000008619 001__ 8619
000008619 005__ 20231129124943.0
000008619 0247_ $$2DOI$$a10.6083/zw12z598c
000008619 037__ $$aETD
000008619 245__ $$aExamining slo regulation of astrocyte morphology and neuronal excitability
000008619 260__ $$bOregon Health and Science University
000008619 269__ $$a2020
000008619 336__ $$aThesis
000008619 502__ $$bM.S.
000008619 520__ $$aAstrocytes are a type of central nervous system glia that have critical roles within the brain, including supporting synapse formation, synaptic transmission, and maintaining proper circuit function. Using the fruit fly Drosophila melanogaster as a model system, we investigated the effects of knocking down slowpoke (slo) on astrocyte morphology and circuit function. slo is the Drosophila ortholog of the alpha subunit of a voltage and calcium gated potassium channel KCNMA1 in humans. Knockdown of slo just in astrocytes with RNAi produced varied results on astrocyte morphogenesis and animal behavior. Knockdown with sloRNAi-104421 resulted in smaller astrocyte cell bodies in the L3 larval ventral nerve cord, despite normal astrocyte process infiltration into the neuropil. Expression of this RNAi line in astrocytes also led to motor defects in both larvae and adult male animals. Expression of additional RNAi lines in astrocytes did not recapitulate the astrocyte cell body phenotype or behavioral defects. Additionally, examination of astrocyte cell body size in slo mutants was also normal. In order to test whether expression of sloRNAi-104421 was exerting its effects in a specific way to astrocytes, we expressed sloRNAi-104421 in other glial subtypes within the larval VNC: ensheathing glia and cortex glia. Within these glial cell subtypes, general morphology of cells was normal, though cortex glia-expression of sloRNAi-104421 produced loss of cortex glia cells in the thoracic region of the neuropil, supporting the hypothesis that sloRNAi-104421 is targeting a gene with cell-specific roles. While the target of sloRNAi-104421 could not be definitively attributed to slowpoke, it is clear that the gene it was disrupting had a profound impact on astrocyte morphology and animal behavior. This adds to the growing body of evidence that astrocytes modulate neuronal circuits and that disruption of astrocytes has profound effects on proper CNS function.
000008619 650__ $$aDrosophila melanogaster$$018059
000008619 650__ $$aBehavior$$015411
000008619 650__ $$aAstrocytes$$015172
000008619 650__ $$aRNA Interference$$034586
000008619 650__ $$aNeuroglia$$022841
000008619 691__ $$aSchool of Medicine$$041369
000008619 692__ $$aVollum Institute$$041509
000008619 7001_ $$aMathieson, Danielle
000008619 8564_ $$9d93c995a-52aa-4eb3-afbc-bae31ebf1185$$s4330618$$uhttps://digitalcollections.ohsu.edu/record/8619/files/Mathieson.Danielle.2020.pdf
000008619 905__ $$a/rest/prod/zw/12/z5/98/zw12z598c
000008619 909CO $$ooai:digitalcollections.ohsu.edu:8619$$pstudent-work
000008619 980__ $$aTheses and Dissertations