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At least 253 records · Page 14Linked to original sources
PubMed2003

VIP- and PACAP-mediated immunomodulation as prospective therapeutic tools.

The immune system and the brain continuously signal to each other, often along the same pathways, which might explain the connection between immunity, the brain and disease. Neuropeptides and their receptors represent part of this communication network, and recent work has examined their relevance to health, proving a potentially crucial clinical significance. The structurally related neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), are emerging as a means of fine tuning in the maintenance a balanced steady state in the immune system. Murine knockout and transgenic models for a VIP receptor suggest that VIP is an endogenous anti-inflammatory mediator with characteristics resembling those of a T-helper-2 cytokine. Thus, through molecular mechanisms that are being discovered, VIP might extend the range of therapeutic treatments available for various disorders, including acute and chronic inflammatory diseases, septic shock and autoimmune diseases.

Adjuvants, Immunologic↗
PubMed2001

[A new history of basal ganglia and physiopathology of Parkinson's disease].

The author analyzes basic and clinical experimental works of the last forty years and reaches the following conclusions: The motor system is an indivisible entity in which the basal ganglia are a key part. An important link in the history of the basal ganglia is the description by Llamas and Reinoso-Suárez in 1965 of connections from the substantia nigra compacta to the globus pallidus medialis and lateralis, and striatum through extremely thin, diffusely distributed fibers. They also described connections from the ventral tegmental area to the basal forebrain and the cerebral cortex. These connections are still not accepted one decade later. Rather than as cortico-basal ganglia-cortical parallel loops, the basal ganglia are actually structured as a widely distributed neuronal network with a great biochemical and connective variety. Basal ganglia intrinsic circuits have an important influential role in this network. Very varied brain structures influence basal ganglia neuronal network, mainly the cerebral cortex and the thalamic nuclei, essentially those that receive output from the basal ganglia. This complex organization provides the foundations for and elucidates the difficulty of explaining the pathophysiology of the clinical manifestations of Parkinson's disease as well as illustrating the need for future multidisciplinary research on this topic.

Basal Ganglia↗
PubMed2006

Development of a three-dimensional multiscale agent-based tumor model: simulating gene-protein interaction profiles, cell phenotypes and multicellular patterns in brain cancer.

Experimental evidence suggests that epidermal growth factor receptor (EGFR)-mediated activation of the signaling protein phospholipase Cgamma plays a critical role in a cancer cell's phenotypic decision to either proliferate or to migrate at a given point in time. Here, we present a novel three-dimensional multiscale agent-based model to simulate this cellular decision process in the context of a virtual brain tumor. Each tumor cell is equipped with an EGFR gene-protein interaction network module that also connects to a simplified cell cycle description. The simulation results show that over time proliferative and migratory cell populations not only oscillate but also directly impact the spatio-temporal expansion patterns of the entire cancer system. The percentage change in the concentration of the sub-cellular interaction network's molecular components fluctuates, and, for the 'proliferation-to-migration' switch we find that the phenotype triggering molecular profile to some degree varies as the tumor system grows and the microenvironment changes. We discuss potential implications of these findings for experimental and clinical cancer research.

Apoptosis↗
PubMed2006

Functional magnetic resonance imaging and cognition at the very early stage of MS.

Dysfunction of high controlled information processing is present in patients with multiple sclerosis (MS) right at the beginning of the disease. One hypothesis is that disruption of communication inside large-scale cortical networks, occurring as a consequence of white matter damage, may constitute the anatomical substrate of cognitive impairment at the very early stage of MS. Disturbance of interregional synchronization might be the main pathogenic factor in controlled information processing deficiency in early MS. Preliminary functional MRI studies (fMRI) have provided important clues to corroborate the connectivity hypotheses. First, brain connectivity assessed by fMRI has brought new data about the influence of diffuse white matter damage on connectivity efficiency inside large-scale networks. These studies have suggested that connectivity disturbances occur inside the working memory network in patients at the very early stage of MS and appear related to the extent of structural white matter damage. Also, fMRI studies have suggested that patients may partially compensate for connectivity impairment by a greater cognitive control. Such a compensatory mechanism could limit the determinant functional impact of diffuse white matter damage on high controlled information processing.

Age of Onset↗
PubMed1979

[Changes in the millivolt potential of brain structures during micropolarization influencing trace phenomena].

In chronic experiments on monkeys and cats, the effects of intracerebral micropolarization modulating memory processes, on the mV potential of cerebral structures, were studied. A connection was revealed between trace fixing and processes of systemic kindling on the one hand, and the following stabilizing of mV potential, on the other hand. The data obtained suggest that the distant changes of the mV potential reflect a general "tuning" of cerebral systems, are realized by means of specialized regulatory neuronal networks and connected with shifts in metabolic processes.

Animals↗
PubMed2004

The focality of the global Alzheimer brain process: is the selective vulnerability of neurons a specific phenomenon of primary neuronal pathobiology?

A focality in the development of a global series of predisposing factors that conditions a progressiveness in the neurodegenerative process of Alzheimer type would appear to arise as a specific lesion of the neuron. Such a neuronal lesion would perhaps disrupt functional connectivity of neuronal networks in a process involving loss of neuronal viability. Indeed, a strict concept of selective vulnerability of neurons in the Alzheimer brain might be simply a preconditioning by microenvironmental factors that interacts with the individual neuron in terms of cellular component depletion or in terms of plasmalemmal disruption. In a final analysis, perhaps, the individual neuron would appear as the essential focus of a process that would account for a conditioning globality of the Alzheimer process that promotes both progressiveness and irreversibility of the brain pathology.

Alzheimer Disease↗
PubMed2005

Developmental refinement of inhibitory sound-localization circuits.

The ability to localize sound rapidly and accurately depends on the precise organization of inhibitory neuronal circuits in the auditory brainstem. However, the rules and mechanisms by which this precision is established during development are still poorly understood. Although activity-dependent reorganization has been known for over a decade to have a central role in this process, more recent studies have revealed an unanticipated degree of reorganization that occurs on levels ranging from cellular phenotype to network connectivity. These results suggest novel mechanisms by which immature inhibitory sound-localization circuits become optimized. Lessons from auditory brainstem circuits thus could provide insight into inhibitory development in other brain areas, where inhibitory networks are less experimentally accessible.

Age Factors↗
PubMed1997

The anatomy of language revisited.

The language areas have been classically viewed as a posterior, perceptual Wernicke's region connected with an anterior, motor Broca's area via a tract of long fibers denominated the arcuate fasciculus. Recent connectional studies in the monkey indicate that there may be few direct connections between the regions strictly corresponding to Broca's or Wernicke's areas, and that inferior parietal areas may serve as a link between them. The proposed connectional pattern of the language regions fits the network of parietotemporal-prefrontal connections that participate in working memory, a type of memory used in immediate cognitive processing. Supporting this concept, brain activation studies in the human during linguistic working memory tasks have determined a close relation between the supramarginal gyrus (parietal area 40) and Broca's area. We suggest that language processing is closely related to working memory networks, and that the language regions in fact originated in evolution from a working memory network for linguistic utterances.

Animals↗
PubMed2003

Major differences in inhibitory synaptic transmission onto two neocortical interneuron subclasses.

Locally projecting GABAergic interneurons are the major providers of inhibition in the neocortex and play a crucial role in several brain functions. Neocortical interneurons are connected via electrical and chemical synapses that may be crucial in modulating complex network oscillations. We investigated the properties of spontaneous and evoked IPSCs in two morphologically and physiologically identified interneuron subtypes, the fast-spiking (FS) and low threshold-spiking (LTS) cells in layer V of rodent sensorimotor cortex. We found that IPSCs recorded in FS cells were several orders of magnitude more frequent, larger in amplitude, and had faster kinetics than IPSCs recorded in LTS cells. GABA(A) receptor alpha- and beta-subunit selective modulators, zolpidem and loreclezole, had different effects on IPSCs in FS and LTS interneurons, suggesting differential expression of GABA(A) receptor subunit subtypes. These pharmacological data indicated that the alpha1 subunit subtype is poorly expressed by LTS cells but makes a large contribution to GABA(A) receptors on FS cells. This was confirmed by experiments performed in genetically modified mice in which the alpha1 subunit had been made insensitive to benzodiazepine-like agonists. These results suggest that differences in IPSC waveform are likely attributable to distinctive expression of GABA(A) receptor subunits in FS and LTS cells. The particular properties of GABAergic input on different interneuronal subtypes might have important consequences for generation and pacing of cortical rhythms underlying several brain functions. Moreover, selective pharmacological manipulation of distinct inhibitory circuits might allow regulation of pyramidal cell activities under specific physiological and pathophysiological conditions.

Action Potentials↗
PubMed2005

Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study.

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.

Adult↗
PubMed2006

Dynamic switching of neural codes in networks with gap junctions.

Population rate coding and temporal coding are common neural codes. Recent studies suggest that these two codes may be alternatively used in one neural system. Based on the fact that there are massive gap junctions in the brain, we explore how this switching behavior may be related to neural codes in networks of neurons connected by gap junctions. First, we show that under time-varying inputs, such neural networks show switching between synchronous and asynchronous states. Then, we quantify network dynamics by three mutual information measures to show that population rate coding carries more information in asynchronous states and temporal coding does so in synchronous states.

Action Potentials↗
PubMed2006

Principles of diffusion tensor imaging and its applications to basic neuroscience research.

The brain contains more than 100 billion neurons that communicate with each other via axons for the formation of complex neural networks. The structural mapping of such networks during health and disease states is essential for understanding brain function. However, our understanding of brain structural connectivity is surprisingly limited, due in part to the lack of noninvasive methodologies to study axonal anatomy. Diffusion tensor imaging (DTI) is a recently developed MRI technique that can measure macroscopic axonal organization in nervous system tissues. In this article, the principles of DTI methodologies are explained, and several applications introduced, including visualization of axonal tracts in myelin and axonal injuries as well as human brain and mouse embryonic development. The strengths and limitations of DTI and key areas for future research and development are also discussed.

Animals↗
PubMed2006

Adult neurogenesis and schizophrenia: a window on abnormal early brain development?

Adult neurogenesis is one of the most rapidly growing areas in neuroscience research and there is great interest in its potential role in the pathophysiology of psychiatric illness. In parallel with early development, adult neurogenesis occurs through the proliferation of precursor cells which migrate to specific regions and differentiate into neurons with characteristics indistinguishable from existing mature neurons. These findings have led to the re-definition of the concept of network plasticity in the adult brain, to include the formation of new neurons as well as new connections. This review examines the idea that adult neurogenesis may be disturbed in schizophrenia. We discuss evidence for abnormal mechanisms of neurogenesis and expression of developmental genes in schizophrenia, the influence of antipsychotic drugs on neurogenesis and the role of candidate schizophrenia susceptibility genes in adult neurogenesis. The recent discovery of molecular markers transiently expressed in newborn neurons within adult neurogenic brain regions could be used to probe whether neurogenesis is disturbed in schizophrenia. Adult neurogenesis could also be used as a unique tool for investigating genes involved in early brain development using post-mortem brains. This is particularly relevant for brain disorders with developmental origins such as schizophrenia.

Adult↗
PubMed2002

A computational perspective on the neural basis of multisensory spatial representations.

We argue that current theories of multisensory representations are inconsistent with the existence of a large proportion of multimodal neurons with gain fields and partially shifting receptive fields. Moreover, these theories do not fully resolve the recoding and statistical issues involved in multisensory integration. An alternative theory, which we have recently developed and review here, has important implications for the idea of 'frame of reference' in neural spatial representations. This theory is based on a neural architecture that combines basis functions and attractor dynamics. Basis function units are used to solve the recoding problem, whereas attractor dynamics are used for optimal statistical inferences. This architecture accounts for gain fields and partially shifting receptive fields, which emerge naturally as a result of the network connectivity and dynamics.

Animals↗
PubMed2005

Stress and the gastrointestinal tract.

Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short- and long-term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain-gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus-pituitary-adrenal axis and pain modulatory systems. Severe or long-term stress can induce long-term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4(+) lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.

Adaptation, Psychological↗
PubMed2003

The informatics of a C57BL/6J mouse brain atlas.

The Mouse Atlas Project (MAP) aims to produce a framework for organizing and analyzing the large volumes of neuroscientific data produced by the proliferation of genetically modified animals. Atlases provide an invaluable aid in understanding the impact of genetic manipulations by providing a standard for comparison. We use a digital atlas as the hub of an informatics network, correlating imaging data, such as structural imaging and histology, with text-based data, such as nomenclature, connections, and references. We generated brain volumes using magnetic resonance microscopy (MRM), classical histology, and immunohistochemistry, and registered them into a common and defined coordinate system. Specially designed viewers were developed in order to visualize multiple datasets simultaneously and to coordinate between textual and image data. Researchers can navigate through the brain interchangeably, in either a text-based or image-based representation that automatically updates information as they move. The atlas also allows the independent entry of other types of data, the facile retrieval of information, and the straight-forward display of images. In conjunction with centralized servers, image and text data can be kept current and can decrease the burden on individual researchers' computers. A comprehensive framework that encompasses many forms of information in the context of anatomic imaging holds tremendous promise for producing new insights. The atlas and associated tools can be found at http://www.loni.ucla.edu/MAP.

Anatomy, Artistic↗
PubMedDate not supplied

Recurrent fractal neural networks: a strategy for the exchange of local and global information processing in the brain.

The regulation of biological networks relies significantly on convergent feedback signaling loops that render a global output locally accessible. Ideally, the recurrent connectivity within these systems is self-organized by a time-dependent phase-locking mechanism. This study analyzes recurrent fractal neural networks (RFNNs), which utilize a self-similar or fractal branching structure of dendrites and downstream networks for phase-locking of reciprocal feedback loops: output from outer branch nodes of the network tree enters inner branch nodes of the dendritic tree in single neurons. This structural organization enables RFNNs to amplify re-entrant input by over-the-threshold signal summation from feedback loops with equivalent signal traveling times. The columnar organization of pyramidal neurons in the neocortical layers V and III is discussed as the structural substrate for this network architecture. RFNNs self-organize spike trains and render the entire neural network output accessible to the dendritic tree of each neuron within this network. As the result of a contraction mapping operation, the local dendritic input pattern contains a downscaled version of the network output coding structure. RFNNs perform robust, fractal data compression, thus coping with a limited number of feedback loops for signal transport in convergent neural networks. This property is discussed as a significant step toward the solution of a fundamental problem in neuroscience: how is neuronal computation in separate neurons and remote brain areas unified as an instance of experience in consciousness? RFNNs are promising candidates for engaging neural networks into a coherent activity and provide a strategy for the exchange of global and local information processing in the human brain, thereby ensuring the completeness of a transformation from neuronal computation into conscious experience.

Brain↗
PubMed1999

[Not Available].

With the increasing application of imaging techniques, characteristic changes in the structure and functional activity of certain neuronal networks and transmitter Systems have been discovered in the brains of patients suffering from various psychiatric disorders. These findings have often been assumed to support biological concepts of the genetic background and causation of these disorders. However, several lines of research are converging to indicate that the initially established genetically programmed neuronal Connectivity is further elaborated, fine tuned and modified by usedependent neuronal and synaptic plasticity. In all socially organized species in general and in human subjects in particular, psychosocial experiences appear to represent the most important trigger of use-dependent adjustments of neuronal Connectivity through the facilitation, modification and reorganization of neuronal networks. In experimental animals, changes in psychosocial rearing conditions were shown to cause profound and persistent changes in the cytoarchitecture, dendritic arborization and synapse formation in individual brain regions as well as in the maturation of monoaminergic afferences. Based on these findings, the mechanisms of the biological affixation of psychosocial experiences are described and the implications of experience dependent neuronal and synaptic plasticity in the prevention and the therapy of mental disorders are outlined.

Attachment↗