Showing papers in "The Neuroscientist in 2004"
TL;DR: Evidence from anatomical, neuroimaging, behavioral, electrophysiological, pharmacological, and biochemical data that implicate the amygdala in pain modulation and emotional responses to pain are reviewed.
Abstract: A reciprocal relationship exists between persistent pain and negative affective states such as fear, anxiety, and depression. Accumulating evidence points to the amygdala as an important site of such interaction. Whereas a key role of the amygdala in the neuronal mechanisms of emotionality and affective disorders has been well established, the concept of the amygdala as an important contributor to pain and its emotional component is still emerging. This article will review and discuss evidence from anatomical, neuroimaging, behavioral, electrophysiological, pharmacological, and biochemical data that implicate the amygdala in pain modulation and emotional responses to pain. The latero-capsular division of the central nucleus of the amygdala is now defined as the “nociceptive amygdala” and integrates nociceptive information with poly-modal information about the internal and external bodily environment. Dependent on environmental conditions and affective states, the amygdala appears to play a dual facilitato...
645 citations
TL;DR: This review summarizes the literature on brain morphological changes that occur throughout the human life span from childhood into old age and examines changes observed postmortem and in vivo where various brain MRI analytic methods have been applied.
Abstract: In this review, the authors summarize the literature on brain morphological changes that occur throughout the human life span from childhood into old age. They examine changes observed postmortem and in vivo where various brain MRI analytic methods have been applied. They evaluate brain changes observed with volumetric image analytic methods and voxel-based morphometric methods that may be used to better localize where changes occur. The primary focus of the review is on recent studies using state-of-the-art cortical pattern-matching techniques to assess age-related changes in cortical asymmetries, gray matter distribution, and brain growth across various age spans. The authors attempt to integrate findings from the in vivo studies with results from postmortem studies and analyze the complicated question of when brain maturation stops and brain aging begins. Analyzing the regional patterns of change initiated at various ages may help elucidate relationships between changing brain morphology and changing cognitive functions that occur throughout life. Long-range longitudinal studies, correlations between imaging and postmortem data, and more advanced image acquisition and analysis technologies will be needed to fully interpret brain morphological changes observed in vivo in relation to development and aging.
540 citations
TL;DR: It has been possible to redefine impairments of executive function in Parkinson’s disease more precisely in terms of the specific neuropsychological, neuroanatomical, and psychopharmacological mechanisms involved.
Abstract: It has been known for many years that the classic motor symptoms of Parkinson's disease are accompanied by deficits of executive function that resemble those seen after frontal lobe damage in humans. What is less clear is how different components of frontostriatal circuitry contribute to these impairments. Recently, improved methods of clinical assessment and classification, combined with novel technical approaches, such as functional neuroimaging, have led to great advances in our understanding of the fundamental mechanisms that drive frontostriatal circuitry. As a direct result, it has been possible to redefine impairments of executive function in Parkinson's disease more precisely in terms of the specific neuropsychological, neuroanatomical, and psychopharmacological mechanisms involved.
490 citations
TL;DR: The authors review current accomplishments in the study of human reward processing and focus their discussion on explanations directed particularly at the role played by the ventral striatum, which may contribute to a better understanding of deficits associated with Parkinson’s disease.
Abstract: Experimental work in animals has identified numerous neural structures involved in reward processing and reward-dependent learning. Until recently, this work provided the primary basis for speculations about the neural substrates of human reward processing. The widespread use of neuroimaging technology has changed this situation dramatically over the past decade through the use of PET and fMRI. Here, the authors focus on the role played by fMRI studies, where recent work has replicated the animal results in human subjects and has extended the view of putative reward-processing neural structures. In particular, fMRI work has identified a set of reward-related brain structures including the orbitofrontal cortex, amygdala, ventral striatum, and medial prefrontal cortex. Moreover, the human experiments have probed the dependence of human reward responses on learned expectations, context, timing, and the reward dimension. Current experiments aim to assess the function of human reward-processing structures to determine how they allow us to predict, assess, and act in response to rewards. The authors review current accomplishments in the study of human reward processing and focus their discussion on explanations directed particularly at the role played by the ventral striatum. They discuss how these findings may contribute to a better understanding of deficits associated with Parkinson's disease.
455 citations
TL;DR: Mechanisms of cerebellar control of balance and locomotion are examined, emphasizing studies of humans and other animals, and Implications for rehabilitation are also considered.
Abstract: The cerebellum is important for movement control and plays a particularly crucial role in balance and locomotion. As such, one of the most characteristic signs of cerebellar damage is walking ataxia. It is not known how the cerebellum normally contributes to walking, although recent work suggests that it plays a role in the generation of appropriate patterns of limb movements, dynamic regulation of balance, and adaptation of posture and locomotion through practice. The purpose of this review is to examine mechanisms of cerebellar control of balance and locomotion, emphasizing studies of humans and other animals. Implications for rehabilitation are also considered.
427 citations
TL;DR: Although the strength of coupling between the legs is stronger than that between the arms, arm and leg movements are similarly regulated by CPG activity and sensory feedback during locomotion.
Abstract: Walking can be a very automated process, and it is likely that central pattern generators (CPGs) play a role in the coordination of the limbs. Recent evidence suggests that both the arms and legs are regulated by CPGs and that sensory feedback also regulates the CPG activity and assists in mediating interlimb coordination. Although the strength of coupling between the legs is stronger than that between the arms, arm and leg movements are similarly regulated by CPG activity and sensory feedback (e.g., reflex control) during locomotion.
389 citations
TL;DR: The challenge remains in the careful perturbation of injury/opioid-induced neuroimmune activation to down-regulate this process without inhibiting beneficial CNS autoimmunity that subserves neuronal protection following injury.
Abstract: One area that has emerged as a promising therapeutic target for the treatment and prevention of chronic pain and opioid tolerance/hyperalgesia is the modulation of the central nervous system (CNS) immunological response that ensues following injury or opioid administration. Broadly defined, central neuroimmune activation involves the activation of cells that interface with the peripheral nervous system and blood. Activation of these cells, as well as parenchymal microglia and astrocytes by injury, opioids, and other stressors, leads to subsequent production of cytokines, cellular adhesion molecules, chemokines, and the expression of surface antigens that enhance a CNS immune cascade. This response can lead to the production of numerous pain mediators that can sensitize and lower the threshold of neuronal firing: the pathologic correlate to central sensitization and chronic pain states. CNS innate immunity and Toll-like receptors, in particular, may be vital players in this orchestrated immune response and may hold the answers to what initiates this complex cascade. The challenge remains in the careful perturbation of injury/opioid-induced neuroimmune activation to down-regulate this process without inhibiting beneficial CNS autoimmunity that subserves neuronal protection following injury.
364 citations
TL;DR: Current data have revealed a more intricate picture in which astrocytes play a key role in supplying lactate as an additional energy substrate in register with glutamatergic activity.
Abstract: Classical neuroenergetics states that glucose is the exclusive energy substrate of brain cells and its full oxidation provides all the necessary energy to support brain function. Recent data have revealed a more intricate picture in which astrocytes play a key role in supplying lactate as an additional energy substrate in register with glutamatergic activity.
291 citations
TL;DR: Evidence that altered transcription of the 5-HT1A receptor can affect the serotonin system and limbic and cortical areas, leading to predisposition to depression is reviewed.
Abstract: The serotonin system is implicated in major depression and suicide and is negatively regulated by somatodendritic 5-HT1A autoreceptors. Desensitization of 5-HT1A autoreceptors is implicated in the 2- to 3-week latency for antidepressant treatments. Alterations in 5-HT1A receptor levels are reported in depression and suicide, and gene knockout of the 5-HT1A receptor results in an anxiety phenotype, suggesting that abnormal transcriptional regulation of this receptor gene may underlie these disorders. The 5-HT1A receptor gene is negatively regulated in neurons by repressors including REST/NRSF, Freud-1, NUDR/Deaf-1, and Hes5. The association with major depression, suicide, and panic disorder of a new functional 5-HT1A polymorphism at C(-1019)G that selectively blocks repression of the 5-HT1A autoreceptor by NUDR further suggests a causative role for altered regulation of this receptor in predisposition to mental illness. The authors review evidence that altered transcription of the 5-HT1A receptor can affect the serotonin system and limbic and cortical areas, leading to predisposition to depression.
256 citations
TL;DR: Present studies are broadly supportive of a neuromodulatory role for Zn2+ at specific excitatory and inhibitory synapses.
Abstract: The role of Zn2+ in the CNS has remained enigmatic for several decades. This divalent cation is accumulated by specific neurons into synaptic vesicles and can be released by stimulation in a Ca2+-dependent manner. Using Zn2+ fluorophores, radiolabeled Zn2+, and selective chelators, the location of this ion and its release pattern have been established across the brain. Given the distribution and possible release under physiological conditions, Zn2+ has the potential to act as a modulator of both excitatory and inhibitory neurotransmission. Excitatory N-methyl-D-aspartate (NMDA) receptors are directly inhibited by Zn2+, whereas non-NMDA receptors appear relatively unaffected. In contrast, inhibitory transmission mediated via GABAAreceptors can be potentiated via a presynaptic mechanism, influencing transmitter release; however, although some tonic GABAergic inhibition may be suppressed by Zn2+, most synaptic GABA receptors are unlikely to be modulated directly by this cation. In the spinal cord, glycinergi...
242 citations
TL;DR: It is argued that understanding collective neural dynamics in a recurrent microcircuit provides a key step in bridging the gap between network memory function and its underlying cellular mechanisms, and shed fundamental insights into the neural basis of spatial working memory impairment associated with mental disorders.
Abstract: The maintenance of a mental image in memory over a time scale of seconds is mediated by the persistent discharges of neurons in a distributed brain network. The representation of the spatial location of a remembered visual stimulus has been studied most extensively and provides the best-understood model of how mnemonic information is encoded in the brain. Neural correlates of spatial working memory are manifested in multiple brain areas, including the prefrontal and parietal association cortices. Spatial working memory ability is severely compromised in schizophrenia, a condition that has been linked to prefrontal cortical malfunction. Recent computational modeling work, in interplay with physiological studies of behaving monkeys, has begun to identify microcircuit properties and neural dynamics that are sufficient to generate memory-related persistent activity in a recurrent network of excitatory and inhibitory neurons during spatial working memory. This review summarizes recent results and discusses issues of current debate. It is argued that understanding collective neural dynamics in a recurrent microcircuit provides a key step in bridging the gap between network memory function and its underlying cellular mechanisms. Progress in this direction will shed fundamental insights into the neural basis of spatial working memory impairment associated with mental disorders.
TL;DR: The authors outline the range of reorganization of human representational cortex, encompassing reconstruction in concurrence with enhanced behaviorally relevant afferent activity; injury-related response dynamics as, for instance, driven by loss of input; and maladaptive reorganization pushed by the interaction between neuroplastic processes and aberrant environmental requirements.
Abstract: Animal and human research over the past decades have increasingly detailed the brain's capacity for reorganization of neural network architecture to adapt to environmental needs. In this article, the authors outline the range of reorganization of human representational cortex, encompassing 1) reconstruction in concurrence with enhanced behaviorally relevant afferent activity (examples include skilled musicians and blind Braille readers); 2) injury-related response dynamics as, for instance, driven by loss of input (examples include stroke, amputation, or in blind individuals); and 3) maladaptive reorganization pushed by the interaction between neuroplastic processes and aberrant environmental requirements (examples include synchronicity of input nurturing focal hand dystonia). These types of neuroplasticity have consequences for both understanding pathological dynamics and therapeutic options. This will be illustrated in examples of motor and language rehabilitation after stroke, the treatment of focal hand dystonia, and concomitants of injury-related reorganization such as phantom limb pain.
TL;DR: It is demonstrated that anatomical patterns of results vary according to the reading skills that characterize dyslexia, and the number and likelihood of atypical anatomical findings in oral and/or written language systems appears to be related to the pattern of impairments in measures of phonology, orthography, and fluency.
Abstract: A neuroanatomical description of dyslexia has been elusive, due in part to the complex cognitive nature of dyslexia. People with dyslexia have varying degrees of impairment in reading skills that engage oral and written language (reading) neural networks. Although findings for the inferior parietal lobule, inferior frontal gyrus, and cerebellum have been relatively consistent across studies, these studies also demonstrate that anatomical patterns of results vary according to the reading skills that characterize dyslexia. The number and likelihood of atypical anatomical findings in oral and/or written language systems appears to be related to the pattern of impairments in measures of phonology, orthography, and fluency. A comprehensive neurobiological understanding of dyslexia will depend on studies of dyslexic individuals with homogeneous perceptual, cognitive, and genetic backgrounds.
TL;DR: Recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory are described.
Abstract: We are rapidly advancing toward an understanding of the molecular events underlying odor transduction, mechanisms of spatiotemporal central odor processing, and neural correlates of olfactory perception and cognition. A thread running through each of these broad components that define olfaction appears to be their dynamic nature. How odors are processed, at both the behavioral and neural level, is heavily dependent on past experience, current environmental context, and internal state. The neural plasticity that allows this dynamic processing is expressed nearly ubiquitously in the olfactory pathway, from olfactory receptor neurons to the higher-order cortex, and includes mechanisms ranging from changes in membrane excitability to changes in synaptic efficacy to neurogenesis and apoptosis. This review will describe recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory.
TL;DR: The assumption that emotional conditions induce long-term neural plasticity in the amygdala suggests that the interrelations between the amygdala and brain regions, such as the hippocampus, may not be static but dynamic.
Abstract: There are two views regarding the role of the amygdala in emotional memory formation. According to one view, the amygdala modulates memory-related processes in other brain regions, such as the hippocampus. According to the other, the amygdala is a site for some aspects of emotional memory. Here the authors adduce behavioral, electrophysiological, and biochemical evidence in support of an integrative view, assuming both roles for the amygdala. This integrative view, however, suggests a level of complexity not referred to before: the assumption that emotional conditions induce long-term neural plasticity in the amygdala suggests that the interrelations between the amygdala and brain regions, such as the hippocampus, may not be static but dynamic. The way the amygdala will affect memory-related processes in the hippocampus may thus largely depend on the previous history of the individual.
TL;DR: No simple rules emerge on the role of NO in learning and memory, but a review of the literature does provide hints on why NO is associated withlearning and memory.
Abstract: Nitric oxide (NO) is widely used in neural circuits giving rise to learning and memory. NO is an unusual neurotransmitter in its modes of release and action. Is its association with learning and memory related to its unusual properties? Reviewing the literature might allow the formulation of a general principle on how NO and memory are related. However, other than confirming that there is indeed a strong association between NO and memory, no simple rules emerge on the role of NO in learning and memory. The effects of NO are not associated with a particular stage or form of memory and are highly dependent on species, strain, and behavior or training paradigm. Nonetheless, a review does provide hints on why NO is associated with learning and memory. Unlike transmitters acting via receptors expressed only in neurons designed to respond to the transmitter, NO is a promiscuous signal that can affect a wide variety of neurons, via many molecular mechanisms. In circuits giving rise to learning and memory, it may be useful to signal some events via a promiscuous messenger having widespread effects. However, each circuit will use the promiscuous signal in a different way, to achieve different ends.
TL;DR: This review summarizes some of the discoveries in the new field of retinoid neurobiology including its functions in neural plasticity and LTP in the hippocampus; its possible role in motor disorders such as Parkinson's disease, motoneuron disease, and Huntington’s disease; its role in regeneration after sciatic nerve and spinal cord injury; and its possible involvement in psychiatric diseases such as depression.
Abstract: The majority of the functions of vitamin A are carried out by its metabolite, retinoic acid (RA), a potent transcriptional activator acting through members of the nuclear receptor family of transcription factors. In the CNS, RA was first recognized to be essential for the control of patterning and differentiation in the developing embryo. It has recently come to light, however, that many of the same functions that RA directs in the embryo are involved in the regulation of plasticity and regeneration in the adult brain. The same intricate metabolic control system of synthetic and catabolic enzymes, combined with cytoplasmic binding proteins, is used in both embryo and adult to create regions of high and low RA to modulate gene transcription. This review summarizes some of the discoveries in the new field of retinoid neurobiology including its functions in neural plasticity and LTP in the hippocampus; its possible role in motor disorders such as Parkinson’s disease, motoneuron disease, and Huntington’s dise...
TL;DR: Genotype/phenotype analysis revealed that the phenotypic spectrum of MECP2 mutations in humans is broader than initially suspected, and Rett syndrome is a prototype for the genetic, molecular, and neurobiological analysis of neurodevelopmental disorders.
Abstract: Rett syndrome, one of the leading causes of mental retardation and developmental regression in girls, is the first pervasive developmental disorder with a known genetic cause. The majority of cases of sporadic Rett syndrome are caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). MeCP2 binds methylated DNA and likely regulates gene expression and chromatin structure. Genotype/phenotype analysis revealed that the phenotypic spectrum of MECP2 mutations in humans is broader than initially suspected: Mutations have been discovered in Rett syndrome variants, mentally retarded males, and autistic children. A variety of in vivo and in vitro models has been developed that allow analysis of MeCP2 function and pathogenic studies of Rett syndrome. Because the neuropathology of Rett syndrome shares certain features with other neurodevelopmental disorders, a common pathogenic process may underlie these disorders. Thus, Rett syndrome is a prototype for the genetic, molecular, and neurobiologic...
TL;DR: In this article, the authors combine contemporary research on plasticity and development with data from human and animal investigations of amblyopic populations to assess what is known and to reexamine some of the key assumptions about human amblyopia.
Abstract: Amblyopia is the condition in which reduced visual function exists despite full optical correction and an absence of observable ocular pathology. Investigation of the underlying neurology of this condition began in earnest around 40 years ago with the pioneering studies conducted by Hubel and Wiesel. Their early work on the impact of monocular deprivation and strabismus initiated what is now a rapidly developing field of cortical plasticity research. Although the monocular deprivation paradigm originated by Hubel and Wiesel remains a key experimental manipulation in studies of cortical plasticity, somewhat ironically, the neurology underlying the human conditions of strabismus and amblyopia that motivated this early work remains elusive. In this review, the authors combine contemporary research on plasticity and development with data from human and animal investigations of amblyopic populations to assess what is known and to reexamine some of the key assumptions about human amblyopia.
TL;DR: Because plasticity of the brain plays a major role in the recovery of function after stroke, the knowledge of the principles of plasticity may help to design strategies to enhance plasticity when it is beneficial, such as after brain infarction.
Abstract: The adult brain maintains the ability for reorganization or plasticity throughout life. Results from neurophysiological and neuroanatomical experiments in animals and noninvasive neuroimaging and electrophysiological studies in humans show considerable plasticity of motor representations with use or nonuse, skill learning, or injury to the nervous system. An important concept of reorganization in the motor cortex is that of a distributed neuronal network in which multiple overlapping motor representations are functionally connected through an extensive horizontal network. By changing the strength of horizontal connections between motor neurons, functionally different neuronal assemblies can form, thereby providing a substrate to construct dynamic motor output zones. Modulation of inhibition and synaptic efficacy are mechanisms involved. Recent evidence from animal experiments indicates that these functional changes are accompanied by anatomical changes. Because plasticity of the brain plays a major role in the recovery of function after stroke, the knowledge of the principles of plasticity may help to design strategies to enhance plasticity when it is beneficial, such as after brain infarction.
TL;DR: A new model of zinc currents and zinc toxicity that offers expanded opportunities for zinc-selective therapeutic chelation interventions is presented, suggesting that the original translocation model was incomplete.
Abstract: It has been nearly 15 years since the suggestion that synaptically released Zn2+ might contribute to excitotoxic brain injury after seizures, stroke, and brain trauma. In the original "zinc-translocation" model, it was proposed that synaptically released Zn2+ ions penetrated postsynaptic neurons, causing injury. According to the model, chelating zinc in the cleft was predicted to be neuroprotective. This proved to be true: zinc chelators have proved to be remarkably potent at reducing excitotoxic neuronal injury in many paradigms. Promising new zinc-based therapies for stroke, head trauma, and epileptic brain injury are under development. However, new evidence suggests that the original translocation model was incomplete. As many as three sources of toxic zinc ions may contribute to excitotoxicity: presynaptic vesicles, postsynaptic zinc-sequestering proteins, and (more speculatively) mitochondrial pools. The authors present a new model of zinc currents and zinc toxicity that offers expanded opportunities for zinc-selective therapeutic chelation interventions.
TL;DR: The early pathological changes identified in Huntington’s disease cellular and animal models are discussed and may be the causes of neurode-generation.
Abstract: Huntington’s disease results from a polyglutamine expansion in the N-terminal region of huntingtin (htt). This abnormality causes protein aggregation and leads to neurotoxicity. Despite its widespread expression in the brain and body, mutant htt causes selective neurodegeneration in Huntington’s disease patient brains. However, Huntington’s disease mouse models expressing mutant htt do not have obvious neurodegeneration despite significant neurological symptoms. Most Huntington’s disease mouse models display the accumulation of toxic N-terminal mutant htt fragments in both the nucleus and neuronal processes, suggesting that these subcellular sites are hotspots for the early neuropathology of Huntington’s disease. Intranuclear htt affects gene expression and may cause neuronal dysfunction. Mutant htt in neuronal processes affects axonal transport and induces degeneration, and these effects may be more relevant to the selective neurodegeneration in Huntington’s disease. Growing evidence has also suggested t...
TL;DR: How Eph receptors and ephrins are integrated into the molecular machinery that supports synaptic function is discussed.
Abstract: Compelling new findings have revealed that receptor tyrosine kinases of the Eph family, along with their ephrin ligands, play an essential role in regulating the properties of developing mature excitatory synapses in the central nervous system. The cell surface localization of both the Eph receptors and the ephrins enables these proteins to signal bidirectionally at sites of cell-to-cell contact, such as synapses. Eph receptors and ephrins have indeed been implicated in multiple aspects of synaptic function, including clustering and modulating N-methyl-D-aspartate receptors, modifying the geometry of postsynaptic terminals, and influencing long-term synaptic plasticity and memory. In this review, we discuss how Eph receptors and ephrins are integrated into the molecular machinery that supports synaptic function.
TL;DR: The authors characterize the biology of the local tissue-protective system, review data that support this concept, and suggest why non-hematopoietic analogues of EPO may be better choices as therapeutics.
Abstract: In the 10 years since neurotrophic activity was first reported for erythropoietin (EPO), a broad understanding of its multiple paracrine/autocrine functions has emerged. Recent studies firmly establish EPO as a multifunctional molecule, typical of the pliotrophic cytokine superfamily of which it is a member. The realization that EPO activates neuroprotection by multiple mechanisms has identified a generalized system of local tissue protection with EPO as a critical component. Here, the authors characterize the biology of the local tissue-protective system, review data that support this concept, and suggest why non-hematopoietic analogues of EPO may be better choices as therapeutics.
TL;DR: The role of the scaffolding protein RACK1 and the regulatory protein DARPP-32 in mediating the distinct effects of ethanol in different brain regions via changes in NMDA receptor phosphorylation and compartmentalization is presented.
Abstract: One of the major targets for ethanol (alcohol) in the brain is the N-methyl-D-aspartate (NMDA) receptor, a glutamate-gated ion channel. Intriguingly, the effects of ethanol on the NMDA receptor are not homogeneous throughout the brain. This review focuses on recent studies revealing molecular mechanisms that mediate the actions of ethanol on the NMDA receptor in different brain regions via changes in NMDA receptor phosphorylation and compartmentalization. Specifically, the role of the scaffolding protein RACK1 and the regulatory protein DARPP-32 in mediating the distinct effects of ethanol is presented.
TL;DR: Neurophysiological evidence suggests that lexical access, semantic associations, and contextual integration may be simultaneous as the brain uses available information in a concurrent manner, with the final goal of rapidly comprehending verbal input.
Abstract: Understanding language relies on concurrent activation of multiple areas within a distributed neural network. Hemodynamic measures (fMRI and PET) indicate their location, and electromagnetic measures (magnetoencephalography and electroencephalography) reveal the timing of brain activity during language processing. Their combination can show the spatiotemporal characteristics (where and when) of the underlying neural network. Activity to written and spoken words starts in sensory-specific areas and progresses anteriorly via respective ventral ("what") processing streams toward the simultaneously active supramodal regions. The process of understanding a word in its current context peaks about 400 ms after word onset. It is carried out mainly through interactions of the temporal and inferior prefrontal areas on the left during word reading and bilateral temporo-prefrontal areas during speech processing. Neurophysiological evidence suggests that lexical access, semantic associations, and contextual integration may be simultaneous as the brain uses available information in a concurrent manner, with the final goal of rapidly comprehending verbal input. Because the same areas may participate in multiple stages of semantic or syntactic processing, it is crucial to consider both spatial and temporal aspects of their interactions to appreciate how the brain understands words.
TL;DR: Both sides of the story are discussed with a particular emphasis on the neuro-protective role of endogenous GCs during immune challenges and the problems in determining whether GCs can be a good therapy for the treatment of neuropathological conditions.
Abstract: The innate immune response is a coordinated set of reactions involving cells of myeloid lineage and a network of signaling molecules. Such a response takes place in the CNS during trauma, stroke, spinal cord injury, and neurodegenerative diseases, suggesting that macrophages/microglia are the cells that perpetuate the progressive neuronal damage. However, there is accumulating evidence that these cells and their secreted proinflammatory molecules have more beneficial effects than detrimental consequences for the neuronal elements. Indeed, a timely controlled innate immune response may limit toxicity in swiftly eliminating foreign materials and debris that are known to interfere with recovery and regeneration. Each step of the immune cascade is under the tight control of stimulatory and inhibitory signals. Glucocorticoids (GCs) act as the critical negative feedback on all myeloid cells, including those present within the brain parenchyma. Because too little is like too much, both an inappropriate feedback ...
TL;DR: In this article, it was shown that the primary motor cortex, which is an executive locus of voluntary limb movements, is primarily responsible for kinematic perception of limb movements.
Abstract: We can precisely control only what we can sense. Sensing limb position or limb movement is essential when we precisely control our limb movements. It has been generally believed that somatic perception takes place in the neuronal network of somatosensory areas. Recent neuroimaging techniques (PET, fMRI, transcranial magnetic stimulation) have revealed in human brains that motor areas participate in somatic perception of limb movements during kinesthetic illusion in the absence of actual limb movement. In particular, the primary motor cortex, which is an executive locus of voluntary limb movements, is primarily responsible for kinesthetic perception of limb movements. This probably forms the most efficient circuits for voluntary limb movements between the controlled muscles and the motor areas.
TL;DR: This review brings together recently described properties and emerging principles of interneuron functions that may convey, into bulbar neuronal networks, a degree of circuit adaptation unmatched by synaptic plasticity alone.
Abstract: Identifying and defining the characteristic features of the inhibitory neurons in the nervous system has become essential for achieving a cellular understanding of complex brain activities. For this, the olfactory bulb is ideally suited because it is readily accessible, it is a laminated structure where local interneurons can be easily distinguished from projecting neurons, and, more important, GABAergic interneurons are continuously replaced. How the newly generated neurons integrate into a preexisting neural network and how basic network functions are maintained when a large percentage of neurons are subjected to continuous renewal are important questions that have recently received new insights. Here, it is seen that the production of bulbar interneurons is specifically adapted to experience-dependent regulation of adult neural networks. In particular, the authors report the degree of sensitivity of the bulbar neurogenesis to the activity level of sensory inputs and, in turn, how the adult neurogenesis adjusts the neural network functioning to optimize information processing. By maintaining a constitutive neurogenesis sensitive to environmental cues, this neuronal recruitment leads to improving sensory abilities. This review brings together recently described properties and emerging principles of interneuron functions that may convey, into bulbar neuronal networks, a degree of circuit adaptation unmatched by synaptic plasticity alone.
TL;DR: Two quantitative parameters (SLN and FLN) are introduced that hold the promise of resolving indeterminacy of existing models in the visual system and suggest a hitherto unsuspected central function of the frontal eye field.
Abstract: It is generally agreed that information flow through the cortex is constrained by a hierarchical architecture. Lack of precise data on areal connectivity leads to indeterminacy of existing models. The authors introduce two quantitative parameters (SLN and FLN) that hold the promise of resolving such indeterminacy. In the visual system, using a very incomplete database, provisional hierarchies are in line with the recent proposal of higher functions of area V1 and suggest a hitherto unsuspected central function of the frontal eye field.