Neuropeptide Y in the recurrent mossy fiber pathway.
In the epileptic brain, hippocampal dentate granule cells become synaptically interconnected through the sprouting of mossy fibers. This new circuitry is expected to facilitate epileptiform discharge. Prolonged seizures induce the long-lasting neoexpression of neuropeptide Y (NPY) in mossy fibers. NPY is released spontaneously from recurrent mossy fiber terminals, reduces glutamate release from those terminals by activating presynaptic Y2 receptors, and depresses granule cell epileptiform activity dependent on the recurrent pathway. These effects are much greater in rats than in C57BL/6 mice, despite apparently equivalent mossy fiber sprouting and neoexpression of NPY. This species difference can be explained by contrasting changes in the expression of mossy fiber Y2 receptors; seizures upregulate Y2 receptors in rats but downregulate them in mice. The recurrent mossy fiber pathway may synchronize granule cell discharge more effectively in humans and mice than in rats, due to its lower expression of either NPY (humans) or Y2 receptors (mice).
Nadler
J Victor
JV
Department of Pharmacology and Cancer Biology and Department of Neurobiology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA. nadle002@acpub.duke.edu
Tu
Bin
B
Timofeeva
Olga
O
Jiao
Yiqun
Y
Herzog
Herbert
H
D000818:Animals; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009478:Neuropeptide Y / Q000378:metabolism / Q000502:physiology*; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D013045:Species Specificity; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D010862:Pilocarpine