Activity-dependent volume transmission by transgene NPY attenuates glutamate release and LTP in the subiculum

TY - JOUR

T1 - Activity-dependent volume transmission by transgene NPY attenuates glutamate release and LTP in the subiculum

AU - Sørensen, Andreas T

AU - Kanter-Schlifke, Irene

AU - Lin, En-Ju D

AU - During, Matthew J

AU - Kokaia, Merab

PY - 2008/10

Y1 - 2008/10

N2 - 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.

AB - 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.

KW - Animals

KW - Animals, Newborn

KW - Arginine

KW - Benzazepines

KW - Biophysical Phenomena

KW - Chi-Square Distribution

KW - Electric Stimulation

KW - Excitatory Postsynaptic Potentials

KW - Female

KW - GABA Antagonists

KW - Genetic Vectors

KW - Glutamic Acid

KW - Green Fluorescent Proteins

KW - Hippocampus

KW - In Vitro Techniques

KW - Long-Term Potentiation

KW - Male

KW - Neurons

KW - Neuropeptide Y

KW - Patch-Clamp Techniques

KW - Phosphopyruvate Hydratase

KW - Picrotoxin

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Neuropeptide Y

KW - Tetrodotoxin

KW - Transgenes

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.mcn.2008.06.014

DO - 10.1016/j.mcn.2008.06.014

M3 - Journal article

C2 - 18652899

SN - 1044-7431

VL - 39

SP - 229

EP - 237

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

IS - 2

ER -