14 research outputs found
Genetic diversity assessed by microsatellite markers in the amphicarpic species Trifolium polymorphum Poir.
Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism
Restricted repetitive behaviors are core symptoms of autism spectrum disorders (ASDs). The range of symptoms encompassed by the repetitive behavior domain includes lower-order stereotypy and self-injury, and higher-order indices of circumscribed interests and cognitive rigidity. Heterogeneity in clinical ASD profiles suggests that specific manifestations of repetitive behavior reflect differential neuropathology. The present studies utilized a set of phenotyping tasks to determine a repetitive behavior profile for the C58/J mouse strain, a model of ASD core symptoms. In an observational screen, C58/J demonstrated overt motor stereotypy, but not over-grooming, a commonly-used measure for mouse repetitive behavior. Amphetamine did not exacerbate motor stereotypy, but had enhanced stimulant effects on locomotion and rearing in C58/J, compared to C57BL/6J. Both C58/J and Grin1 knockdown mice, another model of ASD-like behavior, had marked deficits in marble-burying. In a nose poke task for higher-order repetitive behavior, C58/J had reduced holeboard exploration and preference for non-social, versus social, olfactory stimuli, but did not demonstrate cognitive rigidity following familiarization to an appetitive stimulus. Analysis of available high-density genotype data indicated specific regions of divergence between C58/J and two highly-sociable strains with common genetic lineage. Strain genome comparisons identified autism candidate genes, including Cntnap2 and Slc6a4, located within regions divergent in C58/J. However, Grin1, Nlgn1, Sapap3, and Slitrk5, genes linked to repetitive over-grooming, were not in regions of divergence. These studies suggest that specific repetitive phenotypes can be used to distinguish ASD mouse models, with implications for divergent underlying mechanisms for different repetitive behavior profiles
Of mice and marbles: Novel perspectives on burying behavior as a screening test for psychiatric illness
Comparison of the developmental effects of 5-methoxy-N,N-diisopropyltryptamine (Foxy) to (±)-3,4-methylenedioxymethamphetamine (ecstasy) in rats
Altered neocortical dynamics in a mouse model of Williams-Beuren syndrome
Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by moderate intellectual disability and learning difficulties alongside behavioral abnormalities such as hypersociability. Several structural and functional brain alterations are characteristic of this syndrome, as well as disturbed sleep and sleeping patterns. However, the detailed physiological mechanisms underlying WBS are mostly unknown. Here, we characterized the cortical dynamics in a mouse model of WBS previously reported to replicate most of the behavioral alterations described in humans. We recorded the laminar local field potential generated in the frontal cortex during deep anesthesia and characterized the properties of the emergent slow oscillation activity. Moreover, we performed micro-electrocorticogram recordings using multielectrode arrays covering the cortical surface of one hemisphere. We found significant differences between the cortical emergent activity and functional connectivity between wild-type mice and WBS model mice. Slow oscillations displayed Up states with diminished firing rate and lower high-frequency content in the gamma range. Lower firing rates were also recorded in the awake WBS animals while performing a marble burying task and could be associated with the decreased spine density and thus synaptic connectivity in this cortical area. We also found an overall increase in functional connectivity between brain areas, reflected in lower clustering and abnormally high integration, especially in the gamma range. These results expand previous findings in humans, suggesting that the cognitive deficits characterizing WBS might be associated with reduced excitability, plus an imbalance in the capacity to functionally integrate and segregate information.This work was supported by EU H2020 Research and Innovation Programme under Grant Agreement No. 720270 (HBP SGA2), BFU2017-85048-R Spanish Ministry of Science and CERCA Programme/Generalitat de Catalunya to MVSV