Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of rett syndrome
PLoS ONE. 2010-07-02; 5(7): e11399
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1. PLoS One. 2010 Jul 2;5(7):e11399. doi: 10.1371/journal.pone.0011399.
Synaptic maturation at cortical projections to the lateral amygdala in a mouse
model of Rett syndrome.
Gambino F(1), Khelfaoui M, Poulain B, Bienvenu T, Chelly J, Humeau Y.
(1)Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 et
Université de Strasbourg, Strasbourg, France.
Rett syndrome (RTT) is a neuro-developmental disorder caused by loss of function
of Mecp2–methyl-CpG-binding protein 2–an epigenetic factor controlling DNA
transcription. In mice, removal of Mecp2 in the forebrain recapitulates most of
behavioral deficits found in global Mecp2 deficient mice, including
amygdala-related hyper-anxiety and lack of social interaction, pointing a role of
Mecp2 in emotional learning. Yet very little is known about the establishment and
maintenance of synaptic function in the adult amygdala and the role of Mecp2 in
these processes. Here, we performed a longitudinal examination of synaptic
properties at excitatory projections to principal cells of the lateral nucleus of
the amygdala (LA) in Mecp2 mutant mice and their wild-type littermates. We first
show that during animal life, Cortico-LA projections switch from a tonic to a
phasic mode, whereas Thalamo-LA synapses are phasic at all ages. In parallel, we
observed a specific elimination of Cortico-LA synapses and a decrease in their
ability of generating presynaptic long term potentiation. In absence of Mecp2,
both synaptic maturation and synaptic elimination were exaggerated albeit still
specific to cortical projections. Surprisingly, associative LTP was unaffected at
Mecp2 deficient synapses suggesting that synaptic maintenance rather than
activity-dependent synaptic learning may be causal in RTT physiopathology.
Finally, because the timing of synaptic evolution was preserved, we propose that
some of the developmental effects of Mecp2 may be exerted within an endogenous
program and restricted to synapses which maturate during animal life.
PMID: 20625482 [Indexed for MEDLINE]