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Four-Dimensional Neuronal Signaling by Nitric Oxide: A Computational Analysis
journal contribution
posted on 2023-06-07, 19:49 authored by Andy PhilippidesAndy Philippides, Phil HusbandsPhil Husbands, Michael O'SheaNitric oxide (NO) is now recognized as a transmitter of neurons that express the neuronal isoform of the enzyme nitric oxide synthase. NO, however, violates some of the key tenets of chemical transmission, which is classically regarded as occurring at points of close apposition between neurons. It is the ability of NO to diffuse isotropically in aqueous and lipid environments that has suggested a radically different form of signaling in which the transmitter acts four-dimensionally in space and time, affecting volumes of the brain containing many neurons and synapses. Although ¿volume signaling¿ clearly challenges simple connectionist models of neural processing, crucial to its understanding are the spatial and temporal dynamics of the spread of NO within the brain. Existing models of NO diffusion, however, have serious shortcomings because they represent solutions for ¿point-sources,¿ which have no physical dimensions. Methods for overcoming these difficulties are presented here, and results are described that show how NO spreads from realistic neural architectures with both simple symmetrical and irregular shapes. By highlighting the important influence of the geometry of NO sources, our results provide insights into the four-dimensional spread of a diffusing messenger. We show for example that reservoirs of NO that accumulate in volumes of the nervous system where NO is not synthesized contribute significantly to the temporal and spatial dynamics of NO spread.
History
Publication status
- Published
File Version
- Published version
Journal
Journal of NeuroscienceISSN
0270-6474Publisher
Society for NeurosciencePublisher URL
Issue
3Volume
20Page range
1199-1207ISBN
0270-6474Department affiliated with
- Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes