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Engineering Approaches for Neurobiology

Stoner, Richard M (2010) Engineering Approaches for Neurobiology. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Neurobiological systems span a wide dimensional range. We present a scale-driven methodological development for three biological systems to demonstrate the utility of applied engineering approaches in neurobiology and provide an avenue for future study. Concepts in computational modeling, microfluidic device platforms, and MRI phantoms are examined - starting from the level of a single synapse and concluding with long-distance cortical connectivity.Single synapse models were developed using a Monte Carlo simulation environment to study biophysically realistic mechanisms of spike timing dependent plasticity (STDP). A model of spatiotemporal intracellular Calcium detection was extended to include subunit-specific receptor kinetics and distributions. Using STDP-based activation protocols, global and local molecular time courses were then produced for NR2a and NR2b knockout models. To study network level oscillatory activity, a model of spatially-constrained networks was created based on cyclic geometry to look at the effects of circumference and track-width on spontaneous network activity. Transverse wave activity is demonstrated and characterized by velocity and origin. Microfluidic technology provides an experimental means to extend the study of network organization and activity in vitro. We have developed a microfluidic control platform that integrates multiple design strategies to address the intrinsic spatiotemporal resolution of neurons. Microfluidic devices were fabricated using multilayer soft-lithography with internal valves to guide multiple laminar streams. A control platform using dynamic pressure produces a targeted hydrodynamic stream from variable internal resistance control. Feedback containing video and pressure data provides online analysis of the microfluidic device. Devices were characterized with arbitrary profile generation, profile repeatability, flow rate measurement, and lid-driven flow production. Finally, a microfluidic phantom for diffusion-weighted magnetic resonance imaging was developed for validation studies of long-distance cortical white matter connections. The diffusion phantom provides a reliable physical structure with which high resolution fiber tractography methods can be tested against. The diffusion phantom was fabricated using conventional photolithographic techniques with an internal channel network that mimics white matter fiber tracts and crossings. We show mapped tracts to the features inside of the phantom via post-processing of diffusion-weighted images.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Stoner, Richard Mrms1002@pitt.eduRMS1002
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairZeringue,
Committee MemberBatistia, Aaronabatista@engr.pitt.eduAPB10
Committee MemberKameneva, Marinakamenevamv@upmc.eduMARINA
Committee MemberLeduc, Phillip
Date: 25 June 2010
Date Type: Completion
Defense Date: 3 December 2009
Approval Date: 25 June 2010
Submission Date: 4 December 2009
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: diffusion phantom; microfluidics; neurobiology; recurrent network
Other ID:, etd-12042009-153414
Date Deposited: 10 Nov 2011 20:08
Last Modified: 19 Dec 2016 14:37


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