The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Neurofibromin Regulation of ERK Signaling Modulates GABA Release and Learning
Open accessAbstract
Summary We uncovered a new role for ERK signaling in GABA release, long-term potentiation (LTP) and learning, and show that disruption of this mechanism accounts for the learning deficits in a mouse model for Neurofibromatosis type I (NF1), a common genetic cause for learning disabilities. Genetic, pharmacological, electrophysiological and behavioral data demonstrate that neurofibromin modulates ERK/synapsin I dependent GABA release, which in turn modulate hippocampal LTP and learning. An Nf1 heterozygous null mutation, which results in enhanced ERK and synapsin I phosphorylation, increased pre-synaptic GABA release in the hippocampus which was reversed by pharmacologically down-regulating ERK signaling. Importantly, the learning deficits associated with the Nf1 mutation were rescued by a sub-threshold dose of a GABAA antagonist. Accordingly, Cre-deletions of the Nf1 gene showed that only those deletions involving inhibitory neurons caused hippocampal inhibition, LTP and learning abnormalities. Importantly, our results also revealed lasting increases in GABA release triggered by learning, indicating that the mechanisms uncovered here are of general importance for learning and memory.
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Cites
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Cited by
ERK signalling: A master regulator of cell behaviour, life and fate
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Interneuron dysfunction in psychiatric disorders
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Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke
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Extrasynaptic GABAA Receptors: Their Function in the CNS and Implications for Disease
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Self-citation
Metadata
- Authors
- Cui, Y., Costa, R. M., Murphy, G. G., Elgersma, Y., Zhu, Y., Gutmann, D. H., Parada, L. F., Mody, I., & Silva, A. J.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 135
- Issue
- 3
- Pages
- 549-560
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2129927715
- Cited by
- 440
- References
- 43
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- bronze
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