This is a preprint of a paper published in Proc Natl AcadSci USA 103:14985-14986.

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Functional Units in the Olfactory System

 

Michael Leon* andBrett Johnson

Department ofNeurobiology and Behavior

University ofCalifornia Irvine, CA 92697

 

At each stage of odor coding, the olfactory system isdivided into anatomical subdivisions that appear to serve distinct functions.While the olfactory (piriform) cortex has long been known have anterior andposterior subdivisions with different local architectures (1), the function ofthese anatomical units has been poorly understood. In their article in thisissue of PNAS, Kadohisa and Wilson report that anterior and posterior piriformcortex are differently modified by olfactory experience, suggesting that theprinciples of functional domain organization in the olfactory system extend tohigher levels of processing, where the subdivisions may have separate rolesinvolving odorant discrimination and odor generalization (2).

 

Each olfactory sensory neuron in the olfactory epitheliumexpresses a single type of odorant receptor that binds odorants on the basis oftheir molecular features (3, 4). Different types of receptors are expressed indifferent parts of the nose, some in separate organs (5), or in differentcompartments or zones of the main olfactory epithelium (6). In the mainepithelium, most odorant receptor expression zones may be functional anatomicalunits, as they are organized orthogonally to airflow, establishing aninteraction between chromatographic separation of odorants across the nasalmucosa and receptor specificity to establish the unique activity patternsacross the epithelium that are evoked by different odorant molecules (6).

 

There are specialized peripheral organs in the nose thatproject to separate, small sets of olfactory bulb glomeruli (5), while thezones of the olfactory epithelium project to corresponding zones within theglomerular layer of the bulb (6, Fig. 1). The axons of sensory neuronsexpressing the same odorant receptor converge into glomeruli, which areorganized into modular clusters that respond differentially to aspects ofshared odorant chemistry, such as functional groups, hydrocarbon structure,and/or chemical properties that are determined by the whole molecule (7).  Glomerular modules in the ventral halfof the bulb have responses organized such that larger molecules activate moreventral glomeruli, a pattern that probably reflects chromatographic separationof odorants in the epithelium (8).

 

While these anatomical units exist in the olfactory system,have they been shown to have critical functions in olfactory coding?  Although early bulb ablation studies,most of which were not guided by knowledge of actual odorant responses,questioned the relevance of domain organization in the olfactory bulb, morerecent interventive experiments have confirmed the critical involvement ofspatially restricted regions in the perception of particular odorants.Pharmacological blockade of dorsal bulbar activity interferes withexperience-dependent modification of responses to odorants whose activityinvolves those dorsal regions, but does not affect responses to odorantsactivating only the ventral part of the bulb (9). Chemical ablation ofparticular domains in the epithelium diminishes responses to odorants expectedto be represented in those regions, but does not diminish responses to odorantsexpected to activate intact regions (10). Finally, antibodies to a receptoractivated by octanal reduce both behavioral and focal neuronal responses tothat odorantà. Certainly, there is now very clear evidence forcritical functions of anatomical domains in the olfactory system and thisevidence casts doubt on alternative hypotheses of odor coding that exclusivelyinvolve temporal coding, or hypotheses that depend on an extreme distributionof responses.

 

The mitral cells that report activity to the piriform cortexeach receive input from only one glomerulus, but then amplify, sharpen andfilter the signal before sending it to the piriform (11, 12, ×).  Mitral cells project to a broad set ofhigher brain regions that have rarely been investigated for their function, butthat are likely to serve distinct roles in odor-directed behavior. The largestprojection is to the anterior and posterior piriform cortex, which havedistinct cytoarchitecture and connectivity (1). Mitral cells receiving primaryinput from the same odorant receptors project in a patchy pattern acrosspiriform cortex (13) and the cells that are activated by different odorantreceptors project to different areas in the anterior piriform cortex, such thatdifferent odorants elicit different activity patterns in that structure (14).The responses to different chemical features are thereby thought to be broughtback together in piriform cortex for the perception of odor identity (14).

 

Wilson and Stevenson have pointed out that odor perceptionis likely to be more complex than the simple, faithful representation ofexternal odorants in the brain (15). The final perception of odor that is represented in the brain shouldinvolve an interaction between sensory information being relayed from theperiphery and some central neural representation of what has been alreadylearned about various odors (15). Thus, an experienced cortex may responddifferently to the same odorant than would a na•ve cortex.  In testing for suchexperience-dependent changes, Kadohisa and Wilson found that pyramidal neuronsin anterior piriform cortex indeed become more highly tuned to an odorantmixture when rats are trained to distinguish it from its components (2).  They further found that equivalentneurons in the posterior piriform cortex actually become more broadly tunedfollowing the same experience, thus revealing that different parts of olfactorycortex are differently modified by the same experience (2).  Interestingly, another recent reportusing functional MRI (fMRI) and odorant cross-habituation has shown that theanterior piriform cortex in humans appears to classify odorants according tochemical similarities while posterior piriform cortex classifies odorantsaccording to overall similarities in perceived odors (16, Fig. 1).  Together, these findings suggest thepossibility that anterior piriform cortex may function in discriminatingclosely related odorants, for example, distinguishing geranyl acetate (rose)from methyl anthranilate (orange blossom), while posterior piriform cortex mayfunction to represent perceptual similarities (floral).

 

As is the case for most important scientific findings, thepaper by Kadohisa and Wilson raises a number of questions. Would differentreinforcement contingencies during the odorant experience lead to a differenttype of change in either cortex? Do the changes occur equally for every set ofodorants that might be experienced, or are they specifically relevant to themixtures and components that were tested in the study? Do the piriform changesonly affect the odorants that were actually experienced, or is there sometransference to odorants of similar chemistry or similar perceived odor? Whatis the mechanism by which these differences arise? Are distinct bulbar domainsinvolved in producing the different types of cortical responses?  What are the differences in the projectionsof mitral cells to the anterior and posterior pirifom that could underlie thesedifferences in perception?  Willthere be new anatomical areas identified that underlie other parallel-processedaspects of perception (17)? Would pharmacological interventions or physicallesions affecting anterior piriform cortex affect discrimination learningwithout affecting the learning of perceptual categories? Answers to suchquestions are likely to follow in the coming years.

 

Recent neural network approaches seem to have addressed oneof these questions.  These analyseshave been applied to determine which aspects of rat glomerular layer activitypatterns are used by the piriform to predict either odorant chemical featuresor human odor descriptors, with the unexpected result that the parts of thepattern associated with the chemistry of a given odorant are often adjacent to,but rarely overlap with, the parts of the pattern predicting the perceived odorof the compound¤.  Thus,anterior piriform cortex may be attending to different sets of activated mitralcells (those predicting odorant chemical features) than posterior piriformcortex (which might be attending to mitral cells predicting perceived odor).These findings may provide one aspect of the mechanism underlying thefunctional distinctions in the piriform. 

 

 

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17.   Anderson, A.K., Chrostoff, K., Stappen, I., Panitz, D.,Ghahremani, D.G., Glover, G.H., Gabrielli, J.D.E. & Sobel, N.  (2003) Nature Neurosci. 6, 196-202.

 

×Cleland,T., Johnson, B., Leon, M. & Linster, C.  (2006) Abstr. AChemS Ann. Meeting 28, 75.

à Deutsch,S. & Apfelbach, R.  (2006) Abstr.Assoc. Chemoreception. Sci. Ann. Meeting 28,261.

¤ MadanyMamlouk, A., Teehankee, A., Schuh, E., Martinetz, T., Leon, M. & Johnson,B.A. (2006) Abstr. ECRO Meeting 17,234.

 

* To whom correspondence should be addressed.  Email: mleon@uci.edu.

 

Fig.1. Molecular features in odorant chemicals such asgeranyl acetate bind to odorant receptors expressed in zones of the olfactoryepithelium. The sensory neurons that express the same odorant receptor geneconverge into glomeruli of the olfactory bulb to produce patterns of majorresponse foci such as are shown here in a 3-D rendering of 2-deoxyglucoseuptake evoked by geranyl acetate (only the medial surfaced is shown).  Mitral cells associated with theseglomeruli project in diffuse, but patchy, patterns onto both anterior and posteriorpiriform cortex. As shown by Kadohisa and Wilson (2), odor experience causesresponses in anterior piriform cortex to become more narrowly tuned toparticular odorants, perhaps supporting the type of odorant discriminationresponsible for the specific ÒroseÓ odor of geranyl acetate, while responses inposterior piriform cortex become more broadly tuned, perhaps supporting thetype of odor classification responsible for the general ÒfloralÓ odor shared bygeranyl acetate and odorants of distinct chemical structure.

 

See companion article on page ¥¥¥.