Ultrastructural localization of dynorphin in the dentate gyrus in human temporal lobe epilepsy: A study of reorganized mossy fiber synapses

Substantial reorganization of mossy fibers from granule cells of the dentat e gyrus occurs in a high percentage of humans with medically intractable te mporal lobe epilepsy. To identify these fibers and determine their ultrastr uctural features in human surgical specimens, we used preembedding immunope roxidase labeling of dynorphin A, an opioid peptide that is abundant in nor mal mossy fibers. In electron microscopic preparations, dynorphin A immunor eactivity was highly associated with dense core vesicles and was localized predominantly in axon terminals in the inner molecular layer of the dentate gyrus, although some dynorphin-labeled dense core vesicles were also obser ved in dendritic shafts and spines. The labeled terminal profiles were nume rous, and, whereas they varied greatly in size, many were relatively large (2.3 mu M in mean major diameter). The terminals contained high concentrati ons of clear round vesicles and numerous mitochondrial profiles, formed dis tinct asymmetric synapses, often had irregular shapes, and, thus, exhibited many features of normal mossy fiber terminals. The dynorphin-labeled termi nals formed synaptic contacts primarily with dendritic spines, and some of these spines were embedded in large labeled terminals, suggesting that they were complex spines. The labeled terminals frequently formed multiple syna ptic contacts with their postsynaptic elements, and perforated postsynaptic densities, with and without spinules, were present at some synapses. These findings suggest that the reorganized mossy fiber terminals in humans with temporal lobe epilepsy form abundant functional synapses in the inner mole cular layer of the dentate gyrus, and many of these contacts have ultrastru ctural features that could be associated with highly efficacious synapses. (C) 1999 Wiley-Liss, Inc.