Amygdala-kindled seizures increase the expression of corticotropin-releasing factor (CRF) and CRF-binding protein in GABAergic interneurons of the dentate hilus.
Kindling, a model of temporal lobe epilepsy, induces a number of neuropeptides including corticotropin-releasing factor (CRF). CRF itself can produce limbic seizures which resemble kindling in some aspects. However, tolerance to the convulsant effects of CRF develops rapidly. Hypothetically, this could be explained should seizures also induce the CRF-binding protein (CRF-BP), which has been postulated to restrict the actions of CRF. Therefore, in the present study, we used in situ hybridization to examine the effects of amygdala-kindled seizures on the mRNA levels of CRF and CRF-BP. Kindled seizures markedly elevated CRF and CRF-BP in the dentate gyrus of rats. CRF and CRF-BP were induced almost exclusively in GABAergic interneurons of the dentate hilus. The CRF and CRF-BP interneurons also expressed neuropeptide Y but not cholecystokinin. CRF appeared to have an excitatory role in the dentate gyrus as it decreased the afterhyperpolarization of dentate granule neurons. These results suggest that CRF may contribute to the development of amygdala kindling. However, the compensatory induction of CRF-BP may serve to limit the excitatory effects of CRF in the dentate gyrus.
Smith
M A
MA
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
Weiss
S R
SR
Berry
R L
RL
Zhang
L X
LX
Clark
M
M
Massenburg
G
G
Post
R M
RM
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002766:Cholecystokinin / Q000096:biosynthesis; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000378:metabolism; D012756:Sheep; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002352:Carrier Proteins; D009478:Neuropeptide Y; C067133:corticotropin releasing factor-binding protein; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone