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The abnormal accumulation of α-synuclein seems to have a central role in the pathophysiology of Parkinson's disease and related disorders. Masliah and colleagues review current knowledge regarding the conformational, oligomerization and aggregation states of this protein and how they influence α-synuclein function in health and disease.
Neurotrophins are key regulators of neural circuit development and function. In this Review, Park and Poo examine the mechanisms underlying this regulation, with a specific focus on brain-derived neurotrophic factor — the most widely expressed and studied neurotrophin in the brain.
Sandoval and colleagues discuss emerging evidence for a role of the CNS in the regulation of glucose homeostasis and show that this regulation involves several neural circuits and mechanisms that also control energy balance. Disruption of these overlapping pathways may link the metabolic impairments that are associated with obesity and type 2 diabetes.
Mutations inSCN9A, which encodes the voltage-gated sodium channel NaV1.7, can lead to severe neuropathic pain in humans. In this Review, Waxman and colleagues examine the mechanistic basis of NaV1.7-linked pain and explore strategies for targeting this channel in pain therapy.
In CNS neurons, the somatic membrane potential is subject to subthreshold analogue modulation. This analogue component increases the information content of action potentials and has important implications for information processing in neural networks.
In this Opinion article, Masri and Sassone-Corsi discuss the complex interconnections between circadian rhythms, metabolic processes and epigenetic regulation of gene transcription. They propose that cellular metabolic state and epigenetic mechanisms might work through the circadian clock to regulate neuronal function and influence disease states.
Despite their structural similarities and seemingly coordinated expression patterns, oligodendrocyte transcription factor 1 (OLIG1) and OLIG2 have largely non-overlapping roles in CNS development, brain diseases and neural repair. Here, the authors review the molecular factors that may account for the divergent functions of these proteins.
Down syndrome is the most common genetic form of intellectual disability. In this Review, Mara Dierssen examines the underlying mechanisms that give rise to brain dysfunction in Down syndrome and discusses therapeutic approaches that are under investigation to combat cognitive deficits associated with this condition.
Many animals, from worms to humans, show structural and functional asymmetries in their nervous systems. Concha, Bianco and Wilson describe two fundamental types of nervous system asymmetry and discuss how they emerge during development and influence behaviour.
All cells are influenced by mechanical forces, but the effects of mechanical energy in the brain have received relatively little attention. William Tyler summarizes the main mechanical events that take place in neurons and their effects on neuronal function, and argues for an increased consideration of mechanobiology in neuroscience.
Chronic pain is more prevalent in women than in men. In this Perspective, Jeffrey Mogil argues that this sex bias in clinical pain is due to a sex difference in pain sensitivity and discusses various underlying mechanisms that might account for this difference.
The BCM theory of synaptic plasticity is now 30 years old. In this Perspective article, Cooper and Bear discuss how this theory has advanced our understanding of synaptic plasticity, learning and memory and highlight the important role that theory can have in neuroscience research.
Honeybees exhibit complex social, navigational and communication behaviours, controlled by a nervous system of around 1 million neurons. In this Review, Randolf Menzel discusses the utility of the honeybee as a model organism for the study of a wide range of important cognitive functions, including learning and memory.
Post-traumatic stress disorder is associated with changes in psychophysiological, neuroimaging, endocrinological and genetic measures. Animal studies have begun to elucidate its neurobiological mechanisms. Pitman and colleagues review these findings and discuss directions for research aimed at identifying risk factors, biomarkers and preventive and therapeutic interventions.
Aberrant matrix metalloproteinase (MMP) activity is a well-known contributor to synaptic dysfunction and neuronal loss in CNS injury and disease. In this Review, George W. Huntley discusses how MMPs also make an important contribution to synaptic functional and structural remodelling under nonpathophysiological conditions.
The roles of the perirhinal, parahippocampal and retrosplenial cortices in memory are not well understood. Reviewing studies in rodents, monkeys and humans, Ranganath and Ritchey suggest that these areas are core components of two cortical networks that support different types of memory and different aspects of cognition.
Gut microbiota are increasingly being recognized as influencing many aspects of human health. In this Review, Cryan and Dinan discuss rapidly emerging evidence that the gut microbiota also influence brain and behaviour and may have a role in anxiety, mood, cognition and pain.
The neuropilin and tolloid-like (NETO) proteins were recently identified as auxiliary subunits of kainate-type glutamate receptors, which mainly have a modulatory role in synaptic transmission. In this Review, Copits and Swanson discuss how NETO proteins influence the biophysical properties and the synaptic localization of these receptors.
Adult neurogenesis is often considered an archaic trait that has undergone 'phylogenetic reduction'. Gerd Kempermann proposes that adult neurogenesis in the hippocampus is in fact a late-evolved trait that may provide the cognitive adaptability that is needed to conquer new ecological niches.
Our understanding of neuronal circuit function has benefitted from methods that allow the activity of individual cells and populations of neurons to be monitored. Thomas Knöpfel reviews recent advances in the technology of genetically encoded indicators of neural activity, which are enabling circuits to be examined in an increasingly sophisticated manner.
