The Neuroscientist recent issues

The Neuroscientist Comments

2008-07-25

Perspectives on Neuroscience and Behavior

2008-07-25

Neuronal Targeting in Diabetes Mellitus: A Story of Sensory Neurons and Motor Neurons

Zochodne, D. W., Ramji, N., Toth, C. — 2008-07-25

Diabetes mellitus targets the peripheral nervous system in unique but disabling ways. Although several mechanisms may target peripheral neurons, they render a degenerative pattern of damage that begins in distal terminals. Moreover, sensory neurons are involved early, motor neurons later. By studying a variety of diabetic neuropathy models in rats, mice, and other species, an overall appreciation of its neurodegeneration emerges. Understanding how mechanisms of diabetes complications target peripheral neurons selectively may offer opportunities to intervene before irretrievable neuron loss develops.NEUROSCIENTIST 14(4):311–318, 2008. DOI: 10.1177/1073858408316175

The What, When, Whether Model of Intentional Action

Brass, M., Haggard, P. — 2008-07-25

The question of how we can intentionally control our behavior has an enduring fascination for philosophers, psychologists, and neurologists. Brain imaging techniques such as functional MRI have recently provided new insights into the functional and brain mechanisms involved in intentional action. However, the literature is rather contradictory and does not reveal a consistent picture of the functional neuroanatomy of intentional action. Here the authors argue that this confusion arises partly because intentional action has been treated as a unitary concept within neuroscience, even though experimental studies may focus on any of a number of different aspects of intentional action. To provide a heuristic framework for the investigation of intentional action, the authors propose a model that distinguishes three major components: a component related to the decision about which action to execute (what component), a component that is related to the decision about when to execute an action (when component), and finally the decision about whether to execute an action or not (whether component). Based on this distinction, the authors review some key findings on intentional action and provide neuroscientific evidence for the What, When, Whether (WWW) model of intentional action. NEUROSCIENTIST 14(4):319–325, 2008. DOI: 10.1177/1073858408317417

Cognitive Role of Neurogenesis in Depression and Antidepressant Treatment

Perera, T. D., Park, S., Nemirovskaya, Y. — 2008-07-25

The discovery of newborn neurons in the adult brain has generated enormous interest over the past decade. Although this process is well documented in the hippocampus and olfactory bulb, the possibility of neuron formation in other brain regions is under vigorous debate. Neurogenesis within the adult hippocampus is suppressed by factors that predispose to major depression and stimulated by antidepressant interventions. This pattern has generated the hypothesis that impaired neurogenesis is pathoetiological in depression and stimulation of newborn neurons essential for effective antidepressant action. This review critically evaluates the evidence in support of and in conflict with this theory. The literature is divided into three areas: neuronal maturation, factors that influence neurogenesis rates, and function of newborn neurons. Unique elements in each of these areas allow for the refinement of the hypothesis. Newborn hippocampal neurons appear to be necessary for detecting subtle environmental changes and coupling emotions to external context. Thus speculatively, stress-induced suppression of neurogenesis would uncouple emotions from external context leading to a negative mood state. Persistence of negative mood beyond the duration of the initial stressor can be defined as major depression. Antidepressant-induced neurogenesis therefore would restore coupling of mood with environment, leading to the resolution of depression. This conceptual framework is provisional and merits evaluation in further experimentation. Critically, manipulation of newborn hippocampal neurons may offer a portal of entry for more effective antidepressant treatment strategies.NEUROSCIENTIST 14(4):326–338, 2008. DOI: 10.1177/1073858408317242

Astrocyte Responses after Neonatal Ischemia: The Yin and the Yang

Villapol, S., Gelot, A., Renolleau, S., Charriaut-Marlangue, C. — 2008-07-25

Neonatal encephalopathy is a major predictor of neurodevelopmental disability in term infants and occurs in 1 to 6 of every 1000 live term births. Despite improvements in perinatal practice during the past several decades, the incidence of cerebral palsy attributed to neonatal asphyxia remained essentially unchanged, primarily because management strategies were supportive and not targeted toward the processes of ongoing injury. Traditionally, experimental research in vivo focused on neurons, and more recently, oligodendrocytes whereas astrocytes have been more or less neglected. This review aims at dissecting possible protective as well as destructive roles of astrocytes in the immature ischemic brain to stimulate further research into this unexplored aspect of brain pathophysiology. NEUROSCIENTIST 14(4):339ndash;344, 2008. DOI: 10.1177/1073858408316003

The Prefrontal Cortex: Functional Neural Development During Early Childhood

Tsujimoto, S. — 2008-07-25

The prefrontal cortex plays an essential role in various cognitive functions, such as planning and reasoning, yet little is known about how such neural mechanisms develop during childhood, particularly in young children. To better understand this issue, the present article reviews the literature on the development of the prefrontal cortex during early childhood, focusing mainly on the changes in structural architecture, neural activity, and cognitive abilities. Neuroanatomically, the prefrontal cortex undergoes considerable maturation during childhood, including a reduction of synaptic and neuronal density, a growth of dendrites, and an increase in white matter volume, thereby forming distributed neural networks appropriate for complex cognitive processing. Concurrently, behavioral performance of various cognitive tasks improves with age, and intercorrelations among performance on each task become weak through development. Furthermore, the correlation between subcategories of intelligence test decreases as general intellectual efficiency increases. In addition, recent neuroimaging findings suggest that the prefrontal cortex is already functional in 4-yearolds and becomes organized into focal, fine-tuned systems through later development. The literature reviewed suggests that fractionation of the functional neural systems plays a key role in the development of prefrontal cortex and such fractionating process has already commenced in preschool children. NEUROSCIENTIST 14(4):345–358, 2008. DOI: 10.1177/1073858408316002

Activity-Dependent Thalamocortical Axon Branching

Hayano, Y., Yamamoto, N. — 2008-07-25

The thalamocortical (TC) projection in the mammalian brain involves fundamental aspects in branch formation during development. TC axons are known to form branches not only in a genetically defined but also in an activity-dependent fashion. Recent evidence indicates that TC axon branching is generated by positive and negative regulators that are expressed with laminar specificity in the developing cortex. Moreover, in vitro studies using organotypic cocultures demonstrate that neural activity, including firing and synaptic activity, controls lamina-specific TC axon branching by altering its remodeling process with addition and elimination. Taken together, activity-dependent mechanisms can contribute to branch formation, affecting expression of branch-promoting and inhibiting factors and/or their receptor molecules. NEUROSCIENTIST 14(4):359–368, 2008. DOI: 10.1177/1073858408317272

Poststroke Neurogenesis: Emerging Principles of Migration and Localization of Immature Neurons

Ohab, J. J., Carmichael, S. T. — 2008-07-25

Stroke induces proliferation of newly born neurons in the subventricular zone, migration of these immature neurons away from the SVZ, and localization within peri-infarct tissues. These 3 processes of proliferation, migration, and localization constitute distinct spatial and temporal zones within poststroke neurogenesis with distinct molecular and cell-cell signaling environments. Immature neurons migrate after stroke in close association with blood vessels and astrocytic processes, in a process that involves matrix metalloproteinases. This poststroke migration shares similar features with normal neuroblast migration in the rostral migratory stream. Immature neurons localize in the peri-infarct cortex in a neurovascular niche where neurogenesis is causally linked to angiogenesis through the vascular factors SDF-1 and angiopoietin-1. Other vascular and neuronal growth factors have also been linked to poststroke neuroblast localization in peri-infarct tissue, including erythropoietin. Most data on poststroke neurogenesis derive from laboratory rodents, which may have an abnormal or blunted degree of neurogenesis and neuroplasticity compared to normal, wild rodents. This will likely affect translational application of the principles of poststroke neurogenesis from mouse to man. NEUROSCIENTIST 14(4):369–380, 2008. DOI: 10.1177/1073858407309545

Role of Dopamine in the Motivational and Cognitive Control of Behavior

Cools, R. — 2008-07-25

Brain dopamine has often been implicated in impulsive and/or inflexible behaviors, which may reflect failures of motivational and/or cognitive control. However, the precise role of dopamine in such failures of behavioral control is not well understood, not least because they implicate paradoxical changes in distinct dopamine systems that innervate dissociable neural circuits. In addition, there are large individual differences in the response to dopaminergic drugs with some individuals benefiting from and others being impaired by the same drug. This complicates progress in the understanding of dopamine's role in behavioral control processes, but also provides a major problem for neuropsychiatry, where some individuals are disproportionately vulnerable to the adverse effects of dopamine-enhancing drugs on motivation and cognition. Recent progress is reviewed from cognitive and behavioral neuroscience research on motivation and cognitive control, which begins to elucidate the factors that mediate the complex roles of mesolimbic, mesocortical, and nigrostriatal dopamine in behavioral control. NEUROSCIENTIST 14(4):381–395, 2008. DOI: 10.1177/1073858408317009

The Neuroscientist Comments

2008-06-06

Perspectives on Neuroscience and Behavior

2008-06-06

Disease Mechanisms in Neuroscience

2008-06-06

Acute Hypoxia, Diabetes, and Neuroimmune Dysregulation: Converging Mechanisms in the Brain

Johnson, D. R., Sherry, C. L., York, J. M., Freund, G. G. — 2008-06-06

Acute hypoxia is experienced by a variety of individuals (neonates to the elderly) and in an assortment of conditions and diseases (terrorist bomb attack to decompensated heart failure). Increasingly, elaboration of inflammatory cytokines appears key to the brain-based response to hypoxia, as evidenced by the biobehaviors of malaise, fatigue, lethargy, and loss of interest in the physical and social environment. These sickness symptoms implicate hypoxia-dependent activation of the neuroimmune system as a key component of acute hypoxia. Type 2 diabetes (T2D) is associated with increased incidence, severity, and delayed recovery from hypoxic events. Why T2D negatively affects acute hypoxia is not well understood. Recent work, however, reveals that anti-inflammatory pathways tied to the interleukin (IL)-1β arm of the neuroimmune system may be critical. In this review, the authors examine the link between acute hypoxia, T2D, and neuroimmunity. NEUROSCIENTIST 14(3):235–239, 2008. DOI: 10.1177/1073858407309544

Defects in Tongue Papillae and Taste Sensation Indicate a Problem with Neurotrophic Support in Various Neurological Diseases

2008-06-06

Neurotrophic support of developing neurons by neurotrophins is of critical importance in the development of fungiform papillae and taste buds. A number of neurological disorders show a decrease or increase in fungiform papillae or taste sensation. These can be grouped into disorders with reduced papillae (Machado-Joseph disease, Stüve-Wiedemann syndrome, familial dysautonomia, dystonia musculorum, and Behçet's disease) and those with taste defects only (Alzheimer's disease, Huntington's disease, hereditary sensory and autonomic neuropathy type IV, and diabetes mellitus). In addition, Parkinson's disease results in increased taste sensation. Here, we hypothesize that the main problem in these disorders is either not enough or too much neurotrophic support. Proneurotrophic drugs such as some antidepressants and aldose reductase inhibitors may prove useful in the treatment of these sensory and central nervous system disorders. Similarly, antineurotrophic drugs may also be useful in Parkinson's disease. Here we show that the protein involved in familial dysautonomia, IKAP, localizes to keratin filaments in HeLa cells, suggesting a role for the keratin cytoskeleton in neurotrophic support. NEUROSCIENTIST 14(3):240–250, 2008. DOI: 10.1177/1073858407312382

Charting Plasticity in the Regenerating Maps of the Mammalian Olfactory Bulb

Belluscio, L., Cummings, D. M. — 2008-06-06

The anatomical organization of a neural system can offer a glimpse into its functional logic. The basic premise is that by understanding how something is put together one can figure out how it works. Unfortunately, organization is not always represented purely at an anatomical level and is sometimes best revealed through molecular or functional studies. The mammalian olfactory system exhibits organizational features at all these levels including 1) anatomically distinct structural layers in the olfactory bulb, 2) molecular maps based upon odorant receptor expression, and 3) functional local circuits giving rise to odor columns that provide a contextual logic for an intrabulbar map. In addition, various forms of cellular plasticity have been shown to play an integral role in shaping the structural properties of most neural systems and must be considered when assessing each system's anatomical organization. Interestingly, the olfactory system invokes an added level of complexity for understanding organization in that it regenerates both at the peripheral and the central levels. Thus, olfaction offers a rare opportunity to study both the structural and the functional properties of a regenerating sensory system in direct response to environmental stimuli. In this review, we discuss neural organization in the form of maps and explore the relationship between regeneration and plasticity. NEUROSCIENTIST 14(3):251–263, 2008. DOI: 10.1177/1073858408315026

Persistent Inward Currents in Spinal Motoneurons and Their Influence on Human Motoneuron Firing Patterns

Heckman, C.J., Johnson, M., Mottram, C., Schuster, J. — 2008-06-06

Persistent inward currents (PICs) are present in many types of neurons and likely have diverse functions. In spinal motoneurons, PICs are especially strong, primarily located in dendritic regions, and subject to particularly strong neuromodulation by the monoamines serotonin and norepinephrine. Because motoneurons drive muscle fibers, it has been possible to study the functional role of their PICs in motor output and to identify PIC-mediated effects on motoneuron firing patterns in human subjects. The PIC markedly amplifies synaptic input, up to fivefold or more, depending on the level of monoaminergic input. PICs also tend to greatly prolong input time course, allowing brief inputs to initiate long-lasting self-sustained firing (i.e., bistable behavior). PIC deactivation usually requires inhibitory input and PIC amplitude can increase to repeated activation. All of these behaviors markedly increase motoneuron excitability. Thus, in the absence of monoaminergic input, motoneuron excitability is very low. Yet PICs have another effect: once active, they tend to sharply limit efficacy of additional synaptic input. All of these PIC effects have been detected in motoneuron firing patterns in human subjects and, hence, PICs are likely a fundamental component of normal motor output. NEUROSCIENTIST 14(3):264–275, 2008. DOI: 10.1177/1073858408314986

Potassium Channels: Newly Found Players in Synaptic Plasticity

Kim, J., Hoffman, D. A. — 2008-06-06

One of the major issues for modern neuroscience research concerns the molecular and cellular mechanisms that underlie the acquisition, storage, and recollection of memories by the brain. Regulation of the strength of individual synaptic inputs (synaptic plasticity) has, for decades, been the front-running candidate mechanism for cellular information storage, with some direct supporting evidence recently obtained. Research into the molecular mechanisms responsible for changing synaptic strength has, to date, primarily focused on trafficking and properties of the neurotransmitter receptors themselves (AMPARs and NMDARs). However, recent evidence indicates that, subsequent to receptor activation, synaptic inputs are subject to regulation by synaptically located K⁺ channels. It is therefore critical to understand the biophysical properties and subcellular localization (density and distribution) of these channels and how their properties are modulated. Here we will review recent findings showing that two different classes of K⁺ channels (A-type and small conductance, Ca²⁺ -activated K⁺ channels), beyond their traditional role in regulating action potential firing, contribute to the regulation of synaptic strength in the hippocampus. In addition, we discuss how modulation of these channels' properties and expression might contribute to synaptic plasticity. NEUROSCIENTIST 14(3):276–286, 2008. DOI: 10.1177/1073858408315041

Lessons from fMRI about Mapping Cortical Columns

Kim, S.-G., Fukuda, M. — 2008-06-06

Recently developed fMRI can map small functional structures noninvasively and repeatedly without any depth limitation. However, there has been a persistent concern as to whether the high-resolution fMRI signals actually mark the sites of increased neural activity. To examine this outstanding issue, the authors used iso-orientation columns of isoflurane-anesthetized cats as a biological model and confirmed the neural correlation of fMRI iso-orientation maps by comparing them with intrinsic optical imaging maps. The results suggest that highest fMRI signals indeed indicate the sites of increased neuronal activity. Now fMRI can be used to determine plastic and/or developmental change of functional columnar structure possibly on a layer-to-layer basis. In this review, the authors focus mainly on what technical aspects should be considered when mapping functional cortical columns, including imaging techniques and experimental design. NEUROSCIENTIST 14(3):287–299, 2008. DOI: 10.1177/1073858407309541

The Neuroscientist Comments

2008-03-19

Perspectives on Neuroscience and Behavior

2008-03-19

Disease Mechanisms in Neuroscience

2008-03-19

Livin' on the Edge: Imaging Dendritic Spine Turnover in the Peri-Infarct Zone during Ischemic Stroke and Recovery

Brown, C. E., Murphy, T. H. — 2008-03-19

The spontaneous recovery of sensory, motor, and cognitive functions after stroke is thought to be mediated primarily through the reorganization and rewiring of surviving brain circuits. Given that dendritic spine turnover underlies rewiring during normal development and plasticity, this process is likely to play a key role in mediating functional changes that occur during and after stroke. Recently, a new approach has been taken using two-photon microscopy to monitor, in real time, the temporal and spatial progression of dendritic plasticity in the living animal, both while it is experiencing the initial ischemic episode as well as during long-term recovery from stroke damage. Here, we highlight recent evidence showing that stroke can trigger extensive changes in the relatively hardwired adult brain. For example, when dendrites are challenged by acute ischemia, they can disintegrate within minutes of ischemia and rapidly reassemble during reperfusion. Over longer time scales, dendrites in the surviving peri-infarct zone show heightened levels of spine turnover for many weeks after stroke, thereby raising the possibility that future stroke therapies may be able to facilitate or optimize dendritic rewiring to improve functional recovery. NEUROSCIENTIST 14(2):139—146, 2008. DOI: 10.1177/1073858407309854

Reviews: BDNF and Memory Formation and Storage

Bekinschtein, P., Cammarota, M., Izquierdo, I., Medina, J. H. — 2008-03-19

During the past decade, a large body of evidence has implicated BDNF in synaptic plasticity. In this review, we focus on the newer experiments that involve BDNF in different aspects of learning and memory processing—in particular, in memory persistence and storage. NEUROSCIENTIST 14(2):147—156, 2008. DOI: 10.1177/1073858407305850

The Cortical Control of Visually Guided Grasping

Castiello, U., Begliomini, C. — 2008-03-19

People have always been fascinated by the exquisite precision and flexibility of the human hand. When hand meets object, we confront the overlapping worlds of sensorimotor and cognitive functions. The complex apparatus of the human hand is used to reach for objects, grasp and lift them, manipulate them, and use them to act on other objects. This review examines what is known about the control of the hand by the cerebral cortex. It compares and summarizes results from behavioral neuroscience, electrophysiology, and neuroimaging to provide a detailed description of the neural circuits that facilitate the formation of grip patterns in human and nonhuman primates. NEUROSCIENTIST 14(2):157—170, 2008. DOI: 10.1177/1073858407312080

Regulation of Synaptic Transmission by Ambient Extracellular Glutamate

Featherstone, D. E., Shippy, S. A. — 2008-03-19

Many neuroscientists assume that ambient extracellular glutamate concentrations in the nervous system are biologically negligible under nonpathological conditions. This assumption is false. Hundreds of studies over several decades suggest that ambient extracellular glutamate levels in the intact mammalian brain are ~0.5 to ~5 µM. This has important implications. Glutamate receptors are desensitized by glutamate concentrations significantly lower than needed for receptor activation; 0.5 to 5 µM of glutamate is high enough to cause constitutive desensitization of most glutamate receptors. Therefore, most glutamate receptors in vivo may be constitutively desensitized, and ambient extracellular glutamate and receptor desensitization may be potent but generally unrecognized regulators of synaptic transmission. Unfortunately, the mechanisms regulating ambient extracellular glutamate and glutamate receptor desensitization remain poorly understood and understudied. NEUROSCIENTIST 14(2):171—181, 2008. DOI: 10.1177/1073858407308518

The Area Postrema: A Brain Monitor and Integrator of Systemic Autonomic State

Price, C. J., Hoyda, T. D., Ferguson, A. V. — 2008-03-19

The area postrema is a medullary structure lying at the base of the fourth ventricle. The area postrema's privileged location outside of the blood-brain barrier make this sensory circumventricular organ a vital player in the control of autonomic functions by the central nervous system. By virtue of its lack of tight junctions between endothelial cells in this densely vascularized structure and the presence of fenestrated capillaries, peptide and other physiological signals borne in the blood have direct access to neurons that project to brain areas with important roles in the autonomic control of many physiological systems, including the cardiovascular system and systems controlling feeding and metabolism. However, the area postrema is not simply a conduit through which signals flow into the brain, but it is now being recognized as the initial site of integration for these signals as they enter the circuitry of the central nervous system. NEUROSCIENTIST 14(2):182—194, 2008. DOI: 10.1177/1073858407311100

The Motor Cortex and Its Role in Phantom Limb Phenomena

Reilly, K. T., Sirigu, A. — 2008-03-19

Limb amputation results in plasticity of connections between the brain and muscles; the cortical motor representation of the missing limb seemingly disappears. The disappearance of the hand's motor representation is, however, difficult to reconcile with evidence that a perceptual representation of the missing limb persists in the form of a phantom limb endowed with sensory and motor qualities. Here, we argue that despite considerable reorganization within the motor cortex of upper-limb amputees, the representation of the amputated hand does not disappear. We hypothesize that two levels of hand-movement representation coexist within the primary motor cortex; at one level, limb movements are specified in terms of arm and hand motor commands, and at another level, limb movements are specified as muscles synergies. We propose that primary motor cortex reorganization after amputation concerns primarily the upper limb's muscular map but not its motor command map and that the integrity of the motor command map underlies the existence of the phantom limb. NEUROSCIEN-TIST 14(2):195—202, 2008. DOI: 10.1177/1073858407309466

Unawareness of Illness in Neuropsychiatric Disorders: Phenomenological Certainty versus Etiopathogenic Vagueness

Orfei, M. D., Robinson, R. G., Bria, P., Caltagirone, C., Spalletta, G. — 2008-03-19

Awareness of illness is a form of self-knowledge concerning information about the pathological state, its functional consequence, and the way it affects the patient and his interaction with the environment. Unawareness of illness has raised much interest for its consequences on compliance with treatment, prognosis, and the patient's quality of life. This review highlights the great complexity of this phenomenon both at phenomenological and etiopathogenic levels in stroke, traumatic brain injury, psychosis, dementias, and mood disorders. In particular, the clinical expression is characterized by failure to acknowledge being ill, misattribution of symptoms, and noncompliance with treatment. Unawareness of illness may also be linked with characteristics that are peculiar to each individual disturbance, such as symptom duration and cognitive impairment. Despite a long-lasting interest in the clinical characteristics of unawareness, only recently has the focus of research investigated pathogenic mechanisms, with sometimes controversial results. The vast majority of studies have pointed out a remarkable involvement of the right hemisphere. Specifically, functional and structural changes of the dorso-lateral prefrontal cortex and some other frontal areas have often been found to be associated with awareness deficit, as well as parieto-temporal areas and the thalamus, although to a lesser extent. These data indicate the present difficulty of localizing a specific cerebral area involved in unawareness and suggest the existence of possible brain circuits responsible for awareness. In conclusion, phenomenological manifestations of poor awareness are well outlined in their complexity, whereas neuroanatomic and neuropsychological findings are still too vague and sparse and need further, greater efforts to be clarified. NEUROSCIENTIST 14(2): 203—222, 2008. DOI: 10.1177/1073858407309995

The Neuroscientist Comments

2008-01-10

Perspectives on Neuroscience and Behavior

2008-01-10

Disease Mechanisms in Neuroscience

2008-01-10

Mitochondrial Dynamics and Peripheral Neuropathy

Baloh, R. H. — 2008-01-10

Peripheral neuropathy is perhaps the archetypal disease of axonal degeneration, characteristically involving degeneration of the longest axons in the body. Evidence from both inherited and acquired forms of peripheral neuropathy strongly supports that the primary pathology is in the axons themselves and points to disruption of axonal transport as an important disease mechanism. Recent studies in human genetics have further identified abnormalities in mitochondrial dynamics—the fusion, fission, and movement of mitochondria— as a player in the pathogenesis of inherited peripheral neuropathy. This review provides an update on the mechanisms of mitochondrial trafficking in axons and the emerging relationship between the disruption of mitochondrial dynamics and axonal degeneration. Evidence suggests mitochondria are a "critical cargo" whose transport is necessary for proper axonal and synaptic function. Importantly, understanding the regulation of mitochondrial movement and the consequences of decreased axonal mitochondrial function may define new paths for therapeutic agents in peripheral neuropathy and other neurodegenerative diseases. NEUROSCIENTIST 14(1):12—18, 2008. DOI: 10.1177/1073858407307354

Cerebral Disconnectivity: An Early Event in Schizophrenia

Begre, S., Koenig, T. — 2008-01-10

Neuroimaging and electrophysiological investigations have demonstrated numerous differences in brain morphology and function of chronic schizophrenia patients compared to healthy controls. Studying patients at the beginning of their disease without the confounding effects of chronicity, medication, and institutionalization may provide a better understanding of schizophrenia. Recently, at many institutions around the world, special projects have been launched for specialized treatment and research of this interesting patient group. Using the PubMed search engine in this update, the authors summarize recent investigations between January 2002 and September 2006 that focus on whether signs of disconnectivity already exist early in the disease process. They discuss gray and white matter changes, their impact on symptomatology, electroencephalogram-based studies on connectivity, and possible influences of medication. NEUROSCIENTIST 14(1):19—45, 2008. DOI: 10.1177/1073858406298391

Gender-Related Differences in Apoptotic Pathways After Neonatal Cerebral Ischemia

Renolleau, S., Fau, S., Charriaut-Marlangue, C. — 2008-01-10

Many central nervous system (CNS) diseases display sexual dimorphism, specifically a predilection for one gender or a gender-dependent response to treatment. Exposure to circulating sex steroids is felt to be a chief contributor to this phenomenon. However, CNS diseases of childhood and of the elderly also demonstrate gender predominance and/or sexual dimorphism response to therapies. In this short update, we provide information concerning one of the most interesting new emerging concepts related to the influence of the sex in the pathogenesis of developmental brain injuries leading to different levels of neuroprotection between genders after cerebral hypoxia-ischemia or ischemia. NEUROSCIENTIST 14(1):46—52, 2008. DOI: 10.1177/1073858407308889

TNF {alpha}: A Trigger of Autonomic Dysfunction

Hermann, G. E., Rogers, R. C. — 2008-01-10

During disease, infection, or trauma, the cytokine tumor necrosis factor (TNF) causes fever, fatigue, malaise, allodynia, anorexia, gastric stasis associated with nausea, and emesis via interactions with the central nervous system. Our studies have focused on how TNF produces a profound gastric stasis by acting on vago-vagal reflex circuits in the brainstem. Sensory elements of this circuit (i.e., nucleus of the solitary tract [NST] and area postrema) are activated by TNF. In response, the efferent elements (i.e., dorsal motor neurons of the vagus) cause gastroinhibition via their action on the gastric enteric plexus. We find that TNF presynaptically modulates the release of glutamate from primary vagal afferents to the NST and can amplify vagal afferent responsiveness by sensitizing presynaptic intracellular calcium-release mechanisms. The constitutive presence of TNF receptors on these afferents and their ability to amplify afferent signals may explain how TNF can completely disrupt autonomic control of the gut. NEUROSCIENTIST 14(1):53—67, 2008. DOI: 10.1177/1073858407305725

The Endoplasmic Reticulum as an Integrator of Multiple Dendritic Events

Myoung Kyu Park, , Yu Mi Choi, , Yun Kyung Kang, , Petersen, O. H. — 2008-01-10

Dendrites are integrating elements that receive numerous subsets of heterogeneous synaptic inputs, which generate temporally and spatially distinct changes in membrane potential and intracellular Ca²⁺ levels in local domains. The ubiquitously distributed endoplasmic reticulum (ER) in dendrites is luminally connected to the bulk ER in the soma, constituting a huge interconnected intracellular network that allows rapid Ca²⁺ diffusion and equilibration. The ER is an excitable organelle that can elicit or terminate cytosolic Ca²⁺ signals in local or global domains. The absolute level or changes in the Ca²⁺ concentration in the ER lumen are also very important for the synthesis and maturation of proteins, regulation of gene expression, mitochondrial functions, neuronal excitability, and synaptic plasticity. Through the connected lumen of the ER, information from multiple dendritic events in neurons appears to be delivered into the bulk ER in the soma. Therefore, the ER network in neurons is emerging as a conveyor and integrator of signals. In this article, we will discuss the various roles of the ER and the functional and structural organization of the ER network in neurons. NEUROSCIENTIST 14(1):68—77, 2008.

Late-Onset Epileptogenesis and Seizure Genesis: Lessons From Models of Cerebral Ischemia

Epsztein, J., Ben-Ari, Y., Represa, A., Crepel, V. — 2008-01-10

Patients surviving ischemic stroke often express delayed epileptic syndromes. Late poststroke seizures occur after a latency period lasting from several months to years after the insult. These seizures might result from ischemia-induced neuronal death and associated morphological and physiological changes that are only partly elucidated. This review summarizes the long-term morphofunctional alterations observed in animal models of both focal and global ischemia that could explain late-onset seizures and epileptogenesis. In particular, this review emphasizes the change in GABAergic and glutamatergic signaling leading to hyperexcitability and seizure genesis. NEUROSCIENTIST 14(1):78—90, 2008.

Neurogenesis in the Cerebellum

Carletti, B., Rossi, F. — 2008-01-10

In the past few years, genetic fate mapping experiments have changed our vision of cerebellar development, particularly in redefining the origin of gabaergic and glutamatergic neurons of the cerebellar cortex and highlighting the precise spatio-temporal sequence of their generation. Here the authors review cerebellar neurogenesis and discuss the fate mapping studies with other new information stemming from transplantation experiments, in an effort to link the developmental potential of neural progenitor populations of the cerebellum with their spatio-temporal origin. NEUROSCIENTIST 14(1):91—100, 2008.

Encephalization, Emergent Properties, and Psychiatry: A Minicolumnar Perspective

Casanova, M. F., Tillquist, C. R. — 2008-01-10

The focus of the authors' attention is the consequence of brain growth understood in terms of the development of networks of cortical cell minicolumns, the elemental information-processing units of the brain. The authors view cortical growth, encephalization, and the emergence of higher cognitive functions in humans as the consequence of an increase in the number of minicolumns and their connections. Encephalization has proceeded via weak linkages of canonical circuits, which facilitate the emergence of novel cortical functions. In addition to reframing the evolution of mind, this perspective provides a conceptual framework for a better understanding of the origin and maladaptive nature of certain psychiatric conditions. NEUROSCIENTIST 14(1):101—118, 2008. DOI: 10.1177/1073858407309091

Functional Anatomic Models of Language: Assembling the Pieces

Ben Shalom, D., Poeppel, D. — 2008-01-10

In the past few years, a series of influential review articles have summarized the state of the art with respect to cortical models of language organization. The present article is a mini-review and conceptual meta-analysis of several of the most prominent recent contributions. Based on the models, the authors extract some generalizations to arrive at a more robust model that 1) does justice to the range of neurological data, 2) is more connected to research in linguistics and psycholinguistics, and 3) stimulates hypothesis-driven research in this domain. In particular, the article attempts to unify a few of the current large-scale models of the functional neuroanatomy of language in a more principled manner. First, the authors argue that the relevant type of processing in a given cortical area, that is, memorizing (temporal cortex) versus analyzing (parietal) versus synthesizing (frontal), lies at the basis of local neuronal structure and function. Second, from an anatomic perspective, more dorsal regions within each of these (temporal, parietal, and frontal) systems specialize more in phonological processing, middle areas in syntactic processing, and more ventral areas in semantic processing. NEUROSCIENTIST 14(1):119—127, 2008.