EDITORIAL FOCUS
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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ARTICLE |
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.
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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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Copyright © 2000 the American Physiological Society