title: Impaired locomotor learning and altered cerebellar synaptic plasticity in pep-19/PCP4-null mice.
abstract: PEP-19/PCP4 maps within the Down syndrome critical region and encodes a small, predominantly neuronal, IQ motif protein. Pep-19 binds calmodulin and inhibits calmodulin-dependent signaling, which is critical for synaptic function, and therefore alterations in Pep-19 levels may affect synaptic plasticity and behavior. To investigate its possible role, we generated and characterized pep-19/pcp4-null mice. Synaptic plasticity at excitatory synapses of cerebellar Purkinje cells, which express the highest levels of Pep-19, was dramatically altered in pep-19/pcp4-null mice. Instead of long-term depression, pep-19/pcp4-null mice exhibited long-term potentiation at parallel fiber-Purkinje cell synapses. The mutant mice have a marked deficit in their ability to learn a locomotor task, as measured by improved performance upon repeated testing on an accelerating rotarod. Thus, our data indicate that pep-19/pcp4 is a critical determinant of synaptic plasticity in cerebellum and locomotor learning.
authors.affiliation: Department of Developmental Neurobiology, St Jude Children’s Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, Tennessee 38105-3678, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.forename: Jay A
authors.initials: JA
authors.lastname: Blundon
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Rong
authors.forename: Stanislav S
authors.initials: SS
authors.lastname: Zakharenko
authors.forename: James I
authors.initials: JI
authors.lastname: Morgan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology* / Q000502:physiology; D005260:Female; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology*; D045442:Rotarod Performance Test
chemical_list: D009419:Nerve Tissue Proteins; C489091:Pcp4 protein, mouse