Climbing Fiber-Purkinje Cell Dysfunction in ATXN1 Mice
Medical Science Liaison, Tris Pharma
Medical Science Liaison, Ironshore Pharmaceuticals & Development, Inc. Minnesota
Undergraduate Institution and Major/Degree:
Michigan State University (2002), BS in Biochemistry and Molecular Biology
Formation of topologically precise, functional synapses is requisite for maturation of the nervous system, as well as for the development of proper motor behaviors. Specifically, climbing fibers (CF) originating in the inferior olivary nucleus of the brainstem send excitatory projections to Purkinje cells (PC) in the cerebellar cortex, contacting them on the soma and proximal dendrites. Early in development PCs are contacted by several CFs. Extraneous CF projections are recessively eliminated in a higly-regulated manner such that each PC is contacted by only one CF in the adult cerebellum. This one-to-one relationship is appears to be essential for proper synaptogenesis of parallel fiber (PF)-PC synapses, as well as motor coordination in the adult. Our recent findings suggest abnormal cerebellar circuitry in a mouse model of spinocerebellar ataxia type 1 (SCA1) that may be a consequence of aberrations in a development plan. I plan to use flavoprotein autoflurescence imaging, behavioral studies, and cellular and molecular approaches to examine the underlying cause(s) that result in cerebellar abnormalities in a conditional SCA1 mouse model.
- Harry Orr
- Tim Ebner
- Walter Low
Courses Taken Beyond the Core Courses:
- NSc 8217: Systems and Computational Neuroscience
- GCD 8213: Selected Topics in Molecular Biology
Conferences Attended and Presentations:
- Society for Neuroscience Annual Meeting Fall 2005, 2006
- Tim Ebner
- Harry Orr
- Ebner BA, Ingram MA, Barnes JA, Duvick LA, Frisch JL, Clark HB, Zoghbi HY, Ebner TJ, Orr HT. Purkinge cell ataxin-1 modulates climbing fiber synaptic input in developing and adult mouse cerebellum. J Neurosci. 2013;33:5806-5820.
- Barnes JA, Ebner BA, Duvick LA, Gao W, Chen G, Orr HT, Ebner TJ. Abnormalities in the climbing fiber-Purkinje cell circuitry contribute to neuronal dysfunction in ATXN1[82Q] mice. J Neurosci. 2011;31(36):12778-12789.
- Duvick L, Barnes J, Ebner B, Agrawal S, Andersen M, Lim J, Giesler GJ, Zoghbi HY Orr HT. SCA-1 like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement at residue 776. Neuron 2010;67:929-935.
- Chen G, Popa LS, Wang X, Gao W, Barnes J, Hendrix CM, Hess EJ, Ebner TJ. Low-frequency oscillations in the cerebellar cortx of the tottering mouse. J Neurophysiol. 2009;101:234-245.
Awards and Honors:
- Fellowship on NIH Training Grant:
Translational Research in Neurobiology of Disease
- Society for Neuroscience
- Midland, Michigan