Date Approved

4-26-2023

Graduate Degree Type

Thesis

Degree Name

Biomedical Sciences (M.H.S.)

Degree Program

Biomedical Sciences

First Advisor

Michael Williams

Second Advisor

Christopher Pearl

Academic Year

2022/2023

Abstract

Granule cells (GCs) of the dentate gyrus (DG) have been understood as a homogeneous class of neurons exhibiting a characteristic limited firing pattern. A subtype of GC called a semilunar granule cell (SGC) has been identified exhibiting variant morphology, electrophysiology, and positioning from normal GCs. SGCs represent an emerging novel subpopulation of GCs, however, there is presently no genetic tool to access SGCs separately from normal GCs. To provide access for future in vivo studies of this population, we examined two genetic strategies for putative SGC specificity in mouse brain slices. Morphological analysis was performed for quantitative identification of putative SGCs in a total of 822 neurons. Experimental neurons possessed between one and four primary dendrites (PDs) in both strategies. The mean circularity index (CI) of somas from both strategies was .88 . Intersectional strategy somas were found to express 1.95 PDs on average, while enhancer trap strategy somas had an average of 2.2 PDs. 114 dendritic spans were measured in our intersectional strategy, neurons with greater than one PD had 64.5% greater spans than neurons with only one PD. Our enhancer trap strategy for SGC access is tamoxifen-inducible, allowing for temporal control over transgene expression. Our intersectional strategy utilizes the differential co-expression of transgenic populations to specifically access SGCs, allowing for induction scheme variation. Our results suggest these methods may be used to access SGC populations, however, the heterogeneous morphological characterization of SGCs and lack of specific SGC markers in the literature limit confident identification of this population. Our study supplements available literature by providing a large scale manual analysis of individual SGC morphology. These strategies open the possibility for manipulation of the SGC population, such as through inactivation, in order to further explore the relationship of this population to cognitive processing in vivo.

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