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Olfactory receptor neurons are complex odorant information processors. Focus on "Excitation, inhibition, and suppression by odors in isolated toad and rat olfactory receptor neurons"

George Gomez

Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104-3308


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OLFACTION IS CONSIDERED TO BE a primitive sensory system in evolutionary terms, yet it has proven to be biologically complex. It is commonly thought that the sense of smell in humans is less developed than in most other vertebrate species, yet we are able to detect and, with training, discriminate among thousands of different odors. We accomplish this with a population of ~1,000,000 olfactory receptor neurons that express ~1,000 different types of odorant receptor molecules (ORs). The binding of odorant molecules to ORs triggers a biochemical cascade in the olfactory receptor neurons, which culminates in the generation of a receptor current and action potentials that are transmitted to the olfactory bulb (6). Recent advances in molecular biology and genetics have allowed researchers to focus their attention on the identity, expression pattern, and ligand specificity of ORs. Odorant information is first encoded by olfactory receptor neurons, which typically express one type of OR (1). Many different odorants can stimulate one cell (and thus one type of OR), and one odorant can activate cells that express different types of ORs (in different cells); thus the code is hypothesized to be a combinatorial code (3). Because axons of cells expressing the same OR project into one (or a few) glomerulus in the olfactory bulb, this combinatorial code is directly translated into a glomerular code, where odorant identity is discriminated by a specific pattern of activation across the glomeruli in the olfactory bulb (4). Based on this scheme, it is easy to consider olfactory neurons as merely the bearers of ORs and that OR identity alone determines the cell's stimulus-encoding capability.

However, physiological studies on olfactory receptor neurons demonstrate that this is not the case. Olfactory neurons are active participants in olfactory coding, filtering the odor information before sending a neural signal to the olfactory bulb. When stimulated with odorants, olfactory neurons can generate excitatory or inhibitory responses, or a combination of both. The results from the current article in focus by Sanhueza et al. (Ref. 5, see p. C31 in this issue) add a twist to the study of the complex nature of the olfactory neuron. This study is the latest installment in a body of work that elucidates the nature of odorant-elicited inhibition and suppression. This work shows that olfactory cell responses can be excitatory, inhibitory, and suppressed by the application of odorants at relatively high concentrations. Suppression occurs in a large majority of cells and affects the net current that is generated by the cells in response to a stimulus. Furthermore, some cells respond to odorant mixtures with all three types of responses: excitation, inhibition, and suppression. Although it is not certain whether individual odorants can produce all three effects or whether each component of the mixture produces one type of response and the net output of the cell integrates these individual response types, these findings imply that a single olfactory neuron is capable of responding to different odorant mixtures with different currents and, consequently, different spiking outputs. The data presented in this manuscript provide a cellular mechanistic basis for neurophysiological data (extracellularly recorded spikes): receptor cell output is dependent not only on stimulus quality but also on intensity and duration. Given the same stimulus, some cells respond to stimulus onset with phasic bursts followed by tonic activity for the duration of the stimulus pulse, others respond only to stimulus onset, and still others respond to both stimulus onset and removal. Other cells maintain tonic firing activity and lower their firing activity when the stimulus is delivered (2). It is also known that mixture interactions at the single cell level can significantly alter cell spiking activity, either enhancing or suppressing spike output.

Thus, although the anatomic and molecular biological data provide clear-cut hypotheses on the coding of olfactory stimuli, the issue of coding is far from resolved. Olfactory neurons act as dynamic filters that constantly modulate their firing activity based on the stimulus quality (mixtures vs. single odorants), intensity, and previous exposure to stimulation (adaptation), and all these properties translate into neural information that may be relayed to second-order neurons in the olfactory bulbs. The report of Sanhueza and colleagues highlights the complexities of cellular responses to mixtures of odorants and the possible effects of mixture interactions. If further experiments reveal that the suppression phenomena are only observed at high stimulus concentrations, then this work also has implications for stimulus intensity coding. In any case, olfactory neurons must be viewed as complex units that represent an important step in the filtering of stimulus information, and a full understanding of coding schemes in olfaction must take their properties into account.

Odorants are detectable by organisms in the micro- to nano- and picomolar range. Thus, when electrophysiological studies are conducted using micro- to millimolar levels of stimuli (as was the case in this study), the results are often criticized as not being in the "physiological range." However, it is not really known what the actual concentration of odorant molecules is in the immediate vicinity of an OR in a living organism. Olfactory cells in situ are surrounded by mucus that has substances such as odorant binding proteins that may assist in the delivery (or removal) of odorant molecules to the ORs. When experiments are conducted in vitro, the normal external milieu of the cell is lost. Thus the equivalent stimulus intensity in vitro to the nano- and picomolar levels reported in vivo is not known. It is interesting to note that electrophysiologists often use micromolar stimulus concentrations for in vitro experiments to obtain a reasonable number of observable cell responses. Whether this is due to the health or viability of olfactory cells following dissociation or due to the lack of the appropriate extracellular milieu remains to be determined. In any case, the suppression and inhibition effects observed by Sanhueza and colleagues may occur in vivo if the organism is faced with a very strong odor, making these findings behaviorally significant. It can also be argued that, at high stimulus concentrations, odorants often elicit nonspecific effects such as membrane partitioning and/or destabilization (since many odorants are hydrophobic), competitive nonspecific binding to ORs, or nonspecific effects on ion channels. In situ, olfactory neurons must be able to function over a wide range of stimulus intensities and cope with the effects of strong odorant stimulation. The effects of inhibition and suppression observed in this manuscript, whether they are side effects of the biophysical properties of cell membranes and ion channels or inherent properties built into olfactory neurons, must be taken into account by the system when decoding receptor cell output.

In summary, the work presented here by Sanhueza and colleagues demonstrates the complexity of information coding potential of single olfactory neurons. This highlights the ability of peripheral olfactory neurons to function as integrator units in the first steps of encoding complex olfactory information.


    FOOTNOTES

Address for reprint requests and other correspondence: G. Gomez, Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104-3308 (E-mail: gomez{at}monell.org).


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REFERENCES

1.   Buck, LB. Information coding in the vertebrate olfactory system. Annu Rev Neurosci 19: 517-544, 1996[ISI][Medline].

2.   Getchell, TV, and Shepherd GM. Responses of olfactory receptor cells to step pulses of odour at different concentrations in the salamander. J Physiol (Lond) 282: 521-540, 1978[Abstract].

3.   Malnic, B, Hirono J, Sato T, and Buck LB. Combinatorial receptor codes for odors. Cell 96: 713-723, 1999[ISI][Medline].

4.   Rubin, BD, and Katz LC. Optical imaging of odorant representations in the mammalian olfactory bulb. Neuron 23: 499-511, 1999[ISI][Medline].

5.   Sanhueza, M, Schmachtenberg O, and Bacigalupo J. Excitation, inhibition, and suppression by odors in isolated toad and rat olfactory receptor neurons. Am J Physiol Cell Physiol 279: C31-C39, 2000[Abstract/Free Full Text].

6.   Schild, D, and Restrepo D. Transduction mechanisms in vertebrate olfactory receptor cells. Physiol Rev 78: 429-466, 1998[Abstract/Free Full Text].


Am J Physiol Cell Physiol 279(1):C19-C20
0363-6143/00 $5.00 Copyright © 2000 the American Physiological Society




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