PMID:16399702

Citation	Moretti, P, Levenson, JM, Battaglia, F, Atkinson, R, Teague, R, Antalffy, B, Armstrong, D, Arancio, O, Sweatt, JD and Zoghbi, HY (2006) Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J. Neurosci. 26:319-27
Abstract	Loss-of-function mutations or abnormal expression of the X-linked gene encoding methyl CpG binding protein 2 (MeCP2) cause a spectrum of postnatal neurodevelopmental disorders including Rett syndrome (RTT), nonsyndromic mental retardation, learning disability, and autism. Mice expressing a truncated allele of Mecp2 (Mecp2(308)) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals. We investigated learning and memory, neuronal morphology, and synaptic function in Mecp2(308) mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2(308) mutant males (Mecp2(308/Y)). The morphology of dendritic arborizations, the biochemical composition of synaptosomes and postsynaptic densities, and brain-derived neurotrophic factor expression were not altered in these mice. However, reduced postsynaptic density cross-sectional length was identified in asymmetric synapses of area CA1 of the hippocampus. In the hippocampus of symptomatic Mecp2(308/Y) mice, Schaffer-collateral synapses exhibited enhanced basal synaptic transmission and decreased paired-pulse facilitation, suggesting that neurotransmitter release was enhanced. Schaffer-collateral long-term potentiation (LTP) was impaired. LTP was also reduced in the motor and sensory regions of the neocortex. Finally, very early symptomatic Mecp2(308/Y) mice had increased basal synaptic transmission and deficits in the induction of long-term depression. These data demonstrate a requirement for MeCP2 in learning and memory and suggest that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT.
Links	PubMed Online version:10.1523/JNEUROSCI.2623-05.2006
Keywords	Animals; Disease Models, Animal; Female; Learning/physiology; Male; Memory/physiology; Memory Disorders/genetics; Memory Disorders/physiopathology; Methyl-CpG-Binding Protein 2/genetics; Methyl-CpG-Binding Protein 2/physiology; Mice; Mice, Transgenic; Mutation; Neuronal Plasticity/genetics; Rett Syndrome/genetics; Rett Syndrome/physiopathology; Synaptic Transmission/physiology
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