Recent Journal Articles: Neuroscience -- Neurotransmitter.net

Recent Articles in Annual Review of Neuroscience

Gold JI, Shadlen MN
The neural basis of decision making.
Annu Rev Neurosci. 2007;30535-74.
The study of decision making spans such varied fields as neuroscience, psychology, economics, statistics, political science, and computer science. Despite this diversity of applications, most decisions share common elements including deliberation and commitment. Here we evaluate recent progress in understanding how these basic elements of decision formation are implemented in the brain. We focus on simple decisions that can be studied in the laboratory but emphasize general principles likely to extend to other settings. [Abstract]

Schlaggar BL, McCandliss BD
Development of neural systems for reading.
Annu Rev Neurosci. 2007;30475-503.
Functional and structural neuroimaging studies of adult readers have provided a deeper understanding of the neural basis of reading, yet such findings also elicit new questions about how developing neural systems come to support this learned ability. A developmental cognitive neuroscience approach provides insights into how skilled reading emerges in the developing brain, yet also raises new methodological challenges. This review focuses on functional changes that occur during reading acquisition in cortical regions associated with both the perception of visual words and spoken language, and it examines how such functional changes differ within developmental reading disabilities. We integrate these findings within an interactive specialization framework of functional development and propose that such a framework may provide insights into how individual differences at several levels of observation (genetics, white matter tract structure, functional organization of language, cultural organization of writing systems) impact the emergence of neural systems involved in reading ability and disability. [Abstract]

Shapiro L, Love J, Colman DR
Adhesion molecules in the nervous system: structural insights into function and diversity.
Annu Rev Neurosci. 2007;30451-74.
The unparalleled complexity of intercellular connections in the nervous system presents requirements for high levels of both specificity and diversity for the proteins that mediate cell adhesion. Here we describe recent advances toward understanding the molecular mechanisms that underlie adhesive binding, specificity, and diversity for several well-characterized families of adhesion molecules in the nervous system. Although many families of adhesion proteins, including cadherins and immunoglobulin superfamily members, are utilized in neural and nonneural contexts, nervous system-specific diversification mechanisms, such as precisely regulated alternative splicing, provide an important means to enable their function in the complex context of the nervous system. [Abstract]

Schultz W
Multiple dopamine functions at different time courses.
Annu Rev Neurosci. 2007;30259-88.
Many lesion studies report an amazing variety of deficits in behavioral functions that cannot possibly be encoded in great detail by the relatively small number of midbrain dopamine neurons. Although hoping to unravel a single dopamine function underlying these phenomena, electrophysiological and neurochemical studies still give a confusing, mutually exclusive, and partly contradictory account of dopamine's role in behavior. However, the speed of observed phasic dopamine changes varies several thousand fold, which offers a means to differentiate the behavioral relationships according to their time courses. Thus dopamine is involved in mediating the reactivity of the organism to the environment at different time scales, from fast impulse responses related to reward via slower changes with uncertainty, punishment, and possibly movement to the tonic enabling of postsynaptic motor, cognitive, and motivational systems deficient in Parkinson's disease. [Abstract]

Gao Q, Horvath TL
Neurobiology of feeding and energy expenditure.
Annu Rev Neurosci. 2007;30367-98.
Significant advancements have been made in the past century regarding the neuronal control of feeding behavior and energy expenditure. The effects and mechanisms of action of various peripheral metabolic signals on the brain have become clearer. Molecular and genetic tools for visualizing and manipulating individual components of brain homeostatic systems in combination with neuroanatomical, electrophysiological, behavioral, and pharmacological techniques have begun to elucidate the molecular and neuronal mechanisms of complex feeding behavior and energy expenditure. This review highlights some of these advancements that have led to the current understanding of the brain's involvement in the acute and chronic regulation of energy homeostasis. [Abstract]

Vargas ME, Barres BA
Why is Wallerian degeneration in the CNS so slow?
Annu Rev Neurosci. 2007;30153-79.
Wallerian degeneration (WD) is the set of molecular and cellular events by which degenerating axons and myelin are cleared after injury. Why WD is rapid and robust in the PNS but slow and incomplete in the CNS is a longstanding mystery. Here we review current work on the mechanisms of WD with an emphasis on deciphering this mystery and on understanding whether slow WD in the CNS could account for the failure of CNS axons to regenerate. [Abstract]

Vosshall LB, Stocker RF
Molecular architecture of smell and taste in Drosophila.
Annu Rev Neurosci. 2007;30505-33.
The chemical senses-smell and taste-allow animals to evaluate and distinguish valuable food resources from dangerous substances in the environment. The central mechanisms by which the brain recognizes and discriminates attractive and repulsive odorants and tastants, and makes behavioral decisions accordingly, are not well understood in any organism. Recent molecular and neuroanatomical advances in Drosophila have produced a nearly complete picture of the peripheral neuroanatomy and function of smell and taste in this insect. Neurophysiological experiments have begun to provide insight into the mechanisms by which these animals process chemosensory cues. Given the considerable anatomical and functional homology in smell and taste pathways in all higher animals, experimental approaches in Drosophila will likely provide broad insights into the problem of sensory coding. Here we provide a critical review of the recent literature in this field and comment on likely future directions. [Abstract]

Banerjee S, Bhat MA
Neuron-glial interactions in blood-brain barrier formation.
Annu Rev Neurosci. 2007;30235-58.
The blood brain barrier (BBB) evolved to preserve the microenvironment of the highly excitable neuronal cells to allow for action potential generation and propagation. Intricate molecular interactions between two main cell types, the neurons and the glial cells, form the underlying basis of the critical functioning of the nervous system across species. In invertebrates, interactions between neurons and glial cells are central in establishing a functional BBB. However, in vertebrates, the BBB formation and function is coordinated by interactions between neurons, glial cells, and endothelial cells. Here we review the neuron-glial interaction-based blood barriers in invertebrates and vertebrates and provide an evolutionary perspective as to how a glial-barrier system in invertebrates evolved into an endothelial barrier system. We also summarize the clinical relevance of the BBB as this protective barrier becomes disadvantageous in the pharmacological treatment of various neurological disorders. [Abstract]

Vollrath MA, Kwan KY, Corey DP
The micromachinery of mechanotransduction in hair cells.
Annu Rev Neurosci. 2007;30339-65.
Mechanical stimuli generated by head movements and changes in sound pressure are detected by hair cells with amazing speed and sensitivity. The mechanosensitive organelle, the hair bundle, is a highly elaborated structure of actin-based stereocilia arranged in precise rows of increasing height. Extracellular linkages contribute to its cohesion and convey forces to mechanically gated channels. Channel opening is nearly instantaneous and is followed by a process of sensory adaptation that keeps the channels poised in their most sensitive range. This process is served by motors, scaffolds, and homeostatic mechanisms. The molecular constituents of this process are rapidly being elucidated, especially by the discovery of deafness genes and antibody targets. [Abstract]

McAllister AK
Dynamic aspects of CNS synapse formation.
Annu Rev Neurosci. 2007;30425-50.
The mammalian central nervous system (CNS) requires the proper formation of exquisitely precise circuits to function correctly. These neuronal circuits are assembled during development by the formation of synaptic connections between thousands of differentiating neurons. Proper synapse formation during childhood provides the substrate for cognition, whereas improper formation or function of these synapses leads to neurodevelopmental disorders, including mental retardation and autism. Recent work has begun to identify some of the early cellular events in synapse formation as well as the molecular signals that initiate this process. However, despite the wealth of information published on this topic in the past few years, some of the most fundamental questions about how, whether, and where glutamatergic synapses form in the mammalian CNS remain unanswered. This review focuses on the dynamic aspects of the early cellular and molecular events in the initial assembly of glutamatergic synapses in the mammalian CNS. [Abstract]

Eichenbaum H, Yonelinas AP, Ranganath C
The medial temporal lobe and recognition memory.
Annu Rev Neurosci. 2007;30123-52.
The ability to recognize a previously experienced stimulus is supported by two processes: recollection of the stimulus in the context of other information associated with the experience, and a sense of familiarity with the features of the stimulus. Although familiarity and recollection are functionally distinct, there is considerable debate about how these kinds of memory are supported by regions in the medial temporal lobes (MTL). Here, we review evidence for the distinction between recollection and familiarity and then consider the evidence regarding the neural mechanisms of these processes. Evidence from neuropsychological, neuroimaging, and neurophysiological studies of humans, monkeys, and rats indicates that different subregions of the MTL make distinct contributions to recollection and familiarity. The data suggest that the hippocampus is critical for recollection but not familiarity. The parahippocampal cortex also contributes to recollection, possibly via the representation and retrieval of contextual (especially spatial) information, whereas perirhinal cortex contributes to and is necessary for familiarity-based recognition. The findings are consistent with an anatomically guided hypothesis about the functional organization of the MTL and suggest mechanisms by which the anatomical components of the MTL interact to support the phenomenology of recollection and familiarity. [Abstract]

Murray EA, Bussey TJ, Saksida LM
Visual perception and memory: a new view of medial temporal lobe function in primates and rodents.
Annu Rev Neurosci. 2007;3099-122.
The prevailing view of medial temporal lobe (MTL) function has two principal elements: first, that the MTL subserves memory but not perception, and second, that the many anatomically distinctive parts of the MTL function together in the service of declarative memory. Recent neuropsychological studies have, however, challenged both opinions. First, studies in rodents, nonhuman primates, and humans suggest that the perirhinal cortex represents information about objects for both mnemonic and perceptual purposes. Second, the idea that MTL components contribute to declarative memory in similar ways has also been contradicted. Whereas the perirhinal cortex plays an essential role in familiarity-based object recognition, the hippocampus contributes little, if at all, to this function. In both primates and rodents, the hippocampus contributes to the memory and perception of places and paths, whereas the perirhinal cortex does so for objects and the contents of scenes. [Abstract]

Orr HT, Zoghbi HY
Trinucleotide repeat disorders.
Annu Rev Neurosci. 2007;30575-621.
The discovery that expansion of unstable repeats can cause a variety of neurological disorders has changed the landscape of disease-oriented research for several forms of mental retardation, Huntington disease, inherited ataxias, and muscular dystrophy. The dynamic nature of these mutations provided an explanation for the variable phenotype expressivity within a family. Beyond diagnosis and genetic counseling, the benefits from studying these disorders have been noted in both neurobiology and cell biology. Examples include insight about the role of translational control in synaptic plasticity, the role of RNA processing in the integrity of muscle and neuronal function, the importance of Fe-S-containing enzymes for cellular energy, and the dramatic effects of altering protein conformations on neuronal function and survival. It is exciting that within a span of 15 years, pathogenesis studies of this class of disorders are beginning to reveal pathways that are potential therapeutic targets. [Abstract]

Wallis JD
Orbitofrontal cortex and its contribution to decision-making.
Annu Rev Neurosci. 2007;3031-56.
Damage to orbitofrontal cortex (OFC) produces an unusual pattern of deficits. Patients have intact cognitive abilities but are impaired in making everyday decisions. Here we review anatomical, neuropsychological, and neurophysiological evidence to determine the neuronal mechanisms that might underlie these impairments. We suggest that OFC plays a key role in processing reward: It integrates multiple sources of information regarding the reward outcome to derive a value signal. In effect, OFC calculates how rewarding a reward is. This value signal can then be held in working memory where it can be used by lateral prefrontal cortex to plan and organize behavior toward obtaining the outcome, and by medial prefrontal cortex to evaluate the overall action in terms of its success and the effort that was required. Thus, acting together, these prefrontal areas can ensure that our behavior is most efficiently directed towards satisfying our needs. [Abstract]

Knudsen EI
Fundamental components of attention.
Annu Rev Neurosci. 2007;3057-78.
A mechanistic understanding of attention is necessary for the elucidation of the neurobiological basis of conscious experience. This chapter presents a framework for thinking about attention that facilitates the analysis of this cognitive process in terms of underlying neural mechanisms. Four processes are fundamental to attention: working memory, top-down sensitivity control, competitive selection, and automatic bottom-up filtering for salient stimuli. Each process makes a distinct and essential contribution to attention. Voluntary control of attention involves the first three processes (working memory, top-down sensitivity control, and competitive selection) operating in a recurrent loop. Recent results from neurobiological research on attention are discussed within this framework. [Abstract]

Parrish JZ, Emoto K, Kim MD, Jan YN
Mechanisms that regulate establishment, maintenance, and remodeling of dendritic fields.
Annu Rev Neurosci. 2007;30399-423.
Although dendrite arborization patterns are hallmarks of neuronal type and critical determinants of neuronal function, how dendritic arbors take shape is still largely unknown. Transcription factors play important roles in specifying neuronal types and have a profound influence on dendritic arbor size and complexity. The space that a dendritic arbor occupies is determined largely by a combination of growth-promoting signals that regulate arbor size, chemotropic cues that steer dendrites into the appropriate space, and neurite-neurite contacts that ensure proper representation of the dendritic field and appropriate synaptic contacts. Dendritic arbors are largely maintained over the neuron's lifetime, but in some cases, dendritic arbors are refined, in large part as a result of neuronal activity. In this review, we summarize our current understanding of the cellular and molecular mechanisms that regulate dendritic field formation and influence the shaping of dendritic arbors. [Abstract]

Fields HL, Hjelmstad GO, Margolis EB, Nicola SM
Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement.
Annu Rev Neurosci. 2007;30289-316.
Ventral tegmental area (VTA) neuron firing precedes behaviors elicited by reward-predictive sensory cues and scales with the magnitude and unpredictability of received rewards. These patterns are consistent with roles in the performance of learned appetitive behaviors and in positive reinforcement, respectively. The VTA includes subpopulations of neurons with different afferent connections, neurotransmitter content, and projection targets. Because the VTA and substantia nigra pars compacta are the sole sources of striatal and limbic forebrain dopamine, measurements of dopamine release and manipulations of dopamine function have provided critical evidence supporting a VTA contribution to these functions. However, the VTA also sends GABAergic and glutamatergic projections to the nucleus accumbens and prefrontal cortex. Furthermore, VTA-mediated but dopamine-independent positive reinforcement has been demonstrated. Consequently, identifying the neurotransmitter content and projection target of VTA neurons recorded in vivo will be critical for determining their contribution to learned appetitive behaviors. [Abstract]

Madsen E, Gitlin JD
Copper and iron disorders of the brain.
Annu Rev Neurosci. 2007;30317-37.
Copper and iron are transition elements essential for life. These metals are required to maintain the brain's biochemistry such that deficiency or excess of either copper or iron results in central nervous system disease. This review focuses on the inherited disorders in humans that directly affect copper or iron homeostasis in the brain. Elucidation of the molecular genetic basis of these rare disorders has provided insight into the mechanisms of copper and iron acquisition, trafficking, storage, and excretion in the brain. This knowledge permits a greater understanding of copper and iron roles in neurobiology and neurologic disease and may allow for the development of therapeutic approaches where aberrant metal homeostasis is implicated in disease pathogenesis. [Abstract]

Chen ZL, Yu WM, Strickland S
Peripheral regeneration.
Annu Rev Neurosci. 2007;30209-33.
Whereas the central nervous system (CNS) usually cannot regenerate, peripheral nerves regenerate spontaneously after injury because of a permissive environment and activation of the intrinsic growth capacity of neurons. Functional regeneration requires axon regrowth and remyelination of the regenerated axons by Schwann cells. Multiple factors including neurotrophic factors, extracellular matrix (ECM) proteins, and hormones participate in Schwann cell dedifferentiation, proliferation, and remyelination. We describe the current understanding of peripheral axon regeneration and focus on the molecules and potential mechanisms involved in remyelination. [Abstract]

Taube JS
The head direction signal: origins and sensory-motor integration.
Annu Rev Neurosci. 2007;30181-207.
Navigation first requires accurate perception of one's spatial orientation within the environment, which consists of knowledge about location and directional heading. Cells within several limbic system areas of the mammalian brain discharge allocentrically as a function of the animal's directional heading, independent of the animal's location and ongoing behavior. These cells are referred to as head direction (HD) cells and are believed to encode the animal's perceived directional heading with respect to its environment. Although HD cells are found in several areas, the principal circuit for generating this signal originates in the dorsal tegmental nucleus and projects serially, with some reciprocal connections, to the lateral mammillary nucleus --> anterodorsal thalamus --> PoS, and terminates in the entorhinal cortex. HD cells receive multimodal information about landmarks and self-generated movements. Vestibular information appears critical for generating the directional signal, but motor/proprioceptive and landmark information are important for updating it. [Abstract]

Field GD, Chichilnisky EJ
Information processing in the primate retina: circuitry and coding.
Annu Rev Neurosci. 2007;301-30.
The function of any neural circuit is governed by connectivity of neurons in the circuit and the computations performed by the neurons. Recent research on retinal function has substantially advanced understanding in both areas. First, visual information is transmitted to the brain by at least 17 distinct retinal ganglion cell types defined by characteristic morphology, light response properties, and central projections. These findings provide a much more accurate view of the parallel visual pathways emanating from the retina than do previous models, and they highlight the importance of identifying distinct cell types and their connectivity in other neural circuits. Second, encoding of visual information involves significant temporal structure and interactions in the spike trains of retinal neurons. The functional importance of this structure is revealed by computational analysis of encoding and decoding, an approach that may be applicable to understanding the function of other neural circuits. [Abstract]

Alvarez VA, Sabatini BL
Anatomical and physiological plasticity of dendritic spines.
Annu Rev Neurosci. 2007;3079-97.
In excitatory neurons, most glutamatergic synapses are made on the heads of dendritic spines, each of which houses the postsynaptic terminal of a single glutamatergic synapse. We review recent studies demonstrating in vivo that spines are motile and plastic structures whose morphology and lifespan are influenced, even in adult animals, by changes in sensory input. However, most spines that appear in adult animals are transient, and the addition of stable spines and synapses is rare. In vitro studies have shown that patterns of neuronal activity known to induce synaptic plasticity can also trigger changes in spine morphology. Therefore, it is tempting to speculate that the plastic changes of spine morphology reflect the dynamic state of its associated synapse and are responsible to some extent for neuronal circuitry remodeling. Nevertheless, morphological changes are not required for all forms of synaptic plasticity, and whether changes in the spine shape and size significantly impact synaptic signals is unclear. [Abstract]

Hyman SE, Malenka RC, Nestler EJ
Neural mechanisms of addiction: the role of reward-related learning and memory.
Annu Rev Neurosci. 2006;29565-98.
Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons. Here we review progress in identifying candidate mechanisms of addiction. [Abstract]

Dellovade T, Romer JT, Curran T, Rubin LL
The hedgehog pathway and neurological disorders.
Annu Rev Neurosci. 2006;29539-63.
The hedgehog pathway is a major regulator of embryonic development, and mutations that decrease its activity are known to be associated with severe defects in nervous system development. Recent evidence suggests hedgehog continues to function in adult tissue, normal as well as diseased, by regulating both cell proliferation and the production of growth and angiogenic factors. In the adult nervous system, this dual ability is especially important in regulating the behavior of neural stem and progenitor cells. This review summarizes information connecting hedgehog signaling and neural diseases, including neurodegenerative disorders and brain tumors, particularly medulloblastoma. We also describe the discovery and utility of small molecule agonists and antagonists of this pathway and their potential as novel types of therapeutics. [Abstract]

Pezet S, McMahon SB
Neurotrophins: mediators and modulators of pain.
Annu Rev Neurosci. 2006;29507-38.
The neurotrophin family of neurotrophic factors are well-known for their effects on neuronal survival and growth. Over the past decade, considerable evidence has accumulated from both humans and animals that one neurotrophin, nerve growth factor (NGF), is a peripheral pain mediator, particularly in inflammatory pain states. NGF is upregulated in a wide variety of inflammatory conditions, and NGF-neutralizing molecules are effective analgesic agents in many models of persistent pain. Such molecules are now being evaluated in clinical trials. NGF regulates the expression of a second neurotrophin, brain-derived neurotrophic factor (BDNF), in nociceptors. BDNF is released when nociceptors are activated, and it acts as a central modulator of pain. The chapter reviews the evidence for these roles (and briefly the effects of other neurotrophins), the range of conditions under which they act, and their mechanism of action. [Abstract]

Wu MC, David SV, Gallant JL
Complete functional characterization of sensory neurons by system identification.
Annu Rev Neurosci. 2006;29477-505.
System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm provides an objective method for evaluating and comparing computational models. In this chapter we review many of the system identification algorithms that have been used in sensory neurophysiology, and we show how they can be viewed as variants of a single statistical inference problem. We then review many of the practical issues that arise when applying these methods to neurophysiological experiments: stimulus selection, behavioral control, model visualization, and validation. Finally we discuss several problems to which system identification has been applied recently, including one important long-term goal of sensory neuroscience: developing models of sensory systems that accurately predict neuronal responses under completely natural conditions. [Abstract]

Raichle ME, Mintun MA
Brain work and brain imaging.
Annu Rev Neurosci. 2006;29449-76.
Functional brain imaging with positron emission tomography and magnetic resonance imaging has been used extensively to map regional changes in brain activity. The signal used by both techniques is based on changes in local circulation and metabolism (brain work). Our understanding of the cell biology of these changes has progressed greatly in the past decade. New insights have emerged on the role of astrocytes in signal transduction as has an appreciation of the unique contribution of aerobic glycolysis to brain energy metabolism. Likewise our understanding of the neurophysiologic processes responsible for imaging signals has progressed from an assumption that spiking activity (output) of neurons is most relevant to one focused on their input. Finally, neuroimaging, with its unique metabolic perspective, has alerted us to the ongoing and costly intrinsic activity within brain systems that most likely represents the largest fraction of the brain's functional activity. [Abstract]

Montague PR, King-Casas B, Cohen JD
Imaging valuation models in human choice.
Annu Rev Neurosci. 2006;29417-48.
To make a decision, a system must assign value to each of its available choices. In the human brain, one approach to studying valuation has used rewarding stimuli to map out brain responses by varying the dimension or importance of the rewards. However, theoretical models have taught us that value computations are complex, and so reward probes alone can give only partial information about neural responses related to valuation. In recent years, computationally principled models of value learning have been used in conjunction with noninvasive neuroimaging to tease out neural valuation responses related to reward-learning and decision-making. We restrict our review to the role of these models in a new generation of experiments that seeks to build on a now-large body of diverse reward-related brain responses. We show that the models and the measurements based on them point the way forward in two important directions: the valuation of time and the valuation of fictive experience. [Abstract]

Cannon SC
Pathomechanisms in channelopathies of skeletal muscle and brain.
Annu Rev Neurosci. 2006;29387-415.
Ion channelopathies are a diverse array of human disorders caused by mutations in ion channel genes. This review focuses on the pathogenic mechanisms of channelopathies affecting skeletal muscle and brain arising from mutations of voltage-gated ion channels and fast ligand-gated ion channels expressed at the surface membrane. Derangements in channel function alter the electrical excitability of the cell and thereby increase susceptibility to transient symptomatic attacks including myasthenia, periodic paralysis, myotonic stiffness, seizures, headache, dyskinesia, or episodic ataxia. Although these disorders are rare, they stand out as exemplary cases for which disease pathogenesis can be traced from a point mutation to altered protein function, to altered cellular activity, and to clinical phenotype. The study of these disorders has provided insights on channel structure-function relations, the physiological roles of ion channels, and rational approaches toward therapeutic intervention for many disorders of cellular excitability. [Abstract]

Montcouquiol M, Crenshaw EB, Kelley MW
Noncanonical Wnt signaling and neural polarity.
Annu Rev Neurosci. 2006;29363-86.
The Wnt signaling pathway regulates multiple events in development and disease in both vertebrates and invertebrates. Recently, the noncanonical Wnt signaling cascades, those that do not signal through beta-catenin, have gained prominence for their role in the regulation of cellular polarity. It is not surprising that cellular polarization influences a number of different developmental events within the nervous system, including neurulation and neural tube closure, cellular migration, and uniform orientation of cells within an epithelial plane (planar cell polarity). In this review, we describe the differences between the canonical and noncanonical pathways, summarize recent data illustrating the roles of the noncanonical Wnt pathway in different polarizing events during neural development, and discuss the potential molecular mechanisms that underlie the generation of cellular asymmetry and polarity. [Abstract]

Recent Articles in Nature Reviews Neuroscience

Rutishauser U
Polysialic acid in the plasticity of the developing and adult vertebrate nervous system.
Nat Rev Neurosci. 2007 Dec 5;
Polysialic acid (PSA) is a cell-surface glycan with an enormous hydrated volume that serves to modulate the distance between cells. This regulation has direct effects on several cellular mechanisms that underlie the formation of the vertebrate nervous system, most conspicuously in the migration and differentiation of progenitor cells and the growth and targeting of axons. PSA is also involved in a number of plasticity-related responses in the adult CNS, including changes in circadian and hormonal patterns, adaptations to pain and stress, and aspects of learning and memory. The ability of PSA to increase the plasticity of neural cells is being exploited to improve the repair of adult CNS tissue. [Abstract]

Patterson K, Nestor PJ, Rogers TT
Where do you know what you know? The representation of semantic knowledge in the human brain.
Nat Rev Neurosci. 2007 Dec;8(12):976-87.
Mr M, a patient with semantic dementia--a neurodegenerative disease that is characterized by the gradual deterioration of semantic memory--was being driven through the countryside to visit a friend and was able to remind his wife where to turn along the not-recently-travelled route. Then, pointing at the sheep in the field, he asked her "What are those things?" Prior to the onset of symptoms in his late 40s, this man had normal semantic memory. What has gone wrong in his brain to produce this dramatic and selective erosion of conceptual knowledge? [Abstract]

Lamb TD, Collin SP, Pugh EN
Evolution of the vertebrate eye: opsins, photoreceptors, retina and eye cup.
Nat Rev Neurosci. 2007 Dec;8(12):960-76.
Charles Darwin appreciated the conceptual difficulty in accepting that an organ as wonderful as the vertebrate eye could have evolved through natural selection. He reasoned that if appropriate gradations could be found that were useful to the animal and were inherited, then the apparent difficulty would be overcome. Here, we review a wide range of findings that capture glimpses of the gradations that appear to have occurred during eye evolution, and provide a scenario for the unseen steps that have led to the emergence of the vertebrate eye. [Abstract]

Schmucker D
Molecular diversity of Dscam: recognition of molecular identity in neuronal wiring.
Nat Rev Neurosci. 2007 Dec;8(12):915-20.
Our understanding of how the enormously complex task of interconnecting millions of nerve cells is accomplished remains rudimentary. What molecular mechanisms control its exquisite specificity? Can we pinpoint single molecular interactions that might help to explain some of the specificity requirements that underlie neuronal wiring? A series of recent studies on the molecular diversity of the Drosophila melanogaster cell-surface receptor Down syndrome cell-adhesion molecule (Dscam) provide one exceptional example of a novel mechanistic model of neuronal-wiring specificity, progressing from structural studies of single protein-protein interactions to biochemical analysis in vitro and to an understanding of complex neuronal differentiation at the single-cell or tissue levels. [Abstract]

Tzingounis AV, Wadiche JI
Glutamate transporters: confining runaway excitation by shaping synaptic transmission.
Nat Rev Neurosci. 2007 Dec;8(12):935-47.
Traditionally, glutamate transporters have been viewed as membrane proteins that harness the electrochemical gradient to slowly transport glutamate from the extracellular space into glial cells. However, recent studies have shown that glutamate transporters on glial and neuronal membranes also rapidly bind released glutamate to shape synaptic transmission. In this Review, we summarize the properties of glutamate transporters that influence synaptic transmission and are subject to regulation and plasticity. We highlight how the diversity of glutamate-transporter function relates to transporter location, density and affinity. [Abstract]

Martin S, Wilkinson KA, Nishimune A, Henley JM
Emerging extranuclear roles of protein SUMOylation in neuronal function and dysfunction.
Nat Rev Neurosci. 2007 Dec;8(12):948-59.
Post-translational protein modifications are integral components of signalling cascades that enable cells to efficiently, rapidly and reversibly respond to extracellular stimuli. These modifications have crucial roles in the CNS, where the communication between neurons is particularly complex. SUMOylation is a post-translational modification in which a member of the small ubiquitin-like modifier (SUMO) family of proteins is conjugated to lysine residues in target proteins. It is well established that SUMOylation controls many aspects of nuclear function, but it is now clear that it is also a key determinant in many extranuclear neuronal processes, and it has also been implicated in a wide range of neuropathological conditions. [Abstract]

Gamper N, Shapiro MS
Regulation of ion transport proteins by membrane phosphoinositides.
Nat Rev Neurosci. 2007 Dec;8(12):921-34.
Over the past decade, there has been an explosion in the number of membrane transport proteins that have been shown to be sensitive to the abundance of phosphoinositides in the plasma membrane. These proteins include voltage-gated potassium and calcium channels, ion channels that mediate sensory and nociceptive responses, epithelial transport proteins and ionic exchangers. Each of the regulatory lipids is also under multifaceted regulatory control. Phosphoinositide modulation of membrane proteins in neurons often has a dramatic effect on neuronal excitability and synaptic transmitter release. The repertoire of lipid signalling mechanisms that regulate membrane proteins is intriguingly complex and provides a rich array of topics for neuroscience research. [Abstract]

Rost�ne W, Kitabgi P, Parsadaniantz SM
Chemokines: a new class of neuromodulator?
Nat Rev Neurosci. 2007 Nov;8(11):895-903.
Chemokines are not only found in the immune system or expressed in inflammatory conditions: they are constitutively present in the brain in both glial cells and neurons. Recently, the possibility has been raised that they might act as neurotransmitters or neuromodulators. Although the evidence is incomplete, emerging data show that chemokines have several of the characteristics that define neurotransmitters. Moreover, their physiological actions resemble those of neuromodulators in the sense that chemokines usually have few effects by themselves in basal conditions, but modify the induced release of neurotransmitters or neuropeptides. These findings, together with the pharmacological development of agonists and antagonists that are selective for chemokine receptors and can cross the blood-brain barrier, open a new era of research in neuroscience. [Abstract]

Squire LR, Wixted JT, Clark RE
Recognition memory and the medial temporal lobe: a new perspective.
Nat Rev Neurosci. 2007 Nov;8(11):872-83.
Recognition memory is widely viewed as consisting of two components, recollection and familiarity, which have been proposed to be dependent on the hippocampus and the adjacent perirhinal cortex, respectively. Here, we propose an alternative perspective: we suggest that the methods traditionally used to separate recollection from familiarity instead separate strong memories from weak memories. A review of work with humans, monkeys and rodents finds evidence for familiarity signals (as well as recollection signals) in the hippocampus and recollection signals (as well as familiarity signals) in the perirhinal cortex. We also indicate ways in which the functions of the medial temporal lobe structures are different, and suggest that these structures work together in a cooperative and complementary way. [Abstract]

Guthrie S
Patterning and axon guidance of cranial motor neurons.
Nat Rev Neurosci. 2007 Nov;8(11):859-71.
The cranial motor nerves control muscles involved in eye, head and neck movements, feeding, speech and facial expression. The generic and specific properties of cranial motor neurons depend on a matrix of rostrocaudal and dorsoventral patterning information. Repertoires of transcription factors, including Hox genes, confer generic and specific properties on motor neurons, and endow subpopulations at various axial levels with the ability to navigate to their targets. Cranial motor axon projections are guided by diffusible cues and aided by guideposts, such as nerve exit points, glial cells and muscle primordia. The recent identification of genes that are mutated in human cranial dysinnervation disorders is now shedding light on the functional consequences of perturbations of cranial motor neuron development. [Abstract]

Kauer JA, Malenka RC
Synaptic plasticity and addiction.
Nat Rev Neurosci. 2007 Nov;8(11):844-58.
Addiction is caused, in part, by powerful and long-lasting memories of the drug experience. Relapse caused by exposure to cues associated with the drug experience is a major clinical problem that contributes to the persistence of addiction. Here we present the accumulated evidence that drugs of abuse can hijack synaptic plasticity mechanisms in key brain circuits, most importantly in the mesolimbic dopamine system, which is central to reward processing in the brain. Reversing or preventing these drug-induced synaptic modifications may prove beneficial in the treatment of one of society's most intractable health problems. [Abstract]

Wilkinson LS, Davies W, Isles AR
Genomic imprinting effects on brain development and function.
Nat Rev Neurosci. 2007 Nov;8(11):832-43.
In a small fraction of mammalian genes--at present estimated at less than 1% of the total--one of the two alleles that is inherited by the offspring is partially or completely switched off. The decision as to which one is silenced depends on which allele was inherited from the mother and which from the father. These idiosyncratic loci are known as imprinted genes, and their existence is an evolutionary enigma, as they effectively nullify the advantages of diploidy. Although they are small in number, these genes have important effects on physiology and behaviour, and many are expressed in the brain. There is increasing evidence that imprinted genes influence brain function and behaviour by affecting neurodevelopmental processes. [Abstract]

Murray RM, Morrison PD, Henquet C, Di Forti M
Cannabis, the mind and society: the hash realities.
Nat Rev Neurosci. 2007 Nov;8(11):885-95.
Cannabis has been known for at least 4,000 years to have profound effects on the mind--effects that have provoked dramatically divergent attitudes towards it. Some societies have regarded cannabis as a sacred boon for mankind that offers respite from the tribulations of everyday life, whereas others have demonized it as inevitably leading to 'reefer madness'. The debate between the protagonists and prohibitionists has recently been re-ignited, but unfortunately this debate continues mainly in ignorance of our new understanding of the effects of cannabis on the brain and of studies that have quantified the extent of the risks of long-term use. [Abstract]

Li Q, Lee JA, Black DL
Neuronal regulation of alternative pre-mRNA splicing.
Nat Rev Neurosci. 2007 Nov;8(11):819-31.
Alternative pre-mRNA splicing has an important role in the control of neuronal gene expression. Many neuronal proteins are structurally diversified through the differential inclusion and exclusion of sequences in the final spliced mRNA. Here, we discuss common mechanisms of splicing regulation and provide examples of how alternative splicing has important roles in neuronal development and mature neuron function. Finally, we describe regulatory proteins that control the splicing of some neuronally expressed transcripts. [Abstract]

Lipton SA
Pathologically activated therapeutics for neuroprotection.
Nat Rev Neurosci. 2007 Oct;8(10):803-8.
Many drugs that have been developed to treat neurodegenerative diseases fail to gain approval for clinical use because they are not well tolerated in humans. In this article, I describe a series of strategies for the development of neuroprotective therapeutics that are both effective and well tolerated. These strategies are based on the principle that drugs should be activated by the pathological state that they are intended to inhibit. This approach has already met with success, and has led to the development of the potentially neuroprotective drug memantine, an N-methyl-D-aspartate (NMDA)-type and glutamate receptor antagonist. [Abstract]

Herzog ED
Neurons and networks in daily rhythms.
Nat Rev Neurosci. 2007 Oct;8(10):790-802.
Biological pacemakers dictate our daily schedules in physiology and behaviour. The molecules, cells and networks that underlie these circadian rhythms can now be monitored using long-term cellular imaging and electrophysiological tools, and initial studies have already suggested a theme--circadian clocks may be crucial for widespread changes in brain activity and plasticity. These daily changes can modify the amount or activity of available genes, transcripts, proteins, ions and other biologically active molecules, ultimately determining cellular properties such as excitability and connectivity. Recently discovered circadian molecules and cells provide preliminary insights into a network that adapts to predictable daily and seasonal changes while remaining robust in the face of other perturbations. [Abstract]

Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM
Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity.
Nat Rev Neurosci. 2007 Oct;8(10):766-75.
At the end of the 1980s, it was clearly demonstrated that cells produce nitric oxide and that this gaseous molecule is involved in the regulation of the cardiovascular, immune and nervous systems, rather than simply being a toxic pollutant. In the CNS, nitric oxide has an array of functions, such as the regulation of synaptic plasticity, the sleep-wake cycle and hormone secretion. Particularly interesting is the role of nitric oxide as a Janus molecule in the cell death or survival mechanisms in brain cells. In fact, physiological amounts of this gas are neuroprotective, whereas higher concentrations are clearly neurotoxic. [Abstract]

Maden M
Retinoic acid in the development, regeneration and maintenance of the nervous system.
Nat Rev Neurosci. 2007 Oct;8(10):755-65.
Retinoic acid (RA) is involved in the induction of neural differentiation, motor axon outgrowth and neural patterning. Like other developmental molecules, RA continues to play a role after development has been completed. Elevated RA signalling in the adult triggers axon outgrowth and, consequently, nerve regeneration. RA is also involved in the maintenance of the differentiated state of adult neurons, and disruption of RA signalling in the adult leads to the degeneration of motor neurons (motor neuron disease), the development of Alzheimer's disease and, possibly, the development of Parkinson's disease. The data described here strongly suggest that RA could be used as a therapeutic molecule for the induction of axon regeneration and the treatment of neurodegeneration. [Abstract]

Piomelli D, Astarita G, Rapaka R
A neuroscientist's guide to lipidomics.
Nat Rev Neurosci. 2007 Oct;8(10):743-54.
Nerve cells mould the lipid fabric of their membranes to ease vesicle fusion, regulate ion fluxes and create specialized microenvironments that contribute to cellular communication. The chemical diversity of membrane lipids controls protein traffic, facilitates recognition between cells and leads to the production of hundreds of molecules that carry information both within and across cells. With so many roles, it is no wonder that lipids make up half of the human brain in dry weight. The objective of neural lipidomics is to understand how these molecules work together; this difficult task will greatly benefit from technical advances that might enable the testing of emerging hypotheses. [Abstract]

Bramham CR, Wells DG
Dendritic mRNA: transport, translation and function.
Nat Rev Neurosci. 2007 Oct;8(10):776-89.
Many cellular functions require the synthesis of a specific protein or functional cohort of proteins at a specific time and place in the cell. Local protein synthesis in neuronal dendrites is essential for understanding how neural activity patterns are transduced into persistent changes in synaptic connectivity during cortical development, memory storage and other long-term adaptive brain responses. Regional and temporal changes in protein levels are commonly coordinated by an asymmetric distribution of mRNAs. This Review attempts to integrate current knowledge of dendritic mRNA transport, storage and translation, placing particular emphasis on the coordination of regulation and function during activity-dependent synaptic plasticity in the adult mammalian brain. [Abstract]

Pridmore S
Therapeutic use of rTMS.
Nat Rev Neurosci. 2007 Sep 12; [Abstract]

Ridding MC, Rothwell JC
Therapeutic use of rTMS.
Nat Rev Neurosci. 2007 Sep 12; [Abstract]

Hyman SE
Can neuroscience be integrated into the DSM-V?
Nat Rev Neurosci. 2007 Sep;8(9):725-32.
To date, the diagnosis of mental disorders has been based on clinical observation, specifically: the identification of symptoms that tend to cluster together, the timing of the symptoms' appearance, and their tendency to resolve, recur or become chronic. The Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Disease, the manuals that specify these diagnoses and the criteria for making them, are currently undergoing revision. It is thus timely to ask whether neuroscience has progressed to the point that the next editions of these manuals can usefully incorporate information about brain structure and function. [Abstract]

Curtis MA, Faull RL, Eriksson PS
The effect of neurodegenerative diseases on the subventricular zone.
Nat Rev Neurosci. 2007 Sep;8(9):712-23.
During brain development, one of the most important structures is the subventricular zone (SVZ), from which most neurons are generated. In adulthood the SVZ maintains a pool of progenitor cells that continuously replace neurons in the olfactory bulb. Neurodegenerative diseases induce a substantial upregulation or downregulation of SVZ progenitor cell proliferation, depending on the type of disorder. Far from being a dormant layer, the SVZ responds to neurodegenerative disease in a way that makes it a potential target for therapeutic intervention. [Abstract]

Fox MD, Raichle ME
Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging.
Nat Rev Neurosci. 2007 Sep;8(9):700-11.
The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease. [Abstract]

Kullmann DM, Lamsa KP
Long-term synaptic plasticity in hippocampal interneurons.
Nat Rev Neurosci. 2007 Sep;8(9):687-99.
Rapid memory formation relies, at least in part, on long-term potentiation (LTP) of excitatory synapses. Inhibitory interneurons of the hippocampus, which are essential for information processing, have recently been found to exhibit not one, but two forms of LTP. One form resembles LTP that occurs in pyramidal neurons, which depends on N-methyl-D-aspartate receptors and is triggered by coincident pre- and postsynaptic activity. The other depends on Ca2+ influx through glutamate receptors that preferentially open when the postsynaptic neuron is at rest. Here we review these contrasting forms of LTP and describe how they are mirrored by two forms of long-term depression. We further discuss how the remarkable plasticity of glutamatergic synapses on interneurons greatly enhances the computational capacity of the cortical microcircuit. [Abstract]

Huang ZJ, Di Cristo G, Ango F
Development of GABA innervation in the cerebral and cerebellar cortices.
Nat Rev Neurosci. 2007 Sep;8(9):673-86.
In many areas of the vertebrate brain, such as the cerebral and cerebellar cortices, neural circuits rely on inhibition mediated by GABA (gamma-aminobutyric acid) to shape the spatiotemporal patterns of electrical signalling. The richness and subtlety of inhibition are achieved by diverse classes of interneurons that are endowed with distinct physiological properties. In addition, the axons of interneurons display highly characteristic and class-specific geometry and innervation patterns, and thereby distribute their output to discrete spatial domains, cell types and subcellular compartments in neural networks. The cellular and molecular mechanisms that specify and modify inhibitory innervation patterns are only just beginning to be understood. [Abstract]

Schacter DL, Addis DR, Buckner RL
Remembering the past to imagine the future: the prospective brain.
Nat Rev Neurosci. 2007 Sep;8(9):657-61.
A rapidly growing number of recent studies show that imagining the future depends on much of the same neural machinery that is needed for remembering the past. These findings have led to the concept of the prospective brain; an idea that a crucial function of the brain is to use stored information to imagine, simulate and predict possible future events. We suggest that processes such as memory can be productively re-conceptualized in light of this idea. [Abstract]

Ballatore C, Lee VM, Trojanowski JQ
Tau-mediated neurodegeneration in Alzheimer's disease and related disorders.
Nat Rev Neurosci. 2007 Sep;8(9):663-72.
Advances in our understanding of the mechanisms of tau-mediated neurodegeneration in Alzheimer's disease (AD) and related tauopathies, which are characterized by prominent CNS accumulations of fibrillar tau inclusions, are rapidly moving this previously underexplored disease pathway to centre stage for disease-modifying drug discovery efforts. However, controversies abound concerning whether or not the deleterious effects of tau pathologies result from toxic gains-of-function by pathological tau or from critical losses of normal tau function in the disease state. This Review summarizes the most recent advances in our knowledge of the mechanisms of tau-mediated neurodegeneration to forge an integrated concept of those tau-linked disease processes that drive the onset and progression of AD and related tauopathies. [Abstract]

Peelen MV, Downing PE
The neural basis of visual body perception.
Nat Rev Neurosci. 2007 Aug;8(8):636-48.
The human body, like the human face, is a rich source of socially relevant information about other individuals. Evidence from studies of both humans and non-human primates points to focal regions of the higher-level visual cortex that are specialized for the visual perception of the body. These body-selective regions, which can be dissociated from regions involved in face perception, have been implicated in the perception of the self and the 'body schema', the perception of others' emotions and the understanding of actions. [Abstract]