Cirinelli, Lacey Anne
(2015)
Network Level Manipulation of Neuronal Populations via Microtechnology: Epilepsy on a Chip.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
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Unpublished |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: |
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| ETD Committee: |
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| 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: |
28 Jan 2020 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/23724 |
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