Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome.
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, incl...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2896423?pdf=render |
| _version_ | 1811271897127583744 |
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| author | Frédéric Gambino Malik Khelfaoui Bernard Poulain Thierry Bienvenu Jamel Chelly Yann Humeau |
| author_facet | Frédéric Gambino Malik Khelfaoui Bernard Poulain Thierry Bienvenu Jamel Chelly Yann Humeau |
| author_sort | Frédéric Gambino |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T22:29:20Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T22:29:20Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-495d893b635c46309e444019b66832022022-12-22T03:14:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0157e1139910.1371/journal.pone.0011399Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome.Frédéric GambinoMalik KhelfaouiBernard PoulainThierry BienvenuJamel ChellyYann HumeauRett 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.http://europepmc.org/articles/PMC2896423?pdf=render |
| spellingShingle | Frédéric Gambino Malik Khelfaoui Bernard Poulain Thierry Bienvenu Jamel Chelly Yann Humeau Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome. PLoS ONE |
| title | Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome. |
| title_full | Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome. |
| title_fullStr | Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome. |
| title_full_unstemmed | Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome. |
| title_short | Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome. |
| title_sort | synaptic maturation at cortical projections to the lateral amygdala in a mouse model of rett syndrome |
| url | http://europepmc.org/articles/PMC2896423?pdf=render |
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