Showing papers in "Annual Review of Neuroscience in 2005"
TL;DR: In this article, the locus coeruleus-norepinephrine (LC-NE) system plays a more complex and specific role in the control of behavior than investigators previously thought.
Abstract: Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a new theory of LC-NE function. LC neurons exhibit two modes of activity, phasic and tonic. Phasic LC activation is driven by the outcome of task-related decision processes and is proposed to facilitate ensuing behaviors and to help optimize task performance (exploitation). When utility in the task wanes, LC neurons exhibit a tonic activity mode, associated with disengagement from the current task and a search for alternative behaviors (exploration). Monkey LC receives prominent, direct inputs from the anterior cingulate (ACC) and orbitofrontal cortices (OFC), both of which are thought to monitor task-related utility. We propose that these frontal areas produce the above patterns of LC activity to optimize utility on both short and long timescales.
3,441 citations
TL;DR: Advances in the understanding of adult neurogenesis will not only shed light on the basic principles of adult plasticity, but also may lead to strategies for cell replacement therapy after injury or degenerative neurological diseases.
Abstract: Forty years since the initial discovery of neurogenesis in the postnatal rat hippocampus, investigators have now firmly established that active neurogenesis from neural progenitors continues throughout life in discrete regions of the central nervous systems (CNS) of all mammals, including humans. Significant progress has been made over the past few years in understanding the developmental process and regulation of adult neurogenesis, including proliferation, fate specification, neuronal maturation, targeting, and synaptic integration of the newborn neurons. The function of this evolutionarily conserved phenomenon, however, remains elusive in mammals. Adult neurogenesis represents a striking example of structural plasticity in the mature CNS environment. Advances in our understanding of adult neurogenesis will not only shed light on the basic principles of adult plasticity, but also may lead to strategies for cell replacement therapy after injury or degenerative neurological diseases.
1,817 citations
TL;DR: The challenge the authors face is to learn enough about the mechanisms of plasticity to modulate them to achieve the best behavioral outcome for a given subject.
Abstract: Plasticity is an intrinsic property of the human brain and represents evolution’s invention to enable the nervous system to escape the restrictions of its own genome and thus adapt to environmental pressures, physiologic changes, and experiences. Dynamic shifts in the strength of preexisting connections across distributed neural networks, changes in task-related cortico-cortical and corticosubcortical coherence and modifications of the mapping between behavior and neural activity take place in response to changes in afferent input or efferent demand. Such rapid, ongoing changes may be followed by the establishment of new connections through dendritic growth and arborization. However, they harbor the danger that the evolving pattern of neural activation may in itself lead to abnormal behavior. Plasticity is the mechanism for development and learning, as much as a cause of pathology. The challenge we face is to learn enough about the mechanisms of plasticity to modulate them to achieve the best behavioral outcome for a given subject.
1,556 citations
TL;DR: A synthetic overview of the rich literature on MT is attempted with the goal of answering the question, What does MT do?
Abstract: The small visual area known as MT or V5 has played a major role in our understanding of the primate cerebral cortex. This area has been historically important in the concept of cortical processing streams and the idea that different visual areas constitute highly specialized representations of visual information. MT has also proven to be a fertile culture dish--full of direction- and disparity-selective neurons--exploited by many labs to study the neural circuits underlying computations of motion and depth and to examine the relationship between neural activity and perception. Here we attempt a synthetic overview of the rich literature on MT with the goal of answering the question, What does MT do?
944 citations
TL;DR: Examples of exuberant axonal projections and synaptic connections and potential cellular and molecular mechanisms that underlie axon retraction and degeneration are reviewed and how they might relate to each other in development and disease are considered.
Abstract: The selective elimination of axons, dendrites, axon and dendrite branches, and synapses, without loss of the parent neurons, occurs during normal development of the nervous system as well as in response to injury or disease in the adult. The widespread developmental phenomena of exuberant axonal projections and synaptic connections require both small-scale and large-scale axon pruning to generate precise adult connectivity, and they provide a mechanism for neural plasticity in the developing and adult nervous system, as well as a mechanism to evolve differences between species in a projection system. Such pruning is also required to remove axonal connections damaged in the adult, to stabilize the affected neural circuits, and to initiate their repair. Pruning occurs through either retraction or degeneration. Here we review examples of these phenomena and consider potential cellular and molecular mechanisms that underlie axon retraction and degeneration and how they might relate to each other in development and disease.
815 citations
TL;DR: The Olfactory nervous system of insects and mammals exhibits many similarities, which suggests that the mechanisms for olfactory learning may be shared, and the genes identified to participate in Drosophila olfaction learning have conserved roles in mammalian organisms.
Abstract: The olfactory nervous system of insects and mammals exhibits many similarities, which suggests that the mechanisms for olfactory learning may be shared. Molecular genetic investigations of Drosophila learning have uncovered numerous genes whose gene products are essential for olfactory memory formation. Recent studies of the products of these genes have continued to expand the range of molecular processes known to underlie memory formation. Recent research has also broadened the neuroanatomical areas thought to mediate olfactory learning to include the antennal lobes in addition to a previously accepted and central role for the mushroom bodies. The roles for neurons extrinsic to the mushroom body neurons are becoming better defined. Finally, the genes identified to participate in Drosophila olfactory learning have conserved roles in mammalian organisms, highlighting the value of Drosophila for gene discovery.
538 citations
TL;DR: This work reviews network models of internally generated activity, focusing on three types of network dynamics: sustained responses to transient stimuli, which provide a model of working memory; oscillatory network activity; and chaotic activity, which models complex patterns of background spiking in cortical and other circuits.
Abstract: Neural network modeling is often concerned with stimulus-driven responses, but most of the activity in the brain is internally generated. Here, we review network models of internally generated activity, focusing on three types of network dynamics: (a) sustained responses to transient stimuli, which provide a model of working memory; (b) oscillatory network activity; and (c) chaotic activity, which models complex patterns of background spiking in cortical and other circuits. We also review propagation of stimulus-driven activity through spontaneously active networks. Exploring these aspects of neural network dynamics is critical for understanding how neural circuits produce cognitive function.
513 citations
TL;DR: The formation of synapses in the vertebrate central nervous system is a complex process that occurs over a protracted period of development, demonstrating the existence of multiple molecules that influence not only when and where synapses form but also synaptic specificity and stability.
Abstract: The formation of synapses in the vertebrate central nervous system is a complex process that occurs over a protracted period of development. Recent work has begun to unravel the mysteries of synaptogenesis, demonstrating the existence of multiple molecules that influence not only when and where synapses form but also synaptic specificity and stability. Some of these molecules act at a distance, steering axons to their correct receptive fields and promoting neuronal differentiation and maturation, whereas others act at the time of contact, providing positional information about the appropriateness of targets and/or inductive signals that trigger the cascade of events leading to synapse formation. In addition, correlated synaptic activity provides critical information about the appropriateness of synaptic connections, thereby influencing synapse stability and elimination. Although synapse formation and elimination are hallmarks of early development, these processes are also fundamental to learning, memory, and cognition in the mature brain.
484 citations
TL;DR: It is likely that the visual attributes of color, form, and motion are not neatly segregated by V1 into different stripe compartments in V2, but there are just two main streams, originating from cytochrome oxidase patches and interpatches, that project to V2.
Abstract: Primary and secondary visual cortex (V1 and V2) form the foundation of the cortical visual system. V1 transforms information received from the lateral geniculate nucleus (LGN) and distributes it to separate domains in V2 for transmission to higher visual areas. During the past 20 years, schemes for the functional organization of V1 and V2 have been based on a tripartite framework developed by Livingstone & Hubel (1988). Since then, new anatomical data have accumulated concerning V1's input, its internal circuitry, and its output to V2. These new data, along with physiological and imaging studies, now make it likely that the visual attributes of color, form, and motion are not neatly segregated by V1 into different stripe compartments in V2. Instead, there are just two main streams, originating from cytochrome oxidase patches and interpatches, that project to V2. Each stream is composed of a mixture of magno, parvo, and konio geniculate signals. Further studies are required to elucidate how the patches and...
448 citations
TL;DR: Delineating the physiological roles of the actin cytoskeleton in supporting synaptic transmission and synaptic plasticity paves the way for gaining molecular insights into when and how synaptic machineries couple synapse form and function.
Abstract: Synapses are highly specialized intercellular junctions that mediate the transmission of information between axons and target cells. A fundamental property of synapses is their ability to modify the efficacy of synaptic communication through various forms of synaptic plasticity. Recent developments in imaging techniques have revealed that synapses exhibit a high degree of morphological plasticity under basal conditions and also in response to neuronal activity that induces alterations in synaptic strength. The underlying molecular basis for this morphological plasticity has attracted much attention, yet its functional significance to the mechanisms of synaptic transmission and synaptic plasticity remains elusive. These morphological changes ultimately require the dynamic actin cytoskeleton, which is the major structural component of synapses. Delineating the physiological roles of the actin cytoskeleton in supporting synaptic transmission and synaptic plasticity, therefore, paves the way for gaining molecular insights into when and how synaptic machineries couple synapse form and function.
438 citations
TL;DR: The Eph family of receptor tyrosine kinases and their ligands, the ephrins, remain the only molecules that meet all criteria for graded topographic guidance molecules, although others fulfill some criteria.
Abstract: Gradients of axon guidance molecules have long been postulated to control the development of the organization of neural connections into topographic maps. We review progress in identifying molecules required for mapping and the mechanisms by which they act, focusing on the visual system, the predominant model for map development. The Eph family of receptor tyrosine kinases and their ligands, the ephrins, remain the only molecules that meet all criteria for graded topographic guidance molecules, although others fulfill some criteria. Recent reports further define their modes of action and new roles for them, including EphB/ephrin-B control of dorsal-ventral mapping, bidirectional signaling of EphAs/ephrin-As, bifunctional action of ephrins as attractants or repellents in a context-dependent manner, and complex interactions between multiple guidance molecules. In addition, spontaneous patterned neural activity has recently been shown to be required for map refinement during a brief critical period. We speculate on additional activities required for map development and suggest a synthesis of molecular and cellular mechanisms within the context of the complexities of map development.
TL;DR: This work has identified gene products required for nervous system function and elucidated the molecular and neural bases of behaviors in the nematode Caenorhabditis elegans.
Abstract: A current challenge in neuroscience is to bridge the gaps between genes, proteins, neurons, neural circuits, and behavior in a single animal model. The nematode Caenorhabditis elegans has unique features that facilitate this synthesis. Its nervous system includes exactly 302 neurons, and their pattern of synaptic connectivity is known. With only five olfactory neurons, C. elegans can dynamically respond to dozens of attractive and repellant odors. Thermosensory neurons enable the nematode to remember its cultivation temperature and to track narrow isotherms. Polymodal sensory neurons detect a wide range of nociceptive cues and signal robust escape responses. Pairing of sensory stimuli leads to long-lived changes in behavior consistent with associative learning. Worms exhibit social behaviors and complex ultradian rhythms driven by Ca2+ oscillators with clock-like properties. Genetic analysis has identified gene products required for nervous system function and elucidated the molecular and neural bases of ...
TL;DR: This empathizing-systemizing theory explains other psychological models such as impairments of executive function or central coherence, and may have a neurobiological basis in abnormally low activity of brain regions subserving social cognition, along with abnormally high activity of regions sub serving lower-level, perceptual processing--a pattern that may result from a skewed balance of local versus long-range functional connectivity.
Abstract: Although the neurobiological understanding of autism has been increasing exponentially, the diagnosis of autism spectrum conditions still rests entirely on behavioral criteria Autism is therefore most productively approached using a combination of biological and psychological theory The triad of behavioral abnormalities in social function, communication, and restricted and repetitive behaviors and interests can be explained psychologically by an impaired capacity for empathizing, or modeling the mental states governing the behavior of people, along with a superior capacity for systemizing, or inferring the rules governing the behavior of objects This empathizing-systemizing theory explains other psychological models such as impairments of executive function or central coherence, and may have a neurobiological basis in abnormally low activity of brain regions subserving social cognition, along with abnormally high activity of regions subserving lower-level, perceptual processing—a pattern that may resul
TL;DR: It is argued that these genetic links are partly mediated by brain structure that is likewise under strong genetic control, and that a measure of cognitive ability has been shown highly heritable across many studies.
Abstract: Genetic influences on brain morphology and IQ are well studied. A variety of sophisticated brain-mapping approaches relating genetic influences on brain structure and intelligence establishes a regional distribution for this relationship that is consistent with behavioral studies. We highlight those studies that illustrate the complex cortical patterns associated with measures of cognitive ability. A measure of cognitive ability, known as g, has been shown highly heritable across many studies. We argue that these genetic links are partly mediated by brain structure that is likewise under strong genetic control. Other factors, such as the environment, obviously play a role, but the predominant determinant appears to genetic.
TL;DR: The postganglionic sympathetic neuron has been an amenable model for studying peripheral nervous system formation as mentioned in this paper, and factors that control several developmental events, including multiple stages of axon extension, neuron survival and death, dendritogenesis, synaptogenesis, and establishment of functional diversity, have been identified in this neuron type.
Abstract: The precise coordination of the many events in nervous system development is absolutely critical for the correct establishment of functional circuits. The postganglionic sympathetic neuron has been an amenable model for studying peripheral nervous system formation. Factors that control several developmental events, including multiple stages of axon extension, neuron survival and death, dendritogenesis, synaptogenesis, and establishment of functional diversity, have been identified in this neuron type. This knowledge allows us to integrate the various intricate processes involved in the formation of a functional sympathetic nervous system and thereby create a paradigm for understanding neuronal development in general.
TL;DR: The combination of finely resolved optical field sensing and finely resolved Optical field actuation will open new dimensions for the analysis of the connectivity, dynamics, and plasticity of neuronal circuits, and perhaps even for replacing lost--or designing novel--functionalities.
Abstract: Proteins with engineered sensitivities to light are infiltrating the biological mechanisms by which neurons generate and detect electrochemical signals. Encoded in DNA and active only in genetically specified target cells, these proteins provide selective optical interfaces for observing and controlling signaling by defined groups of neurons in functioning circuits, in vitro and in vivo. Light-emitting sensors of neuronal activity (reporting calcium increase, neurotransmitter release, or membrane depolarization) have begun to reveal how information is represented by neuronal assemblies, and how these representations are transformed during the computations that inform behavior. Light-driven actuators control the electrical activities of central neurons in freely moving animals and establish causal connections between the activation of specific neurons and the expression of particular behaviors. Anchored within mathematical systems and control theory, the combination of finely resolved optical field sensing and finely resolved optical field actuation will open new dimensions for the analysis of the connectivity, dynamics, and plasticity of neuronal circuits, and perhaps even for replacing lost--or designing novel--functionalities.
TL;DR: Current phenotype- and genotype-driven approaches to discover novel CNS-expressed genes, as well as current approaches to carry out large-scale, gene-expression screens in the CNS are summarized.
Abstract: Over the past two decades, molecular genetic studies have enabled a common conceptual framework for the development and basic function of the nervous system. These studies, and the pioneering efforts of mouse geneticists and neuroscientists to identify and clone genes for spontaneous mouse mutants, have provided a paradigm for understanding complex processes of the vertebrate brain. Gene cloning for human brain malformations and degenerative disorders identified other important central nervous system (CNS) genes. However, because many debilitating human disorders are genetically complex, phenotypic screens are difficult to design. This difficulty has led to large-scale, genomic approaches to discover genes that are uniquely expressed in brain circuits and regions that control complex behaviors. In this review, we summarize current phenotype- and genotype-driven approaches to discover novel CNS-expressed genes, as well as current approaches to carry out large-scale, gene-expression screens in the CNS.