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  • Title: Ultrastructural heterogeneity of enkephalin-containing terminals in the rat hippocampal formation.
    Author: Commons KG, Milner TA.
    Journal: J Comp Neurol; 1995 Jul 31; 358(3):324-42. PubMed ID: 7560290.
    Abstract:
    Opioid peptides, including leu-enkephalin (LE), are important neuromodulators in the hippocampal formation where they may play a role in learning and memory as well as epileptogenesis. We examined the cellular substrates that underlie the function of LE in each lamina of the rat hippocampal formation by immunocytochemistry at the electron microscopic level in single section analysis. LE-like immunoreactivity (LE-LI) was primarily associated with large dense-core vesicles (80-100 nm), usually found in axons and axon terminals, but was also observed in perikarya and occasionally in dendrites. The morphology and synaptic associations of LE-LI-containing terminals were strikingly distinct in each region of the hippocampal formation. In the molecular layer of the dentate gyrus, terminals with LE-LI were typically small (0.6 microns) and formed primarily asymmetric (excitatory type) synapses on single dendritic spines, which is consistent with the presence of LE in the lateral perforant path. In the hilus of the dentate gyrus, two types of LE-containing terminals were present: (1) small round terminals that were heterogeneous in size (0.4-1 microns) and in type of contact formed and (2) larger (3-5 microns) terminals exhibiting the characteristic morphology of mossy fiber boutons that formed asymmetric synapses on spines. This variation in morphology and the type of contact suggests LE may have a heterogeneous influence on diverse hilar interneurons. In the CA3 region of the hippocampus, LE-LI was localized to large mossy fiber boutons (3-7 microns) that formed multiple asymmetric synapses on complex spiny dendritic processes and often formed puncta adherentia with the shafts of large CA3 pyramidal cell dendrites, indicating that this peptide may be directly released onto pyramidal cells. At the border of stratum radiatum and lacunosum moleculare in the CA1 region of the hippocampus, LE-labeled terminals averaged 0.8 microns in diameter and often formed symmetric (inhibitory type) synapses on dendritic shafts, which is consistent with a role in disinhibition. In conclusion, these heterogeneous cellular interactions indicate that LE has diverse functional roles and mechanisms of action within each lamina of the hippocampal formation and may directly and indirectly modulate hippocampal cell activity.
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