Cerebral Cortex Advance Access originally published online on July 21, 2004
Cerebral Cortex 2005 15(3):332-340; doi:10.1093/cercor/bhh135
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Cerebral Cortex V 15 N 3 © Oxford University Press 2004; all rights reserved
Layer-specific Production of Nitric Oxide during Cortical Circuit Formation in Postnatal Mouse Brain
Department of Integrated Biosciences, University of Tokyo, Kashiwa 277-8562, Japan
Address correspondence to Tatsuhiro Hisatsune, Department of Integrated Biosciences, The University of Tokyo, 5-1-5 Kashiwanoha, Bioscience Bldg-402, Kashiwa, Chiba 277-8562, Japan. Email: hisatsune{at}k.u-tokyo.ac.jp.
In the developing cerebral cortex, neuronal nitric oxide synthase (nNOS) is expressed abundantly, but temporarily. During the early postnatal stage, cortical neurons located in the multi-layered structure of the cortical plate start forming well-organized cortical circuits, but little is known about the molecular machinery for layer-specific circuit formation. To address the involvement of nitric oxide (NO), we utilized a new NO indicator (DAR-4M) and developed a protocol for the real-time imaging of NO produced in fresh cortical slices upon N-methyl-D-aspartic acid stimulation. At postnatal day 0 (P0), NO production was restricted to the deep layers (layers V and VI) of the somatosensory cortex where transient synapses are formed. At P10, the production of NO was expanded to layer IV where large numbers of thalamocortical axons form synapses. The pattern of NO production could correspond to active sites for synaptic formation. This study is the first clear demonstration of NO production in the postnatal mouse neocortex. The findings presented may reflect a function of NO in relation to the layer-specific development of neural circuits in the neocortex.
Key Words: Ca imaging neuronal nitric oxide synthase nitric oxide imaging NMDA stimulation somatosensory cortex
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