Ultrastructural evidence for presynaptic mu opioid receptor modulation of synaptic plasticity in NMDA-receptor-containing dendrites in the dentate gyrus.
Physiological studies have demonstrated that long-term potentiation (LTP) induction in N-methyl-D-aspartate (NMDA) receptor containing dentate granule cells following lateral perforant path stimulation is opioid dependent, involving mu-opioid receptors (MORs) on gamma-aminobutyric acid (GABA)-ergic neurons. To determine the cellular relationships of MORs to postsynaptic NMDA receptor-containing dendrites, immunoreactivity (-I) against MOR and the NMDA receptor subunit 1 (NMDAR1) was examined in the outer molecular layer of the dentate gyrus using electron microscopy. MOR-I was predominantly in axons and axon terminals. NMDAR1-I was almost exclusively in spiny dendrites, but was also in a few terminals. Using immunogold particles to localize precisely NMDAR1, one-third of the NMDAR1-I was detected on the dendritic plasmalemma; in dendritic spines plasmalemmal immunogold particles were near synaptic densities. Many MOR-labeled axons and terminals contacted NMDAR1-labeled dendrites. MOR-labeled terminals formed symmetric (inhibitory-type) synapses on NMDAR1-labeled dendritic shafts or nonsynaptically contacted NMDAR1-labeled shafts and spines. MOR-labeled axons often abutted NMDAR1-containing dendritic spines which received asymmetric (excitatory-type) synapses from unlabeled terminals. Occasionally, MOR-labeled terminals and dendrites were apposed to NMDAR1-containing terminals. These results provide anatomical evidence that endogenous enkephalins or exogenous opioid agonists could inhibit GABAergic terminals that modulate granule cell dendrites, thus boosting depolarizing events in granule cells and facilitating the activation of NMDA receptors located on their dendrites.
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA. tmilner@mail.med.cornell.edu
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D000818:Animals; D003712:Dendrites / Q000737:chemistry / Q000648:ultrastructure*; D018891:Dentate Gyrus / Q000737:chemistry / Q000648:ultrastructure*; D007395:Interneurons / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009473:Neuronal Plasticity; D017729:Presynaptic Terminals / Q000737:chemistry / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000648:ultrastructure*; D017450:Receptors, Opioid, mu / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure*
C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu