bluuebunny/crossref_metadata_2025 huggingface dataset:
Degeneration, Trophic Interactions, and Repair of Severed Axons: A Reconsideration of Some Common Assumptions
Authors: Bittner George D. , Schallert Timothy , Peduzzi Jean D.
Published: April 2009

We suggest that several interrelated properties of severed axons (degeneration, trophic dependencies, initial repair, and eventual repair) differ in important ways from commonly held assumptions about those properties. Specifically, (1) axotomy does not necessarily produce rapid degeneration of distal axonal segments because (2) the trophic maintenance of nerve axons does not necessarily depend entirely on proteins transported from the perikaryon—but instead axonal proteins can be trophically maintained by slowing their degradation and/or by acquiring new proteins via axonal synthesis or transfer from adjacent cells (e.g., glia). (3) The initial repair of severed distal or proximal segments occurs by barriers (seals) formed amid accumulations of vesicles and/or myelin delaminations induced by calcium influx at cut axonal ends—rather than by collapse and fusion of cut axolemmal leaflets. (4) The eventual repair of severed mammalian CNS axons does not necessarily have to occur by neuritic outgrowths, which slowly extend from cut proximal ends to possibly reestablish lost functions weeks to years after axotomy—but instead complete repair can be induced within minutes by polyethylene glycol to rejoin (fuse) the cut ends of surviving proximal and distal stumps. Strategies to repair CNS lesions based on fusion techniques combined with rehabilitative training and induced axonal outgrowth may soon provide therapies that can at least partially restore lost CNS functions.
Brain Cytosolic Phospholipase A2: Localization, Role, and Involvement in Neurological Diseases
Authors: Farooqui Akhlaq A. , Ong Wei Yi , Horrocks Lloyd A. , Farooqui Tahira
Published: April 2009

Cytosolic phospholipase A2(cPLA2) hydrolyzes the arachidonoyl group from the sn-2 position of glycerophospholipids generating arachidonic acid and lysophospholipids. The products of the cPLA2-catalyzed reaction act as second messengers themselves or further metabolize to eicosanoids, platelet activating factor, and lysophosphatidic acid. cPLA2has not been purified from brain tissue. Immunocytochemical studies have indicated that cPLA2is expressed in neurons and astrocytes. The hindbrain and spinal cord contain dense immunoreactivity for cPLA2. Activity and immunoreactivity of cPLA2are markedly increased in ischemia, Alzheimer’s disease, and kainic acid neurotoxicity. This increase in cPLA2activity and immunoreactivity is accompanied by marked alterations in neural membrane phospholipid composition and the accumulation of lipid peroxides and eicosanoids. At present, it is not known whether the increased activity and immunoreactivity of cPLA2in neural trauma (e.g., in ischemia) and neurodegenerative disease (Alzheimer’s disease) is the cause or effect of neurodegeneration. Recent studies on the role of this enzyme in brain tissue suggest that cPLA2may be involved in synaptic plasticity, generation of second messengers, axon regeneration, and neurodegeneration.
Respiratory Rhythm Generation: Plasticity of a Neuronal Network
Authors: Richter Diethelm W. , Mironov Sergej L. , Büsselberg Dietrich , Lalley Peter M. , Bischoff Anne M. , Wilken Bernd
Published: April 2009

The exchange of gases between the external environment and the organism is controlled by a neural network of medullary neurons that produces rhythmic activity that ultimately leads to periodic contractions of thoracic, abdominal, and diaphragm muscles. This occurs in three neural phases: inspiration, postinspiration, and expiration. The present article deals with the mechanisms underlying respiratory rhythm generation and the processes of dynamic adjustment of respiratory activity by neuromodulation as it occurs during normoxia and hypoxia. The respiratory rhythm originates from the “pre-Bötzinger complex,” which is a morphologically defined region within the lower brainstem. There is a primary oscillating network consisting of reciprocally connected early-inspiratory and postinspiratory neurons, whereas various other subgroups of respiratory neurons shape the activity pattern. Rhythm generation and pattern formation result from neuronal interactions within the network, that is, from cooperative adjustments of intrinsic membrane properties and synaptic processes in the respiratory neurons. There is evidence that in neonatal mammals, as well as under certain pathological situations in adult mammals, the respiratory rhythm derives from early-inspiratory burster neurons that drive inspiratory output neurons. The respiratory network is influenced by a variety of neuromodulators. Stimulation of appropriate receptors mostly activates signal pathways that converge on cAMP-dependent protein kinase and protein kinase C. Both pathways exert modulatory effects on voltage- and ligand-controlled ion channels. Many neuromodulators are continuously released within the respiratory region or accumulated under pathological conditions such as hypoxia. The functional significance of such ongoing neuromodulation is seen in variations of network excitability. In this review, the authors concentrate on the modulators serotonin, adenosine, and opioids.
The Ups and Downs of Neurotransmitter Transporters
Authors: Beckman Matthew L. , Quick Michael W.
Published: April 2009

Plasma membrane neurotransmitter transporters are a family of integral membrane proteins, found on both neurons and glia, that have the capacity to influence neuronal signaling through a number of mechanisms including transmitter reuptake and ionic flux. Clinically, these proteins are of interest because their dysfunction is associated with several neurological and psychiatric disorders, and because they are the targets of many drugs of abuse and therapy. In this review, the authors focus on one of the more recent, fascinating discoveries about neurotransmitter transporters; namely, that transporter function is regulated by altering the number of transporters on the cell surface. These data suggest that transporter expression is in continual flux and that transporters respond to their environment in an effort to maintain baseline transmitter levels in the brain. The authors examine the mechanisms underlying changes in transporter number, discuss clinical disorders that are correlated with transporter expression, and suggest that controlling transporter redistribution may be a future therapeutic strategy for disorders related to abnormal transmitter levels.
Is There a Neuropathology of Schizophrenia? Recent Findings Converge on Altered Thalamic-Prefrontal Cortical Connectivity
Authors: Lewis David A.
Published: April 2009

Schizophrenia is a serious and chronic brain disorder whose underlying neuropathology has proven difficult to identify. This article reviews the current status of neuropathological studies in terms of how they inform the diagnosis, pathogenesis, pathophysiology, and mechanisms of treatment of schizophrenia. Although additional studies are required, substantial data converge on the hypothesis that the pathophysiology of schizophrenia is associated with alterations in thalamic-prefrontal cortical connectivity.
Glutamate-Induced White Matter Injury: Excitotoxicity without Synapses
Authors: Stys Peter K. , Li Shuxin
Published: April 2009

White matter of the brain and spinal cord is irreversibly damaged by ischemia and trauma. Recent evidence indicates that despite the absence of synaptic elements, excitotoxic mechanisms play an important role in the pathogenesis of white matter damage. Glial cells, including astrocytes and oligodendrocytes, possess non-NMDA glutamate receptors and are injured by excessive exposure to AMPA/kainate agonists. In addition, the myelin sheath itself appears to respond directly to glutamate stimulation via AMPA receptors, which may also lead to injury of this key constituent of myelinated axons. During white matter anoxia/ischemia or trauma, endogenous glutamate is released mainly from axoplasmic pools in a nonvesicular fashion through Na+-dependent glutamate transporters, stimulated to operate in the glutamate efflux mode by collapse of transmembrane ion gradients and depolarization. It appears that parallel mechanisms are triggered by injurious stimuli, involving reverse Na+-Ca2+ exchange and voltage-gated Ca2+ channels producing Ca2+ overload of the axon cylinder, whereas glutamate release with AMPA receptor overactivation causes Ca2+-dependent damage to the ensheathing myelin and sup-porting glia. The emerging complexity of white matter injury mechanisms requires a thorough understanding of the interrelated steps to optimize therapeutic design.
Phencyclidine Model of Frontal Cortical Dysfunction in Nonhuman Primates
Authors: Jentsch J. David , Taylor Jane R. , Roth Robert H.
Published: April 2009

Long-term intake of noncompetitive N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists, such as phencyclidine (PCP), can simulate schizophrenia-like symptomatology in human subjects and can produce aberrant behavior in animals. The behavioral changes produced by PCP in animals have been suggested to model certain primary symptoms of idiopathic psychotic disorders, and the neurobiological substrates affected by PCP have been implicated in the pathophysiology of schizophrenia. This review considers the validity of PCP-induced behaviors in animals as a model of the human disorder, and a developing hypothesis of PCP-induced neurochemical dysfunction within the prefrontal cortex is presented. The behavioral and neurochemical effects of PCP may support the notion that altered glutamatergic/dopaminergic interactions within prefrontal cortex contribute to the cognitive dysfunction of schizophrenia.
GPI-Anchored Proteins and Glycosphingolipid-Rich Rafts: Platforms for Adhesion and Signaling
Authors: Trotter Jacqueline , Klein Corinna , Krämer Eva-Maria
Published: April 2009

Glycosylphosphatidylinositol (GPI)-anchored proteins in mammalian cells play a role in adhesion and signaling. They are sorted in the trans-Golgi network into glycosphingolipid- and cholesterol-rich microdomains termed rafts. Such rafts can be isolated from many cell types including epithelial cells, neural cells, and lymphocytes. In polarized cells, the rafts segregate in distinct regions of the cell. The rafts constitute platforms for signal transduction via raft-associated srcfamily tyrosine kinases. This review compares the sorting, distribution, and signaling of GPI-anchored proteins and rafts in epithelial cells, lymphocytes, and neural cells. A possible involvement of rafts in distinct diseases is also addressed.
Those Were the (Phrenological) Days
Authors: Castro-Caldas Alexandre , Grafman Jordan
Published: April 2009

Phrenology is nowadays often considered as a pseudoscience and a reason for ironic comments. This theory was based on the ideas of Franz Joseph Gall (1758-1828). He was indeed a fine neuroscientist that called attention to the cerebral cortex and suggested for the first time that mental functions were the result of the activity of cortical “organs.” The methodology used reveals interesting predictive aspects for what our current practice is. However, the interpretations of the observations were often more in accordance with the predicted heuristic model than with the real findings. Spurzheim (1776-1832) was first his student and then his collaborator. He traveled around the world lecturing and making phrenology a popular science.
Cellular Repair of Complex Cortical Circuitry
Authors: Gates Monte A. , Fricker-Gates Rosemary A. , Magavi Sanjay S. , Macklis Jeffrey D.
Published: April 2009

The mammalian neocortex is a highly complex structure that consists of a large number of distinct cell types and connections unparalleled throughout the rest of the mammalian central nervous system (CNS). The neocortex is responsible for high-level functions including sensorimotor integration, associative behavior, and cognition. Although many studies demonstrate that embryonic tissue or precursor cells transplanted into the embryonic or neonatal cortex can integrate and connect with a wide variety of targets, such connectivity in most studies using adult recipients has been quite limited (1, 2). In contrast, relatively recent advances in transplantation paradigms from our laboratory and other laboratories have made apparent the possibility of successful reconstruction of complex cortical circuitry in the adult mammalian brain by transplantation or by manipulation of endogenous precursors in situ. These advances include the ability to isolate increasingly specific populations of immature neurons and precursors from donor animals, and the establishment of a highly selective model of targeted degeneration in the neocortex (3-10, Leavitt, unpublished observations). Such advances now allow both the transplantation of more defined and specific populations of immature neocortical neuroblasts and precursors, and also make it possible to study the cellular, anatomic, and functional efficacy of both transplantation and manipulation of endogenous precursors in situ (9, 11) in increasingly refined models of neocortical degeneration. The neocortex has become a model system for studying circuitry formation, regional specification, cell specification, and cell autonomous versus environmental influences on neuronal development and function in the CNS. Although neocortical transplantation paradigms have proven very useful for elucidating how complex circuits and CNS cytoarchitecture evolve in the mammalian brain, more recent work using cell transplantation has made apparent the possibility of cell replacement and complex circuit repair in the neocortex. Our most recent results (9, 11) suggest that neuronal replacement therapies for neurodegenerative disease and other CNS injury may even some day be possible via molecular manipulation of endogenous neural precursors in situ, without transplantation. Although only fanciful just several years ago, it now appears that studies of cellular repopulation and circuitry reconstruction in the neocortex may provide a foundation toward developing cellular therapies for degenerative or acquired disease in neocortex and other regions of the CNS.
Exploiting Nonneural Cells to Rebuild the Nervous System: From Bone Marrow to Brain
Authors: Azizi S. Ausim
Published: April 2009

Bone marrow, in addition to hematopoietic precursors, contains cells that are considered stem cells of nonhematopoietic tissues. These cells are referred to as marrow stromal cells or mesenchymal stem cells. Marrow stromal cells, because of their ability to survive, integrate, and migrate within the central nervous system, can be used as an alternative source of cells for neural transplantation and repair. They can be expanded rapidly in culture and can be induced to express markers of neural cells. Moreover, implanted into the developing brain, these cells can integrate without disrupting the host brain architecture and can assume the fate of neural cells. They can be genetically transduced and can elaborate transgene products. Because large numbers of stromal cells can be obtained from small aspirates of bone marrow, these cells are potentially useful for treating a variety of neurological diseases.
Neurogenesis and Gliogenesis in the Postischemic Brain
Authors: Liu Jialing , Bernabeu Ramon , Lu Aigang , Sharp Frank R.
Published: April 2009

Stem cells are found throughout the adult mammalian brain, including the subventricular zone (SVZ) adjacent to the lateral ventricles, and in the hippocampal dentate subgranular zone (SGZ). Cells born in the SVZ migrate to the olfactory bulb. Those born in the SGZ migrate into the granule cell layer. Following 5 or 10 min of global ischemia in the adult gerbil, there is a tenfold increase in the birth of new cells in the SGZ as assessed using bromo-deoxy-uridine incorporation. This begins at 7 days, peaks at 11 days, and decreases thereafter. Over the ensuing month, approximately one-fourth of the newborn cells disappear. Of the remaining cells, 60% migrate into the granule cell layer where two-thirds of these become NeuN, calbindin, and MAP-2 immunostained neurons. The remaining 40% of the cells migrate into the dentate hilus where one-fourth of these become glial fibrillary acidic protein-labeled astrocytes. Death of CA1 pyramidal neurons does not stimulate neurogenesis because ischemia-induced tolerance—which does not produce CA1 injury—also stimulated cell proliferation. It is proposed that ischemia-induced neurogenesis contributes to the recovery of function, specifically of anterograde and retrograde recent memory function that is lost following global ischemia in man.
Axonal Damage in Traumatic Brain Injury
Authors: Smith Douglas H. , Meaney David F.
Published: April 2009

Axonal damage is one of the most common and important pathologic features of traumatic brain injury. Severe diffuse axonal injury, resulting from inertial forces applied to the head, is associated with prolonged unconsciousness and poor outcome. The susceptibility of axons to mechanical injury appears to be due to both their viscoelastic properties and their highly organized structure in white matter tracts. Although axons are supple under normal conditions, they become brittle when exposed to rapid deformations associated with brain trauma. Accordingly, rapid stretch of axons can damage the axonal cytoskeleton, resulting in a loss of elasticity and impairment of axoplasmic transport. Subsequent swelling of the axon occurs in discrete bulb formations or in elongated varicosities that accumulate organelles. Calcium entry into damaged axons is thought to initiate further damage by the activation of proteases and the induction of mitochondrial swelling and dysfunction. Ultimately, swollen axons may become disconnected and contribute to additional neuropathologic changes in brain tissue. However, promising new therapies that reduce proteolytic activity or maintain mitochondrial integrity may attenuate progressive damage of injured axons following experimental brain trauma. Future advancements in the prevention and treatment of traumatic axonal injury will depend on our collective understanding of the relationship between the biomechanics and pathophysiology of various phases of axonal trauma.
Sodium Channel β Subunits: Anything but Auxiliary
Authors: Isom Lori L.
Published: April 2009

Voltage-gated sodium channels are glycoprotein complexes responsible for initiation and propagation of action potentials in excitable cells such as central and peripheral neurons, cardiac and skeletal muscle myocytes, and neuroendocrine cells. Mammalian sodium channels are heterotrimers, composed of a central, pore-forming α subunit and two auxiliary β subunits. The α subunits form a gene family with at least 10 members. Mutations in α subunit genes have been linked to paroxysmal disorders such as epilepsy, long QT syndrome, and hyperkalemic periodic paralysis in humans, and motor endplate disease and cerebellar ataxia in mice. Three genes encode sodium channel β subunits with at least one alternative splice product. A mutation in the β1 subunit gene has been linked to generalized epilepsy with febrile seizures plus type 1 (GEFS + 1) in a human family with this disease. Sodium channel β subunits are multifunctional. They modulate channel gating and regulate the level of channel expression at the plasma membrane. More recently, they have been shown to function as cell adhesion molecules in terms of interaction with extracellular matrix, regulation of cell migration, cellular aggregation, and interaction with the cytoskeleton. Structure-function studies have resulted in the preliminary assignment of functional domains in the β1 subunit. A sodium channel signaling complex is proposed that involves β subunits as channel modulators as well as cell adhesion molecules, other cell adhesion molecules such as neurofascin and contactin, RPTPβ, and extracellular matrix molecules such as tenascin.
Mechanisms of Axonal Plasticity: Lessons from the Olfactory Pathway
Authors: Treloar Helen B. , Bartolomei Juan C. , Lipscomb Brian W. , Greer Charles A.
Published: April 2009

The olfactory pathway has emerged recently as an effective model for studying general principles of axon extension and regeneration. A variety of both trophic as well as repulsive molecules are found in the olfactory pathway and are being characterized for their roles in promoting the high capacity for plasticity and growth in olfactory receptor cell axons. In addition, olfactory ensheathing cells, which line the olfactory nerve, have been shown to promote axon extension not only in the olfactory pathway but also in the injured spinal cord. This review summarizes some of our current knowledge of these mechanisms and how they may function collectively to promote axon plasticity.
The Inherited Episodic Ataxias: How Well Do We Understand the Disease Mechanisms?
Authors: Kullmann Dimitri M. , Rea Ruth , Spauschus Alexander , Jouvenceau Anne
Published: April 2009

The past few years have seen the elucidation of several neurological diseases caused by inherited mutations of ion channels. In contrast to many other types of genetic disorders, the “channelopathies” can be studied with high precision by applying electrophysiological methods. This review evaluates the success of this approach in explaining the mechanisms of two forms of episodic ataxia that are known to be caused by mutations of ion channels: episodic ataxia type 1 (EA1, caused by K+ channel mutations) and episodic ataxia type 2 (EA2, caused by Ca2+ channel mutations). Although both of these disorders are rare, they raise many important questions about the roles of identified channels in brain function. Indeed, a resolution of the mechanisms by which both diseases occur will represent a major milestone in understanding diseases of the CNS, in addition to opening the way to novel possible treatments.
The Spinal Cord Research Foundation: Two Decades of Progress
Authors: Kelley Melinda S.
Published: April 2009

Over the course of the past 24 years, the Paralyzed Veterans of America’s Spinal Cord Research Foundation (SCRF) has provided support for more than 400 research grants in a wide range of areas, from improved wheelchair design to axon pathfinding in Drosophila. The Founders of SCRF, as well as its current trustees, believe that it is imperative to target a broad range of research areas to maximize the quality of life for people, both veterans and nonveterans, with paralysis. This approach has involved the support of basic science and clinical research directed towards repair of the spinal cord, as well as research into improved treatments for complications of spinal cord dysfunction and other projects, including engineering grants and conferences, that may enhance the quality of life for people with paralysis within the immediate future.
Glial Tumor Invasion: A Role for the Upregulation and Cleavage of BEHAB/Brevican
Authors: Nutt Catherine L. , Matthews Russell T. , Hockfield Susan
Published: April 2009

Glial tumors, gliomas, are the most common primary intracranial tumors. Their distinct ability to invade the normal surrounding tissue makes them difficult to control and nearly impossible to completely remove surgically, and it accounts for the extraordinarily high lethality associated with gliomas. The ability of these transformed glial cells to invade the normal surrounding tissue is relatively unique in the adult CNS, which under most circumstances, is inhibitory to cell movement. The extracellular matrix (ECM) can modulate, in part, the permissiveness of a tissue to cell movement. Accordingly, the ability of gliomas to modify the ECM of the CNS may mediate the invasiveness of these cells. One ECM molecule that shows dramatic upregulation in gliomas is BEHAB (brain enriched hyaluronan binding)/brevican, a brain-specific chondroitin sulfate proteoglycan. BEHAB/brevican expression is also upregulated during periods of increased glial cell motility in development and following brain injury. Experimental evidence suggests that in glioma, in addition to upregulation of BEHAB/brevican, proteolytic processing of the full-length protein also may contribute to invasion. Here, the authors present a review of the literature on glial tumor invasion by modulation of the ECM and propose a two-step model for BEHAB/brevican’s role in this process.
Maxi-K Potassium Channels: Form, Function, and Modulation of a Class of Endogenous Regulators of Intracellular Calcium
Authors: Gribkoff Valentin K. , Starrett John E. , Dworetzky Steven I.
Published: April 2009

Large-conductance calcium-activated (maxi-K, BK) potassium channels are widely distributed in the brain. Maxi-K channels function as neuronal calcium sensors and contribute to the control of cellular excitability and the regulation of neurotransmitter release. Little is currently known of any significant role of maxi-K channels in the genesis of neurological disease. Recent advances in the molecular biology and pharmacology of these channels have revealed sources of phenotypic variability and demonstrated that they can be successfully modulated by pharmacological agents. A potential role is suggested in the treatment of conditions such as ischemic stroke and cognitive disorders.
Under One Roof: The Miami Project to Cure Paralysis Model for Spinal Cord Injury Research
Authors: Kleitman Naomi
Published: April 2009

Concentrating a wide range of spinal cord injury (SCI) research laboratories in a single location to accelerate progress and draw attention to the promise of SCI research has made The Miami Project to Cure Paralysis one of the most publicly recognized and often controversial research groups in the neurosciences. A “Center of Excellence” at the University of Miami School of Medicine, the Miami Project also serves as a model for SCI research programs being developed nationally and internationally. Founded in 1985, the Miami Project set out on an unprecedented path—to develop a research center dedicated to improving treatments for SCI by bridging basic and clinical science. In doing so, neurosurgeon Barth Green, M.D., enlisted not only a multidisciplinary team of scientists but also a devoted following of financial donors and volunteer research subjects, and support from the University of Miami and Florida legislature. Highly visible spokespersons, including cofounder ex-Miami Dolphin Nick Buoniconti and his son Marc, brought the issue of SCI paralysis and the promise of research before the public, the media, and sports communities. As progress in the neurosciences has raced ahead, public attention to medical research, and SCI research in particular, has grown exponentially. This review will assess the Miami Project as a model for disease-based research that unites academic, philanthropic, and patient communities in a common cause.
Book Review: Serotonergic Neuromodulation in the Cerebellar Cortex: Cellular, Synaptic, and Molecular Basis
Authors: Dieudonné Stéphane
Published: April 2009

The cerebellum, like most sensorimotor areas of the brain, receives a serotonergic innervation from neurons of the reticular formation. It is well established that local application of serotonin modulates the firing rate of cerebellar Purkinje cells in vivo and in vitro, but the mechanisms by which serotonin affects the cerebellar function are still poorly understood. Whereas interactions between serotonin, glutamate, and GABA have been reported to increase or decrease the firing frequency of Purkinje cells, there is little evidence for a modulation of excitatory and inhibitory synapses by serotonin in the cerebellar cortex. Changes in the intrinsic electrical properties of Purkinje cells upon application of serotonin have also been reported, but their impact on Purkinje cell firing is unclear. The recent finding that serotonin specifically modulates the activity of Lugaro cells, a class of inhibitory interneurons of the cerebellar cortex, offers new insights on the action of this neuromodulator. The peculiar axonal projection and specific interneuronal targets of the Lugaro cells suggest that the action of serotonin might occur upstream of Purkinje cells through a resetting of the computational properties of the cerebellar cortex. Understanding the mechanisms of the serotonergic modulation of the cerebellar cortex is of clinical relevance, as abnormal serotonin metabolism has been observed in animal models and pathological cases of motor disorders involving the cerebellum, and as chronic intravenous administration of L-5-hydroxytryptophan (5-HTP), a precursor of serotonin, was the first treatment shown to improve significantly cerebellar symptoms.
Book Review: Plasmalogens: Workhorse Lipids of Membranes in Normal and Injured Neurons and Glia
Authors: Farooqui Akhlaq A. , Horrocks Lloyd A.
Published: April 2009

Plasmalogens are unique glycerophospholipids because they have an enol ether double bond at the sn-1 position of the glycerol backbone. They are found in all mammalian tissues, with ethanolamine plasmalogens 10-fold higher than choline plasmalogens except in muscles. The enol ether double bond at the sn-1 position makes plasmalogens more susceptible to oxidative stress than the corresponding ester-bonded glycerophospholipids. Plasmalogens are not only structural membrane components and a reservoir for second messengers but may also be involved in membrane fusion, ion transport, and cholesterol efflux. Plasmalogens may also act as antioxidants, thus protecting cells from oxidative stress. Receptor-mediated degradation of plasmalogens by plasmalogen-selective phospholipase A2results in the generation of arachidonic acid, eicosanoids, and platelet activating factor. Low levels of these metabolites have trophic effects, but at high concentration they are cytotoxic and may be involved in allergic response, inflammation, and trauma. Levels of plasmalogens are decreased in several neurological disorders including Alzheimer’s disease, ischemia, and spinal cord trauma. This may be due to the stimulation of plasmalogen-selective phospholipase A2. A deficiency of plasmalogens in peroxisomal disorders and Niemann-Pick type C disease indicates that this deficiency may be due to the decreased activity of plasmalogen synthesizing enzymes that occur in peroxisomes.
Book Review: Molecular Basis for the Perception of Pain
Authors: Hill R. G.
Published: April 2009

It is perhaps presumptuous to talk about the molecular basis of a subjective sensation such as pain, but defined conformational changes in membrane proteins, controlled by a family of extra- and intracellular messenger molecules, are known to underlie the activation of sensory nerve terminals and the process of synaptic neurotransmission, which are necessary for pain perception. Furthermore, a subset of neurotransmission processes has a permissive, and possibly exclusive, role in pain perception. Clearly, the experience of pain in the clinical sense with all its affective components of unpleasantness and suffering cannot yet be fully understood in molecular terms, but the process of nociception, whereby the signal generated as a result of tissue damaging or potentially damaging peripheral stimuli reaches and evokes neuronal activity in the central nervous system, is becoming better characterized. Recent advances in neurobiology have given us insights that are already helping improve understanding of the events that lead to a patient experiencing pain and, it is hoped, will also lead to more successful treatment strategies.
Nogo: A Molecular Determinant of Axonal Growth and Regeneration
Authors: Grandpré Tadzia , Strittmatter Stephen M.
Published: April 2009

Following injury, axons of the adult mammalian central nervous system (CNS) fail to regenerate. As a result, CNS trauma generally results in severe and persistent functional deficits. The inability of CNS axons to regenerate is largely associated with nonneuronal aspects of the CNS environment that are inhibitory to axonal elongation. This inhibition is mediated by the glial scar, including reactive astrocytes, and by the myelin-associated neurite outgrowth inhibitors chondroitin sulfate proteoglycans, myelin-associated glyco-protein, and Nogo. Nogo is an integral membrane protein that localizes to CNS, but not peripheral nervous system, myelin. In vitro characterization of Nogo has demonstrated its function as a potent inhibitor of axon elongation. In vivo neutralization of Nogo activity results in enhanced axonal regeneration and functional recovery following CNS injury as well as increased plasticity in uninjured CNS fibers. These findings suggest that Nogo may be a major contributor to the nonpermissive nature of the CNS environment. NEURO-SCIENTIST 7(5):377-386, 2001
Book Review: Glutamate on Demand: Astrocytes as a Ready Source
Authors: Mazzanti Mary , Sul Jai-Yoon , Haydon Philip G.
Published: April 2009

The past decade of studies has changed our view of the integrative capacities and roles of glia. A picture is emerging in which neurons and astrocytes, a subtype of glial cell, are in a continuous regulatory dialogue. Initial studies demonstrated that chemical transmitters, which are released from neurons, induce elevations of astrocytic calcium. Furthermore, stimulation of neuronal afferents at modest frequencies induces a calcium response in astrocytes that is graded with stimulation frequency. The consequence of this astrocytic calcium response is now beginning to be appreciated in that changes in calcium level can induce the release of the chemical transmitter glutamate from this nonneuronal cell. During the past few years, it has been shown that by releasing glutamate, astrocytes can regulate synaptic transmission and contribute to certain forms of synaptic plasticity. The roles played in information processing by this glial feedback loop remain to be determined. However, it is likely that the results of these recent studies will signal a new way of thinking about the nervous system, in which the glial cell comes to the forefront of our attention.
Book Review: Bilateral Activity and Callosal Connections in the Somatosensory Cortex
Authors: Iwamura Yoshiaki , Taoka Miki , Iriki Atsushi
Published: April 2009

Earlier studies recording single neuronal activity in the postcentral somatosensory cortex of monkeys converged in suggesting that the bilateral receptive fields were related exclusively to the body midline including the trunk, perioral face, and oral cavity. These neurons were recorded mostly in the rostral part of the gyrus, areas 3b and 1. However, the authors recently found a substantial number of neurons with bilateral receptive fields on extremities, hand/digits, shoulders/arms, or legs/feet in the caudalmost part (areas 2 and 5) of the postcentral gyrus. The authors review these results and discuss functional implications of the bilateral representation in the postcentral somatosensory cortex.
Neural Plasticity after Human Spinal Cord Injury: Application of Locomotor Training to the Rehabilitation of Walking
Authors: Harkema Susan J.
Published: April 2009

Recovery of locomotion has been considered unattainable following a clinically complete or severe incomplete spinal cord injury even after conventional therapy. However, the locomotion of spinal animals can be improved by training that provides complex temporal patterns of sensory information related to stepping that is interpreted by the spinal cord. This review discusses the evidence that suggests human spinal networks can integrate and interpret complex sensory signals to produce functional efferent output and adapt to repetitive training. Locomotor training, a new rehabilitative approach, is based on principles that promote the movement of limbs and trunk to generate sensory information consistent with locomotion to improve the potential for the recovery of walking after neurologic injury.
Book Review: Molecular Regulation of Circadian Rhythms in Drosophila and Mammals
Authors: Meyer-Bernstein Elizabeth L. , Sehgal Amita
Published: April 2009

Through the use of genetically amenable model systems, we have begun to form a relatively clear idea as to the molecular mechanisms that constitute a functioning circadian clock. It is now known that mechanisms that underlie overt rhythms are conserved across species. At the basic core of the clock lies a transcriptional/translational feedback loop. The primary components of this loop are called clock genes and are similar for the fruit fly, Drosophila melanogaster, and mammalian systems. However, many questions regarding their regulation remain unanswered. In addition to their localization in brain areas associated with pacemaking function, clock genes are also found in peripheral tissues where their presence may confer circadian regulation upon local, tissue-specific functions. The light-dark cycle is the primary environmental stimulus for the synchronization of the circadian clock. In Drosophila, light is known to induce the degradation of a clock component resulting in the synchronization of the core clock mechanism. Photic signals are transmitted to the clock, at least in part, by the blue light photoreceptor cryptochrome. Although expression of several mammalian clock gene products is also altered in response to light, the photoreceptor(s) involved have not yet been defined.
Book Review: Gene Therapy with Herpes Simplex Virus Vectors: Progress and Prospects for Clinical Neuroscience
Authors: Latchman David S.
Published: April 2009

Gene delivery to the nervous system represents perhaps the ultimate challenge of gene therapy in view of the complexity of this system, the wide variety of intractable neurological diseases, and the need to deliver the gene to nondividing cells. Although a variety of systems for such gene delivery are under development, herpes simplex virus has unique advantages in terms of its large genome size and its ability to naturally enter a latent state in neuronal cells. Considerable progress has been made in the effective disablement of this virus while retaining its ability to deliver genes and in producing long-term expression of the foreign gene. It is likely that these viruses may ultimately be of use in human gene therapy procedures for otherwise intractable neurological diseases such as Parkinson’s disease.
Coding of Objects in the Prefrontal Cortex in Monkeys and Humans
Authors: Rainer Gregor , Ranganath Charan
Published: April 2009

The prefrontal cortex is an area of high-level association cortex that plays an important part in the processing of visual objects. In this update, we summarize recent experimental findings that have investigated object processing in the frontal cortex in monkeys and humans. We highlight several common themes that have emerged from the study of these different systems, including the short-term maintenance of object information in working memory and the processing of novel information. Together, these findings suggest that regions of the prefrontal cortex participate in the selection, maintenance, and evaluation of task-relevant attributes. At a larger level, the convergence of findings from monkey and human studies demonstrates that concurrent investigation of scientific questions in both species can be a fruitful approach and promises to lead to future advances.
Prostaglandin D2 in Sleep-Wake Regulation: Recent Progress and Perspectives
Authors: Hayaishi Osamu , Urade Yoshihiro
Published: April 2009

Prostaglandin (PG) D2is one of the most active endogenous sleep-promoting substances, which induces physiological sleep in rodents, primates, and most probably in humans as well. In this update article, we review recent experimental results concerning the molecular mechanisms underlying sleep-wake regulation by PGD2, the link between the humoral regulation by the PGD2system, and the neural network involved in the promotion of non-rapid eye movement (NREM) sleep and the abnormality of NREM sleep regulation found in gene-manipulated mice for PGD synthase.
Book Review: Recruiting the Immune Response to Promote Axon Regeneration in the Injured Spinal Cord
Authors: David Samuel , Ousman Shalina S.
Published: April 2009

Myelin contains molecules that can inhibit the growth and regeneration of axons. Neutralizing the activity of these inhibitors can enhance axon regeneration in the adult mammalian central nervous system (CNS). The complexity of the CNS-immune system interactions after CNS trauma is now beginning to be better understood. Recent studies indicate that both cell-mediated and antibody-mediated immune responses can help in promoting axon regeneration after CNS injury. It is hoped that such advances will lead to the development of safe and effective vaccine and cytokine treatments for spinal cord injuries.
Book Review: Neurotrophins and Plasticity in the Visual Cortex
Authors: Caleo Matteo , Maffei Lamberto
Published: April 2009

The visual cortex is one of the favorite models for the study of experience-dependent changes in neuronal structure and function. A number of recent investigations indicate that the neurotrophic factors of the nerve growth factor family (neurotrophins) play a pivotal role in visual cortical plasticity. Neurotrophins and their receptors are present in the cortex during the critical period for plasticity, and neurotrophin levels are regulated by electrical activity. Neurotrophins modulate synaptic transmission and patterns of neuronal connectivity in the cortex. This review summarizes the in vivo and in vitro data that demonstrate the involvement of neurotrophins in visual cortical plasticity and discusses the possible mechanisms of their action.
Glutamate and the Presynaptic Control of Spinal Sensory Transmission
Authors: Huettner James E. , Kerchner Geoffrey A. , Zhuo Min
Published: April 2009

Sensory neurons, in particular the small- and medium-diameter cells that sense painful stimuli, express both ionotropic and metabotropic glutamate receptors, which may regulate transmission between sensory neurons and their targets in the spinal cord dorsal horn. Although the roles that these receptors play in normal physiology are not completely understood, recent work has provided strong evidence for their ability to modulate transmitter release from primary afferent terminals.
Review: Neural Coding and the Basic Law of Psychophysics
Authors: Johnson Kenneth O. , Hsiao Steven S. , Yoshioka Takashi
Published: April 2009

There have been three main ideas about the basic law of psychophysics. In 1860, Fechner used Weber’s law to infer that the subjective sense of intensity is related to the physical intensity of a stimulus by a logarithmic function (the Weber-Fechner law). A hundred years later, Stevens refuted Fechner’s law by showing that direct reports of subjective intensity are related to the physical intensity of stimuli by a power law. MacKay soon showed, however, that the logarithmic and power laws are indistinguishable without examining the underlying neural mechanisms. Mountcastle and his colleagues did so, and, on the basis of transducer functions obeying power laws, inferred that subjective intensity must be related linearly to the neural coding measure on which it is based. In this review, we discuss these issues and we review a series of studies aimed at the neural mechanisms of a very complex form of subjective experience—the experience of roughness produced by a textured surface. The results, which are independent of any assumptions about the form of the psychophysical law, support the idea that the basic law of psychophysics is linearity between subjective experience and the neural activity on which it is based.
Review: Plasticity of the Visual Cortex after Injury: What’s Different about the Young Brain?
Authors: Payne Bertram R. , Lomber Stephen G.
Published: April 2009

The repercussions of localized injury of the cerebral cortex in young brains differ from the repercussions triggered by equivalent damage of the mature brain. In the young brain, some distant neurons are more vulnerable to the lesion, whereas others survive and expand their projections to bypass damaged and degenerated structures. The net result is sparing of neural processing and behaviors. This article summarizes both the modifications in visual pathways resulting from visual cortex lesions sustained early in life and the neural and behavioral processes that are spared or permanently impaired. Experiments using reversible deactivation show that at least two highly localizable functions of normal cerebral cortex are remapped across the cortical surface as a result of an early lesion of the primary visual cortex. Moreover, the redistributions have spread the essential neural operations underlying orienting behavior from the visual parietal cortex to a normally functionally distinct type of cortex in the visual temporal system, and in the opposite direction for complex-pattern recognition. Similar functional reorganizations may underlie sparing of neural processes and behavior following early lesions in other cerebral systems, and these other systems may respond well to emerging therapeutic strategies designed to enhance the sparing of functions.
Calcium Dysregulation in the Aging Brain
Authors: Foster Thomas C. , Kumar Ashok
Published: April 2009

The idea that age-related cognitive decline is associated with disruption of calcium (Ca2+) homeostasis has been investigated over the past two decades. Much of this work has focused on the hippocampus because hippocampal-dependent memory is age sensitive. It is now well established that Ca2+-dependent processes such as susceptibility to neurotoxicity, the afterhyperpolarization amplitude, induction of synaptic plasticity, and long-term potentiation and long-term depression are altered with age. Recent work has identified changes in Ca2+signaling pathways that may underlie the development of these biological markers of aging. This review considers recent findings concerning interactions between the various Ca2+-dependent processes, with special emphasis on the role of altered Ca2+ regulation and disruption of Ca2+ signaling pathways in mediating the expression of biological and behavioral markers of brain aging.
The Thalamic Reticular Nucleus: More Than a Sensory Nucleus?
Authors: Mc Alonan Kerry , Brown Verity J.
Published: April 2009

Sensory information is routed to the cortex via the thalamus, but despite this sensory bombardment, animals must attend selectively to stimuli that signal danger or opportunity. Sensory input must be filtered, allowing only behaviorally relevant information to capture limited attentional resources. Located between the thalamus and cortex is a thin lamina of neurons called the thalamic reticular nucleus (Rt). The thalamic reticular nucleus projects exclusively to thalamus, thus forming an essential component of the circuitry mediating sensory transmission. This article presents evidence supporting a role for Rt beyond the mere relay of sensory information. Rather than operating as a component of the sensory relay, the authors suggest that Rt represents an inhibitory interface or “attentional gate,” which regulates the flow of information between the thalamus and cortex. Recent findings have also implicated Rt in higher cognitive functions, including learning, memory, and spatial cognition. Drawing from recent insights into the dynamic nature of the thalamic relay in awake, behaving animals, the authors present a speculative account of how Rt might regulate thalamocortical transmission and ultimately the contents of consciousness.