During zebrafish development, each of the three segmental primary motoneurons projecting into axial muscle chooses a stereotyped axonal trajectory. In unplugged mutants, two of the three motoneurons fail to select the correct cell-type specific path. Granato and colleagues find that unplugged encodes a homolog of MuSK, which in mammals is required neuromuscular junction assembly. In zebrafish, unplugged is important in guidance, altering the extracellular matrix at key axon path choice points. The zebrafish larvae in this image (seven days post-fertilization) show labeled presynaptic nerve terminals (znp1/SV2, green) and postsynaptic acetylcholine receptors (red). (p 1303)

During development, neurons migrate along glial fibers to take their place within the cortical layers. Hatten and colleagues show that overexpression of mPar6α disrupts the coordinated cytoskeletal mechanisms that enable this migration. The cover image shows young cerebellar granule cells migrating along Bergmann glia fibers. The centrosome and nuclei are labeled with dynein intermediate chain (red), and the perinuclear microtubule cage is marked with beta-tubulin (green). In the migrating neurons, the centrosome is positioned forward of the nucleus. Image rendered by Nick Didkovsky. pp 1169 and 1195

Scientists are making great strides in understanding how the brain determines and is influenced by our sexuality. This month, we highlight several areas of research in this fascinating (and at times controversial) field. Two reviews discuss sexual differentiation of the brain and behavior during development, puberty and adulthood. A third review examines the neural basis of a complex sex-related social behavior, pair bonding. The controversy and ethical issues surrounding the scientific study of sexual behavior are discussed in an accompanying commentary. Cover image: "The Kiss" by Gustav Klimt. (pp 1029-1054)

Estimates suggest that people can maintain about seven items in short-term memory. For deaf users of American Sign Language, however, this estimate has been closer to five items. Daphne Bavelier and colleagues now report that deaf and hearing people have similar working memory resources. The lower capacity measured in the deaf is not due to phonological factors, item duration or lower memory abilities. Thus, they conclude that the widely touted seven-item capacity may be due to speakers' reliance on auditory-based representations in memory. (p 997)

Neurons in primary visual cortex demonstrate orientation selectivity-preferentially responding to bars or gratings tilted at certain angles-but the anatomical basis for this selectivity is unclear. Mooser and colleagues examined the spatial arrangement of feedforward axonal connections from non-oriented neurons in layer 4 to neurons in layer 2/3, where orientation selectivity first arises in tree shrew visual cortex. They found that terminations in layer 2/3 were distributed most densely along the axis of preferred orientation of the target neurons. These results provide anatomical evidence of an intracortical feedforward mechanism for orientation selectivity (pp 796 and 872)

Color vision requires different cone photoreceptors with differing absorbance spectra. Two studies from the groups of Hornstein and Li examined the specificity of gap junctional coupling between cones in mammals. They found that red and green cones can couple indiscriminately with each other, but blue cones only form junctions with other blue cones. The authors propose how this differential coupling could affect color vision. (pp 745 and 751)

Motion-sensitive neurons at higher processing stages in the visual system often have complex receptive fields. Haag and Borst studied how the microcircuitry of vertical system (VS) cells relates to their receptive field tuning in the blowfly. They found that electrical coupling between VS cells causes an elongation of the receptive field, and in some cases tuning to rotational flow fields. Thus, VS cells receive local motion information through their connections to other VS cells, as well as via their own dendrites. (pp 569 and 628)

To understand the brain, we must confront its complexity. Thus efforts to 'scale up' data production in neuroscience are on the rise. In this issue, we present a special focus on this topic, a collection of perspective articles that highlight the use of high-throughput methodologies in neuroscience and discuss their current progress and future challenges. Some of the available database resources are described for those who wish to explore this topic further. This special focus is sponsored by the National Institutes of Health. (pp 425-487)

In competitive games, the outcome of one player's choices often depends on the strategy chosen by each opponent. Lee and colleagues now show that activity in the prefrontal cortex may provide signals to update estimates of expected reward in monkeys playing a simple game against a computer opponent. Such signals could underlie the generation of random behavior for strategic purposes. The authors also used a reinforcement-learning algorithm to predict the monkeys' choices. (pp 319 and 404).

Injured axons cannot regenerate efficiently in the adult central nervous system because signals from myelin inhibit their growth. This effect is mediated by a receptor complex that includes p75NTR and NogoR, but these two proteins are not sufficient for receptor activity in vitro. In this issue, Mi and colleagues identify LINGO-1 (red staining in cover image) as a third necessary component of this receptor complex (pp 221).

Dendritic voltage-gated ion channels help regulate the propogation of signals to and from the cell body. Johnston and colleagues now report that synaptic plasticity can trigger long-lasting increases in dendritic excitability near potentiated synapses via A-type potassium channels, suggesting a new locus for memory storage and a substrate for metaplasticity. (pp 98 and 126)

Two papers in this issue examine the rapid movements (saccades) that our eyes make when scanning a visual scene. Visual information processing is suppressed during saccades. Thilo and colleagues report that the site of this suppression is early in the visual pathway, before the visual cortex. On the other hand, it is controversial whether saccades may have a role in visual processing. John Ross and Anna Ma-Wyatt found that saccades contribute to perception by erasing past visual information and strengthening visual associations. Eye movement fixation sequence recorded by Iain D. Gilchrist. (pp 13 and 65)