RT Journal Article SR Electronic T1 Fear Deficits in Hypomyelinated Tppp Knockout Mice JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0170-20.2020 DO 10.1523/ENEURO.0170-20.2020 A1 Huy Nguyen A1 Lindsey M. Meservey A1 Nao Ishiko-Silveria A1 Mu Zhou A1 Ting-Ting Huang A1 Meng-meng Fu YR 2020 UL http://www.eneuro.org/content/early/2020/08/31/ENEURO.0170-20.2020.abstract AB Oligodendrocytes in the central nervous system (CNS) produce myelin sheaths that insulate axons to facilitate efficient electrical conduction. These myelin sheaths contain lamellar microtubules that enable vesicular transport into the inner sheath. Mechanistically, oligodendrocytes rely on Golgi outpost organelles and the associated protein tubulin polymerization promoting protein (TPPP) to nucleate or form new microtubules outside of the cell body. Consequently, elongation of lamellar microtubules is defective in Tppp knockout (KO) mice, which have thinner and shorter myelin sheaths. We now explore the behavioral phenotypes of Tppp KO mice using a number of different assays. In open-field assays, Tppp KO mice display similar activity levels and movement patterns as wildtype mice, indicating that they do not display anxiety behavior. However, Tppp KO mice lack fear responses by two types of assays, traditional fear-conditioning assays and looming fear assays, which test for innate fear responses. Deficits in fear-conditioning, which is a memory dependent task, as well as in spatial memory tests support possible short-term memory defects in Tppp KO mice. Together, our experiments indicate a connection between CNS myelination and behavioral deficits.SIGNIFICANCE STATEMENT Oligodendrocytes are cells in the brain that make myelin sheaths, which wrap concentrically around axons to provide insulation that facilitates electrical conduction. Fear responses have historically been attributed to neuronal activity. However, emerging literature indicates that mouse models with defective myelination display long-term fear deficits. Here, we look at a specific mouse model that lacks an oligodendrocyte-specific protein that is important for building the cellular structure of microtubules, which allow for transport to and along the myelin sheath. These mice display deficits in both memory-dependent fear as well as innate fear responses. Thus, our work indicates that myelin structure is important for fear response.