Showing papers in "Nature Reviews Neuroscience in 2000"
TL;DR: This article focuses on the neuronal changes that occur in response to complex stimulation by an enriched environment and emphasizes the behavioural and neurobiological consequences of specific elements of enrichment, especially exercise and learning.
Abstract: Neuronal plasticity is a central theme of modern neurobiology, from cellular and molecular mechanisms of synapse formation in Drosophila to behavioural recovery from strokes in elderly humans. Although the methods used to measure plastic responses differ, the stimuli required to elicit plasticity are thought to be activity-dependent. In this article, we focus on the neuronal changes that occur in response to complex stimulation by an enriched environment. We emphasize the behavioural and neurobiological consequences of specific elements of enrichment, especially exercise and learning.
2,281 citations
TL;DR: Studies indicate that the prefrontal cortex is central in this process, providing an infrastructure for synthesizing a diverse range of information that lays the foundation for the complex forms of behaviour observed in primates.
Abstract: One of the enduring mysteries of brain function concerns the process of cognitive control. How does complex and seemingly willful behaviour emerge from interactions between millions of neurons? This has long been suspected to depend on the prefrontal cortex--the neocortex at the anterior end of the brain--but now we are beginning to uncover its neural basis. Nearly all intended behaviour is learned and so depends on a cognitive system that can acquire and implement the 'rules of the game' needed to achieve a given goal in a given situation. Studies indicate that the prefrontal cortex is central in this process. It provides an infrastructure for synthesizing a diverse range of information that lays the foundation for the complex forms of behaviour observed in primates.
1,786 citations
TL;DR: How the cognitive and neural coding mechanisms that underlie declarative memory work together to create and re-create fully networked representations of previous experiences and knowledge about the world are described.
Abstract: Recent neurobiological studies have begun to reveal the cognitive and neural coding mechanisms that underlie declarative memory--our ability to recollect everyday events and factual knowledge. These studies indicate that the critical circuitry involves bidirectional connections between the neocortex, the parahippocampal region and the hippocampus. Each of these areas makes a unique contribution to memory processing. Widespread high-order neocortical areas provide dedicated processors for perceptual, motor or cognitive information that is influenced by other components of the system. The parahippocampal region mediates convergence of this information and extends the persistence of neocortical memory representations. The hippocampus encodes the sequences of places and events that compose episodic memories, and links them together through their common elements. Here I describe how these mechanisms work together to create and re-create fully networked representations of previous experiences and knowledge about the world.
1,466 citations
TL;DR: Recent neurophysiological studies in primates that have revealed that neurons in a limited number of brain structures carry specific signals about past and future rewards provide the first step towards an understanding of how rewards influence behaviour before they are received.
Abstract: The fundamental biological importance of rewards has created an increasing interest in the neuronal processing of reward information. The suggestion that the mechanisms underlying drug addiction might involve natural reward systems has also stimulated interest. This article focuses on recent neurophysiological studies in primates that have revealed that neurons in a limited number of brain structures carry specific signals about past and future rewards. This research provides the first step towards an understanding of how rewards influence behaviour before they are received and how the brain might use reward information to control learning and goal-directed behaviour.
1,282 citations
TL;DR: The Rho family of small GTPases act as intracellular molecular switches that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus, underscoring their importance in the development and function of the nervous system.
Abstract: The Rho family of small GTPases act as intracellular molecular switches that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. Recent evidence implicates Rho GTPases in the regulation of neuronal morphogenesis, including migration, polarity, axon growth and guidance, dendrite elaboration and plasticity, and synapse formation. Signalling pathways from membrane receptors to Rho GTPases and from Rho GTPases to the actin cytoskeleton are beginning to be discovered. Mutations in these signalling pathways have been reported in human neurological diseases, which underscores their importance in the development and function of the nervous system.
1,000 citations
TL;DR: In this article, mutations in four out of five KCNQ genes underlie diseases including cardiac arrhythmias, deafness and epilepsy, and provide a model for the study of the "safety margin" that separates normal from pathological levels of channel expression.
Abstract: Humans have over 70 potassium channel genes, but only some of these have been linked to disease. In this respect, the KCNQ family of potassium channels is exceptional: mutations in four out of five KCNQ genes underlie diseases including cardiac arrhythmias, deafness and epilepsy. These disorders illustrate the different physiological functions of KCNQ channels, and provide a model for the study of the 'safety margin' that separates normal from pathological levels of channel expression. In addition, several KCNQ isoforms can associate to form heteromeric channels that underlie the M-current, an important regulator of neuronal excitability.
798 citations
TL;DR: This perspective examines the origins of this dogma, its perseverance in the face of contradictory evidence, and its final collapse as a central assumption in the field of neuroscience.
Abstract: For over 100 years a central assumption in the field of neuroscience has been that new neurons are not added to the adult mammalian brain. This perspective examines the origins of this dogma, its perseverance in the face of contradictory evidence, and its final collapse. The acceptance of adult neurogenesis may be part of a contemporary paradigm shift in our view of the plasticity and stability of the adult brain.
778 citations
TL;DR: The most important (and least understood) considerations regarding the use of transcranial magnetic stimulation for cognitive neuroscience are discussed and advances in theUse of this technique for the replication and extension of findings from neuropsychology are outlined.
Abstract: Transcranial magnetic stimulation has been used to investigate almost all areas of cognitive neuroscience. This article discusses the most important (and least understood) considerations regarding the use of transcranial magnetic stimulation for cognitive neuroscience and outlines advances in the use of this technique for the replication and extension of findings from neuropsychology. We also take a more speculative look forward to the emerging development of strategies for combining transcranial magnetic stimulation with other brain imaging technologies and methods in the cognitive neurosciences.
777 citations
TL;DR: This review discusses how passive and active dendritic properties, and the functional characteristics of the synapse, shape these three elements of synaptic integration.
Abstract: A fundamental function of nerve cells is the transformation of incoming synaptic information into specific patterns of action potential output. An important component of this transformation is synaptic integration--the combination of voltage deflections produced by a myriad of synaptic inputs into a singular change in membrane potential. There are three basic elements involved in integration: the amplitude of the unitary postsynaptic potential; the manner in which non-simultaneous unitary events add in time (temporal summation), and the addition of unitary events occurring simultaneously in separate regions of the dendritic arbor (spatial summation). This review discusses how passive and active dendritic properties, and the functional characteristics of the synapse, shape these three elements of synaptic integration.
668 citations
TL;DR: The standard use of population codes for encoding and decoding information is reviewed, and how population codes can be used to support neural computations such as noise removal and nonlinear mapping is considered.
Abstract: Information is encoded in the brain by populations or clusters of cells, rather than by single cells. This encoding strategy is known as population coding. Here we review the standard use of population codes for encoding and decoding information, and consider how population codes can be used to support neural computations such as noise removal and nonlinear mapping. More radical ideas about how population codes may directly represent information about stimulus uncertainty are also discussed.
641 citations
TL;DR: It is shown that functional neuroimaging is revealing much more than where attention happens in the brain; it is beginning to answer some of the oldest and deepest questions about what visual attention is and how it works.
Abstract: We are not passive recipients of the information that impinges on our retinae, but active participants in our own perceptual processes. Visual experience depends critically on attention. We select particular aspects of a visual scene for detailed analysis and control of subsequent behaviour, but ignore other aspects so completely that moments after they disappear from view we cannot report anything about them. Here we show that functional neuroimaging is revealing much more than where attention happens in the brain; it is beginning to answer some of the oldest and deepest questions about what visual attention is and how it works.
TL;DR: It is argued that consolidation is not a one-time event, but instead is reiterated with subsequent activation of the memories, opening up a new dimension in the study of memory consolidation.
Abstract: 'Consolidation' has been used to describe distinct but related processes. In considering the implications of our recent findings on the lability of reactivated fear memories, we view consolidation and reconsolidation in terms of molecular events taking place within neurons as opposed to interactions between brain regions. Our findings open up a new dimension in the study of memory consolidation. We argue that consolidation is not a one-time event, but instead is reiterated with subsequent activation of the memories.
TL;DR: A review of advances with a special focus on accessory factors and highlights new aspects of clathrin-mediated endocytosis revealed by the study of these factors.
Abstract: Clathrin-mediated endocytosis is a special form of vesicle budding important for the internalization of receptors and extracellular ligands, for the recycling of plasma membrane components, and for the retrieval of surface proteins destined for degradation. In nerve terminals, clathrin-mediated endocytosis is crucial for synaptic vesicle recycling. Recent structural studies have provided molecular details of coat assembly. In addition, biochemical and genetic studies have identified numerous accessory proteins that assist the clathrin coat in its function at synapses and in other systems. This review summarizes these advances with a special focus on accessory factors and highlights new aspects of clathrin-mediated endocytosis revealed by the study of these factors.
TL;DR: This review focuses on the molecular organization of excitatory synapses and the processes involved in the dynamic regulation of glutamate receptors.
Abstract: Dynamic regulation of synaptic efficacy is one of the mechanisms thought to underlie learning and memory. Many of the observed changes in efficacy, such as long-term potentiation and long-term depression, result from the functional alteration of excitatory neurotransmission mediated by postsynaptic glutamate receptors. These changes may result from the modulation of the receptors themselves and from regulation of protein networks associated with glutamate receptors. Understanding the interactions in this synaptic complex will yield invaluable insight into the molecular basis of synaptic function. This review focuses on the molecular organization of excitatory synapses and the processes involved in the dynamic regulation of glutamate receptors.
TL;DR: The dominantly inherited neurodegenerative disorders, where eight unrelated diseases have been revealed to possess the same type of mutation — an expanded polyglutamine encoding sequence — affecting different genes, are revealed.
Abstract: Two decades ago, molecular genetic analysis provided a new approach for defining the roots of inherited disorders This strategy has proved particularly powerful because, with only a description of the inheritance pattern, it can uncover previously unsuspected mechanisms of pathogenesis that are not implicated by known biological pathways or by the disease manifestations Nowhere has the impact of molecular genetics been more evident than in the dominantly inherited neurodegenerative disorders, where eight unrelated diseases have been revealed to possess the same type of mutation--an expanded polyglutamine encoding sequence--affecting different genes
TL;DR: It is suggested that Hebbian mechanisms are used primarily for learning and for short-term memory but often cannot, by themselves, recruit the events required to maintain a long-termMemory, while heterosynaptic plasticity commonly recruits long- term memory mechanisms that lead to transcription and to synaptic growth.
Abstract: In 1894, Ramon y Cajal first proposed that memory is stored as an anatomical change in the strength of neuronal connections. For the following 60 years, little evidence was recruited in support of this idea. This situation changed in the middle of the twentieth century with the development of cellular techniques for the study of synaptic connections and the emergence of new formulations of synaptic plasticity that redefined Ramon y Cajal's idea, making it more suitable for testing. These formulations defined two categories of plasticity, referred to as homosynaptic or Hebbian activity-dependent, and heterosynaptic or modulatory input-dependent. Here we suggest that Hebbian mechanisms are used primarily for learning and for short-term memory but often cannot, by themselves, recruit the events required to maintain a long-term memory. In contrast, heterosynaptic plasticity commonly recruits long-term memory mechanisms that lead to transcription and to synpatic growth. When jointly recruited, homosynaptic mechanisms assure that learning is effectively established and heterosynaptic mechanisms ensure that memory is maintained.
TL;DR: This work has shown that plasticity of Hox gene expression has been observed in the hindbrain and cranial neural crest of chick, mouse and zebrafish embryos, and that craniofacial development is not dependent on neural crest pre-patterning, but is regulated by a more complex integration of cell and tissue interactions.
Abstract: Understanding the patterning mechanisms that control head development--particularly the neural crest and its contribution to bones, nerves and connective tissue--is an important problem, as craniofacial anomalies account for one-third of all human congenital defects. Classical models for craniofacial patterning argue that the morphogenic program and Hox gene identity of the neural crest is pre-patterned, carrying positional information acquired in the hindbrain to the peripheral nervous system and the branchial arches. Recently, however, plasticity of Hox gene expression has been observed in the hindbrain and cranial neural crest of chick, mouse and zebrafish embryos. Hence, craniofacial development is not dependent on neural crest prepatterning, but is regulated by a more complex integration of cell and tissue interactions.
TL;DR: Some of the processes that contribute to song learning and production are reviewed, with an emphasis on the role of auditory feedback and some of the possible neural substrates involved in these processes, particularly basal ganglia circuitry.
Abstract: Songbirds are one of the best-studied examples of vocal learners. Learning of both human speech and birdsong depends on hearing. Once learned, adult song in many species remains unchanging, suggesting a reduced influence of sensory experience. Recent studies have revealed, however, that adult song is not always stable, extending our understanding of the mechanisms involved in song maintenance, and their similarity to those active during song learning. Here we review some of the processes that contribute to song learning and production, with an emphasis on the role of auditory feedback. We then consider some of the possible neural substrates involved in these processes, particularly basal ganglia circuitry. Although a thorough treatment of human speech is beyond the scope of this article, we point out similarities between speech and song learning, and ways in which studies of these disparate behaviours complement each other in developing an understanding of general principles that contribute to learning and maintenance of vocal behaviour.
TL;DR: Evidence is presented that the spinal motor system is an active participant in several aspects of the production of movement, contributing to functions normally ascribed to `higher' brain regions.
Abstract: The production and control of complex motor functions are usually attributed to central brain structures such as cortex, basal ganglia and cerebellum. In traditional schemes the spinal cord is assigned a subservient function during the production of movement, playing a predominantly passive role by relaying the commands dictated to it by supraspinal systems. This review challenges this idea by presenting evidence that the spinal motor system is an active participant in several aspects of the production of movement, contributing to functions normally ascribed to ‘higher’ brain regions.
TL;DR: Mounting evidence indicates that apolipoprotein E receptors, which are abundantly expressed in most neurons in the central nervous system, also fulfil critical functions during brain development and may profoundly influence the pathogenesis of Alzheimer's disease.
Abstract: Alzheimer's disease is a debilitating neurodegenerative disorder that afflicts an increasing part of our ageing population. An isoform of apolipoprotein E, a protein that mediates the transport of lipids and cholesterol in the circulatory system, predisposes carriers of this allele to the common late-onset form of the disease. How this protein is related to a neurodegenerative disorder is an enigma. Mounting evidence indicates that apolipoprotein E receptors, which are abundantly expressed in most neurons in the central nervous system, also fulfill critical functions during brain development and may profoundly influence the pathogenesis of Alzheimer's disease.
TL;DR: In this article, the authors raise the issue that in addition to aversive, amygdala-dependent memories, other forms of memory are susceptible to the same effect, and review evidence indicating that neuromodulation may have a significant influence on the reconsolidation process.
Abstract: Retrieval of fear conditioning turns memory into a labile state sensitive to disruption. Here, I raise the issue that in addition to aversive, amygdala-dependent memories, other forms of memory are susceptible to the same effect, and I review evidence indicating that neuromodulation may have a significant influence on the reconsolidation process.
TL;DR: Functional imaging studies reveal that attention can also modulate activity in sensory brain areas before stimulus onset, when the observer prepares to attend to an anticipated stimulus.
Abstract: Psychophysical and physiological studies have shown that attending to a stimulus can enhance its sensory processing. Functional imaging studies now reveal that attention can also modulate activity in sensory brain areas before stimulus onset, when the observer prepares to attend to an anticipated stimulus. These preparatory `baseline shifts' in brain activity pose many new questions, and potentially offer new insights into the neural basis of perceptual awareness.
TL;DR: The authors explored the possible relationship between the idea that retrieval creates a new memory trace, increasing the resistance of older memories to disruption, and the possibility of disrupting a stable memory after retrieval challenge some of our widely accepted views on memory consolidation.
Abstract: Recent findings on the possibility of disrupting a stable memory after retrieval challenge some of our widely accepted views on memory consolidation. This article comments on the implications of these and earlier findings to our understanding of consolidation, and explores their possible relationship to the idea that retrieval creates a new memory trace, increasing the resistance of older memories to disruption.
TL;DR: However, as discussed in this paper, other behavioural observations indicate that even this modification to consolidation theory may be insufficient to describe the dynamic properties of memory, which may explain the need to reconsolidate a memory after reactivating it.
Abstract: The observation that retrieval returns a stable memory into a labile state cannot be readily explained by any simple version of consolidation theory. This finding has been interpreted as evidence for the need to reconsolidate a memory after reactivating it. However, as we discuss in this commentary, other behavioural observations indicate that even this modification to consolidation theory may be insufficient to describe the dynamic properties of memory.
TL;DR: Recent evidence for the conservation of a double-loop, autoregulatory feedback mechanism across the best understood eukaryotic circadian systems is described and how these findings may illuminate some long-standing puzzles concerning the authors' subliminal sense of circadian time is discussed.
Abstract: The spectacularly successful race over the past three years to place our understanding of the circadian clockwork of mammals into a molecular framework is beginning to yield the cardinal example of the molecular-genetic control of behaviour. This perspective describes recent evidence for the conservation of a double-loop, autoregulatory feedback mechanism across the best understood eukaryotic circadian systems, and discusses how these findings may illuminate some long-standing puzzles concerning our subliminal sense of circadian time.
TL;DR: The basic characterization of the optomotor reflex provided by this work should increase the usefulness of this task for the behavioural screening of mutant fish, and would seem to indicate the delayed arrival of the Age of Aquarius.
Abstract: Drosophila or the mouse for neurogenetic studies, but the zebrafish is quickly becoming a prime tool in our quest for the relationship between genes and brain function. Several screens have already identified genes essential for the development of this vertebrate, and the promise that the whole sequence of the zebrafish genome will be completed in about two years guarantees that this creature will be the subject of an even more extensive genetic analysis. In preparation for the bonanza to come, two recent papers explore two experimental angles — one genetic and one psychophysical — which illustrate the wide spectrum of opportunities that the study of the zebrafish can offer us. First, Nasevicius and Ekker tested the possibility of knocking down zebrafish genes by injecting modified oligonucleotides known as morpholinos. Morpholinos act by blocking the initiation of translation, which reduces the non-specific effects observed with conventional antisense oligonucleotides. The authors injected diverse morpholinos into the yolk of embryos as young as the one-cell stage and found that the oligonucleotides reduced the expression of targeted proteins effectively. More importantly, morpholino injections phenocopied previously described mutations in some of the target genes and, in other cases, led to the appearance of new phenotypes, which could help to determine the role of genes of unknown function. Although this technology still has some limitations, the use of morpholino oligonucleotides can become a faster, efficient alternative to the production of knockout animals and it could allow the use of classic reverse-genetic approaches in the zebrafish. Most of the genetic screens done in the zebrafish so far have focused on mutations that affect embryonic development. However, the behavioural repertoire of this species could also be exploited if we develop the appropriate tools. By studying the optomotor behaviour of larval zebrafish, Orger et al. have provided us with a good lead to tackle the problem. When a grating is moved under normal fish, they will swim in the direction of the perceived motion (see movies of the stimuli online). The authors asked what features of movement perceived by the fish are responsible of eliciting the swimming behaviour. They found that both first-order, luminance-modulated features and second-order, contrast-modulated motion were equally capable of triggering optomotor responses, a surprising finding considering that only mammals have been thought to detect second-order motion. In addition to challenging the idea that cortical processing is required for the detection of second-order motion, the basic characterization of the optomotor reflex provided by this work should increase the usefulness of this task for the behavioural screening of mutant fish. The Orger et al. study, together with the findings of Nasevicius and Ekker would seem to indicate the delayed arrival of the Age of Aquarius. Juan Carlos López
TL;DR: A recent flurry of reports in the UK media focused on a paper in Nature Neuroscience on the addictive properties of the psychoactive component of marijuana as discussed by the authors, which concerned a report by Steven Goldberg that self-administration behaviour is maintained by delta-9-tetrahydrocannabinol (THC) in squirrel monkeys.
Abstract: A recent flurry of reports in the UK media focused on a paper in Nature Neuroscience on the addictive properties of the psychoactive component of marijuana. They concerned a report by Steven Goldberg that self-administration behaviour is maintained by delta-9-tetrahydrocannabinol (THC) in squirrel monkeys. Previous studies that have tried to establish reliable selfadministration behaviour in animals with THC have been unsuccessful, indicating that marijuana might have less potential for abuse than other drugs such as heroin and cocaine. The press interest was stimulated by the likely impact of these findings on the polarized debate in the UK media regarding the issue of whether to decriminalize marijuana. So how did the media present the story?