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Modeling effects of microvilli on somatic signal propagation

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dc.contributor.authorAldohbeyb, Ahmed A., author
dc.contributor.authorLear, Kevin, advisor
dc.contributor.authorVigh, Jozsef, committee member
dc.contributor.authorBailey, Ryan, committee member
dc.date.accessioned2018-09-10T20:04:41Z
dc.date.available2019-09-06T20:04:15Z
dc.date.issued2018
dc.description.abstractThe electrical behavior of small compartments in neurons such as dendritic spines, synaptic terminals, and microvilli has been of interest for decades. Most of these fine structures are found in the dendrite, where most excitatory inputs are received, or in the axon where the action potential is generated and propagates. However, a recent study has shown expression of sodium voltage-gated channels (VGCs) in the soma of intrinsically photosensitive retinal ganglion cells (ipRGCs). Confocal imaging locates these sodium VGCs outside the main soma membrane, which implies that the VGCs occur in structures that protrude from the soma but are too small to be resolved with conventional optical microscopy. An investigator has hypothesized the voltage-gated sodium channels are positioned in microvilli. The microvilli hypothesis raises the question of the role of voltage-gated sodium channels on microvilli and more specifically what effect they would have on propagation of signals in the soma. The nanoscale dimensions of the microvilli, which are much smaller than patch-clamp probes, prevent conventional electrical studies that isolate individual compartments. In the absence of direct, high-spatial resolution measurements, computational models are valuable tools for developing a better understanding of the electrical behavior of the neuronal compartments. Well known models such as Hodgkin–Huxley models and cable theory have been the foundation of many advances in neuroscience. In this work, initial insights about the role of somatic microvilli are being generated using an equivalent circuit model based on the cable equation. For the circuit model, microvilli stubs containing resistor-capacitor networks and sodium channels are treated as branches off the main soma membrane. Circuit models of the soma membrane without microvilli serve as controls. The circuit models were simulated using Simulink. The results show that voltage-gated sodium channels placed on the main soma membrane or on the microvilli increase the amplitude of somatic signals as they propagate to the axon initial segment. Moreover, restriction of the VGCs to the somatic microvilli reduces the probability of misfires originating from spontaneous ion channel opening while still enhancing above threshold depolarizations propagating in the main soma membrane. For comparison, simulations of somatic signal propagation were also performed using the NEURON software as it readily incorporated the Hodgkin and Huxley model, including both sodium and potassium voltage-gated channels. The dendritic input signal was generated using the current clamp technique. The results show that the presence of VGCs on the main soma membrane lower the threshold for triggering the AIS to generate action potential. However, restricting sodium VGCs to the microvilli only did not initiate an action potential at the AIS. The ability of the microvilli Na+ VGCs to serve as excitatory inputs directly to the soma in the absence of the dendritic input was also investigated using NEURON. Using a current clamp, current was injected at the tip of the microvilli and the signal was recorded at the AIS. The results show that the signal at the AIS increases linearly with the injected current. However, the amplitude of the AIS potential was lower than the microvilli signal due to the high microvilli neck resistance. The results support the view that the microvilli act as electrical compartments that attenuate the microvilli VGCs' signals.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierAldohbeyb_colostate_0053N_14943.pdf
dc.identifier.urihttps://hdl.handle.net/10217/191353
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectmicrovilli
dc.subjectsodium voltage-gated channel
dc.subjectmodel
dc.subjectipRGCs
dc.titleModeling effects of microvilli on somatic signal propagation
dc.typeText
dcterms.embargo.expires2019-09-06
dcterms.embargo.terms2019-09-06
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBioengineering
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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