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162 | MARCH 2003 | VOLUME 4 www.nature.com/reviews/neuro HIGHLIGHTS Don’t call us, we’ll call you We’ve heard it before: mobile phones aren’t good for your brain. First it was a risk of developing tumours, and now it seems that mobile phones can kill neurons. Referring to work by Leif Salford and his colleagues (Lund University, Sweden), BBC News (UK, 5 February 2003) reported that “mobile phones damage key brain cells and could trigger the early onset of Alzheimer’s disease.” In the study, published in Environmental Health Perspectives, Salford and his group exposed rats to two hours of radiation at a level equivalent to that emitted by mobile phones. Fifty days later, the scientists “found long exposure to operating handsets destroys cells in areas of the brain important for memory, movement and learning, and fear it could cause the premature onset of illnesses usually linked to ageing” (The Herald Sun, Australia, 7 February 2003). Speaking to BBC News, Salford is quoted as saying that mobile phones might have the same effect in people, “A rat’s brain is very much the same as a human’s. They have the same blood– brain barrier and neurons.” And in a statement that will horrify teenagers around the world, he added, “maybe we should think about restricting our use of mobile phones.” Not surprisingly, the mobile phone industry received the news with scepticism. In the UK, “a spokeswoman for the Mobile Operators Association dismissed this latest study” (BBC News). In South Africa, the chairman of the Cellular Telecommunications Association is quoted as saying that “governments worldwide had adopted comprehensive international safety guidelines” for the operation of mobile phones (The Mercury, South Africa, 6 February 2003), a statement that will probably not reassure all consumers. Just in case, it might be better to stick to text messaging for now, at least until someone models its effects on rat’s paws. Juan Carlos López IN THE NEWS The development of imaging systems involving calcium-sensitive fluorescent dyes has provided an unprecedented opportunity to observe the activity of neurons and circuits in real time. In a report in Cell, Wang et al. describe how they have used a dye called G-CaMP to study the relationship between structure and function in the Drosophila olfactory system. In Drosophila, each olfactory sensory neuron expresses one of around 80 different odorant receptor subtypes. Projections from neurons that express the same receptor converge in structures called glomeruli in the antennal lobe. The glomeruli are innervated by the dendrites of projection neurons, which relay information to the mushroom bodies and protocerebrum. The fly olfactory system has become a popular model for studying olfactory coding because it is much simpler and more accessible than that of vertebrates, yet the glomerular anatomy of the primary relay centres is strikingly similar. Wang et al. imaged the heads of flies in which either the projection neurons or the sensory neurons expressed the G-CaMP protein. The fluorescent intensity of this protein reflects the intracellular calcium level (a signature of electrical activity), and the authors detected the fluorescence using two-photon microscopy. This sensitive detection system enabled them to generate a high-resolution map of the glomeruli that were activated by different odours at concentrations that the fly would encounter in its natural environment. The authors showed that each odour activated a specific combination of glomeruli. The response patterns were highly reproducible, not only between different trials in the same fly, but also between different flies. Interestingly, imaging of sensory and projection neurons produced the same odour-evoked patterns of glomerular activity, indicating that the pattern generated by the stimulation of sensory neurons is transmitted intact to higher processing centres in the brain. Wang et al. also used this imaging technique to examine the molecular basis of olfactory coding in the fly. Sensory neurons that express the or43a receptor gene project to the DA4 glomerulus, and the authors identified a range of odours that activate DA4, but not another glomerulus,VA1lm. However, when they expressed or43a ectopically in the neurons that project to VA1lm, this glomerulus now responded to the same range of odours as DA4. This implies that the response patterns of individual glomeruli are probably determined by single receptor subtypes. By combining calcium imaging with two-photon microscopy, Wang et al. have generated a model to test various principles of olfactory coding in flies, many of which might also be relevant to vertebrates. In addition to providing new insights into olfaction, this imaging technique is also likely to have more general applications for measuring neuronal activity in the fly brain in relation to various behaviours. Heather Wood References and links ORIGINAL RESEARCH PAPER Wang, J. W. et al. Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain. Cell 112, 271–282 (2003) FURTHER READING Nakai, J. et al. A high signal-to-noise Ca 2+ probe composed of a single green fluorescent protein. Nature Biotech. 19, 137–141 (2001) | Vosshall, L. B. Olfaction in Drosophila. Curr. Opin. Neurobiol. 10, 498–503 (2000) WEB SITES Axel lab: http://cpmcnet.columbia.edu/dept/neurobeh/axel/overview.html Flybase: http://flybase.bio.indiana.edu/ or43a Movies online: http://www.cell.com/cgi/content/full/112/2/271/DC1 Seeing how flies smell OLFACTORY CODING A fly antennal lobe, in which G-CaMP — a calcium-sensitive green fluorescent protein — is expressed only in projection neurons that innervate the lobe. The high signal-to-noise ratio of G-CaMP provides a representation, at cellular resolution, of a defined population of neurons in the brain as the fly is stimulated by odorants at physiological concentrations. Different odours elicit different patterns of activation in the antennal lobe. Courtesy of J. W. Wang, Center for Neurobiology and Behavior, Columbia University, New York, USA.

Olfactory coding: Seeing how flies smell

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162 | MARCH 2003 | VOLUME 4 www.nature.com/reviews/neuro

H I G H L I G H T S

Don’t call us, we’ll call youWe’ve heard it before: mobilephones aren’t good for yourbrain. First it was a risk ofdeveloping tumours, and nowit seems that mobile phonescan kill neurons. Referring towork by Leif Salford and hiscolleagues (Lund University,Sweden), BBC News (UK, 5 February 2003) reported that“mobile phones damage keybrain cells and could triggerthe early onset of Alzheimer’sdisease.” In the study,published in EnvironmentalHealth Perspectives, Salfordand his group exposed rats totwo hours of radiation at alevel equivalent to that emittedby mobile phones. Fifty dayslater, the scientists “foundlong exposure to operatinghandsets destroys cells inareas of the brain importantfor memory, movement andlearning, and fear it couldcause the premature onset ofillnesses usually linked toageing” (The Herald Sun,Australia, 7 February 2003).

Speaking to BBC News,Salford is quoted as sayingthat mobile phones mighthave the same effect inpeople, “A rat’s brain is verymuch the same as a human’s.They have the same blood–brain barrier and neurons.”And in a statement that willhorrify teenagers around theworld, he added, “maybe weshould think about restrictingour use of mobile phones.”

Not surprisingly, the mobilephone industry received thenews with scepticism. In theUK, “a spokeswoman for theMobile Operators Associationdismissed this latest study”(BBC News). In South Africa,the chairman of the CellularTelecommunicationsAssociation is quoted assaying that “governmentsworldwide had adoptedcomprehensive internationalsafety guidelines” for theoperation of mobile phones(The Mercury, South Africa, 6 February 2003), a statementthat will probably not reassureall consumers. Just in case, itmight be better to stick to textmessaging for now, at leastuntil someone models itseffects on rat’s paws.

Juan Carlos López

IN THE NEWS

The development of imaging systems involvingcalcium-sensitive fluorescent dyes has provided anunprecedented opportunity to observe the activity ofneurons and circuits in real time. In a report in Cell,Wang et al. describe how they have used a dye called G-CaMP to study the relationship between structureand function in the Drosophila olfactory system.

In Drosophila, each olfactory sensory neuronexpresses one of around 80 different odorant receptorsubtypes. Projections from neurons that express thesame receptor converge in structures called glomeruliin the antennal lobe. The glomeruli are innervated bythe dendrites of projection neurons, which relayinformation to the mushroom bodies andprotocerebrum. The fly olfactory system has become apopular model for studying olfactory coding because itis much simpler and more accessible than that ofvertebrates, yet the glomerular anatomy of the primaryrelay centres is strikingly similar.

Wang et al. imaged the heads of flies in which eitherthe projection neurons or the sensory neuronsexpressed the G-CaMP protein. The fluorescentintensity of this protein reflects the intracellularcalcium level (a signature of electrical activity), and theauthors detected the fluorescence using two-photonmicroscopy. This sensitive detectionsystem enabled them to generate ahigh-resolution map of theglomeruli that were activated bydifferent odours at concentrationsthat the fly would encounter in itsnatural environment.

The authors showed that eachodour activated a specificcombination of glomeruli. Theresponse patterns were highlyreproducible, not only betweendifferent trials in the same fly, butalso between different flies.Interestingly, imaging of sensoryand projection neurons producedthe same odour-evoked patterns ofglomerular activity, indicating thatthe pattern generated by thestimulation of sensory neurons istransmitted intact to higherprocessing centres in the brain.

Wang et al. also used thisimaging technique to examine themolecular basis of olfactory codingin the fly. Sensory neurons thatexpress the or43a receptor geneproject to the DA4 glomerulus, andthe authors identified a range ofodours that activate DA4, but not

another glomerulus, VA1lm. However, when theyexpressed or43a ectopically in the neurons that projectto VA1lm, this glomerulus now responded to the samerange of odours as DA4. This implies that the responsepatterns of individual glomeruli are probablydetermined by single receptor subtypes.

By combining calcium imaging with two-photonmicroscopy, Wang et al. have generated a model to testvarious principles of olfactory coding in flies, many ofwhich might also be relevant to vertebrates. In additionto providing new insights into olfaction, this imagingtechnique is also likely to have more generalapplications for measuring neuronal activity in the flybrain in relation to various behaviours.

Heather Wood

References and linksORIGINAL RESEARCH PAPER Wang, J. W. et al. Two-photon calciumimaging reveals an odor-evoked map of activity in the fly brain. Cell 112,271–282 (2003)FURTHER READING Nakai, J. et al. A high signal-to-noise Ca2+ probecomposed of a single green fluorescent protein. Nature Biotech. 19, 137–141(2001) | Vosshall, L. B. Olfaction in Drosophila. Curr. Opin. Neurobiol. 10,498–503 (2000)WEB SITESAxel lab: http://cpmcnet.columbia.edu/dept/neurobeh/axel/overview.html Flybase: http://flybase.bio.indiana.edu/or43aMovies online: http://www.cell.com/cgi/content/full/112/2/271/DC1

Seeing how flies smell

O L FA C TO R Y C O D I N G

A fly antennal lobe, in which G-CaMP — a calcium-sensitive green fluorescent protein — is expressed onlyin projection neurons that innervate the lobe. The high signal-to-noise ratio of G-CaMP provides arepresentation, at cellular resolution, of a defined population of neurons in the brain as the fly is stimulated byodorants at physiological concentrations. Different odours elicit different patterns of activation in the antennallobe. Courtesy of J. W. Wang, Center for Neurobiology and Behavior, Columbia University, New York, USA.