Synaptic plasticity and spatial working memory are impaired in the CD mouse model of Williams-Beuren syndrome
Mol Brain. 2016-08-02; 9(1):
DOI: 10.1186/s13041-016-0258-7
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1. Mol Brain. 2016 Aug 2;9(1):76. doi: 10.1186/s13041-016-0258-7.
Synaptic plasticity and spatial working memory are impaired in the CD mouse model
of Williams-Beuren syndrome.
Borralleras C(1)(2)(3), Mato S(4)(5)(6), Amédée T(7), Matute C(4)(5)(6), Mulle
C(7), Pérez-Jurado LA(1)(2)(3), Campuzano V(8)(9)(10).
Author information:
(1)Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra,
Barcelona, Spain.
(2)Neurosciences Program, Institut Hospital del Mar d’Investigacions Mèdiques
(IMIM), Barcelona, Spain.
(3)Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER),
ISCIII, Madrid, Spain.
(4)Department of Neuroscience, Neurotek-University of the Basque Country, Leioa,
Spain.
(5)Achucarro Basque Center for Neuroscience, Zamudio, Spain.
(6)Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas
(CIBERNED), Madrid, Spain.
(7)Interdisciplinary Institute for Neuroscience, CNRS UMR 5297 – University of
Bordeaux, F-33000, Bordeaux, France.
(8)Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra,
Barcelona, Spain. .
(9)Neurosciences Program, Institut Hospital del Mar d’Investigacions Mèdiques
(IMIM), Barcelona, Spain. .
(10)Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER),
ISCIII, Madrid, Spain. .
Mice heterozygous for a complete deletion (CD) equivalent to the most common
deletion found in individuals with Williams-Beuren syndrome (WBS) recapitulate
relevant features of the neurocognitive phenotype, such as hypersociability,
along with some neuroanatomical alterations in specific brain areas. However, the
pathophysiological mechanisms underlying these phenotypes still remain largely
unknown. We have studied the synaptic function and cognition in CD mice using
hippocampal slices and a behavioral test sensitive to hippocampal function. We
have found that long-term potentiation (LTP) elicited by theta burst stimulation
(TBS) was significantly impaired in hippocampal field CA1 of CD animals. This
deficit might be associated with the observed alterations in spatial working
memory. However, we did not detect changes in presynaptic function, LTP induction
mechanisms or AMPA and NMDA receptor function. Reduced levels of Brain-derived
neurotrophic factor (BDNF) were present in the CA1-CA3 hippocampal region of CD
mice, which could account for LTP deficits in these mice. Taken together, these
results suggest a defect of CA1 synapses in CD mice to sustain synaptic strength
after stimulation. These data represent the first description of synaptic
functional deficits in CD mice and further highlights the utility of the CD model
to study the mechanisms underlying the WBS neurocognitive profile.
DOI: 10.1186/s13041-016-0258-7
PMCID: PMC4971717
PMID: 27485321 [Indexed for MEDLINE]