NMDA-R1 subunit of the cerebral cortex co-localizes with neuronal nitric oxide synthase at pre-and postsynaptic sites and in spines

Chiye Aoki, Julianne Rhee, Mona Lubin, Ted M. Dawson

Research output: Contribution to journalArticle

Abstract

The majority of nitric oxide's (NO) physiologic and pathologic actions in the brain has been linked to NMDA receptor activation. In order to determine how the NO-synthesizing enzyme within brain, neuronal NO synthase (nNOS), and NMDA receptors are functionally linked, previous studies have used in situ hybridization techniques in combination with light microscopic immunocytochemistry to show that the two are expressed within single neurons. However, this light microscopic finding does not guarantee that NMDA receptors are distributed sufficiently close to nNOS within single neurons to allow direct interaction of the two. Thus, in this study, dual immuno-electron microscopy was performed to determine whether nNOS and NMDA receptors co-exist within fine neuronal processes. We show that nNOS and the obligatory subunit of functional NMDA receptors, i.e. the NMDA-R1, co-exist within dendritic shafts, spines and terminals of the adult rat visual cortex. Axon terminals form asymmetric synaptic junctions with the dually labeled dendrites, suggesting that the presynaptic terminals release glutamate. Axons and dendrites expressing one without the other also are detected. These results indicate that it is possible for the generation of NO to be temporally coordinated with glutamatergic synaptic transmission at axo-dendritic and axo-axonic junctions and that NO may be generated independently of glutamatergic synaptic transmission. Together, our observations point to a greater complexity than previously recognized for glutamatergic neurotransmission, based on the joint versus independent actions of NO relative to NMDA receptors at pre- versus postsynaptic sites.

Original languageEnglish (US)
Pages (from-to)25-40
Number of pages16
JournalBrain Research
Volume750
Issue number1-2
DOIs
StatePublished - Mar 7 1997

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Nitric Oxide Synthase Type I
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Cerebral Cortex
Spine
Nitric Oxide
Nitric Oxide Synthase
Synaptic Transmission
Presynaptic Terminals
Dendrites
Neurons
Light
Dendritic Spines
Immunoelectron Microscopy
Brain
Visual Cortex
In Situ Hybridization
Axons
Glutamic Acid
Joints

Keywords

  • axo-axonic interaction
  • excitotoxicity
  • glutamate receptor
  • immuno-electron microscopy
  • LTP
  • nitric oxide
  • NMDA receptor
  • retrograde messenger
  • visual cortex

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

NMDA-R1 subunit of the cerebral cortex co-localizes with neuronal nitric oxide synthase at pre-and postsynaptic sites and in spines. / Aoki, Chiye; Rhee, Julianne; Lubin, Mona; Dawson, Ted M.

In: Brain Research, Vol. 750, No. 1-2, 07.03.1997, p. 25-40.

Research output: Contribution to journalArticle

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