In The News: Retail therapy

700 | SEPTEMBER 2003 | VOLUME 4 www.nature.com/reviews/neuro

H I G H L I G H T S

Patterns of pathology

P S Y C H I AT R I C D I S O R D E R S

Neuroanatomical abnormalities thataccompany autism include wide-spread deviations in cortical surfaceanatomy, a new study published inCerebral Cortex indicates. Examiningthe differences between autistic andnormal subjects in the pattern of cor-tical gyri and sulci could provide

clues to the developmental pathologyof the disorder.

Previous studies have describedlimbic and cerebellar pathology inautism, and evidence is accumulatingfor an involvement of neocorticalregions. However, there is no clearconsensus on the neural basis of this

condition. In an attempt to home inon affected areas of the cortex, Levittand co-workers carried out the firstthree-dimensional mapping of corticalsulcal patterns in autistic disorder.

Using MRI (magnetic resonanceimaging) scans of the brains of autisticand normal children, Levitt et al.generated a high-resolution model ofthe cortex for each subject, and builtaverage sulcal maps for the twogroups. A comparison of these mapsrevealed displacements of severalmajor sulci in patients with autism,primarily in frontal and temporalregions. For example, anterior andsuperior shifting of the superior frontalsulcus was detected bilaterally, and theleft and right superior temporal sulci,

It is easy to think of synapticcommunication as one-way traffic,but in many cases, postsynapticcells can also signal back to thepresynaptic neuron to regulatesynapse structure and function.The Drosophila neuromuscularjunction (NMJ) illustrates howretrograde signalling contributesto synapse homeostasis, and twostudies reported in Neuron identifynew components of the signallingmechanism.

In the Drosophila embryo, motorneurons compensate for thegrowth of their target muscles bymaking extra synaptic boutonsand by raising the number ofneurotransmitter release sites ateach synapse. These events rely onbone morphogenetic protein(BMP) signalling through theWishful thinking (Wit) receptoron the presynaptic terminal. Untilnow, the Wit ligand that is releasedby the postsynaptic muscle cellwas unknown. McCabe et al.knocked out the glass bottom boat

(gbb) gene, which codes for a BMPhomologue. This manipulationproduced a phenocopy of the Wit-knockout phenotype, which is characterized by reductions inNMJ size and activity, and defectsin synaptic ultrastructure. In vitrostudies confirmed that Gbb acts asa ligand for Wit. These findingspoint towards a role for Gbb incontrolling the growth of the NMJ.

In the second study, Haghighi et al. investigated the modulationof neurotransmission byretrograde signalling. They foundthat reducing Ca2+/calmodulin-dependent kinase II (CaMKII)activity in the postsynaptic musclecell led to an increase inneurotransmitter release from thepresynaptic neuron. Conversely,activating CaMKII constitutivelyin the muscle cell reduced the levelof synaptic transmission. Theauthors propose that CaMKIIsenses the level of synaptic activityby monitoring Ca2+ levels. Synapticactivity causes an influx of Ca2+

into the muscle. This activatesCaMKII, which in turn triggers aretrograde signal that inhibitsneurotransmitter release from thepresynaptic terminal. Once again,a BMP signal seems to beresponsible, but it is not yetknown whether Gbb is involved.

A third study by Pratt et al.,which was also reported in Neuron,showed that postsynaptic CaMKIIalso mediates synapse remodellingin the mammalian brain. Thisindicates that at least some of theDrosophila retrograde signallingmachinery has been conservedduring evolution, and it seemslikely that further examination ofthe Drosophila NMJ will bring tolight more aspects of retrogradesignalling that apply across theanimal kingdom.

Heather Wood

References and linksORIGINAL RESEARCH PAPERS McCabe, B.et al. The BMP homolog Gbb provides aretrograde signal that regulates synapticgrowth at the Drosophila neuromuscularjunction. Neuron 39, 241–254 (2003) |Haghighi, A. J. et al. Retrograde control ofsynaptic transmission by postsynaptic CaMKIIat the Drosophila neuromuscular junction.Neuron 39, 255–267 (2003) FURTHER READING Pratt, K. G. et al.Activity-dependent remodeling of presynapticinputs by postsynaptic expression of activatedCaMKII. Neuron 39, 269–281 (2003)

Retro styling

S Y N A P T I C P L A S T I C I T Y

IN THE NEWSIN THE NEWSRetail therapyMany people use shopping asa way to cheer themselvesup, but for compulsiveshoppers it can causeprofound misery, not tomention serious financialproblems. However, thanks toa team at Stanford Universityin California, a solution mightbe at hand.

The researchers, led byLorrin Koran, recruited 24compulsive shoppers to theirstudy. According to BBCNews Online (18 July) “onehad bought more than 2000wrenches, another owned 55cameras”. The patients weretreated with theantidepressant citalopram(Celexa) for seven weeks,followed by the drug or aplacebo for a further nineweeks.

All of the patients who tookcitalopram for the entirecourse of the experimentreported that they had lostinterest in shopping. Koran isreported as saying “Patientssaid to me: ‘I go to theshopping mall with my friendsand I don’t buy anything.I can’t believe it and theycan’t believe it’” (BBC NewsOnline). By contrast, five ofthe eight patients in theplacebo group relapsed afterthe drug was withdrawn. It isnot yet known whycitalopram is effective fortreating compulsiveshoppers, but Koransuggests that it might workby altering serotonin levels inthe brain.

Although these initialfindings are encouraging, thetreatment has its drawbacks.As NBC11 News (16 July)reports, “Celexa does havesome side effects, whichinclude loss of sexual desireand sleepiness”. Also, someexperts have questioned thefundamental concept of usingdrugs to treat compulsivebehaviour. Robert Lefeverfrom the PROMIS RecoveryCentre in Kent (UK) says “ofcourse antidepressants helpthe disorder, in the same waythey would help alcoholdependency. They are simplyanother addiction. It’s thesame relation as methadoneto heroin” (BBC News Online).

Heather Wood

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Three-dimensional variability in cortical sulci between the patient and control groups. C, central sulcus; L,lateral sulcus. Courtesy of Jennifer G. Levitt, University of California, Los Angeles.