title: YAC128 Huntington's disease transgenic mice show enhanced short-term hippocampal synaptic plasticity early in the course of the disease.
abstract: Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by a polyglutamine expansion in the gene encoding the protein huntingtin. The disease progresses over decades, but often patients develop cognitive impairments that precede the onset of the classical motor symptoms. Similar to the disease progression in humans, the yeast artificial chromosome (YAC) 128 HD mouse model also exhibits cognitive dysfunction that precedes the onset of the neuropathological and motor impairments characteristic of HD. Thus, the purpose of this study was to evaluate whether short- and long-term synaptic plasticity in the hippocampus, two related biological models of learning and memory processes, were altered in YAC128 mice in early stages of disease progression. We show that the YAC128 hippocampal dentate gyrus (DG) displays marked reductions in paired-pulse depression both at 3 and 6 months of age. In addition, significantly enhanced post-tetanic and short-term potentiation are apparent in YAC128 mice after high-frequency stimulation at this time. Early and late forms of long-term plasticity were not altered at this stage. Together these findings indicate that there may be elevated neurotransmitter release in response to synaptic stimulation in YAC128 mice during the initial phase of disease progression. These abnormalities in short-term plasticity detected at this stage in YAC128 HD transgenic mice indicate that aberrant information processing at the level of the synapses may contribute, at least in part, to the early onset of cognitive deficits that are characteristic of this devastating neurodegenerative disorder.
authors.affiliation: Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, Canada; Department of Biology, University of Victoria, Victoria, BC, Canada. Electronic address: mohamedghilan@gmail.com.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ghilan
authors.affiliation: Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, Canada. Electronic address: crystal.bostrom@gmail.com.
authors.forename: Crystal A
authors.initials: CA
authors.lastname: Bostrom
authors.affiliation: Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, Canada; Department of Biology, University of Victoria, Victoria, BC, Canada. Electronic address: bretthryciw@gmail.com.
authors.forename: Brett N
authors.initials: BN
authors.lastname: Hryciw
authors.affiliation: Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, Canada; Department of Biology, University of Victoria, Victoria, BC, Canada. Electronic address: jess.m.nathan@gmail.com.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Simpson
authors.affiliation: Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, Canada; Brain Research Centre and Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada. Electronic address: brain64@uvic.ca.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Christie
authors.affiliation: Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, Canada. Electronic address: jgil@uvic.ca.
authors.forename: Joana
authors.initials: J
authors.lastname: Gil-Mohapel
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000254:growth & development / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006816:Huntington Disease / Q000503:physiopathology*; D008297:Male; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D046509:Tissue Culture Techniques
keywords: Cognition; Hippocampus; Huntington׳s disease; Long-term potentiation; Short-term plasticity; YAC128 transgenic mice