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Distinct glutamate receptors govern differential levels of nitric oxide production in a layer-specific manner in the rat cerebellar cortex.
Neuroscience. 2004; 125(2):461-72.N

Abstract

To evaluate roles of nitric oxide (NO) in neural functions, it is critical to know how neural inputs activate neuronal NO synthase in individual sites. Although NMDA receptor-dependent mechanism well explains postsynaptic, robust NO production, this sole mechanism does not explain some aspects of NO production in the brain, such as the low-level production of NO and the mechanism for presynaptic NO production. We hypothesized that the glutamate receptor involved in NO production is site-specific and controls the initial NO concentration in each site. We visualized NO production mediated by NMDA, AMPA and type-1 metabotropic glutamate (mGlu-1) receptors in rat cerebellar slices and granule cells in culture, with an NO-specific fluorescent indicator, diaminofluorescein-2. AMPA receptor, but not NMDA or mGlu-1 receptor, was responsible for NO production at parallel fiber terminals, which was blocked by CNQX, tetrodotoxin or voltage-dependent calcium channel blockers. More numbers of electrical stimulation were required for NO production in the molecular layer than in other layers, suggesting that AMPA receptor activation generates NO at lower concentrations through a remote interaction with NO synthase. Although Purkinje cell does not express NO synthase, we detected NO production in Purkinje cell layer following electrical stimulation in the white matter at 50 Hz, but not at 10 Hz. This NO production was tetrodotoxin-sensitive, suggesting occurrence in the basket cell terminals, and required synergistic activation of mGlu-1 and NMDA receptors. In the granule cell layer, activation of AMPA or mGlu-1 receptor produced NO uniformly, while NMDA receptor activation produced NO in discontinuous areas of this layer. Thus, distinct glutamate receptors, including non-NMDA receptors, govern occurrence and level of NO production in a layer-specific manner.

Authors+Show Affiliations

Laboratory for Memory and Learning, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan. dada@libra.ls.m-kaguka.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15062988

Citation

Okada, D, et al. "Distinct Glutamate Receptors Govern Differential Levels of Nitric Oxide Production in a Layer-specific Manner in the Rat Cerebellar Cortex." Neuroscience, vol. 125, no. 2, 2004, pp. 461-72.
Okada D, Yap CC, Kojima H, et al. Distinct glutamate receptors govern differential levels of nitric oxide production in a layer-specific manner in the rat cerebellar cortex. Neuroscience. 2004;125(2):461-72.
Okada, D., Yap, C. C., Kojima, H., Kikuchi, K., & Nagano, T. (2004). Distinct glutamate receptors govern differential levels of nitric oxide production in a layer-specific manner in the rat cerebellar cortex. Neuroscience, 125(2), 461-72.
Okada D, et al. Distinct Glutamate Receptors Govern Differential Levels of Nitric Oxide Production in a Layer-specific Manner in the Rat Cerebellar Cortex. Neuroscience. 2004;125(2):461-72. PubMed PMID: 15062988.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct glutamate receptors govern differential levels of nitric oxide production in a layer-specific manner in the rat cerebellar cortex. AU - Okada,D, AU - Yap,C C, AU - Kojima,H, AU - Kikuchi,K, AU - Nagano,T, PY - 2004/01/23/accepted PY - 2004/4/6/pubmed PY - 2004/7/21/medline PY - 2004/4/6/entrez SP - 461 EP - 72 JF - Neuroscience JO - Neuroscience VL - 125 IS - 2 N2 - To evaluate roles of nitric oxide (NO) in neural functions, it is critical to know how neural inputs activate neuronal NO synthase in individual sites. Although NMDA receptor-dependent mechanism well explains postsynaptic, robust NO production, this sole mechanism does not explain some aspects of NO production in the brain, such as the low-level production of NO and the mechanism for presynaptic NO production. We hypothesized that the glutamate receptor involved in NO production is site-specific and controls the initial NO concentration in each site. We visualized NO production mediated by NMDA, AMPA and type-1 metabotropic glutamate (mGlu-1) receptors in rat cerebellar slices and granule cells in culture, with an NO-specific fluorescent indicator, diaminofluorescein-2. AMPA receptor, but not NMDA or mGlu-1 receptor, was responsible for NO production at parallel fiber terminals, which was blocked by CNQX, tetrodotoxin or voltage-dependent calcium channel blockers. More numbers of electrical stimulation were required for NO production in the molecular layer than in other layers, suggesting that AMPA receptor activation generates NO at lower concentrations through a remote interaction with NO synthase. Although Purkinje cell does not express NO synthase, we detected NO production in Purkinje cell layer following electrical stimulation in the white matter at 50 Hz, but not at 10 Hz. This NO production was tetrodotoxin-sensitive, suggesting occurrence in the basket cell terminals, and required synergistic activation of mGlu-1 and NMDA receptors. In the granule cell layer, activation of AMPA or mGlu-1 receptor produced NO uniformly, while NMDA receptor activation produced NO in discontinuous areas of this layer. Thus, distinct glutamate receptors, including non-NMDA receptors, govern occurrence and level of NO production in a layer-specific manner. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/15062988/Distinct_glutamate_receptors_govern_differential_levels_of_nitric_oxide_production_in_a_layer_specific_manner_in_the_rat_cerebellar_cortex_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306452204000843 DB - PRIME DP - Unbound Medicine ER -