Submission Date

5-4-2020

Document Type

Paper- Restricted to Campus Access

Department

Neuroscience

Second Department

Modern Languages (German)

Adviser

Carlita Favero

Second Adviser

Robin Clouser

Committee Member

Jennifer King

Committee Member

Rebecca Evans

Department Chair

Ellen Dawley

Department Chair

Matthew Mizenko

Project Description

Fetal alcohol spectrum disorder (FASD) is an umbrella term for several disorders caused by prenatal alcohol exposure (PAE). Sensory processing deficits, including under-responsiveness to sensory stimuli and disordered auditory processing, are common across FASDs. Thalamocortical axons (TCAs) carry sensory information from the thalamus to the cortex and are sensitive to PAE. Previous results from our lab revealed that fewer TCAs extend to the cortex properly with PAE, indicating that TCA migration is compromised. TCAs require many guidance mechanisms to reach the cortex, including corridor cells. Corridor cells form a necessary pathway for TCAs through the otherwise nonpermissive medial ganglionic eminence (MGE). Corridor cells are similar to other cell populations, including cortical interneurons, which are affected by PAE. Corridor cells and cortical interneurons are both GABAergic and temporarily occupy the same location in the MGE. I hypothesize that PAE will impact corridor cell number and distribution in the MGE, impairing TCA migration. Pregnant dams received daily subcutaneous injections of either 20% saline or EtOH between embryonic days 7.5 and 13.5, when embryos were removed. One male and female from each litter were identified through sex genotyping, paraffin-embedded, and sectioned in the coronal orientation. Immunohistochemistry for Islet1 labeled corridor cells in the MGE. Using FIJI, images of the MGE were divided into ten equal bins. Islet1+ cells in each bin were counted to measure cell distribution and quantity. PAE caused a marginally significant reduction in corridor cell count. The distribution of cells was not altered by PAE. Altered corridor cell count could impair TCA migration and lead to observed sensory processing deficits in FASD. Future work will study Slit/Robo signaling pathways, which are involved in guidance of both TCAs and corridor cells.

Comments

This work was supported by a Pearlstine Grant and NIAAA #1R21AA025740-01A1.

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