Reviews & Analysis

Many cases of Parkinson's disease (PD) are characterized by not only deficits in movement but also cognitive dysfunction, which can develop into dementia. Here, Irwinet al. review the complex connections between the neuropathological aetiologies that underlie the cognitive deficits associated with PD.

The implications of compartmentalization of protein synthesis and distribution within dendrites are not well understood. In this Opinion article, Hanus and Schuman discuss how the morphological complexity of dendrites and specialist regulatory mechanisms influence protein distribution and therefore the synaptic response to activity.

Hypnosis is used in treatment contexts and, recently, also as an investigative tool in cognitive neuroscience. Oakley and Halligan review the potential for hypnosis to provide insights into brain mechanisms involved in attention, motor control, pain perception, beliefs and volition and also to produce informative analogues of clinical conditions.

Correct functioning of the brain requires stability as well as plasticity of neural circuits, and loss of stability is associated with numerous neurological disorders. In this Review, Koleske discusses recent insights into the molecular mechanisms that govern long-term dendrite and synapse stabilization.

Planar cell polarity (PCP) is regulated by a core set of conserved genes. Tissir and Goffinet describe the emerging roles of these PCP genes in various developmental processes in the nervous system, including neural tube closure, neuronal migration and axon guidance.

Intricate mechanisms regulate iron homeostasis in the CNS. In this Review, Rouault considers the role of brain iron accumulation in several common neurodegenerative disorders and discusses 'neurodegeneration with brain iron accumulation' diseases that are associated with specific genetic mutations.

In order to anticipate and prepare effectively for future experiences, the brain must cope with the inherent uncertainty of future events. In this Review, Grupe and Nitschke show how alterations in the processes by which the brain deals with future uncertainty may contribute to the development of pathological anxiety.

The histaminergic neuromodulatory system has important roles in in the regulation of cognition, sleep and wakefulness, and feeding and energy balance. In this Review, Panula and Nuutinen briefly explore histamine's physiological functions before focusing on its roles in various brain disorders.

Acid-sensing ion channels (ASICs) have been implicated in pain, and neurological and psychiatric disease. Wemmieet al. provide an update on the roles of ASICs in health and disease, and consider the implications for therapy and future lines of research.

Chronic pain is associated with changes in brain structure and function resulting in altered cognition and affect. Bushnellet al. examine the mechanisms underlying the psychological modulation of pain and the potential of mind–body therapies to alleviate chronic pain.

Research in multisensory processing has exploded in recent years, but different experimental and theoretical approaches have yielded conflicting or seemingly unrelated results. In this Review, Fetschet al. present a body of work that attempts to integrate and accommodate these findings.

The subunit composition of NMDA receptors (NMDARs) determines their biophysical, pharmacological and signalling properties. Paolettiet al.examine the contribution of individual receptor subtypes to normal physiology and disease, and the potential benefits of targeting specific NMDAR subtypes to counteract the deleterious effects of deregulated glutamatergic transmission.

Synaptic dysfunction is a key pathophysiological hallmark in several neurodegenerative disorders. In this Review, Lu and colleagues consider a 'synaptic repair'-based therapy for neurodegenerative diseases that targets pathophysiology rather than pathogenesis and discuss BDNF as a potential synaptic repair molecule.

Contexts provide information that is central to understanding the meaning of events. Maren and colleagues describe the neural systems that underlie context processing and consider how deficits in these systems may be involved in several psychiatric conditions.

Sleep is characterized by globally synchronized neuronal activity. Vyazovskiy and Harris propose that the synchronous 'down states' of neuronal populations during sleep enable neurons to perform prophylactic maintenance in the absence of synaptic inputs and spiking activity, and hypothesize that this is a key function of sleep.

Many findings in recent years have shed light on the process of epileptogenesis, whereby the brain becomes predisposed to seizures, but this process is still not well understood. Goldberg and Coulter review several important themes in this research and conclude that they point towards a circuit-level explanation of epileptogenesis.

One of the roles of astrocytes in the brain is to regulate the formation, maturation, function and elimination of synapses and thereby to support the formation of appropriate neural circuits. Clarke and Barres review our current understanding of these vital processes and highlight unanswered questions for future research.

Vision is an active process. Higher-order cognitive influences, including attention, expectation and perceptual task, as well as motor signals, are fed into the sensory apparatus. This enables neurons to dynamically tune their receptive field properties to carry information that is relevant for executing the current behavioural tasks.

Inter-individual differences in the thickness or volume of a brain region often co-vary with inter-individual differences in other brain regions. Alexander-Bloch, Giedd and Bullmore discuss this phenomenon of structural co-variance, its underlying mechanisms and its potential value in the understanding of various brain disorders.

Corticostriatal pathways consist of two distinct classes of cortical pyramidal cells: intratelencephalic and pyramidal tract neurons. In this Review, Shepherd explains how changes in the functional properties of these neurons result in an imbalance in activity that contributes to a wide variety of neurological disorders.