Sensorimotor enhancement in mouse mutants lacking the Purkinje cell-specific Gi/o modulator, Pcp2(L7)

• Published in: Molecular and cellular neuroscience 2009-01, Vol.40 (1), p.62-75
• Main Authors: Iscru, Emilia, Serinagaoglu, Yelda, Schilling, Karl, Tian, Jinbin, Bowers-Kidder, Stephanie L, Zhang, Rui, Morgan, James I, DeVries, A Courtney, Nelson, Randy J, Zhu, Michael X, Oberdick, John
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Animals; Behavior, Animal - physiology; Cerebellum - abnormalities; Cerebellum - cytology; Cerebellum - metabolism; Female; Gene Silencing; GTP-Binding Protein alpha Subunits, Gi-Go - genetics; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - physiology; Neuropeptides - genetics; Neuropeptides - metabolism; Purkinje Cells - cytology; Purkinje Cells - metabolism
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2008.09.002

Pcp2(L7) is a GoLoco domain protein specifically and abundantly expressed in cerebellar Purkinje cells. It has been hypothesized to "tune" G(i/o)-coupled receptor modulation of physiological effectors, including the P-type Ca(2+) channel. We have analyzed a mouse mutant in which the Pcp2(L7) gene was inactivated and find significant anatomical, behavioral and electrophysiological changes. Anatomically, we observed mild cerebellar hypoplasia. Behaviorally, the mutants were altered in modalities atypical for a traditional cerebellar mutant, and oddly, all of these changes could be considered functional enhancements. This includes increased asymptotic performance in gross motor learning, increased rate of acquisition in tone-conditioned fear, and enhanced pre-pulse inhibition of the acoustic startle response. Electrophysiological analysis of Purkinje cells in the mutants reveals depression of the complex spike waveform that may underlie the behavioral changes. Based on these observations we suggest that the Pcp2(L7) protein acts as a sensorimotor damper that modulates time- and sense-dependent changes in motor responses.