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Molecular Feature Detection


Most receptors do not interact with the entirety of their ligand molecules. Rather, there are usually parts of the ligand molecule that can be modified with minimal impact on receptor binding and activation, while other parts of the ligand molecule are more critical. Indeed, one can think of receptors as detectors of these critical molecular features. For olfactory receptors, these hypothesized features have been called "odotopes" in recognition of their similarity to "epitopes" in immunology (46).


This web site involves a large number of experiments using sets of odorant molecules differing systematically in chemical structure in order to explore the detection of molecular features by odorant receptors. In the first experiment dealing with this issue, each of two ethyl esters stimulated 2DG uptake in a part of the bulb that was not activated by either of two isoamyl esters (27). Conversely, each of the two isoamyl esters activated a distinct location that was not stimulated by either of the ethyl esters. The activity patterns were consistent with the recognition of the ethyl and isoamyl groups as distinct molecular features. In addition, all four esters stimulated a larger, overlapping area of the bulb, consistent with the overall similarity in their core structure.  



A set of five odorants sharing a straight-chained, saturated hydrocarbon structure but differing in the nature of their oxygen-containing functional groups were tested to determine whether the olfactory system would recognize functional groups as distinct molecular features (23).  While all of these odorants overlapped in their stimulation of a cluster of glomeruli in more posterior bulb regions, consistent with their shared straight-chain core structure, they activated distinct clusters of glomeruli in more anterior regions, consistent with the notion that the functional groups are recognized as distinct features in a combinatorial code. 



Another set of odorants that shared a carboxylic acid functional group but that differed greatly in their hydrocarbon structures overlapped in their activation of the anterior clusters, consistent with their shared functional group. In contrast, the posterior activity patterns differed greatly among these odorants, consistent with the recognition of the different hydrocarbon structures as distinct molecular features in a combinatorial code (24). The conclusions from these two experiments were consistent with the recognition of functional group-related features by the more anterior glomeruli and hydrocarbon structural features by the more posterior glomeruli. The different combinations of molecular features in different odorants could thereby combine to generate distinct activity patterns and unique odor perceptions. 


 
 
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Mapping Data
Background
Combinatorial Coding
Molecular Features
Glomerular Modules
Chemotopic Progressions
Global Chemotopy
Feature Interactions
Predictive Value
Odorant Concentration
Odorant Contaminants
Effects of Experience
Literature Cited
 
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This Human Brain Project/Neuroinformatics project is funded by the National Institute on Deafness and Other Communication Disorders and the National Institute of Mental Health