期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 39, 期 2, 页码 229-237出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2008.06.014
关键词
Neuropeptide Y; Gene therapy; Synaptic plasticity; Synaptic transmission; Activity-dependent release; Long-term potentiation (LTP); Whole-cell patch-clamp; Subiculum
资金
- European Commission-EPICURE [LSH-CT-2006-037315]
- Swedish Research Council
- Royal Physiographic Society in Lund
- Segerfalk Foundation
- Crafoordska Foundation
- Kock Foundation
- Lars Hiertas Memorial Foundation
Neuropeptide Y (NPY) gene transduction of the brain using viral vectors in epileptogenic regions can effectively suppress seizures in animals, and is being considered as a promising alternative treatment strategy for epilepsy. Therefore, it is fundamental to understand the detailed mechanisms governing the release and action of transgene NPY in neuronal circuitries. Using whole-cell recordings from subicular neurons, we show that in animals transduced by recombinant adeno-associated Viral (rAAV) vector carrying the NPY gene, transgene NPY is released during high-frequency activation of CA1-subicular synapses. Released transgene NPY attenuates excitatory synaptic transmission not only in activated, but also in neighboring, non-activated synapses. Such broad action of transgene NPY may prevent recruitment of excitatory synapses in epileptic activity and could play a key role in limiting the spread and generalization of seizures. (c) 2008 Elsevier Inc. All rights reserved.
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