Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0258-7) contains supplementary material, which is available to authorized users.
Highlights
Williams-Beuren syndrome (WBS, OMIM 194050) is a rare neurodevelopmental disorder caused by a microdeletion of 26-28 genes on chromosome 7q11.23 with an estimated prevalence of 1 in 7500 [1]
Spatial working memory is impaired in complete deletion (CD) mice WBS individuals present working memory impairment, especially in spatial working memory [7, 22]
This behavioral test has been widely used to study spatial working memory and it has been shown to be very sensitive to hippocampus dysfunction, other brain areas are involved in the task
Summary
Williams-Beuren syndrome (WBS, OMIM 194050) is a rare neurodevelopmental disorder caused by a microdeletion of 26-28 genes on chromosome 7q11.23 with an estimated prevalence of 1 in 7500 [1]. The syndrome is characterized by an unusual cognitive profile that includes relatively preserved expressive language and facial processing abilities but dramatic deficits in spatial cognition [4,5,6]. The complete deletion (CD) mouse model was generated in order to mimic the most common and recurrent deletion found in WBS patients, encompassing all single copy genes of the syntenic interval from Gtf2i to Fkbp6 [11]. CD mice presented with many features reminiscent of WBS such as growth deficiency, craniofacial and cardiovascular abnormalities, and several behavioral alterations including hypersociability. CD mice presented an increase proportion of immature neurons in the dentate gyrus together with shorter dendrites and Borralleras et al Molecular Brain (2016) 9:76 decreased spine density in CA1 pyramidal neurons of the hippocampus [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
