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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.
Recent work suggests that the insula forms part of a network that mediates the processing of salient stimuli. In this Opinion article, Lucina Q. Uddin examines the role of the insula in salience processing before outlining that dysfunction of such processing in insular subdivisions might accompany several brain disorders.
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.
Developmental dyslexia occurs across languages and has a major impact on the lives of affected individuals. Here, Usha Goswami considers the evidence for several prominent 'sensory' theories of dyslexia and outlines the key challenges for research in this area.
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.
Despite centuries of recreational use of cannabis, it is only relatively recently that its mechanisms of action, and the existence of endogenous cannabinoids, have been discovered. In this Timeline article, Raphael Mechoulam and colleagues discuss early research on the plant cannabinoids and speculate on the directions this research might take in the future.
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.
The recently discovered hippocampal 'time cells' are thought to represent the flow of time in specific memories. In this Review, Howard Eichenbaum discusses the evidence for the existence of time cells, describes their characteristics and relationship with place cells, and considers their role in memory.
It is commonly thought that the dorsal hippocampus is implicated in memory and spatial navigation and the ventral hippocampus in anxiety-related behaviours. On the basis of gene expression, anatomical and electrophysiology studies, Strange and colleagues propose a new model of hippocampal functional anatomy, in which functional long-axis gradients are superimposed on discrete functional domains.
Dynamic regulation of ion concentrations across the cellular membrane is vital for neuronal function. In this article, Kaila and colleagues review the contribution of members of the cation-chloride cotransporters to neuronal signalling, connectivity, plasticity and disease.
The application of network science to several common neurological disorders challenges the idea that these disorders are either 'local' or 'global'. In this Review, Kees Stam proposes a model of hub overload and failure as a possible final common pathway in diverse neurological disorders.
Social prejudices and stereotyping are pervasive and often operate unconsciously. In this Review, David M. Amodio considers the neural basis of prejudice and stereotyping and discusses the processes through which such biases may form, can influence behaviour and are regulated.
Inhibitory GABAergic synapses on dendritic spines and shafts have a key role in the localized regulation of neuronal Ca2+signalling. In this Progress article, Higley explains how the influences of dendritic inhibition on electrical and biochemical activity in neurons shape synaptic plasticity.
Recent developments in genetic techniques and monitoring neuronal activity are allowing the roles of different neurons in various fly behaviours to be probed. In light of this progress, Alexander Borst reviews the neuronal circuits underlying visual course control inDrosophila melanogaster.
Retinal progenitor cells (RPCs) produce all of the retina's cells through an evolutionarily conserved series of divisions and cell fate decisions. In this article, Cepko describes recent studies that have shed light on the intrinsic and extrinsic mechanisms that drive this process and argues that individual terminally dividing RPCs are molecularly specified to produce particular progeny.
