RT Journal Article
SR Electronic
T1 Learning and Memory and Synaptic Plasticity Are Impaired in a Mouse Model of Rett Syndrome
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 319
OP 327
DO 10.1523/JNEUROSCI.2623-05.2006
VO 26
IS 1
A1 Paolo Moretti
A1 Jonathan M. Levenson
A1 Fortunato Battaglia
A1 Richard Atkinson
A1 Ryan Teague
A1 Barbara Antalffy
A1 Dawna Armstrong
A1 Ottavio Arancio
A1 J. David Sweatt
A1 Huda Y. Zoghbi
YR 2006
UL http://www.jneurosci.org/content/26/1/319.abstract
AB 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 (Mecp2308) 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 Mecp2308 mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2308 mutant males (Mecp2308/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 Mecp2308/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 Mecp2308/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.