Review Articles in 2012

Decision making is influenced by uncertainty, which arises from internal and external noise. A fundamental question is how uncertainty is encoded in the brain and how it influences behaviour. In this Review, Bach and Dolan integrate several theoretical concepts about uncertainty into a hierarchical decision-making framework.

Recent improvements in the technology available for the analysis of genetic variability have revolutionized the study of many diseases. Hardy and colleagues illustrate how genome-wide strategies, including whole-genome and whole-exome sequencing, have been used to improve our understanding of the pathobiological mechanisms of neurological diseases

Functional MRI studies have revealed useful information about the ageing brain. In this Review, Cheryl Grady explains how correlating cognitive decline to changes in brain structure and function is hampered by the complexity of the ageing process.

Behavioural learning is accompanied by loss and gain of synapses, which is thought to be the mechanism by which circuits are altered and 'memory traces' established. Recent research, reviewed here, suggests that learning and memory events involve the rearrangement of ensembles of adjacent synapses on short stretches of dendrites.

Tryptophan metabolism along the kynurenine pathway generates several neuroactive metabolites. Schwarcz and colleagues discuss the regulation of this pathway in the normal brain and in neurological and psychiatric disorders, and consider the potential therapeutic opportunities of targeting this pathway.

Neuronal activity in the brain gives rise to transmembrane and extracellular electromagnetic fields that can be measured in the extracellular medium using several approaches. In this Review, Buzsáki and colleagues provide an overview of the mechanisms that underlie the generation of extracellular currents and fields.

GABA_B receptor activity is integral to the proper functioning of many neural systems. In this Review, Gassmann and Bettler examine our understanding of the subunit composition of such receptors and how this affects GABA_Breceptor properties, neuronal processes and higher brain functions.

Caspases are most well known for their role in programmed cell death (apoptosis), but more recently, it has emerged that when caspases are expressed in a localized and restricted manner, they can regulate normal physiological functions such as circuit refinement through axon pruning and synapse elimination.

The use of sophisticated molecular and genetic techniques has revealed the complexity and diversity of the protein composition of different synapses. Smith and colleagues describe methods for investigating synaptic diversity and show how knowledge gained from these studies can advance our understanding of neural circuit organization and function.

The experience of social rejection, exclusion or loss is often described as 'painful'. Naomi Eisenberger here outlines the evidence that the processing of these forms of 'social pain' share many underlying neural substrates with physical pain mechanisms and considers the implications of this convergent neural circuitry.

A growing body of evidence suggests that many psychiatric illnesses are associated with impaired mitochondrial function. Manji and colleagues review evidence from studies in animal models and humans and discuss strategies for therapeutics aimed at enhancing mitochondrial function in patients with psychiatric disorders.

Local mRNA translation provides an efficient mechanism by which highly polarized cells such as neurons can respond to extrinsic signals. Holt and colleagues describe the growing evidence for the importance of local axonal mRNA translation and protein synthesis in various aspects of nervous system development and function.

On the basis of data from brain network science, Bullmore and Sporns propose that brain organization is shaped by an economical trade-off between minimizing wiring cost and maximizing the efficiency of information transfer between neuronal populations and discuss this idea in the context of psychiatric and neurological disorders.

Optogenetics enables the precise and targeted manipulation of the activity of specific neurons and is a powerful tool for the dissection of neural circuits. Tye and Deisseroth describe the latest refinements in optogenetic technology and show how this approach is being used to investigate the circuits involved in psychiatric and neurological disorders.

The brain is a major target of insulin and insulin-like growth factors (IGFs). Fernandez and Torres-Alemán describe how these peptides enter the CNS to reach specific brain areas and review their actions in the developing and adult brain. They propose that insulin and IGFs regulate diverse processes that are all ultimately involved in energy homeostasis.

Normal ageing is associated with impairments in cognitive function, including memory, and with specific and relatively subtle synaptic alterations in the hippocampus and prefrontal cortex. The authors describe these structural changes reported in monkeys and rodents, how they might affect age-associated cognitive decline and potential strategies to limit their impact.

Dysfunction of the circadian clock contributes to the age-associated decline of brain functions. Here, the authors examine the evidence for this link and the potential underlying molecular mechanisms such as the circadian control of brain metabolism and hormone secretion.

Hypothermia has neuroprotective effects in certain clinical conditions and in animal models of brain insult. Yenari and Han review the mechanisms that underlie these effects. Focusing on animal models of ischaemia, they describe how cooling influences multiple aspects of brain physiology in the acute, subacute and chronic stages of ischaemia.

Adult mammalian CNS axons show little regenerative capacity following injury, in part because they fail to assemble functional growth cones at their tips. However, axons from the mammalian peripheral nervous system and non-mammalian species show more regenerative potential. Here, Bradkeet al. examine the process of growth cone assembly after axonal injury. Understanding why this process does not always succeed may facilitate the development of treatments for CNS-damage-related disability.

Long-term potentiation (LTP) describes the long-lasting increase in the strength of synaptic transmission between two neurons, a process that may be integral to learning and memory. In this Review, Lisman and colleagues examine the central role that calcium/calmodulin-dependent protein kinase II (CaMKII) has in this form of synaptic plasticity. Focusing on postsynaptic mechanisms, the authors discuss CaMKII in the context of both the early and late stages of LTP.