Review Articles in 2011

The efficacy of synaptic transmission depends on the coupling between presynaptic calcium channels and the molecules that trigger exocytosis in response to calcium influx. Jonas and colleagues describe evidence for tight coupling at certain fast mammalian synapses, its contribution to signalling properties and the underlying protein–protein interactions.

Recent studies have shed light on the mechanisms by which stress and glucocorticoids affect glutamate transmission in the prefrontal cortex and the hippocampus. Sanacora and colleagues review these studies and discuss the relevance of these mechanisms for normal brain functioning and for the pathophysiology and potential new treatments of stress-related neuropsychiatric disorders.

The involvement of the RNA-binding protein TDP43 in neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration, has become well established. However, the mechanisms by which the protein is linked to the disease process remain unclear. Trojanowski and colleagues describe our current understanding of TDP43 pathology and discuss how gains of toxic function or losses of normal TDP43 function may contribute to neurodegeneration.

Normalization computes a ratio between the response of an individual neuron and the summed activity of a pool of neurons. Here, the authors review the evidence that it serves as a canonical computation — one that is applied to processing different types of information in multiple brain regions in multiple species.

TheDISC1gene has been implicated in a number of major mental illnesses, which recent research suggests could be linked to its role in a variety of neurodevelopmental processes, thus indicating novel opportunities for therapeutic targeting.

Dysfunction of the blood–brain barrier and other neurovascular deficits are features of several neurodegenerative disorders. In this Review, Berislav Zlokovic explores the evidence indicating that vascular-derived insults initiate and/or contribute to neuronal degeneration in these disorders, most notably in Alzheimer's disease. He also discusses the therapeutic opportunities that are related to these neurovascular deficits.

The compatibility of virtual reality systems with brain imaging techniques and their use for animal research have aided the widespread adoption of virtual reality environments in both experimental and therapeutic domains. Here the authors review advances in virtual reality technology and its applications.

Acquiring new motor skills involves a range of learning processes that are related to the gathering of task-relevant sensory information, decision making and the selection of strategies. Wolpert and colleagues review recent research in human motor learning with an emphasis on the computational mechanisms that are involved.

Functional imaging studies have pointed to a key role for the prefrontal cortex (PFC) in addiction, both through its regulation of limbic regions and its involvement in higher-order executive function. Goldstein and Volkow review these studies, showing that disruption of the PFC in addiction not only underlies compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of non-drug related motivation and self-control.

Current addiction pharmacotherapies have limited success. Focusing on alcohol addiction, Heilig and colleagues review the evidence that genetic heterogeneity in the opioid, corticotropin-releasing factor, GABA and serotonin systems may underlie differential treatment responses, and that personalized therapies tailored to patient genotype may lead to more successful treatment for alcohol addiction.

The regulation of the hedonic properties of food and addictive drugs involves common neural circuits and molecular substrates. Kenny reviews the shared mechanisms that may contribute to both obesity and drug addiction.

Chronic drug exposure induces long-term changes in the brain, which are partly due to alterations in gene expression. Robison and Nestler review the mechanisms by which drugs of abuse alter the transcriptional potential of genes through the regulation of transcription factors and epigenetic mechanisms, including the regulation of gene expression by non-coding RNAs.

Migraine is a complex and disabling brain disorder that is currently difficult to prevent or treat. Goadsby and colleagues review the evidence that regions of the brainstem and forebrain are involved in modulating migraine pain and that dysfunction in these areas may contribute to the pathophysiology of the disorder.

The hippocampal formation has been implicated in many disorders — including Alzheimer's disease, schizophrenia and depression — and in cognitive ageing, but how can one area be central to such diverse conditions? Small and colleagues review a large literature of neuroimaging findings and propose a framework of hippocampal dysfunction in which these conditions differentially target distinct subregions of the hippocampal circuit and are associated with either hippocampal hypermetabolism or hypometabolism.

Neurons in the suprachiasmatic nucleus (SCN) show circadian patterns, not only in gene transcription and protein translation but also in neural activity. Christopher Colwell describes the mechanisms that drive the rhythmic firing patterns of SCN neurons, including the contribution of ion channels, and discusses the mutual regulation of neural activity and the molecular clock.

Animal studies have shown that oxytocin (OXT) and arginine vasopressin (AVP) are crucial regulators of social behaviour. In this Review, Meyer-Lindenberg and colleagues consider behavioural, genetic and neuroimaging studies that show that these peptides also influence social behaviour and cognition in humans, and suggest that the OXT and AVP systems could be targets for the treatment of mental disorders characterized by social dysfunction.

Harris and Thiele review studies of state-dependent cortical processing in rodents and of attention in the primate visual system, and show that the two processes have many similarities. They propose that selective attention involves a process similar to state change, operating at a local level to enhance the representation of otherwise subtle stimuli, while suppressing internally generated activity patterns.

There is currently no effective treatment for glioma, the most common type of brain tumour. Recent technological advances have made it possible to gain a more detailed understanding of the molecular processes underlying tumour cell differentiation and the findings suggest new opportunities for therapeutic intervention.

Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), has neuroprotective effects in models of several neurodegenerative diseases. In this Review, Vila and colleagues discuss the mechanisms by which rapamycin exerts neuroprotection, including effects on autophagy and apoptosis, and on the translation of pro-death and pro-survival proteins.

The importance of interactions between the brain and the digestive system in health and disease has been recognized for centuries. Mayer reviews the neuroanatomy and signalling mechanisms that underlie this bidirectional communication system in health and disease, as well as possible consequences for higher-level executive functions and emotional states.