Loading…
Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity
Mutations in the X-linked gene encoding the transcriptional modulator methyl–CpG-binding protein 2 (MeCP2) impair postnatal development of the brain. Here we use neuronal-type specific gene deletion in mice to show that conditional Mecp2 deletion in GABAergic parvalbumin-expressing (PV) cells ( PV-M...
Saved in:
Published in: | Nature communications 2014-10, Vol.5 (1), p.5036-5036, Article 5036 |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Mutations in the X-linked gene encoding the transcriptional modulator methyl–CpG-binding protein 2 (MeCP2) impair postnatal development of the brain. Here we use neuronal-type specific gene deletion in mice to show that conditional
Mecp2
deletion in GABAergic parvalbumin-expressing (PV) cells (
PV-Mecp2
−/y
) does not cause most Rett-syndrome-like behaviours, but completely abolishes experience-dependent critical period plasticity of primary visual cortex (V1) that develops normal visual functions. However, selective loss of
Mecp2
in GABAergic somatostatin-expressing cells or glutamatergic pyramidal cells does not affect the critical period plasticity. MeCP2-deficient PV cells exhibit high intrinsic excitability, selectively reduced efficacy of recurrent excitatory synapses in V1 layer 4 circuits, and decreased evoked visual responses
in vivo
. Enhancing cortical gamma-aminobutyric acid (GABA) inhibition with diazepam infusion can restore critical period plasticity in both young and adult
PV-Mecp2
−/y
mice. Thus, MeCP2 expression in inhibitory PV cells during the critical period is essential for local circuit functions underlying experience-dependent cortical plasticity.
Critical period plasticity describes a developmental process whereby neural circuits are fine-tuned for specific functions. Here, the authors show that the Rett syndrome protein MeCP2 in GABAergic parvalbumin-expressing neurons is required for critical period plasticity of the visual cortex. |
---|---|
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms6036 |