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Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
Nitric oxide regulates synaptic transmission between spiny projection neurons
Yotam Sagi1, Myriam Heiman2, Jayms D Peterson3
1Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; greengard@rockefeller.edu ysagi@rockefeller.edu.
Nitric oxide (NO) signaling in the striatum boosts vesicular GABA transporter (VGAT) expression in spiny projection neurons (SPNs). This NO-VGAT pathway regulates GABA transmission and motor behavior.
Area of Science:
- Neuroscience
- Molecular Biology
- Basal Ganglia Function
Background:
- Spiny projection neurons (SPNs) in the striatum communicate via recurrent axon collaterals, impacting basal ganglia function.
- The molecular mechanisms governing this intrastriatal communication are not well understood.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) signaling in regulating GABAergic transmission within SPN recurrent collaterals.
- To identify the molecular players involved in NO-mediated regulation of the vesicular GABA transporter (VGAT).
Main Methods:
- Investigated the effect of intrastriatal NO signaling on VGAT expression in SPN recurrent collaterals.
- Examined the impact of down-regulating NO signaling on GABAergic transmission and motor behavior.
- Utilized molecular techniques to identify signaling pathways (PKG1, CREB) involved in NO-mediated VGAT regulation.
Main Results:
- Intrastriatal NO signaling increases VGAT expression in SPN recurrent collaterals.
- Down-regulation of NO signaling attenuates GABAergic signaling, reduces VGAT expression, and impairs motor behavior.
- PKG1 and CREB are key components in the signal transduction pathway linking NO to VGAT transcriptional regulation.
Conclusions:
- NO signaling transcriptionally regulates VGAT expression in the striatum.
- This NO-VGAT pathway is crucial for modulating GABA transmission within SPN local circuits.
- The findings suggest a novel mechanism by which NO influences motor behavior and action selection through transcriptional control of GABAergic signaling.
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