Defective synaptic transmission and structure in the dentate gyrus and selective fear memory impairment in the Rsk2 mutant mouse model of Coffin–Lowry syndrome

@article{Morice2013DefectiveST,
  title={Defective synaptic transmission and structure in the dentate gyrus and selective fear memory impairment in the Rsk2 mutant mouse model of Coffin–Lowry syndrome},
  author={Elise Morice and S{\'e}verine Farley and Roseline Poirier and Glenn Dall{\'e}rac and Carine Chagneau and Solange Pannetier and André Hanauer and Sabrina Davis and Cyrille Vaillend and Serge Laroche},
  journal={Neurobiology of Disease},
  year={2013},
  volume={58},
  pages={156-168}
}

Figures and Tables from this paper

NMDA receptor‐deficient mice display sexual dimorphism in the onset and severity of behavioural abnormalities
TLDR
It is found that while juvenile mutant mice had some ability to problem solve in the puzzle box test, the same mice lost this ability when tested 4 weeks later, and executive function was most impaired in peri‐adolescent mice of either sex.
DMM021246 1389..1400
TLDR
It is concluded that RSK is required for normal synaptic morphology and function and loss of RSK function interferes with ERK signaling at different levels, which emphasizes the importance of fine-tuning ERK activity in neuronal processes underlying higher brain functions.
Role of p90 ribosomal S6 kinase in long-term synaptic facilitation and enhanced neuronal excitability
TLDR
Inhibition of RSK expression or RSK activity both significantly reduced CREB1 phosphorylation, LTF, and LTEE, suggesting RSK is required for learning-related synaptic plasticity and enhancement in neuronal excitability.
Defective synaptic plasticity in a model of Coffin-Lowry Syndrome is rescued by simultaneously targeting PKA and MAPK pathways
TLDR
Examination of whether individual or dual-drug treatments can restore the deficit in long-term synaptic facilitation of the Aplysia sensorimotor synapse observed in a molecular model of Coffin-Lowry Syndrome found that the combined drugs exerted synergistic effects on both RSK activation and LTF, fully restoring RSK phosphorylation and L TF.
Rsk2 Knockout Affects Emotional Behavior in the IntelliCage
TLDR
Taken together, RSK2 not only plays a role in cognitive processes but also in emotional and reward-related behaviors.
Animal Models for Coffin-Lowry Syndrome: RSK2 and Nervous System Dysfunction
TLDR
Understanding of the pathophysiology of CLS can be improved, which might open the door for development of potential intervention strategies, and some common aspects of RSK2 function in the nervous system have emerged.
...
...

References

SHOWING 1-10 OF 90 REFERENCES
Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin–Lowry syndrome
TLDR
It is suggested that a defect in AMPA neurotransmission and plasticity contribute to mental retardation in CLS patients, the first time that such deregulations have been demonstrated in the mouse model of the Coffin–Lowry syndrome.
Reorganization of inhibitory synapses and increased PSD length of perforated excitatory synapses in hippocampal area CA1 of dystrophin-deficient mdx mice.
TLDR
It is suggested that increased inhibitory synapse density reflects tenuous compensation of altered clustering of alpha2 subunit-containing GABA(A)-Rs in CA1 dendrites, whereas increased PSD length in perforated synapses suggests secondary alterations in excitatory synapse organization associated with enhanced synaptic excitation.
Smaller Dendritic Spines, Weaker Synaptic Transmission, but Enhanced Spatial Learning in Mice Lacking Shank1
TLDR
The results affirm the importance of Shank1 for synapse structure and function in vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders.
Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.
TLDR
It is concluded that loss of major Shank3 species produces biochemical, cellular and morphological changes, leading to behavioral abnormalities in mice that bear similarities to human ASD patients with SHANK3 mutations.
Deletion of the Coffin–Lowry Syndrome Gene Rsk2 in Mice is Associated With Impaired Spatial Learning and Reduced Control of Exploratory Behavior
TLDR
The observed behavioral changes are in line with observations made in other mouse models of human mental retardation and support a role of Rsk2 in cognitive functions.
Importance of Shank3 Protein in Regulating Metabotropic Glutamate Receptor 5 (mGluR5) Expression and Signaling at Synapses*
TLDR
It is demonstrated that a deficit in mGluR5-mediated intracellular signaling in Shank3 knockdown neurons can be compensated by 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)-benzamide, raising the possibility that pharmacological augmentation of mGLUR5 activity represents a possible new therapeutic approach for patients with Shank3 mutations.
Genes, plasticity and mental retardation
Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin‐Lowry syndrome
TLDR
It is suggested that the dopaminergic dysregulation in mrsk2_KO mice may be caused, at least in part, by tyrosine hydroxylase hyperactivity, and this cortical hyperdopaminergia may explain some non‐cognitive but also cognitive alterations exhibited by mRSk2-KO mice.
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction
TLDR
It is shown that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction and a critical role for SHANK3 in the normal development of neuronal connectivity is demonstrated.
...
...