Olfactory coding in Drosophila larvae investigated by cross-adaptation
Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK
* Author for correspondence (e-mail: cobb{at}manchester.ac.uk)
Accepted 26 July 2005
![]() |
Summary |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: olfaction, Drosophila melanogaster, adaptation, maggot
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Intercellular processes such as lateral inhibition may also be involved in
mediating long-term adaptation (Urban,
2002). This process might be relatively complex, involving
positive and negative signals and interactions at various levels. A given
olfactory receptor neuron can be both inhibited and stimulated, depending on
the stimulus applied to it (Hallem et al.,
2004
; Oka et al.,
2004
), while higher processing units such as glomeruli can show
both lateral excitation and lateral inhibition, producing a sharpening of the
olfactory code (Schoppa and Urban,
2003
).
Paradoxically, one of the effects of olfactory adaptation to a given odour
can be to enable the organism to detect small changes in the levels of other
substances (Kelling et al.,
2002; Fain, 2003
).
This effect, coupled with the fact that in the natural world animals are often
in the presence of continuous background odours (e.g. from food sources, nests
or conspecifics), suggests that adaptation may play an important role in
shaping and tuning the olfactory response. The precise processes that lead to
such increased sensitivity through adaptation are not known but can be
presumed to be consequences of some or all of the mechanisms outlined
above.
Adaptation can be used as a tool to reveal the organisation of the
organism's sensory response: if adaptation following stimulation with stimulus
A leads to a decline in the response to both stimulus A and stimulus B, it can
be concluded that some or all aspects of the sensory processing of the two
stimuli are shared. This approach, known as cross-adaptation, has been
employed in studies of chemosensation in a range of organisms, including
bacteria (Gestwicki and Kiessling,
2002), lobsters (Daniel et al.,
1994
), mice (Kelliher et al.,
2003
), frogs (Takeuchi et al.,
2003
), houseflies (Kelling et
al., 2002
), C. elegans
(Colbert and Bargmann, 1995
),
Manduca sexta (Dolzer et al.,
2003
) and Drosophila adults
(de Bruyne et al., 1999
) and
larvae (Cobb and Domain,
2000
).
A simple model of olfactory processing would predict that cross-adaptation should be reciprocal (i.e. pre-stimulation with odour A affects odour B and vice versa); more complex models might predict an element of asymmetry - for example, a short-chain molecule could lead to adaptation in the processing pathways responsible for the response to a longer-chain molecule, but the reciprocal effect would not occur because the larger molecule would have low or no affinity with the receptors associated with the response to the smaller molecule. As these hypothetical examples imply, this simple technique has the added advantage of generating hypotheses about coding that can eventually be tested by more complex approaches, such as electrophysiology.
Fruit fly maggots combine the genetic manipulability of adult D.
melanogaster with a substantially lower level of complexity. For example,
the peripheral olfactory system of the larva consists of 21 receptor neurons,
as against 1300 in the adult (Cobb,
1999). The larval olfactory receptor neurons project into the
antennal lobe of the larval brain, where they each project to a single
glomerulus in the antennal lobe, as in the adult brain and in vertebrates
(Python and Stocker, 2002
;
Ramaekers et al., 2005
). This
combination of reduced receptor complexity and fundamental homology with more
complex organisms, combined with a very limited behavioural repertoire and the
ability to detect over 60 odours (Cobb,
1999
), makes the larva a useful preparation for studying basic
processes in olfactory coding.
The Drosophila genome is thought to contain around 60 olfactory
receptor genes (Clyne et al.,
1999; Vosshall et al.,
1999
), of which 13 are apparently not expressed in the adult
(Robertson et al., 2003
). It
has long been argued that, in most organisms except C. elegans, only
one type of receptor gene is expressed in each olfactory receptor neuron.
However, the evidence for this `rule' is less solid than initially appeared
(Mombaerts, 2004
) and it has
recently been shown in Drosophila adults that one class of olfactory
receptor neurons expresses more than one type of olfactory receptor
(Goldman et al., 2005
). This
also appears to be the case in some Drosophila larval receptor
neurons - a total of 23 Or genes have recently been reported to be
expressed in the larva, for 21 olfactory sensory neurons
(Kreher et al., 2005
).
In a previous study, we used cross-adaptation to investigate olfactory
coding of alcohols in Drosophila larvae
(Cobb and Domain, 2000). That
study suggested that a form of lateral inhibition - occurring either
peripherally or centrally - underlay the ability of the maggot olfactory
system to produce a variety of attractive and repulsive responses to different
alcohols. Here, we use adaptation to study the olfactory responses of
Drosophila larvae to another homologous series of ecologically
meaningful odours - short-chain acetic esters or aliphatic acetates. The
genetic bases of larval responses to these odours have been studied and have
been shown to include factors on all major chromosomes, with specific and
separate anosmias to pentyl acetate and hexyl acetate, indicating that these
odours can be distinguished by larvae (Cobb
and Dannet, 1994
). The present study not only provides information
about the organisation of the olfactory response to these important odours but
it also enables us to test the generality of the lateral inhibition model we
developed for the coding of alcohols.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Olfactory tests
Olfactory responses were measured following Cobb and Domain
(2000). Briefly, approximately
50 larvae were placed in the centre of a Petri dish filled with 2.5% agar. Two
12.7 mm-diameter filter papers (one for the test odour, one as a control) were
positioned on opposite sides of the dish, on the lid of a small
micro-centrifuge tube, which prevented larvae from coming into contact with
the test odour, thereby excluding gustatory effects. Standard test odour
volumes (1 µl for butyl...heptyl acetate; 2.5 µl for all other odours)
were applied to the filter paper using a micro-pipette or a micro-syringe. For
dose-response curves, test volumes were varied as described in the text. All
chemicals were used undiluted and were Merck analysis grade. After 5 min, the
number of larvae on the control and odour sides, and the number of
`non-choosers' in a 5 mm-wide central strip, were recorded. A response index
(RI) was calculated:
RI=[(nodour-ncontrol)/ntotal]x100,
which varies between -100 (total repulsion) and +100 (complete attraction).
During testing, maggots will initially disperse at random before meeting the
diffusing odour and moving towards it or away from it, depending on whether
they are attracted or repulsed (Cobb,
1999
). Some maggots fail to `choose' by either remaining in the
start circle or finding themselves in the central strip at the time the number
of maggots is counted. The `no-choice' zones make up
11% of the total
surface area of the Petri dish. Tests where >30% of maggots failed to
choose were discarded; these very rare tests always involved situations in
which a relatively high proportion of maggots failed to leave the start
circle, normally because they had been damaged while being collected from the
agar plate. In control responses to the seven aliphatic acetates tested here,
the mean percentage of maggots failing to choose was 17.45±1.14%. In
the case of tests following auto-adaptation, the figure was slightly lower
(14.92±0.87%), indicating that adaptation did not in any way reduce the
mobility of the larvae. In both cases, this figure is higher than the surface
area of the no-choice zone (11%); this is due to the fact that in virtually
all tests some larvae did not leave the start circle. 6-22 replicates were
performed for each test; data were either pooled to form a single overall
index that could be tested using a contingency test (for defining the
experimental conditions for adaptation - see below) or mean response indices
and standard errors were calculated to provide a measure of the variability
between dishes and allow for testing by analysis of variance (ANOVA) or
t-test. This test does not involve any `stampede effect'; the
response of each individual larva is independent from the behaviour of those
around it (M. Kaiser and M. Cobb, manuscript in preparation). The response
index is a sensitive and robust phenotype that has enabled genetic factors
controlling quantitative variation in the olfactory response to be localised
(Cobb and Dannet, 1994
).
Adaptation
After having been washed from the yeast, larvae were placed in a clean
agar-covered Petri dish and pre-stimulated with one of the acetic esters: the
odour was loaded onto a filter disc placed on the lid of a micro-centrifuge
tube. Pre-stimulation volume/duration combinations for each odour that
produced auto-adaptation were determined in preliminary experiments.
Auto-adaptation was defined as the total distribution of larvae that did not
differ significantly from the distribution observed in control tests without
an odour stimulation, when compared using 2. Pre-stimulation
combinations were: methyl acetate, 40 µl, 20 min; ethyl acetate, 40 µl,
25 min; propyl acetate, 35 µl, 25 min; butyl acetate, 25 µl, 15 min;
pentyl acetate, 10 µl, 10 min; hexyl acetate, 10 µl, 15 min; heptyl
acetate, 10 µl, 15 min. In the case of hexyl acetate, control responses
were not significantly different from 0, so it was impossible to detect
auto-adaptation. For this odour, the same volume/time combination as heptyl
acetate was chosen. Pre-stimulation began at an appropriate point such that
the total time between being washed from the yeast and being tested was 60
min.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
To test for significant effects in Table 1, we used t-tests to compare the responses to each test odour following pre-stimulation with the control responses to that odour. In order to take account of the multiple comparisons of each test odour, Bonferroni's correction was applied (a significance threshold of P=0.007). Fig. 2 shows a graphical representation of the results of this analysis of Table 1: coloured blocks represent significant changes in the response to a test odour (in all cases, the change was a significant reduction in attractiveness); a blank block indicates no significant change compared with control levels. To measure the nature of the reduction in attractiveness, multiple one-sample t-tests were carried out on the effects of pre-stimulation for each test odour, comparing the observed results with a theoretical score of 0 (indifference, i.e. no mean attraction or repulsion). Again, Bonferroni's correction was applied. Purple blocks indicate that the behavioural response was indifferent (no significant difference from zero as measured by a one-sample t-test). Red blocks indicate that the test odour was still significantly attractive; blue blocks indicate that the test odour was significantly repulsive.
|
Test responses to ethyl acetate were completely abolished by pre-stimulation with all odours except hexyl acetate, which still significantly reduced the attractiveness of this test odour.
Conversely, pre-stimulation with ethyl acetate led to full cross-adaptation
only in the cases of propyl and butyl adaptation, with a significant reduction
in the response to pentyl acetate. Test responses to propyl acetate were
abolished by pre-stimulation with all seven aliphatic acetates. In the cases
of pre-stimulation with hexyl and heptyl acetate, the t-test
comparisons with control responses were not significant with Bonferroni's
correction (t22=2.74, P=0.011;
t22=2.25, P=0.035, respectively), but an
inspection of Table 1 shows
that the responses to propyl acetate following pre-stimulation are approaching
zero. The existence of a significant reduction in the response to propyl
acetate following pre-stimulation with hexyl and heptyl acetate was confirmed
by comparison of the total frequencies of attracted, repulsed and non-choosing
larvae in control and pre-adapted conditions (hexyl 2=15.61,
d.f.=2, P=0.0004; heptyl
2=24.30, d.f.=2,
P=0.0001). Pre-stimulation with propyl acetate had varying effects:
it abolished responses to ethyl and propyl acetate, had no effect on butyl
acetate and rendered pentyl acetate and hexyl acetate repulsive.
Butyl acetate and pentyl acetate induced similar effects: their control responses were not significantly different (t22=1.52, P=n.s.) and, if the striking results of their reciprocal cross-adaptation were excluded (butyl-pentyl=-19.58; pentyl-butyl=31.89; see below), the two odours had identical effects when they were used as pre-stimulation. However, responses to these odours showed different effects following pre-stimulation with heptyl acetate (no effect on pentyl acetate, significantly reduced attraction for butyl acetate) and propyl acetate (no effect on butyl acetate, significant repulsion for pentyl acetate). The indifferent response to hexyl acetate under control conditions was transformed into a significantly repulsive response following pre-stimulation with propyl...pentyl acetate and heptyl acetate.
Some of the most intriguing results are to be found in the nine cells containing the test results for butyl, pentyl and hexyl acetate, following pre-stimulation with the same three acetates (broken boxes in Table 1 and Fig. 2). Each of the three pairs of cross-adaptation combinations (on either side of the leading diagonal) shows non-reciprocal cross-adaptation. Particularly striking are the negative responses induced by testing with pentyl and hexyl acetate (the control tests are strongly positive and indifferent, respectively) - similar results were found following pre-stimulation with propyl acetate.
Testing for changes in sensitivity
In many sensory modalities, stimuli that are attractive at low doses can
become repulsive at a high dose (think of spilling a bottle of perfume):
repulsive responses observed following adaptation may be due to changes in
larval sensitivity to the test odour. Fig.
3 shows theoretical curves illustrating this hypothesis.
Fig. 3A shows the effect of
increased sensitivity in a system with a linear dose-response curve: low doses
that induce no response in controls show a response after treatment. However,
in a system in which high doses induce a negative response
(Fig. 3B), it is possible that
a dose that produces an attractive dose in control conditions will induce a
repulsive response after treatment (arrow on
Fig. 3B).
|
|
|
Following cross-adaptation, larvae were consistently less attracted to the stimulus odours, and in many cases the response became repulsive, but, again, none of the curves resembled those predicted in Fig. 3. Pre-stimulation with both pentyl acetate and hexyl acetate produced a significant reduction in the response to butyl acetate with increasing test dose (Fig. 5A; F4,39=29.202, F4,42=7.044, respectively, P<0.001), but the effect of pentyl acetate was not significantly different from auto-adaptation (F4,70=1.658, P=n.s.). With the exception of the final 10 µl test, the dose-response curve to pentyl acetate (Fig. 5B) showed a significant change with concentration following pre-stimulation with butyl acetate and hexyl acetate (F3,58=4.333, P=0.008). The dose-response curves to hexyl acetate (Fig. 5C) showed a lower overall response after pre-stimulation with butyl acetate and pentyl acetate, in particular at 1 µl. The response was significantly lower after pre-stimulation with pentyl acetate compared with butyl acetate (F1,48=11.32, P=0.0015), but cross-adaptation curves showed the same dose-response interaction (F3,48=1.55, P=n.s.).
Cross-adaptation between functional groups
The effect of pre-stimulation with acetic esters on the olfactory response
to odorants with other functional groups was tested with six alcohols
(butanol...nonanol) and three acids (heptanoic, octanoic and nonanoic).
Table 2 gives the mean response
indices for these tests; as for Table
1, the data were compared using multiple t-tests for each
test odour, using Bonferroni's correction (raising the significance level to
P=0.017). Fig. 6 shows
a graphical representation of the results of these tests. Full
cross-adaptation was observed in the case of methyl acetate, which abolished
the response to three of the alcohols tested here (butanol, pentanol and
hexanol) and to heptanoic and octanoic acid. Pre-stimulation with ethyl
acetate had no significant effects on the responses to any of the odours
studied in this experiment. Strikingly, adaptation with propyl acetate induced
a significant repulsive response to nonanoic acid, showing that larvae can
detect this odour and will respond to it under certain circumstances.
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Both this decline in attractiveness and the overall phenomenon of
cross-adaptation could be an example of receptor cross-talk, where stimulation
of one class of receptor leads to an alteration (generally a potentiation) of
the response of another receptor class
(Hill, 1998). Cross-talk often
involves protein phosphorylation mediated by G-protein coupled receptor
kinases within a given neuron
(Vasquez-Prado et al., 2003
),
such as those implicated in olfactory adaptation in C. elegans
(L'Etoile et al., 2002
). This
hypothesis raises three possibilities, which are not mutually exclusive:
`Classic' receptor cross-talk would be expected to produce a clear leftward
shift in dose-response curves, resulting in increased sensitivity (e.g.
Fig. 3B), or an increase in the
maximal response of the system (Selbie and
Hill, 1998). Increases in sensitivity following cross-adaptation
have been observed in electrophysiological studies on lobster receptor cells
(Borroni and Atema, 1989
), rat
trigeminal nerve (Farley and Silver,
1992
) and the housefly antenna
(Kelling et al., 2002
).
However, none of the data presented in Figs
4 and
5 fit this profile. In
particular, although the maximal (negative) response may have been increased
in some cases (e.g. Fig. 4A),
there is no evidence for an increase in the sensitivity of the olfactory
system at the lower doses tested here.
This may be a function of the relatively narrow range of volumes we used,
but it may also be due to the phenotype being measured. Because this study was
conducted on a behavioural response, it is difficult to interpret the observed
changes in response thresholds in terms of the activity of receptor neurons.
The work by Kreher et al.
(2005) on the response
profiles of larval olfactory receptors in an adult in vivo expression
system studied only two of the acetates used here (ethyl acetate and pentyl
acetate) and casts little light on our findings. Electrophysiological studies
of receptor neuron activity in both unadapted and adapted conditions and
functional anatomical investigations of the organisation of central sensory
structures will be necessary to prove the existence of receptor cross-talk: we
are actively pursuing both these lines of research.
In a previous study (Cobb and Domain,
2000), responses to octanol were transformed from a control
response of indifference to repulsion after pre-stimulation with C7-C9
alcohols. To test whether this effect may also have involved changes in
attraction thresholds, the responses of larvae to varying doses of octanol
were studied following pre-stimulation with octanol. Following
pre-stimulation, the response to octanol was transformed into a strong
repulsive response at all volumes, which was significantly different from
control levels (F1,96=63.45, P<0.0001;
Fig. 7). This result further
indicates that changes in response threshold underlie some examples of
olfactory adaptation in Drosophila larvae and underlines the
importance of taking into account the possibility that changes in sensitivity
may underlie apparent adaptation effects. This interpretation has not been
excluded in previous whole-organism studies of adaptation (e.g.
Colbert and Bargmann, 1995
;
Cobb and Domain, 2000
).
|
Whatever mechanism(s) underlie these results, they provide an insight into more straightforward aspects of sensory coding, as initially intended. Methyl acetate had a major effect on all the acetic esters studied except heptyl acetate (C9) and on three alcohols and acids. In the case of the aliphatic acetates, we interpret this to mean that methyl acetate does not have a specific detection pathway but is processed by all the pathways associated with distinguishing ethyl...pentyl acetate. This interpretation is reinforced by the fact that the response to methyl acetate was not qualitatively altered by pre-stimulation with any odour: at least one pathway processing C3-C8 aliphatic acetates was open following pre-stimulation and was able to detect methyl acetate.
Similar results have been found for hexanol
(Cobb and Domain, 2000), which
affected responses to all other alcohols tested but was not reciprocally
affected by them. That result was interpreted as an example of lateral
inhibition. Here, we are less categorical, appreciating that either peripheral
or central mechanisms, or both, may be involved. Our hypothesis that methyl
acetate is detected by the processing pathways involved in detecting the other
aliphatic acetates studied here would suggest that the cross-functional group
data (Table 2), in which methyl
acetate showed a major effect, may be due to the joint action of all pathways
involved with processing C3-C8 acetates. One way of testing this hypothesis
would be to carry out a multiple cross-adaptation test in which larvae were
pre-stimulated with several or all C3-C8 acetic esters. However, it remains
possible that methyl acetate has a processing pathway (either intra- or
intercellular) that exerts an inhibitory effect on all others, similar to that
hypothesised for hexanol.
The similar effects seen following pre-stimulation with ethyl acetate indicate that methyl and ethyl acetate share most if not all of their processing pathways. However, the striking differences in the cross-functional group data (Table 2), in which ethyl acetate had no effect on alcohols or acids, show that these odours can be distinguished by the larval olfactory neural network. The aliphatic acetate cross-adaptation data (Table 1) showed that test responses to propyl acetate were affected by pre-stimulation with all acetic esters tested here, perhaps suggesting that there is no specific propyl acetate processing pathway. The transformation of nonanoic acid into a repulsive odour following pre-stimulation with propyl acetate might disprove this hypothesis, but the effect of pre-stimulation with butyl and pentyl acetate would have to be studied first to exclude the possibility that this effect is mediated by processing pathways primarily associated with these two odours.
The data in Table 1 show
that maggots respond to butyl and pentyl acetate in very similar manners, but
the existence of a specific genetic anosmia to pentyl acetate
(Cobb and Dannet, 1994) shows
that larvae can discriminate the two odours. Hexyl and heptyl acetate appear
to be processed separately from the other odours, as shown by the lack of
cross-adaptation shown by test responses to these two odours (with the
exception of methyl and ethyl acetate on hexyl acetate). The existence of a
specific anosmia to hexyl acetate (Cobb and
Dannet, 1994
) confirms this.
Taken as a whole, these data show no clear evidence for any of the 16
odours studied here being odour equivalents. Naturally occurring odour
sources, to which the larval olfactory system will have been tuned by natural
selection, will consist of complex mixtures of these and many other components
(Stensmyr et al., 2003).
Nevertheless, larvae can apparently distinguish all these odours, process them
using related but separate pathways and respond to them in different manners.
They achieve this with only 21 olfactory neurons and what can be assumed to be
a roughly equivalent number of olfactory receptor molecule types. This
neurobiological feat remains largely unexplained, but we can expect it to
reveal principles of olfactory coding that may be common to a range of
organisms and not merely restricted to either holometabolous larvae or even
insects. The next challenge will be to discover the anatomical and biochemical
nature of the pathways involved in processing these odours and how they
interact to produce the olfactory response, adaptation and alterations in
response threshold.
![]() |
Acknowledgments |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Borroni, P. F. and Atema, J. (1989). Adaptation in chemoreceptor cells. II. The effects of cross-adapting backgrounds depend on spectral tuning. J. Comp. Physiol. A 165,669 -677.[CrossRef]
Clyne, P. J., Warr, C. G., Freeman, M. R., Lessing, D., Kim, J. and Carlson, J. R. (1999). A novel family of divergent seven-transmembrane proteins: candidate odorant receptors in Drosophila. Neuron 22,327 -338.[CrossRef][Medline]
Cobb, M. (1999). What and how do maggots smell? Biol. Rev. 74,425 -459.[CrossRef]
Cobb, M. and Dannet, F. (1994). Multiple genetic control of acetate-induced olfactory responses in Drosophila melanogaster larvae. Heredity 73,444 -455.[Medline]
Cobb, M. and Domain, I. (2000). Olfactory coding in a simple system: adaptation in Drosophila larvae. Proc. R. Soc. Lond. B 267,2119 -2125.[CrossRef][Medline]
Colbert, H. A. and Bargmann, C. I. (1995). Odorant-specific adaptation pathways generate olfactory plasticity in C. elegans. Neuron 14,803 -812.[CrossRef][Medline]
Daniel, P. C., Fine, J. B., Derby, C. D. and Girardot, M.-N. (1994). Non-reciprocal cross-adaptation of spiking responses of individual olfactory receptor neurons of spiny lobsters: evidence for two excitatory transduction pathways. Brain Res. 643,136 -149.[Medline]
de Bruyne, M., Clyne, P. J. and Carlson, J. R.
(1999). Odor coding in a model olfactory organ: The
Drosophila maxillary palp. J. Neurosci.
19,4520
-4532.
Deshpande, M., Venkatesh, K., Rodrigues, V. and Hasan, G. (2000). The inositol 1,4,5-triphosphate receptor is required for maintenance of olfactory adaptation in Drosophila antennae. J. Neurobiol. 43,282 -288.[CrossRef][Medline]
Dolzer, J., Fischer, K. and Stengl, M. (2003).
Adaptation in pheromone-sensitive trichoid sensilla of the hawkmoth
Manduca sexta. J. Exp. Biol.
206,1575
-1588.
Fain, G. L. (2003). Sensory Transduction. Sunderland, MA: Sinauer.
Farley, L. G. and Silver, W. L. (1992). Self- and cross-adaptation to chemical stimulation of the nasal trigeminal nerve in the rat. Chem. Senses 17,507 -518.
Gestwicki, J. E. and Kiessling, L. L. (2002). Inter-receptor communication through arrays of bacterial chemoreceptors. Nature 415,81 -84.[CrossRef][Medline]
Goldman, A. L., Van der Goes van Naters, W., Lessing, D., Warr, C. G. and Carlson, J. R. (2005). Coexpression of two functional odor receptors in one neuron. Neuron 45,661 -666.[CrossRef][Medline]
Hallem, E. A., Ho, M. G. and Carlson, J. R. (2004). The molecular basis of odor coding in the Drosophila antenna. Neuron 117,965 -979.
Hill, S. M. (1998). Receptor crosstalk: Communication through cell signalling pathways. Anat. Rec. 253,42 -48.[CrossRef][Medline]
Kelliher, K. R., Ziesmann, J., Munger, S. D., Reed, R. R. and
Zufall, F. (2003). Importance of the CNGA4 channel gene for
odor discrimination and adaptation in behaving mice. Proc. Natl.
Acad. Sci. USA 100,4299
-4304.
Kelling, F. J., Ilaenti, F. and den Otter, C. J. (2002). Background odour induces adaptation and sensitization of olfactory receptors in the antennae of houseflies. Med. Vet. Entomol. 16,161 -169.[CrossRef][Medline]
Kreher, S. A., Kwon, J. Y. and Carlson, J. R. (2005). The molecular basis of odor coding in the Drosophila larva. Neuron 46,445 -456.[CrossRef][Medline]
L'Etoile, N. D., Coburn, C. M., Eastha, J., Kistler, A., Gallegos, G. and Bargmann, C. I. (2002). The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation in C. elegans. Neuron 36,1079 -1089.[CrossRef][Medline]
Matthews, H. R. and Reisert, J. (2003). Calcium, the two-faced messenger of olfactory transduction and adaptation. Curr. Opin. Neurobiol. 13,469 -475.[CrossRef][Medline]
Mombaerts, P. (2004). Odorant receptor gene choice in olfactory sensory neurons: the one receptor-one neuron hypothesis revisited. Curr. Opin. Neurobiol. 14, 31-36.[CrossRef][Medline]
Oka, Y., Omura, M., Kataoka, H. and Touhara, K.
(2004). Olfactory receptor antagonism between odorants.
EMBO J. 23,120
-126.
Python, F. and Stocker, R. F. (2002). Adult-like complexity of the larval antennal lobe of D. melanogaster despite markedly low numbers of odorant receptor neurons. J. Comp. Neurol. 445,374 -387.[CrossRef][Medline]
Ramaekers, A., Magnenat, E., Marin, E. C., Gendre, N., Jefferis, G. S. X. E., Luo, L. and Stocker, R. F. (2005). Glomerular maps without cellular redundancy at successive levels of the Drosophila larval olfactory circuit. Curr. Biol. 15, 1-11.[CrossRef][Medline]
Robertson, H. M., Warr, C. G. and Carlson, J. R.
(2003). Molecular evolution of the insect chemoreceptor gene
superfamily in Drosophila melanogaster. Proc. Natl. Acad.
Sci. USA 100,14537
-14543.
Schoppa, N. E. and Urban, N. N. (2003). Dendritic processing within olfactory bulb circuits. Trends Neurosci. 26,501 -506.[CrossRef][Medline]
Selbie, L. A. and Hill, S. J. (1998). G protein-coupled-receptor cross-talk: the fine-tuning of multiple signalling pathways. Trends Plant Sci. 19, 87-93.
Stensmyr, M. C., Dekker, T. and Hansson, B. S. (2003). Evolution of the olfactory code in the Drosophila melanogaster subgroup. Proc. R. Soc. Lond. B 270,2333 -2340.[CrossRef]
Takeuchi, H., Imanaka, Y., Hirono, J. and Kurahashi, T.
(2003). Cross-adaptation between olfactory responses induced by
two subgroups of odorant molecules. J. Gen. Physiol.
122,255
-264.
Urban, N. N. (2002). Lateral inhibition in the olfactory bulb and in olfaction. Physiol. Behav. 77,607 -612.[CrossRef][Medline]
Vásquez-Prado, J., Casas-González, P. and García-Sáinz, J. A. (2003). G protein-coupled receptor cross-talk: pivotal roles of protein phosphorylation and protein-protein interactions. Cell Signal. 15,549 -557.[CrossRef][Medline]
Vosshall, L. B., Amrein, H., Morozov, P. S., Rzhetsky, A. and Axel, R. (1999). A spatial map of olfactory receptor expression in the Drosophila antenna. Cell 96,725 -736.[CrossRef][Medline]
Zufall, F. and Leinders-Zufall, T. (2000). The
cellular and molecular basis of odor adaptation. Chem.
Senses 25,473
-481.
Related articles in JEB: