Showing papers in "Nature Reviews Neuroscience in 2009"
TL;DR: This article reviews studies investigating complex brain networks in diverse experimental modalities and provides an accessible introduction to the basic principles of graph theory and highlights the technical challenges and key questions to be addressed by future developments in this rapidly moving field.
Abstract: Recent developments in the quantitative analysis of complex networks, based largely on graph theory, have been rapidly translated to studies of brain network organization. The brain's structural and functional systems have features of complex networks--such as small-world topology, highly connected hubs and modularity--both at the whole-brain scale of human neuroimaging and at a cellular scale in non-human animals. In this article, we review studies investigating complex brain networks in diverse experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans) and provide an accessible introduction to the basic principles of graph theory. We also highlight some of the technical challenges and key questions to be addressed by future developments in this rapidly moving field.
9,700 citations
TL;DR: New findings suggest a fundamental role for the AIC (and the von Economo neurons it contains) in awareness, and thus it needs to be considered as a potential neural correlate of consciousness.
Abstract: The anterior insular cortex (AIC) is implicated in a wide range of conditions and behaviours, from bowel distension and orgasm, to cigarette craving and maternal love, to decision making and sudden insight. Its function in the re-representation of interoception offers one possible basis for its involvement in all subjective feelings. New findings suggest a fundamental role for the AIC (and the von Economo neurons it contains) in awareness, and thus it needs to be considered as a potential neural correlate of consciousness.
5,279 citations
TL;DR: In this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.
Abstract: Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.
4,739 citations
TL;DR: The survival and well-being of all species requires appropriate physiological responses to environmental and homeostatic challenges, so that the respective contributions of the neuroendocrine and autonomic systems are tuned in accordance with stressor modality and intensity.
Abstract: The survival and well-being of all species requires appropriate physiological responses to environmental and homeostatic challenges. The re-establishment and maintenance of homeostasis entails the coordinated activation and control of neuroendocrine and autonomic stress systems. These collective stress responses are mediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and the brainstem, so that the respective contributions of the neuroendocrine and autonomic systems are tuned in accordance with stressor modality and intensity. Limbic regions that are responsible for regulating stress responses intersect with circuits that are responsible for memory and reward, providing a means to tailor the stress response with respect to prior experience and anticipated outcomes.
2,592 citations
TL;DR: Recent research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness.
Abstract: Stress affects cognition and increases noradrenaline and dopamine levels in the prefrontal cortex (PFC). Amy Arnsten discusses the intracellular signalling pathways that mediate the effects of these catecholamines on PFC function during acute and chronic stress, focusing on working memory. An interview with Amy Arnsten for Neuropod is available for
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. The prefrontal cortex (PFC) — the most evolved brain region — subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonged stress exposure causes architectural changes in prefrontal dendrites. Recent research has begun to reveal the intracellular signalling pathways that mediate the effects of stress on the PFC. This research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness.
2,320 citations
TL;DR: Recent evidence for structural forms of synaptic plasticity in the mammalian cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively.
Abstract: Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal the structural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experience-dependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.
1,696 citations
TL;DR: Analysis of signals in tactile afferent neurons and central processes in humans reveals how contact events are encoded and used to monitor and update task performance.
Abstract: During object manipulation tasks, the brain selects and implements action-phase controllers that use sensory predictions and afferent signals to tailor motor output to the physical properties of the objects involved. Analysis of signals in tactile afferent neurons and central processes in humans reveals how contact events are encoded and used to monitor and update task performance.
1,569 citations
TL;DR: Evidence from animal models suggests that a time-limited window of neuroplasticity opens following a stroke, during which the greatest gains in recovery occur, and how to optimally engage and modify surviving neuronal networks is studied.
Abstract: Reductions in blood flow to the brain of sufficient duration and extent lead to stroke, which results in damage to neuronal networks and the impairment of sensation, movement or cognition. Evidence from animal models suggests that a time-limited window of neuroplasticity opens following a stroke, during which the greatest gains in recovery occur. Plasticity mechanisms include activity-dependent rewiring and synapse strengthening. The challenge for improving stroke recovery is to understand how to optimally engage and modify surviving neuronal networks, to provide new response strategies that compensate for tissue lost to injury.
1,554 citations
TL;DR: The unique features of stress-induced plasticity in the amygdala, in association with changes in other brain regions, could have long-term consequences for cognitive performance and pathological anxiety exhibited in people with affective disorders.
Abstract: Emotionally significant experiences tend to be well remembered, and the amygdala has a pivotal role in this process. But the efficient encoding of emotional memories can become maladaptive - severe stress often turns them into a source of chronic anxiety. Here, we review studies that have identified neural correlates of stress-induced modulation of amygdala structure and function - from cellular mechanisms to their behavioural consequences. The unique features of stress-induced plasticity in the amygdala, in association with changes in other brain regions, could have long-term consequences for cognitive performance and pathological anxiety exhibited in people with affective disorders.
1,548 citations
TL;DR: Elucidating the factors that control the activity of these neurons and the effect of noradrenaline in target regions is key to understanding how the brain allocates attention and apprehends the environment to select, store and retrieve information for generating adaptive behaviour.
Abstract: Mood, attention and motivation co-vary with activity in the neuromodulatory systems of the brain to influence behaviour. These psychological states, mediated by neuromodulators, have a profound influence on the cognitive processes of attention, perception and, particularly, our ability to retrieve memories from the past and make new ones. Moreover, many psychiatric and neurodegenerative disorders are related to dysfunction of these neuromodulatory systems. Neurons of the brainstem nucleus locus coeruleus are the sole source of noradrenaline, a neuromodulator that has a key role in all of these forebrain activities. Elucidating the factors that control the activity of these neurons and the effect of noradrenaline in target regions is key to understanding how the brain allocates attention and apprehends the environment to select, store and retrieve information for generating adaptive behaviour.
1,443 citations
TL;DR: How novelties that make us human may have been introduced during evolution are described, based on findings in the embryonic cerebral cortex in different mammalian species.
Abstract: The enlargement and species-specific elaboration of the cerebral neocortex during evolution holds the secret to the mental abilities of humans; however, the genetic origin and cellular mechanisms that generated the distinct evolutionary advancements are not well understood. This article describes how novelties that make us human may have been introduced during evolution, based on findings in the embryonic cerebral cortex in different mammalian species. The data on the differences in gene expression, new molecular pathways and novel cellular interactions that have led to these evolutionary advances may also provide insight into the pathogenesis and therapies for human-specific neuropsychiatric disorders.
TL;DR: The current understanding of the contribution of glia to pathological pain and neuroprotection is reviewed, and how the protective, anti-inflammatory actions ofglia are being harnessed to develop new drug targets for neuropathic pain control is reviewed.
Abstract: Glia have emerged as key contributors to pathological and chronic pain mechanisms. On activation, both astrocytes and microglia respond to and release a number of signalling molecules, which have protective and/or pathological functions. Here we review the current understanding of the contribution of glia to pathological pain and neuroprotection, and how the protective, anti-inflammatory actions of glia are being harnessed to develop new drug targets for neuropathic pain control. Given the prevalence of chronic pain and the partial efficacy of current drugs, which exclusively target neuronal mechanisms, new strategies to manipulate neuron–glia interactions in pain processing hold considerable promise.
TL;DR: Together, the effects of individual mediators on neuronal function and plasticity are integrated, and emerging evidence suggests that there is crosstalk between them that enables fine-tuned responses to diverse challenges.
Abstract: The impact of stress on brain function is increasingly recognized. Various substances are released in response to stress and can influence distinct neuronal circuits, but the functional advantages of having such a diversity of stress mediators remain unclear. Individual neurotransmitter, neuropeptide and steroid stress mediators have specific spatial and temporal niches, but these niches also overlap. In addition, the effects of individual mediators on neuronal function and plasticity are integrated, and emerging evidence suggests that there is crosstalk between them. Together, this results in the stress instruments producing an orchestrated 'symphony' that enables fine-tuned responses to diverse challenges.
TL;DR: Advances on multiple fronts that have highlighted the importance of the retrosplenial cortex for cognition are reviewed, and why specifying its precise functions remains problematic are considered.
Abstract: The past decade has seen a transformation in research on the retrosplenial cortex (RSC). This cortical area has emerged as a key member of a core network of brain regions that underpins a range of cognitive functions, including episodic memory, navigation, imagination and planning for the future. It is now also evident that the RSC is consistently compromised in the most common neurological disorders that impair memory. Here we review advances on multiple fronts, most notably in neuroanatomy, animal studies and neuroimaging, that have highlighted the importance of the RSC for cognition, and consider why specifying its precise functions remains problematic.
TL;DR: The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use and some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.
Abstract: Addiction is associated with neuroplasticity in the corticostriatal brain circuitry that is important for guiding adaptive behaviour. The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use. A failure of the prefrontal cortex to control drug-seeking behaviours can be linked to an enduring imbalance between synaptic and non-synaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.
TL;DR: It is suggested that it is possible to understand the symptoms of mental illness in terms of a disturbed hierarchical Bayesian framework, without recourse to separate considerations of experience and belief.
Abstract: Advances in cognitive neuroscience offer us new ways to understand the symptoms of mental illness by uniting basic neurochemical and neurophysiological observations with the conscious experiences that characterize these symptoms. Cognitive theories about the positive symptoms of schizophrenia — hallucinations and delusions — have tended to treat perception and belief formation as distinct processes. However, recent advances in computational neuroscience have led us to consider the unusual perceptual experiences of patients and their sometimes bizarre beliefs as part of the same core abnormality — a disturbance in error-dependent updating of inferences and beliefs about the world. We suggest that it is possible to understand these symptoms in terms of a disturbed hierarchical Bayesian framework, without recourse to separate considerations of experience and belief.
TL;DR: Research has shown that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways, which shape the functioning of the neural circuits that regulate reward, fear, emotion reactivity and social behaviour.
Abstract: Every individual experiences stressful life events. In some cases acute or chronic stress leads to depression and other psychiatric disorders, but most people are resilient to such effects. Recent research has begun to identify the environmental, genetic, epigenetic and neural mechanisms that underlie resilience, and has shown that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways. These changes shape the functioning of the neural circuits that regulate reward, fear, emotion reactivity and social behaviour, which together are thought to mediate successful coping with stress.
TL;DR: Current understanding of the regulation of microtubule assembly, organization and dynamics in axons and dendrites is reviewed to provide new insight into microtubules' function in neuronal development and their potential contribution to plasticity.
Abstract: During the past decade enormous advances have been made in our understanding of the basic molecular machinery that is involved in the development of neuronal polarity. Far from being mere structural elements, microtubules are emerging as key determinants of neuronal polarity. Here we review the current understanding of the regulation of microtubule assembly, organization and dynamics in axons and dendrites. These studies provide new insight into microtubules' function in neuronal development and their potential contribution to plasticity.
TL;DR: There is mounting evidence that APOE4 contributes to AD pathogenesis by modulating the metabolism and aggregation of amyloid-β peptide and by directly regulating brain lipid metabolism and synaptic functions through APOE receptors.
Abstract: The vast majority of Alzheimer's disease (AD) cases are late-onset and their development is probably influenced by both genetic and environmental risk factors. A strong genetic risk factor for late-onset AD is the presence of the e4 allele of the apolipoprotein E (APOE) gene, which encodes a protein with crucial roles in cholesterol metabolism. There is mounting evidence that APOE4 contributes to AD pathogenesis by modulating the metabolism and aggregation of amyloid-β peptide and by directly regulating brain lipid metabolism and synaptic functions through APOE receptors. Emerging knowledge of the contribution of APOE to the pathophysiology of AD presents new opportunities for AD therapy.
TL;DR: Pain researchers now have at their disposal a much wider range of mutant animals to study, assays that more closely resemble clinical pain states, and dependent measures beyond simple reflexive withdrawal, however, the complexity of the phenomenon of pain has made it difficult to assess the true value of these advances.
Abstract: Many are frustrated with the lack of translational progress in the pain field, in which huge gains in basic science knowledge obtained using animal models have not led to the development of many new clinically effective compounds. A careful re-examination of animal models of pain is therefore warranted. Pain researchers now have at their disposal a much wider range of mutant animals to study, assays that more closely resemble clinical pain states, and dependent measures beyond simple reflexive withdrawal. However, the complexity of the phenomenon of pain has made it difficult to assess the true value of these advances. In addition, pain studies are importantly affected by a wide range of modulatory factors, including sex, genotype and social communication, all of which must be taken into account when using an animal model.
TL;DR: An interactive diagram is developed with the aim to display all of the currently known anatomical connections of the rat parahippocampal–hipp hippocampal network and discuss the functional implications of some relatively underexposed connections.
Abstract: Converging evidence suggests that each parahippocampal and hippocampal subregion contributes uniquely to the encoding, consolidation and retrieval of declarative memories, but their precise roles remain elusive. Current functional thinking does not fully incorporate the intricately connected networks that link these subregions, owing to their organizational complexity; however, such detailed anatomical knowledge is of pivotal importance for comprehending the unique functional contribution of each subregion. We have therefore developed an interactive diagram with the aim to display all of the currently known anatomical connections of the rat parahippocampal-hippocampal network. In this Review, we integrate the existing anatomical knowledge into a concise description of this network and discuss the functional implications of some relatively underexposed connections.
TL;DR: Efforts to understand the signalling pathways and molecular mechanisms that underlie the involvement of TrkB in LTP and learning are described.
Abstract: Understanding the mechanisms that underlie learning is one of the most fascinating and central aims of neurobiological research. Hippocampal long-term potentiation (LTP) is widely regarded as a prime candidate for the cellular mechanism of learning. The receptor tyrosine kinase TrkB (also known as NTRK2), known primarily for its function during PNS and CNS development, has emerged in recent years as a potent regulator of hippocampal LTP. Here I describe efforts to understand the signalling pathways and molecular mechanisms that underlie the involvement of TrkB in LTP and learning.
TL;DR: Recent theoretical and experimental work suggests that spatiotemporal processing emerges from the interaction between incoming stimuli and the internal dynamic state of neural networks, including not only their ongoing spiking activity but also their 'hidden' neuronal states, such as short-term synaptic plasticity.
Abstract: A conspicuous ability of the brain is to seamlessly assimilate and process spatial and temporal features of sensory stimuli. This ability is indispensable for the recognition of natural stimuli. Yet, a general computational framework for processing spatiotemporal stimuli remains elusive. Recent theoretical and experimental work suggests that spatiotemporal processing emerges from the interaction between incoming stimuli and the internal dynamic state of neural networks, including not only their ongoing spiking activity but also their 'hidden' neuronal states, such as short-term synaptic plasticity.
TL;DR: This Review surveys anatomical, neuroimaging, electrophysiological and developmental findings, and considers the question: could the organization of the frontal cortex be hierarchical?
Abstract: The frontal lobes in the brain are a component of the cerebral system that supports goal-directed behaviour. However, their functional organization remains controversial. Recent studies have reported rostro-caudal distinctions in frontal cortex activity based on the abstractness of action representations. In addition, some have proposed that these differences reflect a hierarchical organization, whereby anterior frontal regions influence processing by posterior frontal regions during the realization of abstract action goals as motor acts. However, few have considered whether the anatomy and physiology of the frontal lobes support such a scheme. To address this gap, this Review surveys anatomical, neuroimaging, electrophysiological and developmental findings, and considers the question: could the organization of the frontal cortex be hierarchical?
TL;DR: Electrophysiological studies indicate that polydendrocytes receive synaptic input from neurons, suggesting that they are integrated in the neural network, and this Review highlights recent findings and unresolved questions related to the lineage and function of polydendsia in the CNS.
Abstract: NG2 cells (also known as polydendrocytes) are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes and microglia. They can be identified by the expression of the proteoglycan NG2, have a highly branched morphology and are distributed throughout the grey and white matter. They differentiate into oligodendrocytes in vitro and have often been equated with oligodendrocyte precursor cells. However, whether polydendrocytes are multipotential cells that can give rise to neurons and astrocytes as well as oligodendrocytes is now highly debated. Furthermore, electrophysiological studies indicate that polydendrocytes receive synaptic input from neurons, suggesting that they are integrated in the neural network. This Review highlights recent findings and unresolved questions related to the lineage and function of polydendrocytes in the CNS.
TL;DR: The advent of novel molecular and genetic techniques coupled with recent advances in knowledge of spinal cord development means that a comprehensive understanding of how the motor circuitry is organized and operates may be within the authors' grasp.
Abstract: Neurobiologists have long sought to understand how circuits in the nervous system are organized to generate the precise neural outputs that underlie particular behaviours. The motor circuits in the spinal cord that control locomotion, commonly referred to as central pattern generator networks, provide an experimentally tractable model system for investigating how moderately complex ensembles of neurons generate select motor behaviours. The advent of novel molecular and genetic techniques coupled with recent advances in our knowledge of spinal cord development means that a comprehensive understanding of how the motor circuitry is organized and operates may be within our grasp.
TL;DR: It is established that the same operational definitions and types of evidence underpin the deduction of both reconsolidation and consolidation, thus validating the extrapolation that post-retrieval memory plasticity reflects processes akin to those that stabilized the memory following acquisition.
Abstract: Consolidated memories can re-enter states of transient instability following reactivation, from which they must again stabilize in order to persist, contradicting the previously dominant view that memory and its associated plasticity mechanisms progressively and irreversibly decline with time. We witness exciting times, as neuroscience begins embracing a position, long-held in cognitive psychology, that recognizes memory as a principally dynamic process. In light of remaining controversy, we here establish that the same operational definitions and types of evidence underpin the deduction of both reconsolidation and consolidation, thus validating the extrapolation that post-retrieval memory plasticity reflects processes akin to those that stabilized the memory following acquisition.
TL;DR: New brain imaging technology provides insights into ventral and dorsal neural circuit dysfunction — perhaps related to altered serotonin and dopamine metabolism — that contributes to the puzzling symptoms found in people with eating disorders.
Abstract: Individuals with anorexia nervosa have a relentless preoccupation with dieting and weight loss that results in severe emaciation and sometimes death. It is controversial whether such symptoms are secondary to psychosocial influences, are a consequence of obsessions and anxiety or reflect a primary disturbance of brain appetitive circuits. New brain imaging technology provides insights into ventral and dorsal neural circuit dysfunction — perhaps related to altered serotonin and dopamine metabolism — that contributes to the puzzling symptoms found in people with eating disorders. For example, altered insula activity could explain interoceptive dysfunction, and altered striatal activity might shed light on altered reward modulation in people with anorexia nervosa.
TL;DR: To further understand how the brain processes information, it is important to shift from a single-neuron, multiple-trial framework to multiple-NEuron, single-trial methodologies.
Abstract: To a large extent, progress in neuroscience has been driven by the study of single-cell responses averaged over several repetitions of stimuli or behaviours. However,the brain typically makes decisions based on single events by evaluating the activity of large neuronal populations. Therefore, to further understand how the brain processes information, it is important to shift from a single-neuron, multiple-trial framework to multiple-neuron, single-trial methodologies. Two related approaches--decoding and information theory--can be used to extract single-trial information from the activity of neuronal populations. Such population analysis can give us more information about how neurons encode stimulus features than traditional single-cell studies.
TL;DR: Multiple strategies including retinal tiling, hierarchical and parallel processing and modularity, defined spatially and by cell type-specific connectivity, are used by the visual system to recover the intricate detail of the authors' visual surroundings.
Abstract: Incoming sensory information is sent to the brain along modality-specific channels corresponding to the five senses. Each of these channels further parses the incoming signals into parallel streams to provide a compact, efficient input to the brain. Ultimately, these parallel input signals must be elaborated on and integrated in the cortex to provide a unified and coherent percept. Recent studies in the primate visual cortex have greatly contributed to our understanding of how this goal is accomplished. Multiple strategies including retinal tiling, hierarchical and parallel processing and modularity, defined spatially and by cell type-specific connectivity, are used by the visual system to recover the intricate detail of our visual surroundings.