Abstract
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.
| Original language | English |
|---|---|
| Journal | Molecular and Cellular Neuroscience |
| Volume | 39 |
| Issue number | 2 |
| Pages (from-to) | 229-37 |
| Number of pages | 9 |
| ISSN | 1044-7431 |
| DOIs | |
| Publication status | Published - Oct 2008 |
Keywords
- Animals
- Animals, Newborn
- Arginine
- Benzazepines
- Biophysical Phenomena
- Chi-Square Distribution
- Electric Stimulation
- Excitatory Postsynaptic Potentials
- Female
- GABA Antagonists
- Genetic Vectors
- Glutamic Acid
- Green Fluorescent Proteins
- Hippocampus
- In Vitro Techniques
- Long-Term Potentiation
- Male
- Neurons
- Neuropeptide Y
- Patch-Clamp Techniques
- Phosphopyruvate Hydratase
- Picrotoxin
- Rats
- Rats, Sprague-Dawley
- Receptors, Neuropeptide Y
- Tetrodotoxin
- Transgenes
- Journal Article
- Research Support, Non-U.S. Gov't