Showing papers in "Nature Reviews Neuroscience in 2008"
TL;DR: In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour, which can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals.
Abstract: In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.
5,665 citations
TL;DR: A growing number of studies support the idea that physical exercise is a lifestyle factor that might lead to increased physical and mental health throughout life, at the molecular, cellular, systems and behavioural levels.
Abstract: An emerging body of multidisciplinary literature has documented the beneficial influence of physical activity engendered through aerobic exercise on selective aspects of brain function. Human and non-human animal studies have shown that aerobic exercise can improve a number of aspects of cognition and performance. Lack of physical activity, particularly among children in the developed world, is one of the major causes of obesity. Exercise might not only help to improve their physical health, but might also improve their academic performance. This article examines the positive effects of aerobic physical activity on cognition and brain function, at the molecular, cellular, systems and behavioural levels. A growing number of studies support the idea that physical exercise is a lifestyle factor that might lead to increased physical and mental health throughout life.
2,887 citations
TL;DR: The peak age of onset for many psychiatric disorders is adolescence, a time of remarkable physical and behavioural changes and answers to these questions might enable the understanding of mental health during adolescence.
Abstract: The peak age of onset for many psychiatric disorders is adolescence, a time of remarkable physical and behavioural changes. The processes in the brain that underlie these behavioural changes have been the subject of recent investigations. What do we know about the maturation of the human brain during adolescence? Do structural changes in the cerebral cortex reflect synaptic pruning? Are increases in white-matter volume driven by myelination? Is the adolescent brain more or less sensitive to reward? Finding answers to these questions might enable us to further our understanding of mental health during adolescence.
2,436 citations
TL;DR: How noise affects neuronal networks and the principles the nervous system applies to counter detrimental effects of noise are highlighted, and noise's potential benefits are discussed.
Abstract: Noise — random disturbances of signals — poses a fundamental problem for information processing and affects all aspects of nervous-system function. However, the nature, amount and impact of noise in the nervous system have only recently been addressed in a quantitative manner. Experimental and computational methods have shown that multiple noise sources contribute to cellular and behavioural trial-to-trial variability. We review the sources of noise in the nervous system, from the molecular to the behavioural level, and show how noise contributes to trial-to-trial variability. We highlight how noise affects neuronal networks and the principles the nervous system applies to counter detrimental effects of noise, and briefly discuss noise's potential benefits.
2,350 citations
TL;DR: A framework to investigate different aspects of the neurobiology of decision making is proposed to bring together recent findings in the field, highlight some of the most important outstanding problems, define a common lexicon that bridges the different disciplines that inform neuroeconomics, and point the way to future applications.
Abstract: Neuroeconomics is the study of the neurobiological and computational basis of value-based decision making. Its goal is to provide a biologically based account of human behaviour that can be applied in both the natural and the social sciences. This Review proposes a framework to investigate different aspects of the neurobiology of decision making. The framework allows us to bring together recent findings in the field, highlight some of the most important outstanding problems, define a common lexicon that bridges the different disciplines that inform neuroeconomics, and point the way to future applications.
1,814 citations
TL;DR: It is argued that complex cognitive–emotional behaviours have their basis in dynamic coalitions of networks of brain areas, none of which should be conceptualized as specifically affective or cognitive.
Abstract: The current view of brain organization supports the notion that there is a considerable degree of functional specialization and that many regions can be conceptualized as either 'affective' or 'cognitive'. Popular examples are the amygdala in the domain of emotion and the lateral prefrontal cortex in the case of cognition. This prevalent view is problematic for a number of reasons. Here, I will argue that complex cognitive-emotional behaviours have their basis in dynamic coalitions of networks of brain areas, none of which should be conceptualized as specifically affective or cognitive. Central to cognitive-emotional interactions are brain areas with a high degree of connectivity, called hubs, which are critical for regulating the flow and integration of information between regions.
1,786 citations
TL;DR: Dendritic domains with distinct synaptic inputs, excitability, modulation and plasticity appears to be a common feature that allows synapses throughout the dendritic tree to contribute to action-potential generation.
Abstract: Pyramidal neurons are characterized by their distinct apical and basal dendritic trees and the pyramidal shape of their soma. They are found in several regions of the CNS and, although the reasons for their abundance remain unclear, functional studies — especially of CA1 hippocampal and layer V neocortical pyramidal neurons — have offered insights into the functions of their unique cellular architecture. Pyramidal neurons are not all identical, but some shared functional principles can be identified. In particular, the existence of dendritic domains with distinct synaptic inputs, excitability, modulation and plasticity appears to be a common feature that allows synapses throughout the dendritic tree to contribute to action- potential generation. These properties support a variety of coincidence-detection mechanisms, which are likely to be crucial for synaptic integration and plasticity.
1,543 citations
TL;DR: The supplementary motor complex consists of the supplementary motor area, the supplementary eye field and the pre-supplementary motor area and theories regarding their function vary widely.
Abstract: The supplementary motor complex consists of the supplementary motor area, the supplementary eye field and the pre-supplementary motor area. In recent years, these areas have come under increasing scrutiny from cognitive neuroscientists, motor physiologists and clinicians because they seem to be crucial for linking cognition to action. However, theories regarding their function vary widely. This Review brings together the data regarding the supplementary motor regions, highlighting outstanding issues and providing new perspectives for understanding their functions.
1,492 citations
TL;DR: A representative group of researchers are convened to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex, and the resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells.
Abstract: Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.
1,417 citations
TL;DR: The medial prefrontal cortex and the superior temporal sulcus as mentioned in this paper show altered activity during the performance of social cognitive tasks, such as face recognition and mental-state attribution, during adolescence.
Abstract: The term 'social brain' refers to the network of brain regions that are involved in understanding others. Behaviour that is related to social cognition changes dramatically during human adolescence. This is paralleled by functional changes that occur in the social brain during this time, in particular in the medial prefrontal cortex and the superior temporal sulcus, which show altered activity during the performance of social cognitive tasks, such as face recognition and mental-state attribution. Research also indicates that, in humans, these parts of the social brain undergo structural development, including synaptic reorganization, during adolescence. Bringing together two relatively new and rapidly expanding areas of neuroscience--social neuroscience and the study of brain development during adolescence--will increase our understanding of how the social brain develops during adolescence.
1,402 citations
TL;DR: It is shown that evidence bearing on where the N400 response is generated provides key insights into what it reflects, and this has important consequences for neural models of language comprehension.
Abstract: Measuring event-related potentials (ERPs) has been fundamental to our understanding of how language is encoded in the brain. One particular ERP response, the N400 response, has been especially influential as an index of lexical and semantic processing. However, there remains a lack of consensus on the interpretation of this component. Resolving this issue has important consequences for neural models of language comprehension. Here we show that evidence bearing on where the N400 response is generated provides key insights into what it reflects. A neuroanatomical model of semantic processing is used as a guide to interpret the pattern of activated regions in functional MRI, magnetoencephalography and intracranial recordings that are associated with contextual semantic manipulations that lead to N400 effects.
TL;DR: The mechanisms of remyelination provide critical clues for regeneration biologists that help them to determine why remYelination fails in MS and in other demyelinating diseases and how it might be enhanced therapeutically.
Abstract: Remyelination involves reinvesting demyelinated axons with new myelin sheaths. In stark contrast to the situation that follows loss of neurons or axonal damage, remyelination in the CNS can be a highly effective regenerative process. It is mediated by a population of precursor cells called oligodendrocyte precursor cells (OPCs), which are widely distributed throughout the adult CNS. However, despite its efficiency in experimental models and in some clinical diseases, remyelination is often inadequate in demyelinating diseases such as multiple sclerosis (MS), the most common demyelinating disease and a cause of neurological disability in young adults. The failure of remyelination has profound consequences for the health of axons, the progressive and irreversible loss of which accounts for the progressive nature of these diseases. The mechanisms of remyelination therefore provide critical clues for regeneration biologists that help them to determine why remyelination fails in MS and in other demyelinating diseases and how it might be enhanced therapeutically.
TL;DR: The neural control of micturition is reviewed and how disruption of this control leads to abnormal storage and release of urine.
Abstract: Micturition, or urination, occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. The neural circuitry that controls this process is complex and highly distributed: it involves pathways at many levels of the brain, the spinal cord and the peripheral nervous system and is mediated by multiple neurotransmitters. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary or reflex micturition, leading to urinary incontinence. This is a major health problem, especially in those with neurological impairment. Here we review the neural control of micturition and how disruption of this control leads to abnormal storage and release of urine.
TL;DR: Understanding the acquisition and usage of multisensory integration in the midbrain and cerebral cortex of mammals has been aided by a multiplicity of approaches and some of the challenging questions that remain are examined.
Abstract: Multisensory integration allows information from multiple senses to be combined, with benefits for nervous-system processing. Stein and Stanford discuss the principles of multisensory integration in single neurons in the CNS and consider the questions that the field must address.
TL;DR: Comparisons with the features of natural sleep are helping to understand how anaesthetics work and the neuronal pathways that they affect, and suggests that the thalamus and the neurons that regulate its activity are the key to understanding how anaesthetic-induced loss of consciousness is understood.
Abstract: The mechanisms through which general anaesthetics, an extremely diverse group of drugs, cause reversible loss of consciousness have been a long-standing mystery. Gradually, a relatively small number of important molecular targets have emerged, and how these drugs act at the molecular level is becoming clearer. Finding the link between these molecular studies and anaesthetic-induced loss of consciousness presents an enormous challenge, but comparisons with the features of natural sleep are helping us to understand how these drugs work and the neuronal pathways that they affect. Recent work suggests that the thalamus and the neuronal networks that regulate its activity are the key to understanding how anaesthetics cause loss of consciousness.
TL;DR: The answer to the episodic-memory puzzle requires us to distinguish between the contributions of dorsal and ventral parietal regions and between the influence of top-down and bottom-up attention on memory.
Abstract: The contribution of the parietal cortex to episodic memory is a fascinating scientific puzzle. On the one hand, parietal lesions do not normally yield severe episodic-memory deficits; on the other hand, parietal activations are seen frequently in functional-neuroimaging studies of episodic memory. A review of these two categories of evidence suggests that the answer to the puzzle requires us to distinguish between the contributions of dorsal and ventral parietal regions and between the influence of top-down and bottom-up attention on memory.
TL;DR: The conceptual bases and experimental evidence for this hypothesis suggest a possible mechanism by which intuition and implicit thought might function and explains some of the symptoms that are exhibited by psychiatric patients.
Abstract: The intricate neuronal circuitry of the cerebellum is thought to encode internal models that reproduce the dynamic properties of body parts. These models are essential for controlling the movement of these body parts: they allow the brain to precisely control the movement without the need for sensory feedback. It is thought that the cerebellum might also encode internal models that reproduce the essential properties of mental representations in the cerebral cortex. This hypothesis suggests a possible mechanism by which intuition and implicit thought might function and explains some of the symptoms that are exhibited by psychiatric patients. This article examines the conceptual bases and experimental evidence for this hypothesis.
TL;DR: Understanding the molecular basis of the effects of food on cognition will help to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness.
Abstract: It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness.
TL;DR: It is explained how this neural-level mechanistic account addresses some of the current controversies in the field, such as the role of the hippocampus in imagery and short-term memory, and discusses its broader implications for the neural bases of episodic memory.
Abstract: The hippocampus appears to be crucial for long-term episodic memory, yet its precise role remains elusive. Electrophysiological studies in rodents offer a useful starting point for developing models of hippocampal processing in the spatial domain. Here we review one such model that points to an essential role for the hippocampus in the construction of mental images. We explain how this neural-level mechanistic account addresses some of the current controversies in the field, such as the role of the hippocampus in imagery and short-term memory, and discuss its broader implications for the neural bases of episodic memory.
TL;DR: It is argued that the recent development of transgenic molecular devices will encourage a shift from mechanistic investigations of synaptic plasticity in single neurons towards an analysis of how networks of neurons encode and represent memory, and ways in which this might be achieved.
Abstract: Two facts about the hippocampus have been common currency among neuroscientists for several decades. First, lesions of the hippocampus in humans prevent the acquisition of new episodic memories; second, activity-dependent synaptic plasticity is a prominent feature of hippocampal synapses. Given this background, the hypothesis that hippocampus-dependent memory is mediated, at least in part, by hippocampal synaptic plasticity has seemed as cogent in theory as it has been difficult to prove in practice. Here we argue that the recent development of transgenic molecular devices will encourage a shift from mechanistic investigations of synaptic plasticity in single neurons towards an analysis of how networks of neurons encode and represent memory, and we suggest ways in which this might be achieved. In the process, the hypothesis that synaptic plasticity is necessary and sufficient for information storage in the brain may finally be validated.
TL;DR: An improved understanding of the mechanisms by which altered function of NRG1 and ErbB4 contributes to schizophrenia might eventually lead to the development of more effective therapeutics.
Abstract: Polymorphisms in the genes that encode neuregulin 1 (NRG1) and its receptor ErbB4 have been associated with schizophrenia. Mei and Xiong review the role of NRG1 signalling in neural development and synaptic plasticity and discuss how alterations in NRG1 signalling might contribute to schizophrenia. Schizophrenia is a highly debilitating mental disorder that affects ∼1% of the general population, yet it continues to be poorly understood. Recent studies have identified variations in several genes that are associated with this disorder in diverse populations, including those that encode neuregulin 1 (NRG1) and its receptor ErbB4. The past few years have witnessed exciting progress in our knowledge of NRG1 and ErbB4 functions and the biological basis of the increased risk for schizophrenia that is potentially conferred by polymorphisms in the two genes. An improved understanding of the mechanisms by which altered function of NRG1 and ErbB4 contributes to schizophrenia might eventually lead to the development of more effective therapeutics.
TL;DR: Various intercellular signalling molecules can trigger lasting changes in the ability of synapses to express plasticity; their mechanisms of action are reviewed here, along with a consideration of how metaplasticity might affect learning and clinical conditions.
Abstract: Synaptic plasticity is a key component of the learning machinery in the brain. It is vital that such plasticity be tightly regulated so that it occurs to the proper extent at the proper time. Activity-dependent mechanisms that have been collectively termed metaplasticity have evolved to help implement these essential computational constraints. Various intercellular signalling molecules can trigger lasting changes in the ability of synapses to express plasticity; their mechanisms of action are reviewed here, along with a consideration of how metaplasticity might affect learning and clinical conditions.
TL;DR: Mitochondria are remarkably dynamic organelles that migrate, divide and fuse. as discussed by the authors showed that mutations in the mitochondrial fusion GTPases mitofusin 2 and optic atrophy 1, neurotoxins and oxidative stress all disrupt the cable-like morphology of functional mitochondria.
Abstract: Mitochondria are remarkably dynamic organelles that migrate, divide and fuse. Cycles of mitochondrial fission and fusion ensure metabolite and mitochondrial DNA mixing and dictate organelle shape, number and bioenergetic functionality. There is mounting evidence that mitochondrial dysfunction is an early and causal event in neurodegeneration. Mutations in the mitochondrial fusion GTPases mitofusin 2 and optic atrophy 1, neurotoxins and oxidative stress all disrupt the cable-like morphology of functional mitochondria. This results in impaired bioenergetics and mitochondrial migration, and can trigger neurodegeneration. These findings suggest potential new treatment avenues for neurodegenerative diseases.
TL;DR: New research has identified networks of brain areas, including the pre-supplementary motor area, the anterior prefrontal cortex and the parietal cortex, that underlie voluntary action and may inform debates about the nature of individual responsibility.
Abstract: The capacity for voluntary action is seen as essential to human nature. Yet neuroscience and behaviourist psychology have traditionally dismissed the topic as unscientific, perhaps because the mechanisms that cause actions have long been unclear. However, new research has identified networks of brain areas, including the pre-supplementary motor area, the anterior prefrontal cortex and the parietal cortex, that underlie voluntary action. These areas generate information for forthcoming actions, and also cause the distinctive conscious experience of intending to act and then controlling one's own actions. Volition consists of a series of decisions regarding whether to act, what action to perform and when to perform it. Neuroscientific accounts of voluntary action may inform debates about the nature of individual responsibility.
TL;DR: Findings from human neuroimaging studies in conjunction with data analysis methods that can directly link decisions and signals in the human brain on a trial-by-trial basis are reviewed to lead to a new view about the neural basis of human perceptual decision-making processes.
Abstract: Perceptual decision making is the act of choosing one option or course of action from a set of alternatives on the basis of available sensory evidence. Thus, when we make such decisions, sensory information must be interpreted and translated into behaviour. Neurophysiological work in monkeys performing sensory discriminations, combined with computational modelling, has paved the way for neuroimaging studies that are aimed at understanding decision-related processes in the human brain. Here we review findings from human neuroimaging studies in conjunction with data analysis methods that can directly link decisions and signals in the human brain on a trial-by-trial basis. This leads to a new view about the neural basis of human perceptual decision-making processes.
TL;DR: Current data on the development of the human cerebral cortex is reviewed and the classical model of how the structure that makes us human is formed is updated.
Abstract: In 1970 the Boulder Committee described the basic principles of the development of the CNS, derived from observations on the human embryonic cerebrum Since then, numerous studies have significantly advanced our knowledge of the timing, sequence and complexity of developmental events, and revealed important inter-species differences We review current data on the development of the human cerebral cortex and update the classical model of how the structure that makes us human is formed
TL;DR: The putative pathogenetic roles and common biochemical pathways of some of the most genetically and biologically compelling of these potential AD risk factors are discussed.
Abstract: The genetic underpinnings of Alzheimer's disease (AD) remain largely elusive despite early successes in identifying three genes that cause early-onset familial AD (those that encode amyloid precursor protein (APP) and the presenilins (PSEN1 and PSEN2)), and one genetic risk factor for late-onset AD (the gene that encodes apolipoprotein E (APOE)) A large number of studies that aimed to help uncover the remaining disease-related loci have been published in recent decades, collectively proposing or refuting the involvement of over 500 different gene candidates Systematic meta-analyses of these studies currently highlight more than 20 loci that have modest but significant effects on AD risk This Review discusses the putative pathogenetic roles and common biochemical pathways of some of the most genetically and biologically compelling of these potential AD risk factors
TL;DR: The aim of this Review is to highlight some of the recent progress in elucidating the role of the actin cytoskeleton in synaptic function.
Abstract: Synapse regulation exploits the capacity of actin to function as a stable structural component or as a dynamic filament. Beyond its well-appreciated role in eliciting visible morphological changes at the synapse, the emerging picture points to an active contribution of actin to the modulation of the efficacy of pre- and postsynaptic terminals. Moreover, by engaging distinct pools of actin and divergent signalling pathways, actin-dependent morphological plasticity could be uncoupled from modulation of synaptic strength. The aim of this Review is to highlight some of the recent progress in elucidating the role of the actin cytoskeleton in synaptic function.
TL;DR: This review summarizes what has been learned about the roles of these proteins from transgenic mice and invertebrate species such as flies and worms and suggests an early, preclinical diagnosis of AD and FTD could be within reach.
Abstract: Insoluble protein aggregates have been linked to Alzheimer's disease (AD) and frontotemporal dementia (FTD). Recent work in transgenic mice has shed light on the role of these aggregates by identifying soluble oligomeric species that may interfere with essential cellular mechanisms at an early disease stage. This review summarizes what we have learned about the roles of these proteins from transgenic mice and invertebrate species such as flies and worms. Proteomic and transcriptomic analyses of tissue from these animal models have identified new molecules with crucial roles in disease. Moreover, transgenic animals have been instrumental in defining drug targets and designing novel therapeutic strategies. With advanced imaging techniques that can be used in both humans and mice an early, preclinical diagnosis of AD and FTD could be within reach.
TL;DR: Understanding the mutually inhibitory effects that pain and reward processing have on each other, and the neural mechanisms that underpin such modulation, is important for alleviating unnecessary suffering and improving well-being.
Abstract: Pain and pleasure are powerful motivators of behaviour and have historically been considered opposites. Emerging evidence from the pain and reward research fields points to extensive similarities in the anatomical substrates of painful and pleasant sensations. Recent molecular-imaging and animal studies have demonstrated the important role of the opioid and dopamine systems in modulating both pain and pleasure. Understanding the mutually inhibitory effects that pain and reward processing have on each other, and the neural mechanisms that underpin such modulation, is important for alleviating unnecessary suffering and improving well-being.