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18 SCIENTIFIC AMERICAN March 1996 tion under way in the rem- nant of supernova 1006, this process probably oc- curs in other young super- nova remnants, notes Rob- ert Petre of the Goddard Space Flight Center, one of Koyamas collaborators. But some rays are so potent that even supernova events probably cannot account for their existence. (The most extreme of these rays contain as much energy as a Nolan Ryan fastball crammed into a single sub- atomic particle!) Many researchers have assumed that the high- energy cosmic rays must originate in even greater shocksthose surrounding active, or exploding, gal- axies. In a recent paper in Science, however, Gnter Sigl of the University of Chicago and his colleagues suggest a more exotic possibility. Sigls group analyzed data from the Flys Eye detector in Utah and other, similar ex- periments that study the ash of light and spray of particles unleashed when cosmic rays collide with atoms in the earths upper atmosphere. The research- ers nd an odd gap in the data: at progressively higher energies, the num- ber of cosmic rays seems to trail o but then abruptly increases again. No known process could produce such a gap, so why is it there? One pos- sibility is that the highest-energy cos- mic rays are the product of an entirely new, still hypo- thetical physical mecha- nismthe evaporation of cosmic strings, for instance, or the decay of proposed su- permassive particles. On the other hand, the total num- ber of high-energy cosmic rays detected is quite small, so the perceived gap could be a statistical uctuation, Sigl admits. We dont have the data to tell for sure, he laments. Help may soon be on the way. Last November physi- cists from 19 countries committed themselves to building the Pierre Auger Cosmic Ray Laboratory, a $100-million detector that would far exceed the sensi- tivity of any existing de- vice. Tentatively scheduled to begin op- erating at the beginning of the next century, the Auger Laboratory could quickly settle many current questions about cosmic rays. It could conrm new physics, or it could rule it out, Sigl reects. Either way, it will be very interesting. Corey S. Powell EXPANDING REMNANTS of supernova explosions (such as the Crab Nebula, above) may be the birthplace of many cosmic rays. I magine trying to make sense of a railway map if none of the lines were labeled. It would be nearly im- possible to know which trains ran be- tween which towns. Neuroscientists long faced a similar problem: the chemicals they used to trace lines of communica- tion between brain regions vanished af- ter a single stop. They only went from one station to the next, says Peter L. Strick of the Veterans Administration Medical Center in Syracuse, N.Y. Know- ing but short stretches of certain tracks, he adds, made it exceedingly dicult to determine where any one trainor nerve signalultimately went. Recently, though, Strick has turned to a new, more powerful technique, one that enlists itinerant viruses to chart brain circuits in monkeys. The viruses move from one neuron to another, right on down the line, he notes. Hap- pily, there are strains of virus that do this by crossing over synaptic connec- tions. These viruses cross in only one direction. A strain of the herpes simplex type I virus, for example, follows the ow of nerve impulses through neigh- boring cells: the virus particles pass down a neurons axon, across a synapse, into another neuron, down its axon, over another synapse and so on. A dierent strain moves in the opposite direction. Unlike conventional tracers, a little vi- rus goes a long way. Because the strains are living, they replicate in every cell, thus increasing in number before each leg of the journey. You get an on-line amplication of sorts of the tracer sig- nal, Strick points out. So we can see the signal more clearly than we ever could before. Already the method has revealed new facts about the cerebellum in primates. Traditionally, scientists be- lieved that this structure integrated in- formation from the cerebral cortex with sensory input from the muscles. It then presumably sent nerve signals back to other motor regions in the brain, enabling the body to perform skilled movements. Strick, among others, has found that the cerebellum may also coordinate the movement of thoughts. Using viral trac- ers, he demonstrated that the cerebel- lum sent signals, via the thalamus, to re- gions in the cerebral cortex used solely for cognition, among them areas in the prefrontal cortex involved in short-term memory and decision making. People proposed that the cerebellum had cog- nitive functions back in the 1980s, Strick says, but I thought they were nuts. Now Im a believer. Most recently, he has discovered some far-reaching contacts that the basal gan- glia make. These structures were also thought to preside primarily over mo- tor functions. But viral tracers exposed output from them to sections of the temporal cortex responsible for visual tasks, such as recognizing objects. The nding, Strick suggests, could help ex- plain why Parkinsons disease patients who take dopamine can experience vi- sual hallucinations as a side eect. The dopamine given to humans may act on those same cells in the basal ganglia that in monkeys talk to visual areas in the temporal cortex. Among other projects, Strick plans to determine whether the cerebellum plays a role in focusing attention. Dam- age to it may well provide the physical basis for the attentional decits in au- tistic children. I have spent some 30 years studying motor areas, but this technique is allowing me to look more globally at the circuits in the brain, Strick comments. In time, he adds, the viral tracing technique could elucidate some of the circuits that malfunction in a number of mental and neurologi- cal illnesses. Kristin Leutwyler Viral Tracers Neuroscientists use viruses to map out pathways in the brain NATIONAL OPTICAL ASTRONOMY OBSERVATORIES Copyright 1996 Scientific American, Inc.

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Page 1: Viral Tracers

18 SCIENTIFIC AMERICAN March 1996

tion under way in the rem-nant of supernova 1006,this process probably oc-curs in other young super-nova remnants,Ó notes Rob-ert Petre of the GoddardSpace Flight Center, one ofKoyamaÕs collaborators. Butsome rays are so potentthat even supernova eventsprobably cannot accountfor their existence. (Themost extreme of these rayscontain as much energy asa Nolan Ryan fastballÑcrammed into a single sub-atomic particle!)

Many researchers haveassumed that the high-energy cosmic rays must originate in even greatershocksÑthose surroundingactive, or Òexploding,Ó gal-axies. In a recent paper inScience, however, G�nter Sigl of theUniversity of Chicago and his colleaguessuggest a more exotic possibility. SiglÕsgroup analyzed data from the FlyÕs Eyedetector in Utah and other, similar ex-periments that study the ßash of lightand spray of particles unleashed whencosmic rays collide with atoms in the

earthÕs upper atmosphere. The research-ers Þnd an odd ÒgapÓ in the data: atprogressively higher energies, the num-ber of cosmic rays seems to trail oÝ butthen abruptly increases again.

No known process could producesuch a gap, so why is it there? One pos-sibility is that the highest-energy cos-

mic rays are the product ofan entirely new, still hypo-thetical physical mecha-nismÑthe evaporation ofcosmic strings, for instance,or the decay of proposed su-permassive particles. On theother hand, the total num-ber of high-energy cosmicrays detected is quite small,so the perceived gap Òcouldbe a statistical ßuctuation,ÓSigl admits. ÒWe donÕt havethe dataÓ to tell for sure, helaments.

Help may soon be on theway. Last November physi-cists from 19 countriescommitted themselves tobuilding the Pierre AugerCosmic Ray Laboratory, a$100-million detector thatwould far exceed the sensi-tivity of any existing de-

vice. Tentatively scheduled to begin op-erating at the beginning of the nextcentury, the Auger Laboratory couldquickly settle many current questionsabout cosmic rays. ÒIt could conÞrmnew physics, or it could rule it out,ÓSigl reßects. ÒEither way, it will be veryinteresting.Ó ÑCorey S. Powell

EXPANDING REMNANTS of supernova explosions (such as theCrab Nebula, above) may be the birthplace of many cosmic rays.

Imagine trying to make sense of arailway map if none of the lineswere labeled. It would be nearly im-

possible to know which trains ran be-tween which towns. Neuroscientists longfaced a similar problem: the chemicalsthey used to trace lines of communica-tion between brain regions vanished af-ter a single stop. ÒThey only went fromone station to the next,Ó says Peter L.Strick of the Veterans AdministrationMedical Center in Syracuse, N.Y. Know-ing but short stretches of certain tracks,he adds, made it exceedingly diÛcultto determine where any one trainÑornerve signalÑultimately went.

Recently, though, Strick has turnedto a new, more powerful technique, onethat enlists itinerant viruses to chartbrain circuits in monkeys. ÒThe virusesmove from one neuron to another,right on down the line,Ó he notes. ÒHap-pily, there are strains of virus that dothis by crossing over synaptic connec-tions.Ó These viruses cross in only onedirection. A strain of the herpes simplextype I virus, for example, follows theßow of nerve impulses through neigh-boring cells: the virus particles passdown a neuronÕs axon, across a synapse,

into another neuron, down its axon, overanother synapse and so on. A diÝerentstrain moves in the opposite direction.

Unlike conventional tracers, a little vi-rus goes a long way. Because the strainsare living, they replicate in every cell,thus increasing in number before eachleg of the journey. ÒYou get an on-lineampliÞcation of sorts of the tracer sig-nal,Ó Strick points out. ÒSo we can seethe signal more clearly than we evercould before.Ó Already the method hasrevealed new facts about the cerebellumin primates. Traditionally, scientists be-lieved that this structure integrated in-formation from the cerebral cortexwith sensory input from the muscles. Itthen presumably sent nerve signalsback to other motor regions in thebrain, enabling the body to performskilled movements.

Strick, among others, has found thatthe cerebellum may also coordinate themovement of thoughts. Using viral trac-ers, he demonstrated that the cerebel-lum sent signals, via the thalamus, to re-gions in the cerebral cortex used solelyfor cognition, among them areas in theprefrontal cortex involved in short-termmemory and decision making. ÒPeople

proposed that the cerebellum had cog-nitive functions back in the 1980s,ÓStrick says, Òbut I thought they werenuts. Now IÕm a believer.Ó

Most recently, he has discovered somefar-reaching contacts that the basal gan-glia make. These structures were alsothought to preside primarily over mo-tor functions. But viral tracers exposedoutput from them to sections of thetemporal cortex responsible for visualtasks, such as recognizing objects. TheÞnding, Strick suggests, could help ex-plain why ParkinsonÕs disease patientswho take dopamine can experience vi-sual hallucinations as a side eÝect. Thedopamine given to humans may act onthose same cells in the basal gangliathat in monkeys talk to visual areas inthe temporal cortex.

Among other projects, Strick plansto determine whether the cerebellumplays a role in focusing attention. Dam-age to it may well provide the physicalbasis for the attentional deÞcits in au-tistic children. ÒI have spent some 30years studying motor areas, but thistechnique is allowing me to look moreglobally at the circuits in the brain,ÓStrick comments. In time, he adds, theviral tracing technique could elucidatesome of the circuits that malfunctionin a number of mental and neurologi-cal illnesses. ÑKristin Leutwyler

Viral TracersNeuroscientists use viruses to map out pathways in the brain

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Copyright 1996 Scientific American, Inc.