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Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome.
J Neurosci 2006; 26(1):319-27JN

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.

Authors+Show Affiliations

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16399702

Citation

Moretti, Paolo, et al. "Learning and Memory and Synaptic Plasticity Are Impaired in a Mouse Model of Rett Syndrome." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 26, no. 1, 2006, pp. 319-27.
Moretti P, Levenson JM, Battaglia F, et al. Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J Neurosci. 2006;26(1):319-27.
Moretti, P., Levenson, J. M., Battaglia, F., Atkinson, R., Teague, R., Antalffy, B., ... Zoghbi, H. Y. (2006). Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 26(1), pp. 319-27.
Moretti P, et al. Learning and Memory and Synaptic Plasticity Are Impaired in a Mouse Model of Rett Syndrome. J Neurosci. 2006 Jan 4;26(1):319-27. PubMed PMID: 16399702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. AU - Moretti,Paolo, AU - Levenson,Jonathan M, AU - Battaglia,Fortunato, AU - Atkinson,Richard, AU - Teague,Ryan, AU - Antalffy,Barbara, AU - Armstrong,Dawna, AU - Arancio,Ottavio, AU - Sweatt,J David, AU - Zoghbi,Huda Y, PY - 2006/1/10/pubmed PY - 2006/4/1/medline PY - 2006/1/10/entrez SP - 319 EP - 27 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 26 IS - 1 N2 - 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. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/16399702/Learning_and_memory_and_synaptic_plasticity_are_impaired_in_a_mouse_model_of_Rett_syndrome_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=16399702 DB - PRIME DP - Unbound Medicine ER -