Reviews & Analysis

Amyloid-β and tau exert toxicity in Alzheimer's disease through mechanisms that are gradually becoming understood. This Progress article reviews recent findings regarding their possible interactions and synergistic effects at the synapse, and discusses how these effects may contribute to the pathogenesis of Alzheimer's disease.

What does resting-state network (RSN) activity actually reflect? Deco and colleagues review computational models showing that local dynamics, signal transmission delays and noise contribute to emerging RSNs. They propose that multiple functional connectivity patterns can be expressed around the same anatomical framework, and that the resting brain explores these possible configurations.

Since its proposal in 1997, the synaptic tagging and capture hypothesis has been highly influential in furthering our understanding of memory persistence. Data that have emerged in the intervening years have necessitated a revision and expansion of the original concept, which is discussed in this Review by Redondo and Morris.

Hereditary spastic paraplegias (HSPs) are genetic disorders that cause a length-dependent, distal axonopathy of the corticospinal tract. Reid and colleages review the molecular cell biology underlying HSPs and consider the importance of membrane trafficking and organelle morphogenesis in axonal development and maintenance.

Emotional events result in strong memories, and these are essential for responding appropriately when similar events occur. However, emotional memories are sometimes so strong as to be disabling, as in post-traumatic stress disorder. In this article, Yehuda and Morris discuss these issues from the viewpoints of a clinical and a basic neuroscientist.

In this Progress article, Sacktor highlights the key role of protein kinase Mζ (PKMζ) — the constitutively active protein kinase C isoform — in perpetuating the synaptic events underlying long-term memory, and proposes a model of 'synaptic autotagging' by which this enzyme maintains its localization at the synapse.

Recent evidence suggests that mutations inLRRK2are linked to Parkinson's disease. In this Progress article, Mark Cookson discusses how these mutations might affect LRRK2 function and its interactions with other proteins that have been implicated in Parkinson's disease, specifically α-synuclein and tau.

Neurons in the dorsal horn of the spinal cord process sensory information and transmit it to the brain. Andrew Todd describes the complex neuronal organization and circuitry of this region and discusses the changes in the dorsal horn that that could underlie hyperalgesia and allodynia.

Sensory synapses of the auditory and visual systems need to encode a wide dynamic range of stimuli. Matthews and Fuchs discuss how it is increasingly certain that the ribbon synapse, a highly specialized structure capable of sustained and rapid transmitter release, plays a key part.

Nogo proteins inhibit axonal regeneration after injury, but recent studies have shed light on their physiological role in the intact CNS. Martin Schwab reviews the current knowledge of the complex receptor interactions of Nogo proteins and their role in stabilizing CNS wiring during development and in adulthood.

Recent research has revealed similarities between speech and birdsong on different levels. Bolhuis et al. discuss parallels between humans and songbirds in terms of vocal learning, the neural networks underlying vocalization and the role of FOXP2, highlighting both general and species-specific principles.

A subcortical pathway is assumed to mediate non-conscious visual processing of emotional stimuli. In this provocative Perspective, Pessoa and Adolphs argue that this pathway does not exist in primates and propose novel roles for the amygdala and the cortex in visual emotion processing.

The extracellular matrix (ECM) plays a key part in diverse cellular processes. Dityatev and colleagues review how the ECM can have opposing effects on neuronal function — promoting plasticity or homeostasis of synaptic contacts — depending on the physiological context and regulation by key proteases.

In this Review, Redgraveet al. provide an updated model of basal ganglia architecture in which spatially segregated functional territories contribute to goal-directed and habitual control circuits. They propose that in Parkinson's disease, selective dopamine loss impairs habitual control and distorts goal-directed behaviours.

To celebrate the first 10 years ofNature Reviews Neuroscience, we invited the authors of the most cited article of each year to look back on the state of their field at the time of publication and the impact their article has had, and to discuss the questions that might be answered in the next 10 years.

Lightman and Conway-Campbell review findings showing that, superimposed on its well-known circadian rhythm, the HPA axis shows ultradian, oscillatory activity. They describe how the resulting pulsatile release of glucocorticoids maintains optimal responsiveness of the HPA axis and the brain processes regulated by these hormones.

Activation of NMDARs can both promote neuronal health and kill neurons. In this Review, Hardingham and Bading discuss the downstream effects of stimulation of synaptic NMDARs and extrasynaptic NMDARs that result in promotion of neuroprotection and cell death, respectively.

Glucocorticoid hormones modulate the acquisition and consolidation of memories of stressful events. Krugers and colleagues review recent evidence that glucocorticoids achieve this through rapid and persistent effects on AMPA receptors by activation of mineralocorticoid receptors and glucocorticoid receptors, respectively.

Emotional stimuli, such as a fear-expressing face, can be processed without being consciously perceived and can influence behaviour. Tamietto and de Gelder describe the subcortical pathway that processes such stimuli, and discuss whether subcortical versus cortical processing of stimuli translate into non-conscious versus conscious perception. An interview with Beatrice de Gelder for Neuropod is available for download.

Reliable propagation of spiking activity in the brain is vital for information processing. Kumar, Rotter and Aertsen now propose that under certain conditions asynchronous and synchronous propagation of spiking activity can co-exist in a modular neuronal network, and they suggest experimental strategies to test this hypothesis.