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Electrophysiological characterization of the cerebellar Purkinje cells from the Pcp2-L7- deficient mice

Iscru, Emilia
http://rave.ohiolink.edu/etdc/view?acc_num=osu1213299492

Abstract Details

2008, Doctor of Philosophy, Ohio State University, Biophysics.
An increasing body of knowledge suggests that the cerebellum performs functions outside its traditionally attributed role in motor coordination. The cerebellum is considered to mediate diverse non-traditional functions ranging from motor learning [DeZeeuw, 1998], emotion [Sacchetti, 2004], to cognition [Kim, 1994; Allen et al., 1997]. Another non-traditional view is that some functions of the cerebellum may be primarily sensory rather than motor, or they concentrate on optimizing motor functions required for sensation [Gao, et al., 1996; Hartmann and Bower, 2001]. However, so far it has been difficult to investigate these non-traditional functions due to the lack of good animal models in which these presumed functions can be explored in isolation without the confusing interference of motor coordination defects. This project explores the possible non-traditional roles of cerebellum using a mouse model ablated of the gene for a Purkinje cell-specific protein called Pcp2-L7 [Oberdick et al., 1988; Luo and Denker, 1999; Zhang et al., 2002; Willard et al., 2006]. Because Pcp2-L7 contains GoLoco domains and has been implicated in the functional regulation of P/Q-type Ca2+ channels [Kinoshita-Kawada et al., 2004] we focussed on the electrophysiological properties of the cerebellar Purkinje cells of the wild type and L7 knockout mice. The GoLoco domain acts both as a binding domain and as a guanine nucleotide dissociation inhibitor (GDI) selective for Gα subunits of heterotrimeric G proteins [Natochin et al., 2001; Willard et al., 2006; Kimple et al., 2001]. Much is known about the biochemistry of these proteins and their effects on mechanisms of G-protein signalling, but the specific downstream effectors and functions in vivo are only just beginning to emerge. The L7 protein has the additional novelty that it is highly expressed cerebellar Purkinje cells and retinal bipolar neurons [Oberdick et al., 1990; Berrebi et al., 1991]. Inactivation of Pcp2-L7 in mice was reported to have no apparent phenotype as determined using behavioral, anatomical, and ultrastructural analysis [Mohn et al., 1997; Vassileva et al., 1997]. Despite the lack of a reported phenotype in the L7 mutant mice, previous work in Xenopus oocyte expression system suggests that one downstream effector of L7 modulation of G-protein signalling is likely the P-type Ca2+ channel which is the primary voltage-dependent Ca2+ channel expressed in Purkinje cells [Kinoshita-Kawada et al., 2004]. As Ca2+ plays a major role in Purkinje cell function and plasticity, and P-type channels are widely held to play an important computational role in these cells, the phenotype of L7 null mutant mice has been re-examined. These recent results suggest subtle but significant anatomical, behavioural and electrophysiological changes in the absence of L7 protein. Based on these observations we propose that the Purkinje cells and L7 serve a sensory damping function that also acts to limit or delay changes in motor performance over time. The entire project is a collaboration between Dr. John Oberdick and Dr. Mike Zhu's laboratories. My focus in this project is the electrophysiological characterization of the wild type and mutant cerebellar Purkinje neurons.
Mike Xi Zhu, PhD (Advisor)
John Oberdick, D. (Committee Member)
Georgia Bishop, A. (Committee Member)
Jackie Wood, D. (Committee Member)

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Citations

  • Iscru, E. (2008). Electrophysiological characterization of the cerebellar Purkinje cells from the Pcp2-L7- deficient mice [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1213299492

    APA Style (7th edition)

  • Iscru, Emilia. Electrophysiological characterization of the cerebellar Purkinje cells from the Pcp2-L7- deficient mice. 2008. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1213299492.

    MLA Style (8th edition)

  • Iscru, Emilia. "Electrophysiological characterization of the cerebellar Purkinje cells from the Pcp2-L7- deficient mice." Doctoral dissertation, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1213299492

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.