Reviews & Analysis

There is currently no effective treatment for glioma, the most common type of brain tumour. Recent technological advances have made it possible to gain a more detailed understanding of the molecular processes underlying tumour cell differentiation and the findings suggest new opportunities for therapeutic intervention.

Chronic fatigue syndrome (CFS) is a debilitating illness that affects many people. The aetiology and pathophysiology of CFS remain poorly understood, and few treatments are available.Nature Reviews Neuroscienceasked four scientists involved in CFS research about their views on the condition and the future of research — including the role of neuroscience — aimed at improving our understanding of this chronic illness.

Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), has neuroprotective effects in models of several neurodegenerative diseases. In this Review, Vila and colleagues discuss the mechanisms by which rapamycin exerts neuroprotection, including effects on autophagy and apoptosis, and on the translation of pro-death and pro-survival proteins.

The importance of interactions between the brain and the digestive system in health and disease has been recognized for centuries. Mayer reviews the neuroanatomy and signalling mechanisms that underlie this bidirectional communication system in health and disease, as well as possible consequences for higher-level executive functions and emotional states.

Aaron Beck's influential cognitive model of depression posits that cognitive biases lead to depressive symptoms. In this Review, Beck and colleagues discuss neuroimaging findings suggesting that both top-down and bottom-up neural mechanisms underlie these biases, and propose a neurobiological architecture of the cognitive model of depression.

The number of individual types of molecules that are involved in synaptic transmission is small enough for the stochastic (random) properties of molecular events to be non-negligible. Triller and colleagues discuss the implications of stochastic reactive and diffusive molecular behaviours for synaptic transmission.

Both theoretical and experimental approaches have demonstrated that noise can improve information processing, but there is substantial scope for new biologically appropriate computational hypotheses and noise sources to be investigated. McDonnell and Ward propose a unifying framework for reconciling theory with experiment.

Macrophages and microglia are major contributors to the inflammatory response that follows spinal cord trauma. Modulating the activation of these cells to harness their beneficial protective and reparative properties could be key for treating spinal cord injuries.

The immediate subjective effects of cocaine are central to its rewarding properties and addictive qualities; however, the mechanisms by which the drug causes these rapid effects were unclear. Wise and Kayatkin describe recent findings that show that cocaine-predictive cues can activate the dopaminergic reward system in less time than it takes for cocaine to reach and block dopamine transporters in the brain.

Alcohol-related violence is a widespread societal problem. Heinz and colleagues review animal and human studies that have provided insights into the links between acute and chronic alcohol intake and aggression, and into the genetic and environmental factors that contribute to individual variability in alcohol-induced aggression.

Computational models can aid the study of complex biological processes such as neural development. In this Review, van Ooyen describes theoretical models of each of the major stages of neural development, and discusses their influence on the current understanding of the mechanisms that govern these events.

Despite protective barriers, the nervous system is vulnerable to the invasion of pathogens. This Review discusses mechanisms by which microbes enter the nervous system and cause persistent or life-threatening infections.

Collieret al. revisit the idea that age-related and Parkinson's disease-related changes in midbrain dopamine neurons are unrelated. They review studies showing that markers of cellular risk factors accumulate with age in a pattern that mimics the pattern of degeneration seen in Parkinson's disease and propose that ageing induces a pre-parkinsonian state.

Neuronal communication in the cerebellum occurs through rate coding, but recent evidence indicates that spatiotemporal spiking patterns also contain information. De Zeeuw and colleagues review the evidence for such spatiotemporal coding in the cerebellum, and show that the two coding mechanisms together may enable precise control of cerebellar output.

Although ubiquitylation is well known for its role in targeting proteins for degradation, more recently — as discussed by Kawabe and Brose — it has emerged that this process is vitally important in the regulation of the cell signalling processes that control numerous aspects of neuronal development.

The global financial downturn has started to affect many, if not all, fields of science. In this Perspective, leading neuroscientists from different countries provide their views on the effects of the economic crisis on neuroscience funding, career prospects, international collaborations and scientists' morale.

Notch signalling is well known for its role in development, but here, Rakic and colleagues describe emerging aspects of Notch signalling in many processes in the adult brain. They propose that context-dependent crosstalk between Notch and various other signalling pathways underlies this pleiotropy.

Lipid dysregulation seems to be crucially involved in the pathogenesis of Alzheimer's disease. Not only do a wide variety of lipids participate in the regulation of amyloidogenesis but amyloid-β itself regulates lipid metabolism, thus offering novel opportunities for therapeutic intervention.

Various proposals have defined the dorsal visual stream as a 'Where' or 'How' pathway. Synthesizing data from anatomical and functional studies, Mishkin and colleagues propose that in the posterior parietal cortex, three different pathways emerge from the dorsal stream, each supporting a different aspect of spatial processing.

Vesicular glutamate transporters are expressed not only in glutamate neurons but also in monoamine, acetylcholine and, intriguingly, GABA neurons. Trudeau and colleagues discuss the role of these transporters in glutamate co-release and vesicular synergy — a process leading to enhanced packaging of the 'primary' transmitter.