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Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome.
J Neurosci. 2006 Jan 04; 26(1):319-27.JN

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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., Armstrong, D., Arancio, O., Sweatt, J. D., & 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), 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 -