000008600 001__ 8600
000008600 005__ 20240124114304.0
000008600 0247_ $$2DOI$$a10.6083/ff365610t
000008600 037__ $$aETD
000008600 245__ $$aInjury-induced inhibition of bystander neurons requires dsarm and signaling from glia
000008600 260__ $$bOregon Health and Science University
000008600 269__ $$a2020
000008600 336__ $$aDissertation
000008600 502__ $$bPh.D.
000008600 520__ $$aHow injury or neurodegenerative disease alter neural circuit function remains unclear. In this thesis, I explored how axotomy affects severed axons and adjacent uninjured 'bystander' neurons in a simple in vivo nerve preparation. Following axotomy, I observed rapid suppression of transport in all axons, whether uninjured or not, and decreased sensory signaling in intact bystander neurons. Unexpectedly, the axon death gene dsarm was required for early changes in bystander neuron cell biology, as were the voltage-gated calcium channel Cacophony (Cac) and MAP kinase signaling. Bystander neurons later recovered, while severed axons degenerated via dSarm/Axundead signaling, and independently of Cac/MAP kinase. Interestingly, suppression of bystander neuron function required Draper receptor and JNK/MMP-1 signaling in glia, indicating glial cells actively suppress bystander neurophysiology. This work identifies a new role for Cac/dSarm/MAPK signaling and glia in the broad suppression of neural circuit function after injury, and defines two genetically and temporally separable phases of dSarm signaling in the injured nervous system.
000008600 542__ $$fIn copyright - single owner
000008600 650__ $$aMitogen-Activated Protein Kinases$$032817
000008600 650__ $$aAxotomy$$031865
000008600 650__ $$aAxons$$015276
000008600 650__ $$aNeurons$$022858
000008600 6531_ $$aglia
000008600 691__ $$aSchool of Medicine$$041369
000008600 692__ $$aVollum Institute$$041509
000008600 7001_ $$aHsu, Jiun-Min
000008600 8564_ $$929686b64-0846-4e8e-896b-ed4284e3a507$$s17996636$$uhttps://digitalcollections.ohsu.edu/record/8600/files/Hsu.JiunMin.2020.pdf
000008600 905__ $$a/rest/prod/ff/36/56/10/ff365610t
000008600 909CO $$ooai:digitalcollections.ohsu.edu:8600$$pstudent-work
000008600 980__ $$aTheses and Dissertations