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Journal of Neuroscience, Vol 14, 3736-3750, Copyright © 1994 by Society for Neuroscience
Dynorphin opioids present in dentate granule cells may function as retrograde inhibitory neurotransmitters
CT Drake, GW Terman, ML Simmons, TA Milner, DD Kunkel, PA Schwartzkroin and C Chavkin
Department of Pharmacology, University of Washington, Seattle 98195.
The granule cell population response to perforant path stimulation
decreased significantly within seconds following release of endogenous
dynorphin from dentate granule cells. The depression was blocked by the
opioid receptor antagonists naloxone and norbinaltorphimine, suggesting
that the effect was mediated by dynorphin activation of kappa 1 type opioid
receptors. Pharmacological application of dynorphin B in the molecular
layer was effective at reducing excitatory synaptic transmission from the
perforant path, but application in the hilus had no significant effect.
These results suggest that endogenous dynorphin peptides may be released
from a local source within the dentate molecular layer. By light
microscopy, dynorphin-like immunoreactivity (dynorphin-LI) was primarily
found in granule cell axons in the hilus and stratum lucidum with only a
few scattered fibers evident in the molecular layer. At the extreme ventral
pole of the hippocampus, a diffuse band of varicose processes was also seen
in the molecular layer, but this band was not present in more dorsal
sections similar to those used for the electrophysiological studies.
Electron microscopic analysis of the molecular layer midway along the
septotemporal axis revealed that dynorphin-LI was present in dense-core
vesicles in both spiny dendrites and unmyelinated axons with the majority
(74%) of the dynorphin-LI-containing dense-core vesicles found in
dendrites. Neuronal processes containing dynorphin-LI were observed
throughout the molecular layer. The results suggest that dynorphin release
from granule cell processes in the molecular layer regulates excitatory
inputs entering the hippocampus from cerebral cortex, thus potentially
counteracting such excitation-induced phenomena as epileptogenesis or
long-term potentiation.
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