Submission Date

4-24-2017

Document Type

Paper- Restricted to Campus Access

Department

Neuroscience

Adviser

Carlita Favero

Committee Member

Rebecca Lyczak

Committee Member

Ellen Dawley

Committee Member

Carlita Favero

Department Chair

Ellen Dawley

Project Description

Fetal alcohol spectrum disorders (FASD) result in many developmental abnormalities, including sensation and perception, which are detrimental to life. These abnormalities can result from thalamocortical axon (TCA) misguidance. TCAs connect the thalamus to the cortex, undergoing a complex migration route which requires many guidance cues (Zhou, 2005; Granato, 1995). Of the mechanisms involved, the largest driving factor of TCA migration is the corridor cells, which are guidepost cells. Corridor cells guide the TCAs through the medial ganglionic eminence (MGE), an otherwise non-permissive region to TCAs. Before TCAs pass through the MGE, corridor cells migrate from the lateral ganglionic eminence (LGE), where they are born, to the MGE from embryonic days (E) 10 to E13.5. When the corridor cell population is absent from the MGE, the TCAs cannot innervate the cortex (Lopez-Bendito, 2006). Due to corridor cell importance for proper TCA guidance, the mechanisms controlling corridor cell migration require further inquiry. The Slit/Robo guidance mechanism repels corridor cells and TCAs from moving too ventrally (Bielle, 2011; Blockus, 2014). However, this repulsive mechanism alone is not sufficient enough to explain how corridor cells enter the MGE. Corridor cells are similar to interneurons in origin and location, as well as being GABAergic. GABA positively influences neuron growth and migration (Ben-Ari, 2002). When interneurons are treated with GABAA receptor antagonist bicuculline, interneuron migration is inhibited, indicating GABA’s role in migration (Cuzon, 2006). Corridor cells, like interneurons, may be influenced by GABA. To investigate this hypothesis, slice cultures of E13.5 CD-1 mouse brains were exposed to BrdU at time 0 and 30 minutes, to visualize cells being born over time to analyze migration. Immunohistochemistry for both BrdU and islet1, a transcription factor marking corridor cells, showed cells which were both born at the E13.5 time point of interest and are corridor cells. The current work confirms the protocol is achievable for E13.5 brain slices and the cells of interest can be visualized. Future research will continue and improve on the current protocol. Additionally, experimental slice cultures should be treated with bicuculline to compare the GABAA antagonist-treated slices to control slices.

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