McNair Scholar 2021 Zane Crabtree
Zane Crabtree is a junior at the University of Minnesota – Twin Cities, double majoring in neuroscience and psychology. He is currently employed by two labs studying the neurobiology of neurodegenerative diseases. His long-term research interests involve understanding how the brain generates subjective experience and how this can be modulated pharmacologically. Mr. Crabtree will pursue a Ph.D. in neurobiology when he completes his dual degree.
My dream is to earn a Ph.D. in neurobiology and to contribute to our understanding of phenomenological conscious experience and how evolution has shaped our understanding of ourselves and our environment.
Research project
The Role of Caspase-2 in Long-term Depression and Neurodegenerative Diseases
Abstract: The neurons of patients with Lewy body Diseases (LBD) often contain high levels of misfolded tau protein and α-synuclein, and many patients develop dementia. Caspase-2 is a cysteine-aspartic protease that has been shown to mediate long-term depression (LTD), a form of synaptic plasticity characterized by the internalization of AMPA receptors, which leads to synaptic weakening that is believed to underlie forgetting. Recently, we found that in mice, caspase-2 cleaves tau at aspartate 303, and this process mediates LTD (unpublished data). The A53T α-synuclein variant linked to familial Parkinson’s disease increases the internalization of AMPA receptors in a tau-dependent manner, but the role of caspase-2 and the effect of this process on LTD are unknown. Here, we provide evidence to test the hypothesis that in LBD caspase-2 cleavage of tau leads to excessive synaptic weakening. We measured LTD in hippocampal slices from transgenic mice expressing A53T α-synuclein and non-transgenic littermates in which mouse tau was wild-type or mutated (aspartate-303-glutamate) to render tau resistant to caspase-2 cleavage. Our preliminary data indicate that in mice with wild-type tau, A53T α-synuclein is associated with enhanced LTD, supporting our hypothesis that there is excessive synaptic weakening in LBD. We are obtaining LTD measurements in mice with caspase-2 resistant tau to determine if this enhanced LTD depends on caspase-2 cleavage of tau.
Faculty mentor
Dr. Karen Hsiao Ashe is a distinguished professor, researcher, and founding director of the N. Bud Grossman Center for Memory Research and Care in the Department of Neurology at the University of Minnesota. She has earned respect in the neuroscience community across the world for her extensive contributions to neurodegenerative disease research, including over 100 academic publications. Furthermore, she is the creator of the most widely utilized mouse model of Alzheimer’s disease. Dr. Ashe’s group is currently focused on identifying a drug target for the treatment of dementia associated with Lewy body diseases. Outside of her exemplary academic achievement, she has established a lasting impact on the field of neuroscience through her selection and mentorship of promising undergraduate, graduate, and post-graduate scholars.