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Network Level Manipulation of Neuronal Populations via Microtechnology: Epilepsy on a Chip

Cirinelli, Lacey Anne (2015) Network Level Manipulation of Neuronal Populations via Microtechnology: Epilepsy on a Chip. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Recent studies indicate that oscillations between functional states (ex: ictal, post-ictal) in epilepsy are due to fluctuations in neuronal network firing patterns. However, current epilepsy models are often limited to non-mechanistically identifying the most likely anti-epileptic drug candidates. Therefore, expanding research to the network level is a promising way to examine the mechanisms underlying mental pathologies and possibly assess better ways to treat them. Microtechnology, which allows for control of the local microenvironment, is a reliable way to study whole networks, but is rarely applied to neurological disease. The objective of this project is to combine microtechnology with standard neuroscience techniques in an effort to create a platform for high throughput testing of anti-epileptic drugs. To achieve this, we create “epileptic” neuronal networks in vitro, characterize network morphology and phenotypic connectivity, and evaluate network activity modulation due to genetic manipulations related to epilepsy. This project focuses on the gene SCN1a, which codes for the voltage gated sodium channel Nav1.1. Mutations in SCN1a are linked to Generalized Epilepsy with Febrile Seizures Plus. The central hypothesis is that mutations in SCN1a affect activity properties of individual neurons, thus impacting recurrent activity in small networks, and that examining these networks may provide insight into pathways involved in seizure propagation.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Cirinelli, Lacey Annelac91@pitt.eduLAC910000-0001-8249-6561
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDavidson, Lance Alad43@pitt.eduLAD43
Committee MemberCui, X. Tracyxic11@pitt.eduXIC11
Committee MemberMarra, Kacey G.marrkx@upmc.edu
Committee MemberSeal, Rebecca, P.rpseal@pitt.eduRPSEAL
Date: 28 January 2015
Date Type: Publication
Defense Date: 24 November 2014
Approval Date: 28 January 2015
Submission Date: 1 December 2014
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 149
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: Epilepsy, Nav1.1, SCN1a, Neuronal Networks, Microcontact Printing, Calcium Imaging
Date Deposited: 28 Jan 2015 16:48
Last Modified: 15 Nov 2016 14:25
URI: http://d-scholarship.pitt.edu/id/eprint/23724

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