title: Increased excitability and altered action potential waveform in cerebellar granule neurons of the Ts65Dn mouse model of Down syndrome.
abstract: Down syndrome (DS) is characterized by intellectual disability and impaired motor control. Lack of coordinated movement, poor balance, and unclear speech imply dysfunction of the cerebellum, which is known to be reduced in volume in DS. The principal cause of the smaller cerebellum is a diminished number of granule cells (GCs). These neurons form the 'input layer' of the cerebellar cortex, where sensorimotor information carried by incoming mossy fibers is transformed before it is conveyed to Purkinje cells and inhibitory interneurons. However, it is not known how processing of this information is affected in the hypogranular cerebellum that characterizes DS. Here we explore the possibility that the electrical properties of the surviving GCs are changed. We find that in the Ts65Dn mouse model of DS, GCs have a higher input resistance at voltages approaching the threshold for firing, which causes them to be more excitable. In addition, they fire narrower and larger amplitude action potentials. These subtly modified electrical properties may result in atypical transfer of information at the input layer of the cerebellum.
authors.affiliation: School of Physiology & Pharmacology, University of Bristol, University Walk, Bristol, BS8 1TD, UK. m.m.usowicz@bris.ac.uk
authors.forename: Maria M
authors.initials: MM
authors.lastname: Usowicz
authors.forename: Claire L P
authors.initials: CL
authors.lastname: Garden
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002531:Cerebellum / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D019957:Motor Skills Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000473:pathology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D015854:Up-Regulation / Q000502:physiology*