Review Articles in 2015

Bidirectional signalling between nociceptors and immune cells protects the host from potential threats to homeostasis. In this Review, McMahon and colleagues discuss how, when such signalling becomes uncontrolled or dysfunctional, it can contribute to immune-mediated diseases and persistent pain states.

Exposure to one stressor can lead to altered responses to subsequent stressors, implying that the neural circuits that mediate stress responses undergo adaptive changes. Bains and colleagues review mechanisms of synaptic plasticity in the paraventricular nucleus of the hypothalamus that may contribute to such responses.

Placebo effects are positive effects on health that arise from the response of the brain to the contextual information that accompanies the delivery of a treatment. In this Review, Wager and Atlas examine the neural mechanisms that underlie such effects, focusing on placebo analgesia.

Recent methodological progress has greatly facilitated the determination of the connectivity and functional characterization of complex neural circuits. In this Review, Tovote, Fadok and Lüthi examine studies that have adopted circuit-based approaches to gain insight into how the brain governs fear and anxiety.

It is now emerging that the neuroinflammation that is associated with Alzheimer disease may have a key role in driving this disease. In this Review, Heppner, Ransohoff and Becher examine the contribution of the immune system to the pathogenesis of this disorder.

Dysfunction of autophagy — an intracellular degradation pathway for cytosolic material — has been implicated in the pathogenesis of various neurodegenerative diseases. Rubinsztein and colleagues review recent progress in this area, focusing on macroautophagy, and discuss how this process may be manipulated to protect against neurodegeneration.

Exposure to environmental insults such as maternal stress during prenatal and postnatal development or paternal stress experience can have long-term effects on offspring brain function and behaviour. In this Review, Bale describes the mechanisms through which diverse insults reprogramme the epigenome and can even lead to transmission of the phenotype to subsequent generations.

Cannabinoid signalling is a major regulator of neurotransmitter release and plasticity at both excitatory and inhibitory synapses. In this Review, Soltesz and colleagues discuss emerging principles of cannabinoid control of network oscillations and their relevance for epilepsy and related comorbidities.

Early-life stress can contribute to predispositions to antisocial behaviour in adulthood. Similarly, acute or chronic stress during adulthood can alter our social behaviour. Sandi and Haller emphasize the importance of timing of stress for its effects on social behaviour and describe current understanding of the underlying mechanisms.

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.