The Neuroscientist current issue

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