RESEARCH HIGHLIGHTS

G LIOGENESIS IN BRIEF Oligodendrocytes COGNITIVE NEUROSCIENCE Forgetting, reminding and remembering: the retrieval of don’t need ID lost spatial memory. de Hoz, L. et al. PLoS Biol. 2, 1233–1242 (2004) In the developing spinal cord, oligo- The ID seem to inhibit oligo- dendrocyte production is restricted to dendrogenesis by interacting with An important question in the study of memory is whether a narrow ventral domain by the bHLH transcription factors. In the retrograde amnesia represents a deficit in memory storage or opposing actions of an inductive, oligodendrocyte lineage, the class B retrieval. Rats with a partial lesion of the hippocampus, which ventrally-derived sonic hedgehog bHLH factors OLIG1 and OLIG2, prevented them from remembering the location of the platform in signal and an inhibitory, dorsally- which are required for oligodendroge- a water maze task, could be ‘reminded’ of the original location of derived bone morphogenetic nesis, dimerize with class A bHLH fac- the platform by an escape platform in another location. By (BMP) signal. In a recent paper in tors, including the E2A proteins E12 distinguishing reminding from new place learning, this study shows Development,Samanta and Kessler and E47. These heterodimers translo- that a disruption in retrieval can contribute to retrograde amnesia. present new evidence that the inhib- cate to the nucleus, where they activate itory effects of BMP4 on oligoden- the genetic pathways that induce NEUROLOGICAL DISORDERS drogenesis are mediated by members oligodendrocyte differentiation. Using of the inhibitor of differentiation a co-immunoprecipitation assay, Preclinical vCJD after blood transfusion in a PRNP (ID) protein family. Samanta and Kessler showed that both codon 129 heterozygous patient. The authors cultured mouse ID4 and ID2 could bind to the OLIG Peden, A. H. et al. Lancet 364, 527–529 (2004) neural progenitor cells under condi- proteins, and that all four ID proteins The authors describe a patient who was found, at post-mortem, to tions that normally promote the speci- could bind to the E2A proteins. When have preclinical signs of vCJD (variant Creutzfeld–Jakob disease). fication of the oligodendrocyte neural precursor cells were treated The patient had received a blood transfusion 5 years previously lineage. BMP4 caused a reduction in with BMP4, the intracellular localiza- from a donor who went on to develop vCJD. Although oligodendrocyte differentiation and a tion of the OLIG proteins changed heterozygosity at codon 129 of the prion protein PRNP has corresponding increase in astrocyte from predominantly nuclear to pre- been thought to protect against vCJD, this patient was production in these cultures. BMP4 dominantly cytoplasmic. heterozygous at codon 129. It might be that heterozygotes are not also induced the expression of all Taken together, these findings protected, but have a longer incubation period; alternatively, they four ID family members (ID1–4). point to a mechanism in which ID might be vulnerable to infection but not to the disease. Overexpression of Id2 and Id4,but not proteins function in a dominant-nega- Id1 or Id3, mimicked the inhibitory tive manner to sequester the OLIG VISION effects of BMP4 on oligodendrogene- proteins — and perhaps also the E2A sis. Id4 was the more potent inhibitor, proteins — in the cytoplasm, thereby and the combined overexpression of preventing them from entering the Visual pattern recognition in Drosophila is invariant for Id2 and Id4 had a similar effect to Id4 nucleus and activating their target retinal position. alone. Moreover, the authors found . Tang, S. et al. Science 305, 1020–1022 (2004) that they could block the inhibitory Heather Wood Translation invariance is the ability to recognize visual patterns effects of BMP4 by using RNA inter- References and links independent of their retinal location. In previous studies, ference to inhibit Id4 expression. ORIGINAL RESEARCH PAPER Samanta, J. & Drosophila melanogaster were unable to recognize patterns that The ID proteins have a helix– Kessler, J. A. Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on were presented in a new region of the visual field. However, the loop–helix domain, which enables oligodendroglial differentiation. Development 131, stimulus features that were manipulated might have been them to dimerize with basic helix– 4131–4142 (2004) FURTHER READING Rowitch, D. H. Glial occluded by vertical displacements of the stimuli. In this study, loop–helix (bHLH) proteins, but specification in the vertebrate neural tube. Nature which used stimuli that varied in size and colour, flies showed they lack a DNA-binding domain. Rev. Neurosci. 5, 409–419 (2004) pattern recognition independent of retinal position.

CORTICAL PHYSIOLOGY Pre-migratory phase Migratory phase

BMP The contribution of spike threshold to the dichotomy of cortical simple and complex cells. Prieb, N. J. et al. Nature Neurosci. 29 August 2004 (10.1038/nn1310) VZ Simple and complex cells in the cat primary visual cortex are often distinguished by the ratio between modulated and

Shh unmodulated components of spike responses to drifting gratings. If the modulation ratio is taken from the subthreshold membrane E12.5 E14.5 E18.5 potential instead of the spike rate, it is unimodally distributed. Schematic diagram showing oligodendrocyte-specific marker expression (blue) between embryonic day (E) 12.5 and E18.5 in the mouse spinal cord. Oligodendrocytes are generated in a restricted domain in the However, the nonlinear properties of the spike threshold, when ventral half of the neural tube, and they are dispersed throughout the spinal cord during the migratory phase. applied to this distribution, define the two classes of neuron.

NATURE REVIEWS | NEUROSCIENCE VOLUME 5 | OCTOBER 2004 | 741