesting that CB confers some degree of protection for dopaminergic neurons. With respect to connectivity, I show that both TH+ and CB+ neurons receive striatal and dorsal raphe inputs. I investigated the possibility of a progressive loss in midbrain neurons by prolonging the post-lesion survival period. In both models, there is an irreversible neuronal cell loss of TH+, CB+ and TH+/CB+ neurons but the effects of survival time and lesion treatments differ for the three neuronal types. The lesions also appear to be toxic to GABAergic neurons. I explore whether, once neurodegeneration has started, neurons can be rescued by pharmacological intervention. Salicylic acid appears both to reduce microglial activation and significantly improve TH+, but not CB+ or TH+/CB+ neuronal survival. PD appears multifactorial in origin and may involve complex interactions between genetic and environmental influences. I show that a xenobiotic-metabolising enzyme, arylamine N-acetyltransferase may fulfil a neuroprotective role in the SN by limiting the environmental risks. Taken together, this study provides a body of information on two different mouse PD models and highlights possible genetic predispositions to PD neuropathology.
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Vintch, Brett. "Structured hierarchical models for neurons in the early visual system." Thesis, New York University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3591363.
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The early visual system is composed of a set of anatomically distinct areas that are linked together in a hierarchy. This structure uses simple rules at each stage but supports an impressive array of processing capabilities. In order to capture the full range of these computations, neuronal models in these areas should include this hierarchical architecture. Neurons in the earliest stages receive information directly from sensory transducers, yielding linear-like visual representations that are closely tied to visual stimulation. Neurons further downstream are more abstract and nonlinear in their representation, being both more selective for relevant stimulus visual and invariant across irrelevant features. Despite these computational differences, individual neurons among all areas are anatomically similar and they can be described in simple terms; inputs are summed across dendritic synapses and arbors and outputs are generated by a spiking nonlinearity in the soma and axon hillock. This regularity can be exploited to build simple but powerful hierarchical models that approximate the stages of visual processing in cortex.
A realistic model architecture can reduce, and in some cases eliminated altogether, the need for ad-hoc priors or regularizers. Incorporating physiological and anatomical constraints, and careful experimental design (including the choice of stimuli), simplifies models and allows for more direct and efficient estimation procedures. In this thesis I present a series of hierarchical models for neurons in the early visual system (V1 & V2) and show that they can accurately capture the computations performed by real neurons. I also demonstrate that a stage-wise structure avoids overfitting and that it allows for a more efficient estimation procedure than generic statistical models.
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Al-Gonaiah, Majed A. "Investigating xanthine oxidase toxicity models in cultured cerebellar granule neurons." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/1057/.
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In the last few decades, evidence has been accumulating for a role for xanthine oxidoreductase (XOR)-generated toxic reactive oxygen species (ROS) in a variety of pathological conditions that affect different organ systems. This enzyme in mammals exists in two inter-convertible forms: xanthine dehydrogenase (XDH) (the predominant intracellular form under physiological conditions) and xanthine oxidase (XO). A combination of XO and its oxidizable substrate xanthine (X) (or hypoxanthine (HX)) is widely used as a model to produce ROS and to study their effects in a variety of cell culture studies. However, the effect of the combination of XOR and the reduced nicotinamide adenine dinucleotide (NADH) in cell cultures is much less studied. NADH is another oxidizable substrate for XOR that binds to a different site on the enzyme from that of X binding. The aim of this project was to investigate some aspects of the in vitro toxicity of XOR, which might provide more insights into its in vivo toxicity. The main investigation was a comparison between the well studied X / XO and the much less studied NADH / XO toxicity models. Also, secondary studies were undertaken to investigate those aspects of X / XO toxicity where there are uncertainties about them. These studies were performed using primary cell cultures. Cell cultures are now widely used to study different diseases, and although they have their drawbacks, they have their advantages over the in vivo studies. For this project, primary cultures of cerebellar granule neurons (CGNs) were used. In the beginning, some problems were encountered with CGNs. The main problem was the immediate damage induced to the neurons (including those in the control groups) at the intervention/experiments day (i.e. day 8 or 9 after plating) by manipulating the cultures (i.e. aspirating the culture medium, adding treatment and control vehicles, and adding the restoration medium). After several months of investigation, it was serendipitously discovered that the immediate damage seen in the neurons (including those in the control groups) when they are manipulated at the experiments/intervention day was due to glutamate excitotoxicity (through activating its N-methyl-D-aspartate (NMDA) receptors). The source of glutamate was the fresh serum which is present at 10% V/V in the fresh culture medium that is added to the cultures at that day. After solving this problem, it was possible to conduct reliable experiments to investigate XO toxicity models. Regarding investigating XO toxicity, it was found that both of the X / XO and NADH / XO combinations were toxic to cultures of CGNs. However, the concentration of NADH needed to cause the toxicity was much higher than that of the other substrate, X, which is in agreement with previous cell-free experiments that showed that NADH is a much weaker substrate than X for the bovine milk XO used here. Blocking the site of X binding on XO prevented X / XO toxicity, but did not prevent NADH / XO toxicity. On the other hand, blocking the site of NADH binding prevented both X / XO and NADH /XO toxicities. Another difference between the two systems was that deactivating either superoxide or hydrogen peroxide (both are ROS) generated by XO prevented NADH / XO toxicity, whereas although deactivating hydrogen peroxide prevented X / XO toxicity, deactivating superoxide generated from this combination did not. In the NADH / XO system, an extracellular metal contaminant (likely contaminating XO powder/preparation) seemed to be involved in the toxicity. The two toxicity models were similar in the mediation of toxicity by intracellular iron ion. In X / XO toxicity, although superoxide generated extracellularly from the combination has no role in the toxicity, intracellularly produced superoxide seemed to play a role. Conclusions: 1. Culturing/experimental conditions have been optimised for viability studies in CGNs cultures. 2. The combination of NADH and XO induces damage to CGNs, where although blocking the NADH binding site prevents this damage, blocking the X binding site does not. It is feasible that the oxidation of NADH by some forms of XOR (other than the one used here) that are known to be very efficient in oxidizing NADH might produce in vivo toxicity. 3. A possibility raised by this study is that a metal (like the metal contaminant proposed to play a role in NADH / XO toxicity in this study) might contribute to XOR toxicity in vivo. 4. Intracellular superoxide often mediates XOR toxicity. 5. The results add support to many previous studies which suggested that intracellular hydroxyl radical (or a similar species) is involved in XOR toxicity.
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Zhou, Yi-Xiong. "Responses to envelope patterns in visual cortical neurons." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41806.
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Mammalian striate and circumstriate cortical neurons have long been understood as coding spatially localized retinal luminance variations, providing a basis for computing motion, stereopsis, and contours from the retinal image. However, such perceptual attributes do not always correspond to the retinal luminance variations in natural vision. Recordings from area 17 and 18 neurons revealed a specialized nonlinear processing stream that responded to stimulus attributes having no corresponding luminance variations. This nonlinear stream acts in parallel to the conventional luminance processing of single cortical neurons. The two streams were consistent in their preference for orientation and direction of motion, but distinct in processing spatial variations of the stimulus attributes. The ensemble of these neurons provides a combination of stimulus attributes with and without corresponding luminance variations.
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Düsterwald, Kira M. "Exploring the determinants of chloride homeostasis in neurons using biophysical models." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29611.
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Fast synaptic inhibition in the nervous system depends on the transmembrane flux of Cl ions via activated GABAA and glycine receptors. As a result, changes to the neuronal driving force for Cl- are thought to play pivotal roles in many physiological and pathological brain processes. Established theories regarding the determinants of Cl- driving force have recently been questioned based on new experimental data. However, it is experimentally difficult to distinguish the respective contributions of the multiple, dynamically interacting mechanisms which may be important in Cl- homeostasis. Here I present biophysical models of Cl- homeostasis using the pump-leak formulation. By means of numerical and novel analytic solutions, I demonstrate that the Na+/K+-ATPase, ion conductances, impermeant anions, electrodiffusion, water fluxes and cation-chloride cotransporters (CCCs) play roles in setting the Cl- driving force. Importantly, I show that while impermeant anions can contribute to setting [Cl- ]i in neurons, they have a negligible effect on the driving force for Cl locally and cell-wide. In contrast, I demonstrate that CCCs are well-suited for modulating Cl- driving force and hence inhibitory signalling in neurons. This prediction is supported by a meta-analysis of multiple experimental studies, which demonstrates a strong correlation between the expression of the cationchloride cotransporter KCC2 and intracellular Cl concentration. My findings reconcile recent experimental findings and provide a framework for understanding the interplay of different chloride regulatory processes in neurons.
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Zotov, Alexander. "Models of disparity gradient estimation in the visual cortex." Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2008r/zotov.pdf.
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Purvis, Liston Keith. "Models of Single Neurons and Network Dynamics in the Medullary Transverse Slice." Diss., Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/14125.
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The pre-Botzinger complex (pBC) is a sub-circuit of the respiratory central pattern generator. The pBC is required for eupnea and is contained in a transverse slice of the ventrolateral medulla. In the slice, pBC cells are responsible for generating the respiratory rhythm, and hypoglossal motoneurons (HMs) are responsible for transmitting the rhythm out of the brainstem to the muscles. Understanding how the transverse slice rhythm is generated and transmitted is a first step in understanding how this process occurs in vivo. To understand this network, we developed ionic current models of the individual network components and explored how the various ion channels affect single-cell firing characteristics and network dynamics. First, we used the considerable amounts of experimental data from neonatal HMs to develop an HM model. The model was used to explore the roles of ion channels in shaping the complex dynamics of the neonatal HM action potential (AP) and to investigate the age-dependent changes in HMs. We used a genetic algorithm to optimize the HM model to more closely fit experimental measures of AP shape. A comparison of feature-based and template-based fitness functions revealed that a feature-based fitness function performs best when optimizing the HM model to fit characteristics of the neonatal HM AP. Next, we used our existing pBC models to understand how different ionic currents affect rhythmogenesis in the pBC. Our results indicate that intrinsic bursters increase the robustness of rhythm generation in the pBC. Finally, we developed an improved pBC neuron model and explored how various ion channels affect bursting dynamics at the single-cell level. The HM and pBC models developed in this study will be used in future network models of the transverse slice.
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Popova, Dina. "In vitro cellular models for neurotoxicity studies : neurons derived from P19 cells." Doctoral thesis, Umeå universitet, Institutionen för farmakologi och klinisk neurovetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-133030.
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Humans are exposed to a variety of chemicals including environmental pollutants, cosmetics, food preservatives and drugs. Some of these substances might be harmful to the human body. Traditional toxicological and behavioural investigations performed in animal models are not suitable for the screening of a large number of compounds for potential toxic effects. There is a need for simple and robust in vitro cellular models that allow high-throughput toxicity testing of chemicals, as well as investigation of specific mechanisms of cytotoxicity. The overall aim of the thesis has been to evaluate neuronally differentiated mouse embryonal carcinoma P19 cells (P19 neurons) as a model for such testing. The model has been compared to other cellular models used for neurotoxicity assessment: retinoic acid-differentiated human neuroblastoma SH-SY5Y cells and nerve growth factor-treated rat pheochromocytoma PC12 cells. The chemicals assessed in the studies included the neurotoxicants methylmercury, okadaic acid and acrylamide, the drug of abuse MDMA (“ecstasy”) and a group of piperazine derivatives known as “party pills”. Effects of the chemicals on cell survival, neurite outgrowth and mitochondrial function have been assessed. In Paper I, we describe a fluorescence-based microplate method to detect chemical-induced effects on neurite outgrowth in P19 neurons immunostained against the neuron-specific cytoskeletal protein βIII-tubulin. In Paper II, we show that P19 neurons are more sensitive than differentiated SH-SY5Y and PC12 cells for detection of cytotoxic effects of methylmercury, okadaic acid and acrylamide. Additionally, in P19 neurons and differentiated SH-SY5Y cells, we could demonstrate that toxicity of methylmercury was attenuated by the antioxidant glutathione. In Paper III, we show a time- and temperature-dependent toxicity produced by MDMA in P19 neurons. The mechanisms of MDMA toxicity did not involve inhibition of the serotonin re-uptake transporter or monoamine oxidase, stimulation of 5-HT2A receptors, oxidative stress or loss of mitochondrial membrane potential. In Paper IV, the piperazine derivatives are evaluated for cytotoxicity in P19 neurons and differentiated SH-SY5Y cells. The most toxic compound in both cell models was TFMPP. In P19 neurons, the mechanism of action of TFMPP included loss of mitochondrial membrane potential. In conclusion, P19 neurons are a robust cellular model that may be useful in conjunction with other models for the assessment of chemical-induced neurotoxicity.
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Poznanski, R. R., and L. Lee Glenn. "Estimating the Effective Electrotonic Length of Dendritic Neurons With Reduced Equivalent Cable Models." Digital Commons @ East Tennessee State University, 1994. https://dc.etsu.edu/etsu-works/7549.
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White, William E. "Use of Empirically Optimized Perturbations for Separating and Characterizing Pyloric Neurons." Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1368055391.
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Bishop, Matthew William. "Electrophysiological properties of midbrain dopamine neurons in genetic mouse models of Parkinson's disease." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528309.
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Meyer, Georg. "Models of neurons in the ventral cochlear nucleus : signal processing and speech recognition." Thesis, Keele University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334715.
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Takeuchi, Hiroki. "Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone-induced Parkinson's disease models." Kyoto University, 2009. http://hdl.handle.net/2433/124255.
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Luhr, Katarina. "Prion processing and propagation in neuronal and dendritic cell culture models /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-991-9.
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Zhang, Xinmei, and 張新梅. "Generation of mouse models to study intracellular transportation in purkinje cells and melanocytes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B42577779.
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Zhang, Xinmei. "Generation of mouse models to study intracellular transportation in purkinje cells and melanocytes." Click to view the E-thesis via HKUTO, 2004. http://sunzi.lib.hku.hk/hkuto/record/B42577779.
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Clarkson, Jenny, and n/a. "Activation of Gonadotropin-releasing hormone neurons by Kisspeptin in the mouse." University of Otago. Department of Physiology, 2008. http://adt.otago.ac.nz./public/adt-NZDU20081208.114143.
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The gonadotropin-releasing hormone (GnRH) neurons are the final output neurons of a complex neuronal network that controls fertility in all mammals. The GnRH neurons reside in a scattered continuum throughout the anterior hypothalamus. The majority of GnRH neurons project an axon to the median eminence where GnRH is secreted into the hypophyseal-pituitary portal vessels from whence it travels to the anterior pituitary gland. GnRH acts on the gonadotrophs of the anterior pituitary gland to cause the secretion of luteinising hormone (LH) and follicle stimulating hormone (FSH) into the peripheral circulation. LH and FSH act on the gonads to control gametogenesis and steroidogenesis. This thesis focuses on two unanswered questions in reproductive neurobiology that are fundamental to fertility 1) how the GnRH neurons become activated at puberty to produce patterned GnRH secretion and 2) the nature of the positive feedback mechanism that drives the preovulatory GnRH and LH surges.
Recently, a novel neuropeptide called kisspeptin and its G-protein coupled receptor GPR-54 were found to be essential for pubertal activation of GnRH neurons, with GPR-54 mutation or deletion resulting in failed puberty and infertility in humans and mice. In addition, kisspeptin administration potently stimulates GnRH neuron-mediated gonadotropin secretion and advances the onset of pubertal maturation suggesting an important role for kisspeptin in the activation and perhaps post-pubertal modulation of GnRH neurons.
In this thesis I have used immunocytochemical, whole animal manipulations and knockout mouse approaches to investigate the role of kisspeptin in both the activation of GnRH neurons at puberty and in the estrogen positive feedback mechanism in the mouse.
I have demonstrated that kisspeptin neurons are located principally in the rostral periventricular area of the third ventricle (RP3V) and the arcuate nucleus (ARN), which are both known to be important areas for the modulation of GnRH neuronal activity. Kisspeptin fibres are found in abundance throughout the hypothalamus, but of particular interest are the kisspeptin fibres found in close apposition with a subset of GnRH neurons in the rostral preoptic area (rPOA).
The kisspeptin neurons in the RP3V are sexually dimorphic with up to ten times more neurons in the female than the male. The number of kisspeptin neurons in the RP3V increases throughout pubertal development reaching adult levels at the time of puberty in both males and females. In concert with the increase in the number of kisspeptin neurons in the RP3V there is an increase in the percentage of GnRH neurons in the rPOA which exhibited a close apposition with a kisspeptin fibre indicating that kisspeptin neurons may target GnRH neurons to activate them at puberty. Additionally, I demonstrate that the increase in the number of neurons in the RP3V of the female mouse approaching puberty is driven by estrogen secreted from the ovary.
A significant number of kisspeptin neurons in the RP3V were shown to express tyrosine hydroxylase (TH). The number and percentage of kisspeptin cells colocalised with TH cells in the RP3V did not change throughout the estrous cycle. Some colocalisation of kisspeptin and TH was observed at terminal appositions with GnRH neurons in the rPOA, though the magnitude of colocalisation also did not change throughout the estrous cycle.
I demonstrate that RP3V kisspeptin neurons are a critical part of the estrogen positive feedback mechanism which drives the preovulatory GnRH and LH surges. Kisspeptin neurons in the RP3V express steroid receptors and are activated by estrogen positive feedback. Loss of kisspeptin-GPR-54 signalling prevents the GnRH neurons from being activated by estrogen positive feedback indicating that the RP3V kisspeptin neurons not only contribute to the estrogen positive feedback mechanism, but are a critical component of the mechanism.
The results of these studies demonstrate that kisspeptin is an integral component in both the activation of GnRH neurons at puberty and in the estrogen positive feedback mechanism which drives the preovulatory GnRH and LH surges. Therefore, kisspeptin plays an important role in the neuroendocrine control of reproduction in the mouse.
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McCormack, Alison. "The non-human primate as a model of human parkinsonism /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-624-7/.
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Pitcher, Toni Leigh, and n/a. "In vivo electrophysiology of striatal spiny projection neurons in the spontaneously hypertensive rat (SHR)." University of Otago. Department of Anatomy & Structural Biology, 2007. http://adt.otago.ac.nz./public/adt-NZDU20070321.114819.
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The aim of this thesis was to investigate neuronal cellular mechanisms that may underlie the behavioural characteristics of the spontaneously hypertensive rat strain (SHR). The SHR was developed by selective breeding for elevated blood pressure and is also described as having increased levels of locomotor behaviour compared to its normotensive control strain, the Wistar-Kyoto. This hyperactivity and other behaviours, including altered sensitivity to reinforcement, have been used to model aspects of behaviour displayed in attention deficit hyperactivity disorder. In vivo intracellular recording of striatal spiny projection neuron activity in urethaneanaesthetised animals from three genetically related strains: the SHR, Wistar-Kyoto and standard Wistar, was employed to measure basic cellular properties and cellular mechanisms of reward-related learning. This population of neurons was chosen because alterations in their activity can influence behaviour and they are known to show cellular changes (synaptic plasticity) that are associated with learning.
Cellular properties were measured in 71 neurons. Comparison between strains revealed a significant difference in action potential amplitude and duration between the SHR and Wistar-Kyoto strains. Interestingly, when measured at a later time, in a different sample of rats, the SUR action potential amplitude and duration were significantly different from the earlier sample. A change in the membrane potential repolarisation rate following action potential firing also occurred over this time. Twenty-nine of these neurons were also used in a study investigating the neuronal responses to a low dose of amphetamine (0.5 mg/kg). Changes were observed in some cellular properties following intraperitoneal administration of amphetamine.
Synaptic plasticity at the corticostriatal synapses is sensitive to the timing of dopamine release in relation to cortical input. In anaesthetised preparations the spiny projection neuron membrane potential fluctuates between hyperpolarised (DOWN) and depolarised (UP) states, which reflect the level of cortical input. During the present study the responses of nine neurons to the induction of cortical spreading depression were observed to investigate the suitability of this method for use during synaptic plasticity experiments. Spiny projection neurons showed unpredictable responses to cortical spreading depression, therefore this method was not used further. Corticostriatal synaptic plasticity was induced in sixteen spiny projection neurons from two strains: SHR and Wistar. High frequency stimulation of the dopamine neurons in the substantia nigra, during the DOWN-state, did not induce any significant changes in corticostriatal synaptic efficacy. This was also true when high frequency stimulation of dopamine neurons was applied during the UP-state in neurons from the SHR strain.
This thesis represents the first in vivo intracellular study of neuronal physiology in the SHR and Wistar-Kyoto rat strains. Results revealed action potential differences between these two behaviourally distinct rat strains. Synaptic mechanisms thought to underlie reward-related learning were not different between the SHR and Wistar strains, although the observed levels of plasticity were inconsistent with previous literature.
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Reid, Michael Steven. "The Role of Heterogeneity in Rhythmic Networks of Neurons." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/14565.
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Engineers often view variability as undesirable and seek to minimize it, such as when they employ transistor-matching techniques to improve circuit and system performance. Biology, however, makes no discernible attempt to avoid this variability, which is particularly evident in biological nervous systems whose neurons exhibit marked variability in their cellular properties. In previous studies, this heterogeneity has been shown to have mixed consequences on network rhythmicity, which is essential to locomotion and other oscillatory neural behaviors. The systems that produce and control these stereotyped movements have been optimized to be energy efficient and dependable, and one particularly well-studied rhythmic network is the central pattern generator (CPG), which is capable of generating a coordinated, rhythmic pattern of motor activity in the absence of phasic sensory input. Because they are ubiquitous in biological preparations and reveal a variety of physiological behaviors, these networks provide a platform for studying a critical set of biological control paradigms and inspire research into engineered systems that exploit these underlying principles. We are directing our efforts toward the implementation of applicable technologies and modeling to better understand the combination of these two concepts---the role of heterogeneity in rhythmic networks of neurons. The central engineering theme of our work is to use digital and analog platforms to design and build Hodgkin--Huxley conductance-based neuron models that will be used to implement a half-center oscillator (HCO) model of a CPG. The primary scientific question that we will address is to what extent this heterogeneity affects the rhythmicity of a network of neurons. To do so, we will first analyze the locations, continuities, and sizes of bursting regions using single-neuron models and will then use an FPGA model neuron to study parametric and topological heterogeneity in a fully-connected 36-neuron HCO. We found that heterogeneity can lead to more robust rhythmic networks of neurons, but the type and quantity of heterogeneity and the population-level metric that is used to analyze bursting are critical in determining when this occurs.
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Karam, Philippe Chucri. "Modeling passive and active mechanisms in motoneuron dendrites." Thesis, Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/13713.
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Laudanski, Jonathan. "Integrate-and-fire models in the auditory system : Dynamics of single neurons and neural populations." Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523713.
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Aquili, Luca. "Refinement of biologically inspired models of reinforcement learning." Thesis, St Andrews, 2010. http://hdl.handle.net/10023/886.
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Ahmadi, Ferogh Ali. "The mechanism of pesticide rotenone-induced cell death in models of Parkinson's disease /." Connect to full text via ProQuest. IP filtered, 2005.
Find full textAbstract:
Thesis (Ph.D. in Neuroscience) -- University of Colorado at Denver and Health Sciences Center, 2005.Typescript. Includes bibliographical references (leaves 110-128). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;
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Capanni, Niccolo Francesco. "The functionality of spatial and time domain artificial neural models." Thesis, Robert Gordon University, 2006. http://hdl.handle.net/10059/241.
Full textAbstract:
This thesis investigates the functionality of the units used in connectionist Artificial Intelligence systems. Artificial Neural Networks form the foundation of the research and their units, Artificial Neurons, are first compared with alternative models. This initial work is mainly in the spatial-domain and introduces a new neural model, termed a Taylor Series neuron. This is designed to be flexible enough to assume most mathematical functions. The unit is based on Power Series theory and a specifically implemented Taylor Series neuron is demonstrated. These neurons are of particular usefulness in evolutionary networks as they allow the complexity to increase without adding units. Training is achieved via various traditiona and derived methods based on the Delta Rule, Backpropagation, Genetic Algorithms and associated evolutionary techniques. This new neural unit has been presented as a controllable and more highly functional alternative to previous models. The work on the Taylor Series neuron moved into time-domain behaviour and through the investigation of neural oscillators led to an examination of single-celled intelligence from which the later work developed. Connectionist approaches to Artificial Intelligence are almost always based on Artificial Neural Networks. However, another route towards Parallel Distributed Processing was introduced. This was inspired by the intelligence displayed by single-celled creatures called Protoctists (Protists). A new system based on networks of interacting proteins was introduced. These networks were tested in pattern-recognition and control tasks in the time-domain and proved more flexible than most neuron models. They were trained using a Genetic Algorithm and a derived Backpropagation Algorithm. Termed "Artificial BioChemical Networks" (ABN) they have been presented as an alternative approach to connectionist systems.
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Brook, Sapoty, and mikewood@deakin edu au. "A physical theory of organisation and consequent neural model of spatio-temporal pattern acquisition." Deakin University. School of Architecture and Engineering, 1987. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20050825.121850.
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A neurone model (the FORMON) is proposed which provides a mathematical explanation for a range of psychological phenomena and has potential in Artificial Intelligence applications. A general definition of organisation in terms of entropy and information is formulated. The concept of microcodes is introduced to describe the physical nature of organisation.
Spatio-temporal pattern acquisition and processing functions attributable to individual neurones are reviewed. The criterion for self-organisation in a neurone is determined as the maximisation of mutual organisation. A feedback control system is proposed to satisfy this criterion and provide an integrated long-term memory of spatio-temporal pattern. This pattern acquisition system is shown to be applicable to dendritic pattern recognition and axonal pattern generation. Provision is also made for adaptation, short-term memory and operant learning.
An electro-chemical model of transmission and processing of neural signals is outlined to provide the pattern acquisition functions of the Formon model. A transverse magnetic mode of electrotonic propagation is postulated in addition to the transverse electromagnetic mode.
Configurations of the Formon are categorised in terms of possible pattern processing functions. Connective architectures are proposed as self-organising models of acquisitive semantic and syntactic networks.
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Zhang, Yalun, and 张亚伦. "Pax6/c-Myb regulates neuronal apoptosis in a mouse model of Alzheimer's disease." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47331148.
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Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder which
is characterized by impaired mental functions such as memory, language,
perception, behavior and personality, as well as cognitive skills. The molecular
mechanisms underlying this disease is still largely unknown, but numerous
evidence emerge to support a cell cycle hypothesis which implicates the
deregulation of cell cycle proteins as key mediators of neuronal dysfunction and
loss in AD brains. One of these signals in Aβ-induced neuronal death model is
Cdk/Rb/E2F pathway, where Aβ insult evokes activation of Cdk4/6, which
subsequently phosphorylates pRb protein, resulting in activation of E2F
transcription factors. However, the mechanism(s) by which Cdk/Rb/E2F mediates
neuronal death remains elusive. Therefore, the goal of this project is to
characterize the downstream events of cell cycle pathway, which include the
involvement of transcription factors c-Myb, Pax6 and Patz1 in Aβ-induced
neuronal death signaling. In this study, we showed that Pax6 is a direct target gene
for Both E2F1 and c-Myb. Both Pax6 and c-Myb are up-regulated by Aβ insults in
cultured cortical neurons. And with E2F1 silencing by siRNA, Aβ-induced Pax6
and c-Myb expression is blocked, suggesting E2F1 is responsible for their
elevation. Importantly, siRNA-mediated downregulation of either c-Myb or Pax6
protects neurons from death evoked by Aβ peptide, suggesting they are proapoptotic
proteins, delivering death signals sent from upstream E2F1. Next,
though ChIP assay, we identified two target genes for Pax6. One is Patz1, another
transcription factor that is Aβ-induced pro-apoptotic protein. The other one is
GSK3β, which is a pathogenic kinase involved in Tau protein
hyperphosphorylation and NFT formation. In conclusion, this dissertation shows
that cell cycle regulators Cdk/Rb/E2F modulate neuronal death signals by
activating downstream transcription factors c-Myb and Pax6, further upregulating
GSK3β. We provided evidence suggesting that Aβ induced neurotoxicity leads to
Tau hyperphosphorylation through a mechanism involving cell cycle activation
and subsequent activation of c-Myb/Pax6/GSK3β. In brief, in the present study,
we delineate a transcriptional cascade downstream of cell cycle pathway leads to
neuronal apoptosis as well as Tau/NFT pathology. The characterization of this
novel pathway lends support for development of new therapeutic agents and for
better experimental models for AD. Lastly, the cascade between cell cycle
activation and tauopathy in Aβ-induced neuronal death needs to be further
researched in the future.HKU 3 Minute Thesis Award, Champion (2011)
published_or_final_version
Biochemistry
Doctoral
Doctor of Philosophy
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Weber, Cornelius. "Maximum a posteriori models for cortical modeling feature detectors, topography and modularity." Saarbrücken VDM Verlag Dr. Müller, 2000. http://d-nb.info/989177149/04.
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Weber, Franz. "System identification of optic-flow processing neurons in the fly: single cell and small circuit models." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-139155.
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Hoyland, Darren Stephen. "Integrated data collection and automated parameter estimation in the construction of computational models of neostriatal neurons." Thesis, University of Sheffield, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522410.
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Fain, Misty, Brooke Beasley, Ryan Abens, Kyla Scott, Wesley Gill, and Michelle Chandley. "NTRK2 Gene Expression Levels in Laser Captured Glutamatergic Neurons From Animal Models of Social Behavior Deficits." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/43.
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Autism spectrum disorder (ASD) is a neurodevelopmental disability affecting communication and social behaviors. Research is needed because the percentage of children affected by ASD is 1 in 59, and it is diagnosed in males at a rate of 1 in 42. Animal models must be used, because the neurological changes that lead to ASD occur during prenatal development. In this study, three mouse models were used to represent possible causes of ASD. The BTBR model is a genetically engineered model that displays social behavior deficits and has neuroanatomical findings similar to ASD. The other models include the Poly-IC and valproic acid injected mice which exposes the pregnant mother to a virus activating her immune system or a drug thought to affect brain development, respectively. In all three models the effects of brain-derived neurotrophic factor or BDNF, which is an important cytokine in the brain responsible for synaptic plasticity, maintenance and recognition, are being studied via expression levels of NTRK2. BDNF activates cell signaling cascades in glutamatergic neurons via the TrkB receptor which is encoded by the NTRK2 gene. It was previously found that NTRK2 expression was reduced in glutamatergic cells in people affected by ASD. The first outcome of the study is to determine gene expression differences in glutamatergic neurons captured from the cingulate cortex in all three models as well as in wild type control mice. Additionally, a second outcome of the study is to optimize a new protocol for single cell gene expression using a nested PCR method. This was done by comparing the previously used method for relative end-point PCR with the nested method to identify gene expression alterations. To prepare for the two PCR methods, samples were dehydrated and laser capture microdissection was performed on mouse brain tissue to obtain pyramidal neurons from the cingulate area. This area is highly connected to the limbic system and plays a role in personality and communication. All animal procedures were approved by the ETSU animal care committee. RNA isolation was performed on 1000 cells after which RNA was reverse transcribed into cDNA using the Superscript III cDNA synthesis system. Initial optimization experiments included using various amounts of starting cDNA and determining expression differences using relative end-point PCR and Agilent tape station. The same starting cDNA was used and initially 20 cycles of PCR were performed using Prime5 HotStart Master Mix followed by a quantitative PCR reaction using Powerup on the BioRad CFX96 RT detection system. Gene expression was performed using NTRK2 as the target gene and GAPDH as the reference gene for each method. Both methods will allow the detection of changes in the expression levels of NTRK2 and GAPDH when different sample concentrations are used. This data could help establish a link between maternal immune system activation or exposure to certain drugs during pregnancy with the occurrence of ASD.
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Scullion, Sarah. "Investigating the neurophysiology of layer II/III neurons in the perirhinal cortex in models of dementia." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.684362.
Full textAbstract:
Dementia is a broad category of brain diseases. These are characterised by loss of memory, reasoning, and sometimes personality and behaviour changes. The most common form of dementia is Alzheimer's Disease (AD), histopathologically recognised by extracellular plaques of amyloid-13 (AI3) and intracellular inclusions of neurofibrillary tangles composed of hyperphosphorylated tau. Another common form of dementia is Frontotemporal dementia with parkinsonism- linked to chromosome 17 (FTDP-17), associated with hyperphosphorylated tau. Animal models of these diseases are important in furthering the understanding of dementia. Anatomical and pharmacological lesion studies have demonstrated that the perirhinal (PRh) cortex is essential for recognition memory; failure of this particular form of memory is often an early indicator of AD. Moreover, the PRh cortex can express a form of long-term depression (LTD) that is thought to underlie recognition memory. Aβ has been found to cause dendritic degeneration and to disrupt both synaptic plasticity and working memory in the hippocampus. The present study aims to examine LTD in the PRh cortex during acute oligomeric Aβ42 pre-treatment, mimicking early stages of Aβ pathology in AD. Furthermore, the effects of AI3 pretreatment on intrinsic neuronal firing and plasticity were investigated. Aβ profoundly inhibited a form of NMDAR-dependent LTD. AI3 also altered the firing frequency of mAChR-dependent persistent activity, a cellular correlate to working memory. However, Aβ did not alter any intrinsic neuronal properties, suggesting that acute AI3 application preferentially affects synapses. Recognition memory and LTD in the PRh cortex were investigated in a FTDP-17 model mouse, Tg4510. This model overexpresses a mutant hyperphosphorylated Tau and exhibits profound neuron loss alongside behavioural and memory deficits. The present study found that recognition memory is impaired in Tg4510 mice alongside a deficit in mAChR-dependent LTD in the PRh cortex. Donepezil, a cholinesterase inhibitor, can ameliorate the effect of hyperphosphorylated tau on LTD in the PRh cortex. Interestingly, the LTD examined in this 8-10 month old mouse model was found to be dependent on a different mechanism compared to the 4-5 week old mice used previously. These data explore the neurophysiological characteristics of neurons in layer 111111 of the PRh cortex and provide evidence of the deleterious effects of two pathological molecules involved in AD and tauopathies.
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Ellis, William Joseph. "Application of statistical mechanics to a model neuron /." Title page, contents and abstract only, 1993. http://web4.library.adelaide.edu.au/theses/09PH/09phe479.pdf.
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Norman, Timothy Alfred Jr. "Molecular and morphological analyses of basal forebrain cholinergic neurons in mouse models of aging and Alzheimer's disease." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12173.
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Thesis (M.A.)--Boston UniversityBasal forebrain cholinergic neurons (BFCNs) of the medial septal nuclei, the diagonal bands of Broca and the nucleus basalis magnocellularis synthesize acetylcholine (ACh) and their projections extend to the cerebral cortex, hippocampus and the amygdala. ACh neurotransmission is essential for learning, attention, memory, arousal and sleep. BFCNs are dependent on a regulated neurochemical environment for the induction, development, maturation and maintenance of their phenotype and viability. However, events that compromise this neurochemical environment can contribute to BFCN dysfunction and/or degeneration, decreased ACh levels and disrupted brain function. During normal aging and Alzheimer’s disease (AD) BFCNs become more vulnerable to dysfunction due to trophic factor withdrawal, cell signaling impairments and other cytopathologic changes. AD is characterized by the deposition of Amyloid-beta (Aβ) plaques and neurofibrillary Tau tangles (NFTs) in the cortex and hippocampus. These pathological AD hallmarks overlap with cortical and hippocampal cholinergic dysfunction, implicating both as the drivers of cognitive and behavioral decline associated with AD. Since, BFCNs are highly vulnerable to AD pathophysiology, factors that support the BFCN phenotype may have practical use in preserving neuronal networks and cognitive function. There is now strong evidence that bone morphogenetic protein-9 (BMP9 also known as growth/differentiating factor 2, GDF2) acts as an induction and maintenance factor that regulates BFCN differentiation in-vitro and in-vivo. Here we used transgenic mice that express green fluorescent protein (GFP) in BFCNs to make observations concerning the BFCN phenotype in aging and AD. We found qualitative evidence that BFCNs of the 24-month old WT/ChAT-GFP mice were smaller and more rounded with shorter processes when compared to 6- month old mouse BFCNs. We analyzed the effects of intracerebroventricular infusion of BMP9 on BFCN projection fibers in the APPswe/PS1dE9 mouse model of AD using laser scanning confocal microscopy. BMP9 not only increased the density of cholinergic projection fibers in the hippocampus of wild type and AD model APPswe/PS1dE9 mice, but it also reduced the plaque burden in the hippocampus of the AD mouse model. These data indicate that BMP9 ameliorated two major pathophysiologic hallmarks of AD, observable in these transgenic APPswe/PS1dE9 mice. BMP9 reduced Aβ plaque burden in this AD model, and enhanced the outgrowth and viability of cholinergic fibers within the hippocampus of both wild-type and APPswe/PS1dE9 mice. [TRUNCATED]
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Kaplan, Eitan S. "Visual cortical plasticity : the role of parvalbumin expressing inhibitory neurons and abnormalities in models of neurodevelopmental disorders." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/103210.
Full textAbstract:
Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2016.Cataloged from PDF version of thesis. Vita.
Includes bibliographical references (pages 121-134).
The roles played by cortical inhibitory neurons in experience-dependent plasticity and learning are not well understood. Here we evaluate the participation of parvalbumin-expressing (PV+) GABAergic neurons in two forms of experience-dependent modification of primary visual cortex (V1) in adult mice: ocular dominance (OD) plasticity resulting from monocular deprivation and stimulus-selective response potentiation (SRP) resulting from supplemental visual experience. These two forms of plasticity are triggered by different events but lead to a similar increase in visual cortical response. Both also require the NMDA class of glutamate receptor (NMDAR). However, we find that PV+ inhibitory neurons in V1 play a critical role in the expression of SRP and its behavioral correlate of familiarity recognition, but not in the expression of OD plasticity. Furthermore, NMDARs expressed within PV+ cells play a critical role in SRP, but not in the induction or expression of adult OD plasticity. We also explore the use of visual cortical plasticity paradigms to better understand the function of proteins implicated in autism spectrum disorders (ASDs) and schizophrenia. We find that NMDAR-dependent long-term depression (LTD) and deprived-eye depression in layer 4 of V1 require metabotropic glutamate receptor 5 (mGluR5) signaling during postnatal development. Additionally, schizophrenia-associated protein neurogranin overexpression in V1 disrupts juvenile ocular dominance plasticity. Finally, we evaluate SRP in two models of ASDs associated with excitatory/ inhibitory imbalance: Rett syndrome (RTT) and tuberous sclerosis complex (TSC). Surprisingly, mouse models of RTT and TSC exhibit abnormal SRP phenotypes, but in opposite directions.
by Eitan S. Kaplan.
Ph. D. in Neuroscience
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Wedin, Mattias, and Isak Bengtsson. "A Comparative Study on Machine Learning Models for Automatic Classification of Cell Types from Digitally Reconstructed Neurons." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-301744.
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For the last decade, the use of machine learning in neuroscientific research has become a popular topic. For instance, image recognition has been used together with machine learning to detect and also help improve the diagnostics of diseases. This study compares the accuracy of a Convolutional Neural Network (CNN), a support vector classifier and a random forest classifier to investigate which are better suited for classification of cell types based on digitally reconstructed images from mice. All models were trained on both a larger unbalanced dataset containing 49 different cell types and a smaller balanced dataset containing only 3 types. Each model was evaluated on how accurate they could classify all cell types but also their accuracy on individual cell types. The results showed that the convolutional neural network had the best mean accuracy, with 51 and 83 percent on respective datasets. When looking at classification of individual cell types, all the models had good accuracy on at least a few cell types, but still, the CNN had the best individual accuracy and also consistency. In conclusion, the results showcase that a convolutional neural network is probably better suited when classifying cell types from digitally reconstructed images, but the other methods could also perform well on some of the cell types. However, further research is needed to reach a higher accuracy and reliability of the results.Under det senaste decenniet har användningen av maskininlärning i neurovetenskaplig forskning blivit ett populärt ämne. Exempelvis har bildigenkänning med hjälp av maskininlärning använts för att upptäcka och även förbättra diagnostisering av sjukdomar. I denna studie jämförs noggrannheten i ett Convolutional Neural Network (CNN), en support vector classifier och en random forest classifier för att undersöka vilka som är bättre lämpade för klassificering av celltyper utifrån digitalt rekonstruerade bilder av hjärnceller från möss. Alla modeller tränades på både ett större obalanserad dataset som innehöll 49 olika celltyper och en mindre balanserat dataset som endast innehöll 3 typer. Varje modell utvärderades på hur väl de kunde klassificera alla celltyper men också deras noggrannhet på enskilda celltyper. Resultaten visade att CNN hade bästa medelprecision, med 51 och 83 procent på respektive datamängder. Vid klassificeringen av enskilda celltyper hade alla modeller god noggrannhet på åtminstone några celltyper, även här hade CNN den bästa individuella noggrannheten och var mer konsekvent. Sammanfattningsvis visar resultaten att ett convolutional neural network förmodligen är bättre lämpad vid klassificerar av celltyper från digitalt rekonstruerade bilder av hjärnceller, men även de andra metoderna kan vara lämpliga vid vissa celltyper. Vidare forskning inom ämnet är dock nödvändigt för att nå en högre precision och pålitlighet av resultatet.
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Jiang, Lixian. "Interactions of Neurons, Astrocytes and Microglia with HUCB Cell Populations in Stroke Models: Migration, Neuroprotection and Inflammation." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002552.
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Occhipinti, Rossana. "In Silico Testing of Hypotheses for Brain Energy Metabolism with New Computational Models within a Statistical Framework." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1244144388.
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Tofighi, Roshan. "In vitro models to study mechanisms of neural cell death induced by toxic agents /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-459-4/.
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Galpern, Wendy R. "Neuroprotection and Neurotransplantation Strategies in Models of Parkinson’s Disease." eScholarship@UMMS, 1996. https://escholarship.umassmed.edu/gsbs_diss/143.
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Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic cell death in the substantia nigra pars compacta (SNc) and dopamine (DA) depletion in the striatum. Current pharmacological treatments are aimed at the replacement of striatal DA via the administration of levodopa. While this therapy is beneficial initially, long-term treatment is associated with significant side effects, and disease progression continues. The present experiments investigate neuroprotective and neurotransplantation strategies as alternatives to palliative pharmacologic treatments.
The optimal therapeutic approach to neurodegenerative diseases would be to protect against cell death and prevent disease progression. PD is well-suited for such neuroprotective strategies as primarily one cell population is affected in this disorder. Neurotrophic factors (NTFs) have been identified which support dopaminergic neuronal survival in vitro. In the present studies, the neuroprotective effects of the neurotrophin brain-derived neurotrophic factor (BDNF) have been evaluated in a 1-methyl-4-phenylpyridinium (MPP+) model of substantia nigra (SN) degeneration. BDNF-secreting fibroblasts were implanted dorsal to the SN prior to the infusion of the mitochondrial complex I inhibitor MPP+. Subsequent histological analysis demonstrated that BDNF is able to attenuate MPP+ induced dopaminergic cell loss in the SNc. Moreover, neurochemical evaluation demonstrated that BDNF is able to enhance DA levels in the remaining SN neurons in this same paradigm.
The cause of cell death in neurodegenerative diseases likely involves the interaction of mitochondrial impairment, excitotoxicity, and oxidative stress. In order to evaluate the mechanism of NTF-mediated protection, the ability of nerve growth factor (NGF) to attenuate the production of the oxidant peroxynitrite was evaluated in a model of mitochondrial impairment. NGF was found to decrease the production of 3-nitrotyrosine, the product of peroxynitrite mediated tyrosine nitration. Thus, NTF-mediated neuroprotection may act in part by decreasing reactive oxygen species and oxidative stress.
At present, neuroprotective therapies are not clinically available. An alternate therapeutic approach to PD is the replacement of striatal DA and reconstruction of synaptic circuitry via the intrastriatal transplantation of fetal dopaminergic neurons. Current transplantation protocols using human fetal tissue are constrained by limited tissue availability. In order to investigate an alternate cell source for the treatment of PD, fetal porcine dopaminergic neurons were implanted into the DA depleted striatum of 6-OHDA lesioned rats. Amphetamine-induced rotational recovery was monitored, and graft survival was evaluated 19 weeks after grafting. In immunosuppressed rats, porcine dopaminergic neurons were found to attenuate rotational deficits and extensively reinnervate the host striatum.
The neuroprotective effects of BDNF suggest that NTFs may be important mediators of dopaminergic neuronal survival and function in the adult brain. However, several conditions including appropriate dosage and delivery need to be determined before clinical applications may be achieved. As an alternative to neuroprotection, neurotransplantation not only restores striatal DA but also reconstructs the synaptic circuitry of the basal ganglia. The finding that porcine dopaminergic neurons survive with in adult host brain, reinnervate the DA depleted striatum, and mediate functional recovery suggests that porcine DA neurons may serve as an alternate cell source for transplantation in PD.
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Shi, Tie-Jun. "Regulation of signaling molecules in sensory neurons and spinal cord : studies on nerve injury models and transgenic mice /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4837-2/.
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