PT  - JOURNAL ARTICLE
AU  - Jana Velíšková
AU  - Libor Velíšek
TI  - β-Estradiol Increases Dentate Gyrus Inhibition in Female Rats via Augmentation of Hilar Neuropeptide Y
AID  - 10.1523/JNEUROSCI.0366-07.2007
DP  - 2007 May 30
TA  - The Journal of Neuroscience
PG  - 6054--6063
VI  - 27
IP  - 22
4099  - http://www.jneurosci.org/content/27/22/6054.short
4100  - http://www.jneurosci.org/content/27/22/6054.full
SO  - J. Neurosci.2007 May 30; 27
AB  - The dentate gyrus filters incoming activity into the hippocampus proper. It plays a role in learning and memory and in pathological states such as epilepsy. Some of hilar interneurons of the dentate gyrus express neuropeptide Y (NPY), which modulates granule cell activity. A subpopulation of the NPY-expressing inhibitory interneurons is sensitive to seizure-induced damage. Pretreatment with β-estradiol in ovariectomized rats protects hilar interneurons against seizure-induced injury, including the NPY-containing damage-sensitive subpopulation. Here, we demonstrate that β-estradiol enhances NPY expression within the hilar interneurons. In vitro paired-pulse stimulation of the mixed perforant path revealed β-estradiol-induced augmentation of granule cell network inhibition, which at interstimulus intervals between 200 and 300 ms (corresponding to ∼3–5 Hz) was NPY sensitive and involved Y1 receptors, whereas it was insensitive to GABAB or metabotropic glutamate receptor antagonists. Additionally, β-estradiol pretreatment attenuated propagation of low-frequency (3.3 or 5 Hz) burst activity through the dentate gyrus. Scavenging endogenous NPY by intracerebroventricular administration of anti-NPY antibody accelerated kainic acid-induced seizure onset and increased seizure-induced neuronal damage in the hilus compared with rats treated with β-estradiol alone. Together, we show that β-estradiol upregulates hilar NPY and that this leads to enhancement in dentate gyrus inhibition of incoming frequencies between 3 and 5 Hz. Such frequencies are similar to the discharge frequencies recorded during seizure initiation in some patients with epilepsy. Thus, β-estradiol-induced NPY-sensitive filtering of 3–5 Hz frequencies may be an important regulator of incoming seizure activity, but it could also serve a physiological purpose in modulating information flow into the hippocampus proper.