Review Articles

Astrocytes form borders that separate neural from non-neural tissue in both normal brain tissue and CNS lesions. In this Review, Michael Sofroniew discusses evidence that astrocytes along such borders have crucial roles in both attracting and restricting CNS inflammation, with important implications for diverse CNS disorders.

Ageing affects multiple aspects of brain structure and function, and therefore is likely to influence complex behaviours such as decision making. Samanez-Larkin and Knutson describe age-related changes in the affective and motivational circuits that drive choice, and consider how these influence decision making.

Several psychiatric disorders have been linked to changes in microRNA levels in the circulation and brain. In this Review, Issler and Chen discuss approaches for studying the role of these non-coding RNAs in disease and highlight examples of their potential pathophysiological contributions to psychiatric disorders.

In this Review, Egeland, Zunszain and Pariante examine the complicated relationship between the stress response and adult neurogenesis, which can regulate each other. They discuss the molecular pathways that may underlie this interaction in the dentate gyrus.

Positive effects of mindfulness-based practices on health and cognitive performance have been reported; however, we know little about the underlying mechanisms. Tang and colleagues outline the challenges of meditation research and consider emerging information about the effects of mindfulness meditation on brain structure and function.

The subplate is a transient cortical zone that forms during mammalian brain development and has a crucial role in the formation of intracortical and extracortical circuits. Here, Hoerder-Suabedissen and Molnár review the changing architecture and cellular diversity of this zone in developing mouse and primate brains.

Although often thought of as a disease of the white matter, multiple sclerosis is also characterized by prominent demyelination and degeneration in the grey matter. Calabrese and colleagues discuss current hypotheses regarding the inflammatory and non-inflammatory mechanisms of grey matter damage in multiple sclerosis and its relationship to white matter damage.

Pathological perturbations of the brain can be described and modelled using network science. In this Review, Fornito, Zalesky and Breakspear discuss adaptive and maladaptive neural responses to such insults and consider how connectomics can be used to map, track and predict disease progression.

The cerebellar cortex drives smooth goal-directed movement as well as a range of other functions. Apps and colleagues describe studies that have revealed variations in the cytoarchitecture, molecular composition, physiological properties and vulnerability to cell death of different cerebellar cortical regions, and discuss the idea that these underlie different forms of information processing.

Although we understand much about mechanisms of spatial navigation in the mammalian brain in the context of laboratory investigations, our knowledge of the neural bases of 'real-world' navigation is more limited. Ulanovsky and colleagues here describe how we can approach this problem through experimental research and theoretical models of large-scale navigation in bats and rats.

Various neurodegenerative diseases are characterized by aggregates of pathological proteins, and increasing evidence suggests these disease-associated proteins may 'spread' via neuronal connections. Trojanowski and colleagues describe the molecular mechanisms of such spreading, and present the findings from neuropathological and imaging studies in humans that support this process.

It was traditionally assumed that the spontaneous release of neurotransmitter-containing vesicles at neuronal synapses results from the random activation of the vesicle fusion machinery that underlies action potential-driven evoked release. However, the recent evidence described by Kavalali in this Review now suggests that the mechanisms, regulation and functions of spontaneous neurotransmitter release are distinct from those of evoked neurotransmission.

Neuroinflammatory and neurodegenerative disorders — as well as normal ageing — are accompanied by changes in endocannabinoid signalling. In this Review, Di Marzo and colleagues discuss the different mechanisms through which endocannabinoid signalling both contributes to and mitigates these conditions, and how they could serve as targets for novel therapeutics.

Recent discoveries have shown that both hormonal and brain-derived oestradiol have neuroprotective effects. This Review provides a comprehensive review of the multiple cell types, receptors and signalling cascades that underlie oestradiol-mediated neuroprotection.

Endocannabinoids are involved in regulating neural progenitor cell proliferation, as well as neuronal and glial differentiation. In this Review, Maccarrone, Harkany and colleagues discuss mechanisms of endocannabinoid signalling, the action of plant cannabinoids in the foetal brain, and their exploitation to modulate diseases associated with defective cell cycle control, particularly cancer.

Polyunsaturated fatty acids (PUFAs) and their biologically active derivatives regulate many processes in the brain, including neurotransmission, cell survival and inflammation. Bazinet and Layé review PUFA metabolism and functions in the brain and discuss the potential for PUFA supplementation in psychiatric and neurodegenerative disorders.

Suicide is one of the leading causes of death for people of all ages in the developed world and is associated with various risk factors. Here, Gustavo Turecki reviews the molecular processes that may predispose individuals to suicide, mediate suicidal ideation and behaviour, and trigger suicidal events.

Visual stimuli can often be predicted by other stimuli in the environment — for example, a barking sound would predict the sight of a dog but not a cat. In this Review, Summerfield and de Lange discuss how expectation modulates neural signals and behaviour in response to visual stimuli.

Recent data have shown that orexins regulate not only wakefulness but also feeding, emotional behaviour, reward seeking and autonomic and endocrine responses. Takeshi Sakurai summarizes these findings and proposes that the orexin system regulates the response of the body to its internal and external environments to support various motivated behaviours.

The formation and maturation of the neuromuscular junction require the concerted efforts of the presynaptic nerve terminal, the postsynaptic muscle fibre and perisynaptic Schwann cells. In this Review, Robitaille and colleagues describe the molecular and activity-dependent processes that underlie the development of neuron–muscle contacts.