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Sample records for physiology cognition neuronal

  1. Monitoring and predicting cognitive state and performance via physiological correlates of neuronal signals.

    Science.gov (United States)

    Russo, Michael B; Stetz, Melba C; Thomas, Maria L

    2005-07-01

    Judgment, decision making, and situational awareness are higher-order mental abilities critically important to operational cognitive performance. Higher-order mental abilities rely on intact functioning of multiple brain regions, including the prefrontal, thalamus, and parietal areas. Real-time monitoring of individuals for cognitive performance capacity via an approach based on sampling multiple neurophysiologic signals and integrating those signals with performance prediction models potentially provides a method of supporting warfighters' and commanders' decision making and other operationally relevant mental processes and is consistent with the goals of augmented cognition. Cognitive neurophysiological assessments that directly measure brain function and subsequent cognition include positron emission tomography, functional magnetic resonance imaging, mass spectroscopy, near-infrared spectroscopy, magnetoencephalography, and electroencephalography (EEG); however, most direct measures are not practical to use in operational environments. More practical, albeit indirect measures that are generated by, but removed from the actual neural sources, are movement activity, oculometrics, heart rate, and voice stress signals. The goal of the papers in this section is to describe advances in selected direct and indirect cognitive neurophysiologic monitoring techniques as applied for the ultimate purpose of preventing operational performance failures. These papers present data acquired in a wide variety of environments, including laboratory, simulator, and clinical arenas. The papers discuss cognitive neurophysiologic measures such as digital signal processing wrist-mounted actigraphy; oculometrics including blinks, saccadic eye movements, pupillary movements, the pupil light reflex; and high-frequency EEG. These neurophysiological indices are related to cognitive performance as measured through standard test batteries and simulators with conditions including sleep loss

  2. Neuronal responses to physiological stress

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger David John

    2012-01-01

    damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses......Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged...... by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner...

  3. Young Human Cholinergic Neurons Respond to Physiological Regulators and Improve Cognitive Symptoms in an Animal Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Annamaria Morelli

    2017-10-01

    Full Text Available The degeneration of cholinergic neurons of the nucleus basalis of Meynert (NBM in the basal forebrain (BF is associated to the cognitive decline of Alzheimer’s disease (AD patients. To date no resolutive therapies exist. Cell-based replacement therapy is a strategy currently under consideration, although the mechanisms underlying the generation of stem cell-derived NBM cholinergic neurons able of functional integration remain to be clarified. Since fetal brain is an optimal source of neuronal cells committed towards a specific phenotype, this study is aimed at isolating cholinergic neurons from the human fetal NBM (hfNBMs in order to study their phenotypic, maturational and functional properties. Extensive characterization confirmed the cholinergic identity of hfNBMs, including positivity for specific markers (such as choline acetyltransferase and acetylcholine (Ach release. Electrophysiological measurements provided the functional validation of hfNBM cells, which exhibited the activation of peculiar sodium (INa and potassium (IK currents, as well as the presence of functional cholinergic receptors. Accordingly, hfNBMs express both nicotinic and muscarinic receptors, which were activated by Ach. The hfNBMs cholinergic phenotype was regulated by the nerve growth factor (NGF, through the activation of the high-affinity NGF receptor TrkA, as well as by 17-β-estradiol through a peculiar recruitment of its own receptors. When intravenously administered in NBM-lesioned rats, hfNBMs determined a significant improvement in memory functions. Histological examination of brain sections showed that hfNBMs (labeled with PKH26 fluorescent dye prior to administration reached the damaged brain areas. The study provides a useful model to study the ontogenetic mechanisms regulating the development and maintenance of the human brain cholinergic system and to assess new lines of research, including disease modeling, drug discovery and cell-based therapy for AD.

  4. Neuronal glycogen synthesis contributes to physiological aging.

    Science.gov (United States)

    Sinadinos, Christopher; Valles-Ortega, Jordi; Boulan, Laura; Solsona, Estel; Tevy, Maria F; Marquez, Mercedes; Duran, Jordi; Lopez-Iglesias, Carmen; Calbó, Joaquim; Blasco, Ester; Pumarola, Marti; Milán, Marco; Guinovart, Joan J

    2014-10-01

    Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora's disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. © 2014 The Authors. Aging cell published by the Anatomical Society and John Wiley & Sons Ltd.

  5. Mirror neurons, language, and embodied cognition.

    Science.gov (United States)

    Perlovsky, Leonid I; Ilin, Roman

    2013-05-01

    Basic mechanisms of the mind, cognition, language, its semantic and emotional mechanisms are modeled using dynamic logic (DL). This cognitively and mathematically motivated model leads to a dual-model hypothesis of language and cognition. The paper emphasizes that abstract cognition cannot evolve without language. The developed model is consistent with a joint emergence of language and cognition from a mirror neuron system. The dual language-cognition model leads to the dual mental hierarchy. The nature of cognition embodiment in the hierarchy is analyzed. Future theoretical and experimental research is discussed. Published by Elsevier Ltd.

  6. Anatomy and physiology of phrenic afferent neurons.

    Science.gov (United States)

    Nair, Jayakrishnan; Streeter, Kristi A; Turner, Sara M F; Sunshine, Michael D; Bolser, Donald C; Fox, Emily J; Davenport, Paul W; Fuller, David D

    2017-12-01

    Large-diameter myelinated phrenic afferents discharge in phase with diaphragm contraction, and smaller diameter fibers discharge across the respiratory cycle. In this article, we review the phrenic afferent literature and highlight areas in need of further study. We conclude that 1 ) activation of both myelinated and nonmyelinated phrenic sensory afferents can influence respiratory motor output on a breath-by-breath basis; 2 ) the relative impact of phrenic afferents substantially increases with diaphragm work and fatigue; 3 ) activation of phrenic afferents has a powerful impact on sympathetic motor outflow, and 4 ) phrenic afferents contribute to diaphragm somatosensation and the conscious perception of breathing. Much remains to be learned regarding the spinal and supraspinal distribution and synaptic contacts of myelinated and nonmyelinated phrenic afferents. Similarly, very little is known regarding the potential role of phrenic afferent neurons in triggering or modulating expression of respiratory neuroplasticity. Copyright © 2017 the American Physiological Society.

  7. Cognitive and neuronal correlates of videogaming

    OpenAIRE

    Schlüter, Kim-John

    2016-01-01

    BACKGROUND: Within the past few decades video gaming has become a popular recreational activity all over the world and throughout all social classes. Nevertheless distinct scientific conclusions about potential harm or more importantly benefits of video gaming are lacking. However, recent studies point to possible improvements of some cognitive abilities through the high mental demands of modern games. The prefrontal cortex is the essential neuronal correlate of cognitive processing. Scientif...

  8. Physiological characterisation of human iPS-derived dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Hartfield

    Full Text Available Human induced pluripotent stem cells (hiPSCs offer the potential to study otherwise inaccessible cell types. Critical to this is the directed differentiation of hiPSCs into functional cell lineages. This is of particular relevance to research into neurological disease, such as Parkinson's disease (PD, in which midbrain dopaminergic neurons degenerate during disease progression but are unobtainable until post-mortem. Here we report a detailed study into the physiological maturation over time of human dopaminergic neurons in vitro. We first generated and differentiated hiPSC lines into midbrain dopaminergic neurons and performed a comprehensive characterisation to confirm dopaminergic functionality by demonstrating dopamine synthesis, release, and re-uptake. The neuronal cultures include cells positive for both tyrosine hydroxylase (TH and G protein-activated inward rectifier potassium channel 2 (Kir3.2, henceforth referred to as GIRK2, representative of the A9 population of substantia nigra pars compacta (SNc neurons vulnerable in PD. We observed for the first time the maturation of the slow autonomous pace-making (<10 Hz and spontaneous synaptic activity typical of mature SNc dopaminergic neurons using a combination of calcium imaging and electrophysiology. hiPSC-derived neurons exhibited inositol tri-phosphate (IP3 receptor-dependent release of intracellular calcium from the endoplasmic reticulum in neuronal processes as calcium waves propagating from apical and distal dendrites, and in the soma. Finally, neurons were susceptible to the dopamine neuron-specific toxin 1-methyl-4-phenylpyridinium (MPP+ which reduced mitochondrial membrane potential and altered mitochondrial morphology. Mature hiPSC-derived dopaminergic neurons provide a neurophysiologically-defined model of previously inaccessible vulnerable SNc dopaminergic neurons to bridge the gap between clinical PD and animal models.

  9. Mirror Neurons, Embodied Cognitive Agents and Imitation Learning

    OpenAIRE

    Wiedermann, Jiří

    2003-01-01

    Mirror neurons are a relatively recent discovery; it has been conjectured that these neurons play an important role in imitation learning and other cognitive phenomena. We will study a possible place and role of mirror neurons in the neural architecture of embodied cognitive agents. We will formulate and investigate the hypothesis that mirror neurons serve as a mechanism which coordinates the multimodal (i.e., motor, perceptional and proprioceptive) information and completes it so that the ag...

  10. Nicotinic modulaton of neuronal networks: from receptors to cognition

    NARCIS (Netherlands)

    Mansvelder, H.D.; van Aerde, K.I.; Couey, J.J.; Brussaard, A.B.

    2006-01-01

    Rationale: Nicotine affects many aspects of human cognition, including attention and memory. Activation of nicotinic acetylcholine receptors (nAChRs) in neuronal networks modulates activity and information processing during cognitive tasks, which can be observed in electroencephalograms (EEGs) and

  11. Postoperative cognitive dysfunction : Involvement of neuroinflammation and neuronal functioning

    NARCIS (Netherlands)

    Hovens, Iris B.; Schoemaker, Regien G.; van der Zee, Eddy A.; Absalom, Anthony R.; Heineman, Erik; van Leeuwen, Barbara L.

    Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway.

  12. Advanced Physiological Estimation of Cognitive Status. Part 2

    Science.gov (United States)

    2011-05-24

    fatigue, overload) Technology Transfer Opportunity Technology from PDT – Methods to acquire various physiological signals (EEG, EOG , EMG, ECG, etc...Integrated Hardware for Experiments EEG Sensor Array EOG Sensor Array Eye Tracker Amplifiers and Signal Conditioners Laptop Computer...REPORT Advanced Physiological Estimation of Cognitive Status - Part II 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: This report describes ongoing work

  13. Does cerebellar neuronal integrity relate to cognitive ability?

    International Nuclear Information System (INIS)

    Rae, C.; Lee, M.; Dixon, R.M.; Blamire, A.; Thompson, C.; Styles, P.; Radda, G.K.; University of Sydney, NSW; Karmiloff-Smith, A.; Grant, J.

    1998-01-01

    Full text: Magnetic resonance spectroscopy (MRS) allows the non-invasive measurement of metabolite levels in the brain. One of these is N-acetylaspartate (NA), a molecule found solely in neurones, synthesised there by mitochondria. This compound can be considered as a marker of 1) neuronal density and 2) neuronal mitochondria function. We recently completed a joint MRS and neuropsychological investigation of Williams-Beuren syndrome (WBS), a rare (1/20,000) autosomal dominant disorder caused by a deletion which includes the elastin locus and LIM-kinase. The syndrome has an associated behavioural and cognitive profile which includes hyperactivity, hyperacusis and excessive sociability. Spatial skills are severely affected, while verbal skills are left relatively intact Our investigation showed loss of NA from the cerebellum in WBS compared with normal controls, with the subject population as a whole displaying a continuum of cerebellar NA concentration. Ability at cognitive tests, including the Weschler IQ scale and various verbal and spatial tests, was shown to correlate significantly and positively with the concentration of NA in the cerebellum. This finding can be interpreted in one of two ways: 1. Our sampling of cerebellar metabolite levels represents a 'global' sampling of total brain neuronal density and, as such, is independent of cerebellar integrity. 2. Cerebellar neuronal integrity is associated with performance at cognitive tests. If the latter interpretation is shown to be the case, it will have important implications for our current understanding of cerebellar function. Copyright (1998) Australian Neuroscience Society

  14. Cognitive and neuronal bases of expertise

    OpenAIRE

    Campitelli, Guillermo

    2003-01-01

    This thesis examines the cognitive and neural bases of expertise. In so doing, several psychological phenomena were investigated-imagery. memory and thinking-using different tasks, and a variety of techniques of data gathering, including standard behavioural experiments, questionnaires, eye-movement recording, and functional magnetic resonance imaging (fMRI). Chess players participated in all the studies, and chess tasks were used. The data confirmed the versatility and power of chess as ...

  15. Selective neuronal lapses precede human cognitive lapses following sleep deprivation.

    Science.gov (United States)

    Nir, Yuval; Andrillon, Thomas; Marmelshtein, Amit; Suthana, Nanthia; Cirelli, Chiara; Tononi, Giulio; Fried, Itzhak

    2017-12-01

    Sleep deprivation is a major source of morbidity with widespread health effects, including increased risk of hypertension, diabetes, obesity, heart attack, and stroke. Moreover, sleep deprivation brings about vehicle accidents and medical errors and is therefore an urgent topic of investigation. During sleep deprivation, homeostatic and circadian processes interact to build up sleep pressure, which results in slow behavioral performance (cognitive lapses) typically attributed to attentional thalamic and frontoparietal circuits, but the underlying mechanisms remain unclear. Recently, through study of electroencephalograms (EEGs) in humans and local field potentials (LFPs) in nonhuman primates and rodents it was found that, during sleep deprivation, regional 'sleep-like' slow and theta (slow/theta) waves co-occur with impaired behavioral performance during wakefulness. Here we used intracranial electrodes to record single-neuron activities and LFPs in human neurosurgical patients performing a face/nonface categorization psychomotor vigilance task (PVT) over multiple experimental sessions, including a session after full-night sleep deprivation. We find that, just before cognitive lapses, the selective spiking responses of individual neurons in the medial temporal lobe (MTL) are attenuated, delayed, and lengthened. These 'neuronal lapses' are evident on a trial-by-trial basis when comparing the slowest behavioral PVT reaction times to the fastest. Furthermore, during cognitive lapses, LFPs exhibit a relative local increase in slow/theta activity that is correlated with degraded single-neuron responses and with baseline theta activity. Our results show that cognitive lapses involve local state-dependent changes in neuronal activity already present in the MTL.

  16. Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior

    DEFF Research Database (Denmark)

    Brumback, A C; Ellwood, I T; Kjaerby, C

    2017-01-01

    Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior...... in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered...... SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially...

  17. Diet and cognition: interplay between cell metabolism and neuronal plasticity.

    Science.gov (United States)

    Gomez-Pinilla, Fernando; Tyagi, Ethika

    2013-11-01

    To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long-term neuronal plasticity. The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid docosahexenoic acid, disrupting neuronal signaling. Thus, dietary docosahexenoic acid seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation.

  18. Mirror Neurons, Embodied Cognitive Agents and Imitation Learning

    Czech Academy of Sciences Publication Activity Database

    Wiedermann, Jiří

    2003-01-01

    Roč. 22, č. 6 (2003), s. 545-559 ISSN 1335-9150 R&D Projects: GA ČR GA201/02/1456 Institutional research plan: CEZ:AV0Z1030915 Keywords : complete agents * mirror neurons * embodied cognition * imitation learning * sensorimotor control Subject RIV: BA - General Mathematics Impact factor: 0.254, year: 2003 http://www.cai.sk/ojs/index.php/cai/article/view/468

  19. Physiological Characterization of Vestibular Efferent Brainstem Neurons Using a Transgenic Mouse Model

    Science.gov (United States)

    Leijon, Sara; Magnusson, Anna K.

    2014-01-01

    The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs. PMID:24867596

  20. Anatomic and Physiologic Heterogeneity of Subgroup-A Auditory Sensory Neurons in Fruit Flies.

    Science.gov (United States)

    Ishikawa, Yuki; Okamoto, Natsuki; Nakamura, Mizuki; Kim, Hyunsoo; Kamikouchi, Azusa

    2017-01-01

    The antennal ear of the fruit fly detects acoustic signals in intraspecific communication, such as the courtship song and agonistic sounds. Among the five subgroups of mechanosensory neurons in the fly ear, subgroup-A neurons respond maximally to vibrations over a wide frequency range between 100 and 1,200 Hz. The functional organization of the neural circuit comprised of subgroup-A neurons, however, remains largely unknown. In the present study, we used 11 GAL4 strains that selectively label subgroup-A neurons and explored the diversity of subgroup-A neurons by combining single-cell anatomic analysis and Ca 2+ imaging. Our findings indicate that the subgroup-A neurons that project into various combinations of subareas in the brain are more anatomically diverse than previously described. Subgroup-A neurons were also physiologically diverse, and some types were tuned to a narrow frequency range, suggesting that the response of subgroup-A neurons to sounds of a wide frequency range is due to the existence of several types of subgroup-A neurons. Further, we found that an auditory behavioral response to the courtship song of flies was attenuated when most subgroup-A neurons were silenced. Together, these findings characterize the heterogeneous functional organization of subgroup-A neurons, which might facilitate species-specific acoustic signal detection.

  1. Non-linear leak currents affect mammalian neuron physiology

    Directory of Open Access Journals (Sweden)

    Shiwei eHuang

    2015-11-01

    Full Text Available In their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the same, largely untested, assumption. Here we show that the membrane time constant and input resistance of mammalian neurons (when other major voltage-sensitive and ligand-gated ionic currents are discounted varies non-linearly with membrane voltage, following the prediction of a Goldman-Hodgkin-Katz-based passive membrane model. The model predicts that under such conditions, the time constant/input resistance-voltage relationship will linearize if the concentration differences across the cell membrane are reduced. These properties were observed in patch-clamp recordings of cerebellar Purkinje neurons (in the presence of pharmacological blockers of other background ionic currents and were more prominent in the sub-threshold region of the membrane potential. Model simulations showed that the non-linear leak affects voltage-clamp recordings and reduces temporal summation of excitatory synaptic input. Together, our results demonstrate the importance of trans-membrane ionic concentration in defining the functional properties of the passive membrane in mammalian neurons as well as other excitable cells.

  2. Does rapid and physiological astrocyte-neuron signalling amplify epileptic activity?

    Science.gov (United States)

    Henneberger, Christian

    2017-03-15

    The hippocampus is a key brain region in the pathophysiology of mesial temporal lobe epilepsy. Long-term changes of its architecture and function on the network and cellular level are well documented in epilepsy. Astrocytes can control many aspects of neuronal function and their long-term alterations over weeks, months and years play an important role in epilepsy. However, a pathophysiological transformation of astrocytes does not seem to be required for astrocytes to contribute to epileptic activity. Some of the properties of physiological astrocyte-neuron communication could allow these cells to exacerbate or synchronize neuronal firing on shorter time scales of milliseconds to minutes. Therefore, these astrocyte-neuron interactions are increasingly recognized as potential contributors to epileptic activity. Fast and reciprocal communication between astrocytes and neurons is enabled by a diverse set of mechanisms that could both amplify and counteract epileptic activity. They may thus promote or cause development of epileptic activity or inhibit it. Mechanisms of astrocyte-neuron interactions that can quickly increase network excitability involve, for example, astrocyte Ca 2+ and Na + signalling, K + buffering, gap junction coupling and metabolism. However, rapid changes of astrocyte neurotransmitter uptake and morphology may also underlie or support development of network hyperexcitability. The temporal characteristics of these interactions, their ability to synchronize neuronal activity and their net effect on network activity will determine their contribution to the emergence or maintenance of epileptic activity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  3. Optimal physiological structure of small neurons to guarantee stable information processing

    Science.gov (United States)

    Zeng, S. Y.; Zhang, Z. Z.; Wei, D. Q.; Luo, X. S.; Tang, W. Y.; Zeng, S. W.; Wang, R. F.

    2013-02-01

    Spike is the basic element for neuronal information processing and the spontaneous spiking frequency should be less than 1 Hz for stable information processing. If the neuronal membrane area is small, the frequency of neuronal spontaneous spiking caused by ion channel noise may be high. Therefore, it is important to suppress the deleterious spontaneous spiking of the small neurons. We find by simulation of stochastic neurons with Hodgkin-Huxley-type channels that the leakage system is critical and extremely efficient to suppress the spontaneous spiking and guarantee stable information processing of the small neurons. However, within the physiological limit the potassium system cannot do so. The suppression effect of the leakage system is super-exponential, but that of the potassium system is quasi-linear. With the minor physiological cost and the minimal consumption of metabolic energy, a slightly lower reversal potential and a relatively larger conductance of the leakage system give the optimal physiological structure to suppress the deleterious spontaneous spiking and guarantee stable information processing of small neurons, dendrites and axons.

  4. Trophic factors as modulators of motor neuron physiology and survival: implications for ALS therapy

    Directory of Open Access Journals (Sweden)

    Luis B Tovar-y-Romo

    2014-02-01

    Full Text Available Motor neuron physiology and development depend on a continuous and tightly regulated trophic support from a variety of cellular sources. Trophic factors guide the generation and positioning of motor neurons during every stage of the developmental process. As well, they are involved in axon guidance and synapse formation. Even in the adult spinal cord an uninterrupted trophic input is required to maintain neuronal functioning and protection from noxious stimuli. Among the trophic factors that have been demonstrated to participate in motor neuron physiology are vascular endothelial growth factor (VEGF, glial-derived neurotrophic factor (GDNF, ciliary neurotrophic factor (CNTF and insulin-like growth factor 1 (IGF-1. Upon binding to membrane receptors expressed in motor neurons or neighboring glia, these trophic factors activate intracellular signaling pathways that promote cell survival and have protective action on motor neurons, in both in vivo and in vitro models of neuronal degeneration. For these reasons these factors have been considered a promising therapeutic method for amyotrophic lateral sclerosis (ALS and other neurodegenerative diseases, although their efficacy in human clinical trials have not yet shown the expected protection. In this review we summarize experimental data on the role of these trophic factors in motor neuron function and survival, as well as their mechanisms of action. We also briefly discuss the potential therapeutic use of the trophic factors and why these therapies may have not been yet successful in the clinical use.

  5. COGNITIVE AND PHYSIOLOGICAL INITIAL RESPONSES DURING COOL WATER IMMERSION

    Directory of Open Access Journals (Sweden)

    Alex Buoite Stella

    2014-12-01

    Full Text Available The initial responses during water immersion are the first mechanisms reacting to a strong stimulation of superficial nervous cold receptors. Cold shock induces tachycardia, hypertension, tachypnea, hyperventilation, and reduced end-tidal carbon dioxide fraction. These initial responses are observed immediately after the immersion, they last for about 3 min and have been also reported in water temperatures up to 25 °C. the aim of the present study was to observe cognitive and physiological functions during immersion in water at cool temperature. Oxygen consumption, ventilation, respiratory frequency, heart rate and expired fraction of oxygen were measured during the experiment. A code substitution test was used to evaluate executive functions and, specifically, working memory. This cognitive test was repeated consecutively 6 times, for a total duration of 5 minutes. Healthy volunteers (n = 9 performed the test twice in a random order, once in a dry thermoneutral environment and once while immersed head-out in 18 °C water. The results indicated that all the physiological parameters were increased during cool water immersion when compared with the dry thermoneutral condition (p < 0.05. Cognitive performance was reduced during the cool water immersion when compared to the control condition only during the first 2 min (p < 0.05. Our results suggest that planning the best rescue strategy could be partially impaired not only because of panic, but also because of the cold shock.

  6. Does rapid and physiological astrocyte–neuron signalling amplify epileptic activity?

    Science.gov (United States)

    2016-01-01

    Abstract The hippocampus is a key brain region in the pathophysiology of mesial temporal lobe epilepsy. Long‐term changes of its architecture and function on the network and cellular level are well documented in epilepsy. Astrocytes can control many aspects of neuronal function and their long‐term alterations over weeks, months and years play an important role in epilepsy. However, a pathophysiological transformation of astrocytes does not seem to be required for astrocytes to contribute to epileptic activity. Some of the properties of physiological astrocyte–neuron communication could allow these cells to exacerbate or synchronize neuronal firing on shorter time scales of milliseconds to minutes. Therefore, these astrocyte–neuron interactions are increasingly recognized as potential contributors to epileptic activity. Fast and reciprocal communication between astrocytes and neurons is enabled by a diverse set of mechanisms that could both amplify and counteract epileptic activity. They may thus promote or cause development of epileptic activity or inhibit it. Mechanisms of astrocyte–neuron interactions that can quickly increase network excitability involve, for example, astrocyte Ca2+ and Na+ signalling, K+ buffering, gap junction coupling and metabolism. However, rapid changes of astrocyte neurotransmitter uptake and morphology may also underlie or support development of network hyperexcitability. The temporal characteristics of these interactions, their ability to synchronize neuronal activity and their net effect on network activity will determine their contribution to the emergence or maintenance of epileptic activity. PMID:27106234

  7. Single-neuron identification of chemical constituents, physiological changes, and metabolism using mass spectrometry.

    Science.gov (United States)

    Zhu, Hongying; Zou, Guichang; Wang, Ning; Zhuang, Meihui; Xiong, Wei; Huang, Guangming

    2017-03-07

    The use of single-cell assays has emerged as a cutting-edge technique during the past decade. Although single-cell mass spectrometry (MS) has recently achieved remarkable results, deep biological insights have not yet been obtained, probably because of various technical issues, including the unavoidable use of matrices, the inability to maintain cell viability, low throughput because of sample pretreatment, and the lack of recordings of cell physiological activities from the same cell. In this study, we describe a patch clamp/MS-based platform that enables the sensitive, rapid, and in situ chemical profiling of single living neurons. This approach integrates modified patch clamp technique and modified MS measurements to directly collect and detect nanoliter-scale samples from the cytoplasm of single neurons in mice brain slices. Abundant possible cytoplasmic constituents were detected in a single neuron at a relatively fast rate, and over 50 metabolites were identified in this study. The advantages of direct, rapid, and in situ sampling and analysis enabled us to measure the biological activities of the cytoplasmic constituents in a single neuron, including comparing neuron types by cytoplasmic chemical constituents; observing changes in constituent concentrations as the physiological conditions, such as age, vary; and identifying the metabolic pathways of small molecules.

  8. Sleep in adolescence: physiology, cognition and mental health

    Science.gov (United States)

    Tarokh, Leila; Saletin, Jared M.; Carskadon, Mary A.

    2016-01-01

    Sleep is a core behavior of adolescents, consuming up to a third or more of each day. As part of this special issue on the adolescent brain, we review changes to sleep behaviors and sleep physiology during adolescence with a particular focus on the sleeping brain. We posit that brain activity during sleep may provide a unique window onto adolescent cortical maturation and compliment waking measures. In addition, we review how sleep actively supports waking cognitive functioning in adolescence. Though this review is focused on sleep in healthy adolescents, the striking comorbidity of sleep disruption with nearly all psychiatric and developmental disorders (for reviews see 1,2) further highlights the importance of understanding the determinants and consequences of adolescent sleep for the developing brain. Figure 1 illustrates the overarching themes of our review, linking brain development, sleep development, and behavioral outcomes. PMID:27531236

  9. Aroma Effects on Physiologic and Cognitive Function Following Acute Stress: A Mechanism Investigation

    OpenAIRE

    Chamine, Irina; Oken, Barry S.

    2016-01-01

    Objective: Aromas may improve physiologic and cognitive function after stress, but associated mechanisms remain unknown. This study evaluated the effects of lavender aroma, which is commonly used for stress reduction, on physiologic and cognitive functions. The contribution of pharmacologic, hedonic, and expectancy-related mechanisms of the aromatherapy effects was evaluated.

  10. A hierarchical model for structure learning based on the physiological characteristics of neurons

    Institute of Scientific and Technical Information of China (English)

    WEI Hui

    2007-01-01

    Almost all applications of Artificial Neural Networks (ANNs) depend mainly on their memory ability.The characteristics of typical ANN models are fixed connections,with evolved weights,globalized representations,and globalized optimizations,all based on a mathematical approach.This makes those models to be deficient in robustness,efficiency of learning,capacity,anti-jamming between training sets,and correlativity of samples,etc.In this paper,we attempt to address these problems by adopting the characteristics of biological neurons in morphology and signal processing.A hierarchical neural network was designed and realized to implement structure learning and representations based on connected structures.The basic characteristics of this model are localized and random connections,field limitations of neuron fan-in and fan-out,dynamic behavior of neurons,and samples represented through different sub-circuits of neurons specialized into different response patterns.At the end of this paper,some important aspects of error correction,capacity,learning efficiency,and soundness of structural representation are analyzed theoretically.This paper has demonstrated the feasibility and advantages of structure learning and representation.This model can serve as a fundamental element of cognitive systems such as perception and associative memory.Key-words structure learning,representation,associative memory,computational neuroscience

  11. Physiological basis and image processing in functional magnetic resonance imaging: Neuronal and motor activity in brain

    Directory of Open Access Journals (Sweden)

    Sharma Rakesh

    2004-05-01

    Full Text Available Abstract Functional magnetic resonance imaging (fMRI is recently developing as imaging modality used for mapping hemodynamics of neuronal and motor event related tissue blood oxygen level dependence (BOLD in terms of brain activation. Image processing is performed by segmentation and registration methods. Segmentation algorithms provide brain surface-based analysis, automated anatomical labeling of cortical fields in magnetic resonance data sets based on oxygen metabolic state. Registration algorithms provide geometric features using two or more imaging modalities to assure clinically useful neuronal and motor information of brain activation. This review article summarizes the physiological basis of fMRI signal, its origin, contrast enhancement, physical factors, anatomical labeling by segmentation, registration approaches with examples of visual and motor activity in brain. Latest developments are reviewed for clinical applications of fMRI along with other different neurophysiological and imaging modalities.

  12. Using a hybrid neuron in physiologically inspired models of the basal ganglia

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    Corey Michael Thibeault

    2013-07-01

    Full Text Available Our current understanding of the basal ganglia has facilitated the creation of computational models that have contributed novel theories, explored new functional anatomy and demonstrated results complementing physiological experiments. However, the utility of these models extends beyond these applications. Particularly in neuromorphic engineering, where the basal ganglia's role in computation is important for applications such as power efficient autonomous agents and model-based control strategies. The neurons used in existing computational models of the basal ganglia however, are not amenable for many low-power hardware implementations. Motivated by a need for more hardware accessible networks, we replicate four published models of the basal ganglia, spanning single neuron and small networks, replacing the more computationally expensive neuron models with an Izhikevich hybrid neuron. This begins with a network modeling action-selection, where the basal activity levels and the ability to appropriately select the most salient input is reproduced. A Parkinson's disease model is then explored under normal conditions, Parkinsonian conditions and during subthalamic nucleus deep brain stimulation. The resulting network is capable of replicating the loss of thalamic relay capabilities in the Parkinsonian state and its return under deep brain stimulation. This is also demonstrated using a network capable of action-selection. Finally, a study of correlation transfer under different patterns of Parkinsonian activity is presented. These networks successfully captured the significant results of the originals studies. This not only creates a foundation for neuromorphic hardware implementations but may also support the development of large-scale biophysical models. The former potentially providing a way of improving the efficacy of deep brain stimulation and the latter allowing for the efficient simulation of larger more comprehensive networks.

  13. Measuring Cognitive Load: A Comparison of Self-Report and Physiological Methods

    Science.gov (United States)

    Joseph, Stacey

    2013-01-01

    This study explored three methods to measure cognitive load in a learning environment using four logic puzzles that systematically varied in level of intrinsic cognitive load. Participants' perceived intrinsic load was simultaneously measured with a self-report measure-a traditional subjective measure-and two objective, physiological measures…

  14. Amyloid β Protein Aggravates Neuronal Senescence and Cognitive Deficits in 5XFAD Mouse Model of Alzheimer's Disease

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    Zhen Wei

    2016-01-01

    Conclusions: oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population.

  15. New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function.

    Science.gov (United States)

    Uehara, Takashi; Sumiyoshi, Tomiki; Kurachi, Masayoshi

    2015-01-01

    Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by low activity of glutamatergic projections and PV-positive GABA interneurons in the prefrontal cortex resulted in sustained neural firing and gamma oscillation, leading to impaired cognitive function. Therefore, it is important to develop novel pharmacotherapy targeting GABA neurons and their activities. Clinical evidence suggests serotonin (5-HT) 1A receptor agonist improves cognitive disturbances of schizophrenia, consistent with results from preclinical studies, through mechanism that corrects E-I imbalance via the suppression of GABA neural function. On the other hand, T-817MA, a novel neurotrophic agent, ameliorated loss of PV-positive GABA neurons in the medial prefrontal cortex and reduction of gamma-band activity, as well as cognitive dysfunction in animal model of schizophrenia. In conclusion, a pharmacotherapy to alleviate abnormalities in GABA neurons through 5-HT1A agonists and T-817MA is expected to prevent the onset and/or progression of schizophrenia.

  16. Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA Receptors and Associated Proteins

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    Jesús Avila

    2017-11-01

    Full Text Available Molecular changes associated with neuronal aging lead to a decrease in cognitive capacity. Here we discuss these alterations at the level of brain regions, brain cells, and brain membrane and cytoskeletal proteins with an special focus in NMDA molecular changes through aging and its effect in cognitive decline and Alzheimer disease. Here, we propose that some neurodegenerative disorders, like Alzheimer's disease (AD, are characterized by an increase and acceleration of some of these changes.

  17. New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function

    OpenAIRE

    Jeon, Won Je; Sumiyoshi, Tomiki; Kurachi, Masayoshi

    2015-01-01

    Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive ?-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of exc...

  18. Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

    Directory of Open Access Journals (Sweden)

    Bopanna I Kalappa

    2010-11-01

    trigger action potentials.1 The majority of hippocampal CA1 pyramidal neurons express functional α7-containing nAChRs. In the absence of PNU-120596, a positive allosteric modulator of α7 nAChRs, a lack of responsiveness of some hippocampal CA1 pyramidal neurons to focal application of 0.5-1 mM choline does not imply a lack of expression of functional α7-containing nAChRs in these neurons. Rather, it may indicate a lack of detection of α7-containing nAChR-mediated currents by patch-clamp electrophysiology. 2 PNU-120596 can serve as a powerful tool for detection and enhancement of responsiveness of low densities of functional α7-containing nAChRs such as those present in hippocampal CA1 pyramidal neurons. 3 In the presence of PNU-120596, physiological concentrations of choline activate functional CA1 pyramidal α7-containing nAChRs and produce step-like currents that cause repetitive step-like depolarizations, occasionally triggering bursts of action potentials in CA1 pyramidal neurons. Therefore, the results of this study suggest that in the presence of PNU-120596 and possibly other positive allosteric modulators, endogenous choline may persistently activate CA1 pyramidal α7-containing nAChRs, enhance the excitability of CA1 pyramidal neurons and thus act as a potent therapeutic agent with potential neuroprotective and cognition-enhancing properties.

  19. Cognitive Load Alters Neuronal Processing of Food Odors.

    Science.gov (United States)

    Hoffmann-Hensel, Sonja Maria; Sijben, Rik; Rodriguez-Raecke, Rea; Freiherr, Jessica

    2017-10-31

    Obesity is a major health concern in modern societies. Although decreased physical activity and enhanced intake of high-caloric foods are important risk factors for developing obesity, human behavior during eating also plays a role. Previous studies have shown that distraction while eating increases food intake and leads to impaired processing of food stimuli. As olfaction is the most important sense involved in flavor perception, we used functional magnetic resonance imaging techniques to investigate the influence of cognitive memory load on olfactory perception and processing. Low- and high-caloric food odors were presented in combination with either low or high cognitive loads utilizing a memory task. The efficacy of the memory task was verified by a decrease in participant recall accuracy and an increase in skin conductance response during high cognitive load. Our behavioral data reveal a diminished perceived intensity for low- but not high-caloric food odors during high cognitive load. For low-caloric food odors, bilateral orbitofrontal (OFC) and piriform cortices (pirC) showed significantly lower activity during high compared with low cognitive load. For high-caloric food odors, a similar effect was established in pirC, but not in OFC. Insula activity correlates with higher intensity ratings found during the low cognitive load condition. We conclude lower activity in pirC and OFC to be responsible for diminished intensity perception, comparable to results in olfactory impaired patients and elderly. Further studies should investigate the influence of olfactory/gustatory intensities on food choices under distraction with special regards to low-caloric food. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. The 2014 Nobel Prize in Physiology or Medicine: a spatial model for cognitive neuroscience.

    Science.gov (United States)

    Burgess, Neil

    2014-12-17

    Understanding how the cognitive functions of the brain arise from its basic physiological components has been an enticing final frontier in science for thousands of years. The Nobel Prize in Physiology or Medicine 2014 was awarded one half to John O'Keefe, the other half jointly to May-Britt Moser and Edvard I. Moser "for their discoveries of cells that constitute a positioning system in the brain." This prize recognizes both a paradigm shift in the study of cognitive neuroscience, and some of the amazing insights that have followed from it concerning how the world is represented within the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration

    Directory of Open Access Journals (Sweden)

    William Sealy Hambright

    2017-08-01

    Full Text Available Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD; however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus that are severely afflicted in AD patients might be vulnerable to ferroptosis. To this end, we generated Gpx4BIKO mouse, a mouse model with conditional deletion in forebrain neurons of glutathione peroxidase 4 (Gpx4, a key regulator of ferroptosis, and showed that treatment with tamoxifen led to deletion of Gpx4 primarily in forebrain neurons of adult Gpx4BIKO mice. Starting at 12 weeks after tamoxifen treatment, Gpx4BIKO mice exhibited significant deficits in spatial learning and memory function versus Control mice as determined by the Morris water maze task. Further examinations revealed that the cognitively impaired Gpx4BIKO mice exhibited hippocampal neurodegeneration. Notably, markers associated with ferroptosis, such as elevated lipid peroxidation, ERK activation and augmented neuroinflammation, were observed in Gpx4BIKO mice. We also showed that Gpx4BIKO mice fed a diet deficient in vitamin E, a lipid soluble antioxidant with anti-ferroptosis activity, had an expedited rate of hippocampal neurodegeneration and behavior dysfunction, and that treatment with a small-molecule ferroptosis inhibitor ameliorated neurodegeneration in those mice. Taken together, our results indicate that forebrain neurons are susceptible to ferroptosis, suggesting that ferroptosis may be an important neurodegenerative mechanism in diseases such as AD. Keywords: Ferroptosis, Neurodegeneration, Cognitive impairment, Alzheimer's disease, Glutathione peroxidase 4, Transgenic mice

  2. Essential role of neuron-enriched diacylglycerol kinase (DGK, DGKbeta in neurite spine formation, contributing to cognitive function.

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    Yasuhito Shirai

    Full Text Available BACKGROUND: Diacylglycerol (DG kinase (DGK phosphorylates DG to produce phosphatidic acid (PA. Of the 10 subtypes of mammalian DGKs, DGKbeta is a membrane-localized subtype and abundantly expressed in the cerebral cortex, hippocampus, and caudate-putamen. However, its physiological roles in neurons and higher brain function have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We, therefore, developed DGKbeta KO mice using the Sleeping Beauty transposon system, and found that its long-term potentiation in the hippocampal CA1 region was reduced, causing impairment of cognitive functions including spatial and long-term memories in Y-maze and Morris water-maze tests. The primary cultured hippocampal neurons from KO mice had less branches and spines compared to the wild type. This morphological impairment was rescued by overexpression of DGKbeta. In addition, overexpression of DGKbeta in SH-SY5Y cells or primary cultured mouse hippocampal neurons resulted in branch- and spine-formation, while a splice variant form of DGKbeta, which has kinase activity but loses membrane localization, did not induce branches and spines. In the cells overexpressing DGKbeta but not the splice variant form, DGK product, PA, was increased and the substrate, DG, was decreased on the plasma membrane. Importantly, lower spine density and abnormality of PA and DG contents in the CA1 region of the KO mice were confirmed. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that membrane-localized DGKbeta regulates spine formation by regulation of lipids, contributing to the maintenance of neural networks in synaptic transmission of cognitive processes including memory.

  3. Endoplasmic Reticulum Stress-Mediated Hippocampal Neuron Apoptosis Involved in Diabetic Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2013-01-01

    Full Text Available Poor management of DM causes cognitive impairment while the mechanism is still unconfirmed. The aim of the present study was to investigate the activation of C/EBP Homology Protein (CHOP, the prominent mediator of the endoplasmic reticulum (ER stress-induced apoptosis under hyperglycemia. We employed streptozotocin- (STZ- induced diabetic rats to explore the ability of learning and memory by the Morris water maze test. The ultrastructure of hippocampus in diabetic rats and cultured neurons in high glucose medium were observed by transmission electron microscopy and scanning electron microscopy. TUNEL staining was also performed to assess apoptotic cells while the expression of CHOP was assayed by immunohistochemistry and Western blot assay in these hippocampal neurons. Six weeks after diabetes induction, the escape latency increased and the average frequency in finding the platform decreased in diabetic rats (P<0.05. The morphology of neuron and synaptic structure was impaired; the number of TUNEL-positive cells and the expression of CHOP in hippocampus of diabetic rats and high glucose medium cultured neurons were markedly altered (P<0.05. The present results suggested that the CHOP-dependent endoplasmic reticulum (ER stress-mediated apoptosis may be involved in hyperglycemia-induced hippocampal synapses and neurons impairment and promote the diabetic cognitive impairment.

  4. An approximation to the adaptive exponential integrate-and-fire neuron model allows fast and predictive fitting to physiological data

    Directory of Open Access Journals (Sweden)

    Loreen eHertäg

    2012-09-01

    Full Text Available For large-scale network simulations, it is often desirable to have computationally tractable, yet in a defined sense still physiologically valid neuron models. In particular, these models should be able to reproduce physiological measurements, ideally in a predictive sense, and under different input regimes in which neurons may operate in vivo. Here we present an approach to parameter estimation for a simple spiking neuron model mainly based on standard f-I curves obtained from in vitro recordings. Such recordings are routinely obtained in standard protocols and assess a neuron's response under a wide range of mean input currents. Our fitting procedure makes use of closed-form expressions for the firing rate derived from an approximation to the adaptive exponential integrate-and-fire (AdEx model. The resulting fitting process is simple and about two orders of magnitude faster compared to methods based on numerical integration of the differential equations. We probe this method on different cell types recorded from rodent prefrontal cortex. After fitting to the f-I current-clamp data, the model cells are tested on completely different sets of recordings obtained by fluctuating ('in-vivo-like' input currents. For a wide range of different input regimes, cell types, and cortical layers, the model could predict spike times on these test traces quite accurately within the bounds of physiological reliability, although no information from these distinct test sets was used for model fitting. Further analyses delineated some of the empirical factors constraining model fitting and the model's generalization performance. An even simpler adaptive LIF neuron was also examined in this context. Hence, we have developed a 'high-throughput' model fitting procedure which is simple and fast, with good prediction performance, and which relies only on firing rate information and standard physiological data widely and easily available.

  5. Changes in Olfactory Sensory Neuron Physiology and Olfactory Perceptual Learning After Odorant Exposure in Adult Mice.

    Science.gov (United States)

    Kass, Marley D; Guang, Stephanie A; Moberly, Andrew H; McGann, John P

    2016-02-01

    The adult olfactory system undergoes experience-dependent plasticity to adapt to the olfactory environment. This plasticity may be accompanied by perceptual changes, including improved olfactory discrimination. Here, we assessed experience-dependent changes in the perception of a homologous aldehyde pair by testing mice in a cross-habituation/dishabituation behavioral paradigm before and after a week-long ester-odorant exposure protocol. In a parallel experiment, we used optical neurophysiology to observe neurotransmitter release from olfactory sensory neuron (OSN) terminals in vivo, and thus compared primary sensory representations of the aldehydes before and after the week-long ester-odorant exposure in individual animals. Mice could not discriminate between the aldehydes during pre-exposure testing, but ester-exposed subjects spontaneously discriminated between the homologous pair after exposure, whereas home cage control mice cross-habituated. Ester exposure did not alter the spatial pattern, peak magnitude, or odorant-selectivity of aldehyde-evoked OSN input to olfactory bulb glomeruli, but did alter the temporal dynamics of that input to make the time course of OSN input more dissimilar between odorants. Together, these findings demonstrate that odor exposure can induce both physiological and perceptual changes in odor processing, and suggest that changes in the temporal patterns of OSN input to olfactory bulb glomeruli could induce differences in odor quality. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Emotion, Emotional Expression, and the Cognitive-Physiological Interaction: A Readout View.

    Science.gov (United States)

    Buck, Ross

    A basic tenet of this paper is that, from the time of the ancient Greeks, Western thought has distinguished between rational processes unique to humans and the processes governing animal behavior. A model of motivation, emotion, and the cognitive/physiological interaction that can be applied to both animals and humans is presented. The special…

  7. GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Guillermo Gonzalez-Burgos

    2011-01-01

    Full Text Available Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

  8. GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.

    Science.gov (United States)

    Gonzalez-Burgos, Guillermo; Fish, Kenneth N; Lewis, David A

    2011-01-01

    Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

  9. Managing brain extracellular K+ during neuronal activity: The physiological role of the Na+/K+-ATPase subunit isoforms

    Directory of Open Access Journals (Sweden)

    Brian Roland eLarsen

    2016-04-01

    Full Text Available AbstractDuring neuronal activity in the brain, extracellular K+ rises and is subsequently removed to prevent a widespread depolarization. One of the key players in regulating extracellular K+ is the Na+/K+-ATPase, although the relative involvement and physiological impact of the different subunit isoform compositions of the Na+/K+-ATPase remain unresolved. The various cell types in the brain serve a certain temporal contribution in the face of network activity; astrocytes respond directly to the immediate release of K+ from neurons, whereas the neurons themselves become the primary K+ absorbers as activity ends. The kinetic characteristics of the catalytic α subunit isoforms of the Na+/K+-ATPase are, partly, determined by the accessory β subunit with which they combine. The isoform combinations expressed by astrocytes and neurons, respectively, appear to be in line with the kinetic characteristics required to fulfill their distinct physiological roles in clearance of K+ from the extracellular space in the face of neuronal activity.Understanding the nature, impact and effects of the various Na+/K+-ATPase isoform combinations in K+ management in the central nervous system might reveal insights into pathological conditions such as epilepsy, migraine, and spreading depolarization following cerebral ischemia. In addition, particular neurological diseases occur as a result of mutations in the α2- (familial hemiplegic migraine type 2 and α3 isoforms (rapid-onset dystonia parkinsonism/alternating hemiplegia of childhood. This review addresses aspects of the Na+/K+-ATPase in the regulation of extracellular K+ in the central nervous system as well as the related pathophysiology. Understanding the physiological setting in non-pathological tissue would provide a better understanding of the pathological events occurring during disease.

  10. Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice.

    Science.gov (United States)

    Cabral-Costa, J V; Andreotti, D Z; Mello, N P; Scavone, C; Camandola, S; Kawamoto, E M

    2018-06-05

    Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.

  11. The PM1 neurons, movement sensitive centrifugal visual brain neurons in the locust: anatomy, physiology, and modulation by identified octopaminergic neurons.

    Science.gov (United States)

    Stern, Michael

    2009-02-01

    The locust's optic lobe contains a system of wide-field, multimodal, centrifugal neurons. Two of these cells, the protocerebrum-medulla-neurons PM4a and b, are octopaminergic. This paper describes a second pair of large centrifugal neurons (the protocerebrum-medulla-neurons PM1a and PM1b) from the brain of Locusta migratoria based on intracellular cobalt fills, electrophysiology, and immunocytochemistry. They originate and arborise in the central brain and send processes into the medulla of the optic lobe. Double intracellular recording from the same cell suggests input in the central brain and output in the optic lobe. The neurons show immunoreactivity to gamma-amino-butyric acid and its synthesising enzyme, glutamate decarboxylase. The PM1 cells are movement sensitive and show habituation to repeated visual stimulation. Bath application of octopamine causes the response to dishabituate. A very similar effect is produced by electrical stimulation of one of an octopaminergic PM4 neuron. This effect can be blocked by application of the octopamine antagonists, mianserin and phentolamine. This readily accessible system of four wide-field neurons provides a system suitable for the investigation of octopaminergic effects on the visual system at the cellular level.

  12. Cognitive Deficits Associated with Nav1.1 Alterations: Involvement of Neuronal Firing Dynamics and Oscillations.

    Directory of Open Access Journals (Sweden)

    Alex C Bender

    Full Text Available Brain oscillations play a critical role in information processing and may, therefore, be essential to uncovering the mechanisms of cognitive impairment in neurological disease. In Dravet syndrome (DS, a mutation in SCN1A, coding for the voltage-gated sodium channel Nav1.1, is associated with severe cognitive impairment and seizures. While seizure frequency and severity do not correlate with the extent of impairment, the slowing of brain rhythms may be involved. Here we investigate the role of Nav1.1 on brain rhythms and cognition using RNA interference. We demonstrate that knockdown of Nav1.1 impairs fast- and burst-firing properties of neurons in the medial septum in vivo. The proportion of neurons that fired phase-locked to hippocampal theta oscillations was reduced, and medial septal regulation of theta rhythm was disrupted. During a working memory task, this deficit was characterized by a decrease in theta frequency and was negatively correlated with performance. These findings suggest a fundamental role for Nav1.1 in facilitating fast-firing properties in neurons, highlight the importance of precise temporal control of theta frequency for working memory, and imply that Nav1.1 deficits may disrupt information processing in DS via a dysregulation of brain rhythms.

  13. Cognitive flexibility and undergraduate physiology students: increasing advanced knowledge acquisition within an ill-structured domain.

    Science.gov (United States)

    Rhodes, Ashley E; Rozell, Timothy G

    2017-09-01

    Cognitive flexibility is defined as the ability to assimilate previously learned information and concepts to generate novel solutions to new problems. This skill is crucial for success within ill-structured domains such as biology, physiology, and medicine, where many concepts are simultaneously required for understanding a complex problem, yet the problem consists of patterns or combinations of concepts that are not consistently used or needed across all examples. To succeed within ill-structured domains, a student must possess a certain level of cognitive flexibility: rigid thought processes and prepackaged informational retrieval schemes relying on rote memorization will not suffice. In this study, we assessed the cognitive flexibility of undergraduate physiology students using a validated instrument entitled Student's Approaches to Learning (SAL). The SAL evaluates how deeply and in what way information is processed, as well as the investment of time and mental energy that a student is willing to expend by measuring constructs such as elaboration and memorization. Our results indicate that students who rely primarily on memorization when learning new information have a smaller knowledge base about physiological concepts, as measured by a prior knowledge assessment and unit exams. However, students who rely primarily on elaboration when learning new information have a more well-developed knowledge base about physiological concepts, which is displayed by higher scores on a prior knowledge assessment and increased performance on unit exams. Thus students with increased elaboration skills possibly possess a higher level of cognitive flexibility and are more likely to succeed within ill-structured domains. Copyright © 2017 the American Physiological Society.

  14. Acupuncture at the Taixi (KI3) acupoint activates cerebral neurons in elderly patients with mild cognitive impairment

    OpenAIRE

    Chen, Shangjie; Xu, Maosheng; Li, Hong; Liang, Jiuping; Yin, Liang; Liu, Xia; Jia, Xinyan; Zhu, Fen; Wang, Dan; Shi, Xuemin; Zhao, Lihua

    2014-01-01

    Our previous findings have demonstrated that acupuncture at the Taixi (KI3) acupoint in healthy youths can activate neurons in cognitive-related cerebral cortex. Here, we investigated whether acupuncture at this acupoint in elderly patients with mild cognitive impairment can also activate neurons in these regions. Resting state and task-related functional magnetic resonance imaging showed that the pinprick senstation of acupuncture at the Taixi acupoint differed significantly between elderly ...

  15. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery

    NARCIS (Netherlands)

    Kok, W F; Koerts, Janneke; Tucha, O; Scheeren, T W L; Absalom, A R

    Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein β, as well as plasma-free

  16. Toward the Computational Representation of Individual Cultural, Cognitive, and Physiological State: The Sensor Shooter Simulation; TOPICAL

    International Nuclear Information System (INIS)

    RAYBOURN, ELAINE M.; FORSYTHE, JAMES C.

    2001-01-01

    This report documents an exploratory FY 00 LDRD project that sought to demonstrate the first steps toward a realistic computational representation of the variability encountered in individual human behavior. Realism, as conceptualized in this project, required that the human representation address the underlying psychological, cultural, physiological, and environmental stressors. The present report outlines the researchers' approach to representing cognitive, cultural, and physiological variability of an individual in an ambiguous situation while faced with a high-consequence decision that would greatly impact subsequent events. The present project was framed around a sensor-shooter scenario as a soldier interacts with an unexpected target (two young Iraqi girls). A software model of the ''Sensor Shooter'' scenario from Desert Storm was developed in which the framework consisted of a computational instantiation of Recognition Primed Decision Making in the context of a Naturalistic Decision Making model[1]. Recognition Primed Decision Making was augmented with an underlying foundation based on our current understanding of human neurophysiology and its relationship to human cognitive processes. While the Gulf War scenario that constitutes the framework for the Sensor Shooter prototype is highly specific, the human decision architecture and the subsequent simulation are applicable to other problems similar in concept, intensity, and degree of uncertainty. The goal was to provide initial steps toward a computational representation of human variability in cultural, cognitive, and physiological state in order to attain a better understanding of the full depth of human decision-making processes in the context of ambiguity, novelty, and heightened arousal

  17. Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals

    Directory of Open Access Journals (Sweden)

    Xiao-Bing eGao

    2015-10-01

    Full Text Available The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc and long-term behavioral changes (such as reward seeking and addiction, stress response, etc in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation and long-term changes (such as cocaine seeking in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological behavioral, and mental health implications of these findings will be discussed.

  18. Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals

    Science.gov (United States)

    Gao, Xiao-Bing; Hermes, Gretchen

    2015-01-01

    The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH) and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc.) and long-term behavioral changes (such as reward seeking and addiction, stress response, etc.) in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation) and long-term changes (such as cocaine seeking) in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological, behavioral, and mental health implications of these findings will be discussed. PMID:26539086

  19. Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

    Science.gov (United States)

    Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

    2014-10-01

    Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Physiological, anatomical and genetic identification of CPG neurons in the developing mammalian spinal cord

    DEFF Research Database (Denmark)

    Kiehn, Ole; Butt, Simon J.B.

    2003-01-01

    . These latter experiments have defined EphA4 as a molecular marker for mammalian excitatory hindlimb CPG neurons. We also review genetic approaches that can be applied to the mouse spinal cord. These include methods for identifying sub-populations of neurons by genetically encoded reporters, techniques to trace...... network connectivity with cell-specific genetically encoded tracers, and ways to selectively ablate or eliminate neuron populations from the CPG. We propose that by applying a multidisciplinary approach it will be possible to understand the network structure of the mammalian locomotor CPG...

  1. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment

    Directory of Open Access Journals (Sweden)

    Saswati ePaul

    2015-04-01

    Full Text Available A substantial number of studies on basal forebrain cholinergic neurons (BFCN have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer’s disease (AD, and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine, glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, which could help decipher disease states and propose leads for pharmacological intervention.

  2. Aroma Effects on Physiologic and Cognitive Function Following Acute Stress: A Mechanism Investigation.

    Science.gov (United States)

    Chamine, Irina; Oken, Barry S

    2016-09-01

    Aromas may improve physiologic and cognitive function after stress, but associated mechanisms remain unknown. This study evaluated the effects of lavender aroma, which is commonly used for stress reduction, on physiologic and cognitive functions. The contribution of pharmacologic, hedonic, and expectancy-related mechanisms of the aromatherapy effects was evaluated. Ninety-two healthy adults (mean age, 58.0 years; 79.3% women) were randomly assigned to three aroma groups (lavender, perceptible placebo [coconut], and nonperceptible placebo [water] and to two prime subgroups (primed, with a suggestion of inhaling a powerful stress-reducing aroma, or no prime). Participants' performance on a battery of cognitive tests, physiologic responses, and subjective stress were evaluated at baseline and after exposure to a stress battery during which aromatherapy was present. Participants also rated the intensity and pleasantness of their assigned aroma. Pharmacologic effects of lavender but not placebo aromas significantly benefited post-stress performance on the working memory task (F(2, 86) = 5.41; p = 0.006). Increased expectancy due to positive prime, regardless of aroma type, facilitated post-stress performance on the processing speed task (F(1, 87) = 8.31; p = 0.005). Aroma hedonics (pleasantness and intensity) played a role in the beneficial lavender effect on working memory and physiologic function. The observable aroma effects were produced by a combination of mechanisms involving aroma-specific pharmacologic properties, aroma hedonic properties, and participant expectations. In the future, each of these mechanisms could be manipulated to produce optimal functioning.

  3. How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition

    DEFF Research Database (Denmark)

    Siebner, Hartwig R; Hartwigsen, Gesa; Kassuba, Tanja

    2009-01-01

    Transcranial magnetic stimulation (TMS) uses a magnetic field to "carry" a short lasting electrical current pulse into the brain where it stimulates neurones, particularly in superficial regions of cerebral cortex. TMS can interfere with cognitive functions in two ways. A high intensity TMS pulse...... in the human brain. This transient neurodisruption has been termed a "virtual lesion". Smaller intensities of stimulation produce less activity; in such cases, cognitive operations can probably continue but are disrupted because of the added noisy input from the TMS pulse. It is usually argued that if a TMS...... pulse affects performance, then the area stimulated must provide an essential contribution to behaviour being studied. However, there is one exception to this: the pulse could be applied to an area that is not involved in the task but which has projections to the critical site. Activation of outputs...

  4. Anatomical differences in the mirror neuron system and social cognition network in autism.

    Science.gov (United States)

    Hadjikhani, Nouchine; Joseph, Robert M; Snyder, Josh; Tager-Flusberg, Helen

    2006-09-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social and emotional skills, the anatomical substrate of which is still unknown. In this study, we compared a group of 14 high-functioning ASD adults with a group of controls matched for sex, age, intelligence quotient, and handedness. We used an automated technique of analysis that accurately measures the thickness of the cerebral cortex and generates cross-subject statistics in a coordinate system based on cortical anatomy. We found local decreases of gray matter in the ASD group in areas belonging to the mirror neuron system (MNS), argued to be the basis of empathic behavior. Cortical thinning of the MNS was correlated with ASD symptom severity. Cortical thinning was also observed in areas involved in emotion recognition and social cognition. These findings suggest that the social and emotional deficits characteristic of autism may reflect abnormal thinning of the MNS and the broader network of cortical areas subserving social cognition.

  5. Human Cognitive Limitations. Broad, Consistent, Clinical Application of Physiological Principles Will Require Decision Support.

    Science.gov (United States)

    Morris, Alan H

    2018-02-01

    Our education system seems to fail to enable clinicians to broadly understand core physiological principles. The emphasis on reductionist science, including "omics" branches of research, has likely contributed to this decrease in understanding. Consequently, clinicians cannot be expected to consistently make clinical decisions linked to best physiological evidence. This is a large-scale problem with multiple determinants, within an even larger clinical decision problem: the failure of clinicians to consistently link their decisions to best evidence. Clinicians, like all human decision-makers, suffer from significant cognitive limitations. Detailed context-sensitive computer protocols can generate personalized medicine instructions that are well matched to individual patient needs over time and can partially resolve this problem.

  6. Where the thoughts dwell: The physiology of neuronal-glial "diffuse neural net"

    Czech Academy of Sciences Publication Activity Database

    Verkhratsky, Alexei; Parpura, V.; Rodríguez Arellano, Jose Julio

    2011-01-01

    Roč. 66, 1-2 (2011), s. 133-151 ISSN 0165-0173 R&D Projects: GA ČR GA309/09/1696; GA ČR GA305/08/1384 Institutional research plan: CEZ:AV0Z50390703 Keywords : human brain * glia * neurone Subject RIV: FH - Neurology Impact factor: 10.342, year: 2011

  7. Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.

    Science.gov (United States)

    Xu, Xiaofeng; Zhang, Bin; Lu, Kaili; Deng, Jiangshan; Zhao, Fei; Zhao, Bing-Qiao; Zhao, Yuwu

    2016-07-01

    Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.

  8. C. elegans model of neuronal aging

    OpenAIRE

    Peng, Chiu-Ying; Chen, Chun-Hao; Hsu, Jiun-Min; Pan, Chun-Liang

    2011-01-01

    Aging of the nervous system underlies the behavioral and cognitive decline associated with senescence. Understanding the molecular and cellular basis of neuronal aging will therefore contribute to the development of effective treatments for aging and age-associated neurodegenerative disorders. Despite this pressing need, there are surprisingly few animal models that aim at recapitulating neuronal aging in a physiological context. We recently developed a C. elegans model of neuronal aging, and...

  9. He said what? Physiological and cognitive responses to imagining and witnessing outgroup racism.

    Science.gov (United States)

    Karmali, Francine; Kawakami, Kerry; Page-Gould, Elizabeth

    2017-08-01

    Responses to outgroup racism can have serious implications for the perpetuation of bias, yet research examining this process is rare. The present research investigated self-reported, physiological, and cognitive responses among "experiencers" who witnessed and "forecasters" who imagined a racist comment targeting an outgroup member. Although previous research indicates that experiencers self-reported less distress and chose a racist partner more often than forecasters, the present results explored the possibility that experiencers may actually be distressed in such situation but regulate their initial affective reactions. The results from Experiment 1 demonstrated that participants in both roles showed (a) no activation of the hypothalamic pituitary adrenal stress axis (decreased cortisol) and (b) activation of the sympathetic autonomic nervous system (increased skin conductance). However, experiencers but not forecasters displayed a physiological profile indicative of an orienting response (decreased heart rate and increased skin conductance) rather than a defensive response (increased heart rate and increased skin conductance). Furthermore, the results from Experiment 2 provided additional evidence that experiencers are not distressed or regulating their emotional responses. In particular, experiencers showed less cognitive impairment on a Stroop task than forecasters. Together these findings indicate that when people actually encounter outgroup bias, they respond with apathy and do not censure the racist. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. Cognitive Behavior Evaluation Based on Physiological Parameters among Young Healthy Subjects with Yoga as Intervention

    Directory of Open Access Journals (Sweden)

    H. Nagendra

    2015-01-01

    Full Text Available Objective. To investigate the effect of yoga practice on cognitive skills, autonomic nervous system, and heart rate variability by analyzing physiological parameters. Methods. The study was conducted on 30 normal young healthy engineering students. They were randomly selected into two groups: yoga group and control group. The yoga group practiced yoga one and half hour per day for six days in a week, for a period of five months. Results. The yoga practising group showed increased α, β, and δ EEG band powers and significant reduction in θ and γ band powers. The increased α and β power can represent enhanced cognitive functions such as memory and concentration, and that of δ signifies synchronization of brain activity. The heart rate index θ/α decreased, neural activity β/θ increased, attention resource index β/(α+θ increased, executive load index (δ+θ/α decreased, and the ratio (δ+θ/(α+β decreased. The yoga practice group showed improvement in heart rate variability, increased SDNN/RMSSD, and reduction in LF/HF ratio. Conclusion. Yoga practising group showed significant improvement in various cognitive functions, such as performance enhancement, neural activity, attention, and executive function. It also resulted in increase in the heart rate variability, parasympathetic nervous system activity, and balanced autonomic nervous system reactivity.

  11. Reactivity to Social Stress in Subclinical Social Anxiety: Emotional Experience, Cognitive Appraisals, Behavior, and Physiology

    Science.gov (United States)

    Crişan, Liviu G.; Vulturar, Romana; Miclea, Mircea; Miu, Andrei C.

    2016-01-01

    Recent research indicates that subclinical social anxiety is associated with dysfunctions at multiple psychological and biological levels, in a manner that seems reminiscent of social anxiety disorder (SAD). This study aimed to describe multidimensional responses to laboratory-induced social stress in an analog sample selected for social anxiety symptoms. State anxiety, cognitive biases related to negative social evaluation, speech anxiety behaviors, and cortisol reactivity were assessed in the Trier Social Stress Test (TSST). Results showed that social anxiety symptoms were associated with increased state anxiety, biased appraisals related to the probability and cost of negative social evaluations, behavioral changes in facial expression that were consistent with speech anxiety, and lower cortisol reactivity. In addition, multiple interrelations between responses in the TSST were found, with positive associations between subjective experience, cognitive appraisals, and observable behavior, as well as negative associations between each of the former two types of response and cortisol reactivity. These results show that in response to social stressors, subclinical social anxiety is associated with significant changes in emotional experience, cognitive appraisals, behaviors, and physiology that could parallel those previously found in SAD samples. PMID:26858658

  12. Neurocognitive Poetics: methods and models for investigating the neuronal and cognitive- affective bases of literature reception

    Directory of Open Access Journals (Sweden)

    Arthur M Jacobs

    2015-04-01

    Full Text Available A long tradition of research including classical rhetoric, aesthetics and poetics theory, formalism and structuralism, as well as current perspectives in (neurocognitive poetics has investigated structural and functional aspects of literature reception. Despite a wealth of literature published in specialised journals like Poetics, however, still little is known about how the brain processes and creates literary and poetic texts. Still, such stimulus material might be suited better than other genres for demonstrating the complexities with which our brain constructs the world in and around us, because it unifies thought and language, music and imagery in a clear, manageable way, most often with play, pleasure, and emotion (Schrott & Jacobs, 2011. In this paper, I discuss methods and models for investigating the neuronal and cognitive-affective bases of literary reading together with pertinent results from studies on poetics, text processing, emotion, or neuroaesthetics, and outline current challenges and future perspectives.

  13. Cognitive, physical and physiological responses of school boy cricketers to a 30-over batting simulation.

    Science.gov (United States)

    Goble, David; Christie, Candice Jo-Anne

    2017-06-01

    The purpose of this study was to assess how cognitive and physical performance are affected during a prolonged, fatigue-inducing cricket-batting simulation. Fifteen amateur batters from three Eastern Cape schools in South Africa were recruited (mean ± SD: age 17 ± 0.92 years; stature 1.75 ± 0.07 m; body mass 78.3 ± 13.2 kg). Participants completed a 6-stage, 30-over batting simulation (BATEX © ). During the protocol, there were five periods of cognitive assessment (CogState brief test battery, Melbourne, Australia). The primary outcome measures from each cognitive task were speed and accuracy/error rates. Physiological (heart rate) and physical (sprint times) responses were also recorded. Sprint times deteriorated (d = 0.84; P attention and vigilance (d = 0.56; P = 0.21) and attention and working memory (d = 0.61; P = 0.11), reducing task performance after 30 overs. Therefore, prolonged batting with repeated shuttle running fatigues amateur batters and adversely affects higher-order cognitive function. This will affect decision-making, response selection, response execution and other batting-related executive processes. We recommend that training should incorporate greater proportions of centre-wicket batting with repeated, high-intensity shuttle running. This will improve batting-related skills and information processing when fatigued, making practice more representative of competition.

  14. Study on cognition disorder and morphologic change of neurons in hippocampus area following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    洪军; 崔建忠; 周云涛; 高俊玲

    2002-01-01

    Objective: To explore the correlation between cognition disorder and morphologic change of hippocampal neurons after traumatic brain injury (TBI).   Methods: Wistar rat models with severe TBI were made by Marmarous method. The histopathological change of the neurons in the hippocampus area were studied with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated X-dUPT nick end labeling (TUNEL), respectively. The cognitive function was evaluated with the Morris water maze test.   Results: The comprehensive neuronal degeneration and necrosis could be observed in CA2-3 regions of hippocampus at 3 days after injury. Apoptotic positive neurons in CA2-4 regions of hippocampus and dentate gyrus increased in the injured group at 24 hours following TBI. They peaked at 7 days and then declined. Significant impairment of spatial learning and memory was observed after injury in the rats.   Conclusions: The rats have obvious disorders in spatial learning and memory after severe TBI. Meanwhile, delayed neuronal necrosis and apoptosis can be observed in the neurons in the hippocampus area. It suggests that delayed hippocampal cell death may contribute to the functional deficit.

  15. Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease.

    Science.gov (United States)

    Zhang, Heng; Zhang, Ling; Zhou, Dongming; He, Xiao; Wang, Dongpi; Pan, Hongyu; Zhang, Xiaoqin; Mei, Yufei; Qian, Qi; Zheng, Tingting; Jones, Frank E; Sun, Binggui

    2017-10-01

    Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The struggle of giving up personal goals: affective, physiological, and cognitive consequences of an action crisis.

    Science.gov (United States)

    Brandstätter, Veronika; Herrmann, Marcel; Schüler, Julia

    2013-12-01

    A critical phase in goal striving occurs when setbacks accumulate and goal disengagement becomes an issue. This critical phase is conceptualized as an action crisis and assumed to be characterized by an intrapsychic conflict in which the individual becomes torn between further goal pursuit and goal disengagement. Our theorizing converges with Klinger's conceptualization of goal disengagement as a process, rather than a discrete event. Two longitudinal field studies tested and found support for the hypothesis that an action crisis not only compromises an individual's psychological and physiological well-being, but also dampens the cognitive evaluation of the respective goal. In Study 3, marathon runners experiencing an action crisis in their goal of running marathons showed a stronger cortisol secretion and a lower performance in the race 2 weeks later. Results are interpreted in terms of action-phase-specific mindsets with a focus on self-regulatory processes in goal disengagement.

  17. Early effects of 16O radiation on neuronal morphology and cognition in a murine model

    Science.gov (United States)

    Carr, Hannah; Alexander, Tyler C.; Groves, Thomas; Kiffer, Frederico; Wang, Jing; Price, Elvin; Boerma, Marjan; Allen, Antiño R.

    2018-05-01

    Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory. The aim of the current study is to assess whether behavior, glutamate receptor gene expression, and dendritic structure in the hippocampus are altered in mice after early exposure to 16O radiation in mice. Two weeks post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Y-maze. During Y-maze testing, mice exposed to 0.1 Gy and 0.25 Gy radiation failed to distinguish the novel arm, spending approximately the same amount of time in all 3 arms during the retention trial. Exposure to 16O significantly reduced the expression of Nr1 and GluR1 in the hippocampus and modulated spine morphology in the dentate gyrus and cornu Ammon 1 within the hippocampus. The present data provide evidence that 16O radiation has early deleterious effects on mature neurons that are associated with hippocampal learning and memory.

  18. Reactivity to television food commercials in overweight and lean adults: Physiological, cognitive and behavioural responses.

    Science.gov (United States)

    Boyland, Emma J; Burgon, Rachel H; Hardman, Charlotte A

    2017-08-01

    Recent evidence indicates that acute exposure to food advertising increases food intake. However, little research to date has explored the potential mechanisms underpinning this, such as the extent to which food commercials elicit conditioned physiological responses (e.g. increased salivation). The aim of the current study was to examine salivary, cognitive and consumptive responses to televised food commercials in overweight (N=26) and lean (N=29) adult females. Participants attended two laboratory sessions in a counterbalanced order; in one session they viewed a television show with embedded commercials for unhealthy foods, and in the other session they viewed the same show with non-food commercials. In both conditions, following viewing participants were exposed to an in vivo food cue (freshly cooked pizza) which they were then invited to eat ad libitum. Salivation was measured at baseline, during commercial exposure, and during in vivo exposure. Participants also self-reported components of appetite on visual analogue scales and completed a word stem task. Results indicated little evidence of increased salivary reactivity to the food commercials. In both conditions, lean participants showed reliable salivary responses to the in vivo food cue. In contrast, overweight participants only showed increased salivation to the in vivo cue in the food commercials condition. Food commercial exposure did not increase the number of food-related cognitions or amount of food consumed, but did drive a greater increase in desire to eat prior to pizza consumption than exposure to the control commercials. Exposure to food advertising primes eating-related motivations, and while it may not be associated with increased intake or salivation per se, non-food commercials may attenuate subsequent physiological responses to actual food cues in overweight individuals. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. [Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

    Science.gov (United States)

    Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

    2014-01-01

    Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

  20. Interaction between physiological and cognitive determinants of emotions: experimental studies on Schachter's theory of emotions.

    Science.gov (United States)

    Erdmann, G; Janke, W

    1978-01-01

    This study investigated the interaction between physiological arousal and situation-derived cognitions in the determination of feeling states that is proposed in Schachter's theory of emotions. The degree of bodily arousal was varied by disguised oral administration of a placebo or the sympathicomimetic agent ephedrine. The situational circumstances were varied by instructions offering cues for (a) no emotions ('neutral' control), or the feeling states called (b) 'anger', (c) 'happiness', and (d) anxiety'. The subjects were 72 male students. The dependent variables were blood pressure, heart rate, a list of bodily symptoms, and an adjective check list. The results within the 'anger' and 'happiness' condition were in accordance with Schachter's theory: depending on the type of situation, ephedrine-induced arousal either decreased or increased positive descriptions of mood. The emotional effects of the 'anxiety' condition, however, were independent of the drug-induced arousal level. Contrary to Schachter's theory, anxiety reactions occured also in a state of low physiological arousal and did not increase with increasing arousal.

  1. Lychee Seed Saponins Improve Cognitive Function and Prevent Neuronal Injury via Inhibiting Neuronal Apoptosis in a Rat Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Xiuling Wang

    2017-02-01

    Full Text Available Lychee seed is a traditional Chinese medicine and possesses many activities, including hypoglycemia, liver protection, antioxidation, antivirus, and antitumor. However, its effect on neuroprotection is still unclear. The present study investigated the effects of lychee seed saponins (LSS on neuroprotection and associated mechanisms. We established a rat model of Alzheimer’s disease (AD by injecting Aβ25–35 into the lateral ventricle of rats and evaluated the effect of LSS on spatial learning and memory ability via the Morris water maze. Neuronal apoptosis was analyzed by hematoxylin and eosin stain and terminal deoxynucleotidyl transferase (Tdt-mediated dUTP nick-end labeling analysis, and mRNA expression of caspase-3 and protein expressions of Bax and Bcl-2 by reverse transcription-polymerase chain reaction (RT-PCR and Western blotting, respectively. The results showed that LSS remarkably improved cognitive function and alleviated neuronal injury by inhibiting apoptosis in the hippocampus of AD rats. Furthermore, the mRNA expression of caspase-3 and the protein expression of Bax were downregulated, while the protein expression of Bcl-2 and the ratio of Bcl-2/Bax were increased by LSS. We demonstrate that LSS significantly improves cognitive function and prevent neuronal injury in the AD rats via regulation of the apoptosis pathway. Therefore, LSS may be developed as a nutritional supplement and sold as a drug for AD prevention and/or treatment.

  2. Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2017-01-01

    Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl 3 ) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO 4 ) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.

  3. Comparison of classifiers for decoding sensory and cognitive information from prefrontal neuronal populations.

    Directory of Open Access Journals (Sweden)

    Elaine Astrand

    Full Text Available Decoding neuronal information is important in neuroscience, both as a basic means to understand how neuronal activity is related to cerebral function and as a processing stage in driving neuroprosthetic effectors. Here, we compare the readout performance of six commonly used classifiers at decoding two different variables encoded by the spiking activity of the non-human primate frontal eye fields (FEF: the spatial position of a visual cue, and the instructed orientation of the animal's attention. While the first variable is exogenously driven by the environment, the second variable corresponds to the interpretation of the instruction conveyed by the cue; it is endogenously driven and corresponds to the output of internal cognitive operations performed on the visual attributes of the cue. These two variables were decoded using either a regularized optimal linear estimator in its explicit formulation, an optimal linear artificial neural network estimator, a non-linear artificial neural network estimator, a non-linear naïve Bayesian estimator, a non-linear Reservoir recurrent network classifier or a non-linear Support Vector Machine classifier. Our results suggest that endogenous information such as the orientation of attention can be decoded from the FEF with the same accuracy as exogenous visual information. All classifiers did not behave equally in the face of population size and heterogeneity, the available training and testing trials, the subject's behavior and the temporal structure of the variable of interest. In most situations, the regularized optimal linear estimator and the non-linear Support Vector Machine classifiers outperformed the other tested decoders.

  4. Discrete Emotions Predict Changes in Cognition, Judgment, Experience, Behavior, and Physiology: A Meta-Analysis of Experimental Emotion Elicitations

    Science.gov (United States)

    Lench, Heather C.; Flores, Sarah A.; Bench, Shane W.

    2011-01-01

    Our purpose in the present meta-analysis was to examine the extent to which discrete emotions elicit changes in cognition, judgment, experience, behavior, and physiology; whether these changes are correlated as would be expected if emotions organize responses across these systems; and which factors moderate the magnitude of these effects. Studies…

  5. Synergistic effects of aerobic exercise and cognitive training on cognition, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Yeh, Ting-Ting; Wu, Ching-Yi; Hsieh, Yu-Wei; Chang, Ku-Chou; Lee, Lin-Chien; Hung, Jen-Wen; Lin, Keh-Chung; Teng, Ching-Hung; Liao, Yi-Han

    2017-08-31

    Aerobic exercise and cognitive training have been effective in improving cognitive functions; however, whether the combination of these two can further enhance cognition and clinical outcomes in stroke survivors with cognitive decline remains unknown. This study aimed to determine the treatment effects of a sequential combination of aerobic exercise and cognitive training on cognitive function and clinical outcomes. Stroke survivors (n = 75) with cognitive decline will be recruited and randomly assigned to cognitive training, aerobic exercise, and sequential combination of aerobic exercise and cognitive training groups. All participants will receive training for 60 minutes per day, 3 days per week for 12 weeks. The aerobic exercise group will receive stationary bicycle training, the cognitive training group will receive cognitive-based training, and the sequential group will first receive 30 minutes of aerobic exercise, followed by 30 minutes of cognitive training. The outcome measures involve cognitive functions, physiological biomarkers, daily function and quality of life, physical functions, and social participation. Participants will be assessed before and immediately after the interventions, and 6 months after the interventions. Repeated measures of analysis of variance will be used to evaluate the changes in outcome measures at the three assessments. This trial aims to explore the benefits of innovative intervention approaches to improve the cognitive function, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline. The findings will provide evidence to advance post-stroke cognitive rehabilitation. ClinicalTrials.gov, NCT02550990 . Registered on 6 September 2015.

  6. [Role of hippocampal neuronal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia].

    Science.gov (United States)

    Ming, Hong; Chen, Rui; Wang, Jing; Ju, Jingmei; Sun, Li; Zhang, Guoxing

    2014-12-01

    To investigate the role of hippocampal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia. 45 ICR male mice were randomly divided into 3 groups: the unhandled control group (UC group, n = 15), the chronic intermittent hypoxia (CIH group, n = 15) and the pretreatment memantine group (MEM group, n = 15). CIH and MEM mice were subjected to intermittent hypoxia while UC mice to room air for 8 h per day during 4 weeks. Mice in the MEM group were pretreated with memantine (5 mg/kg) by intraperitoneal injection before the cycle started, and those in the UC group and the CIH group were treated with same volume of physiological saline. Neurobehavioral assessments were performed by Open filed and Morris water maze, [Ca²⁺]i in hippocampal neurons was evaluate by flow cytometry, and the expression of cleaved caspase-3, phospho-ERK1/2 in hippocampus were detected by Western blotting. Compared with the UC group, CIH mice displayed markedly more locomotor activity (P overload, neuron apoptosis, dephosphorylation of ERK1/2, which can be attenuated by memantine. Memantine may have a therapeutic effect in the neurocognitive impairment associated with OSAHS.

  7. Effects of Scopolamine and Melatonin Cotreatment on Cognition, Neuronal Damage, and Neurogenesis in the Mouse Dentate Gyrus.

    Science.gov (United States)

    Chen, Bai Hui; Ahn, Ji Hyeon; Park, Joon Ha; Choi, Soo Young; Lee, Yun Lyul; Kang, Il Jun; Hwang, In Koo; Lee, Tae-Kyeong; Shin, Bich-Na; Lee, Jae-Chul; Hong, Seongkweon; Jeon, Yong Hwan; Shin, Myoung Cheol; Cho, Jun Hwi; Won, Moo-Ho; Lee, Young Joo

    2018-03-01

    It has been demonstrated that melatonin plays important roles in memory improvement and promotes neurogenesis in experimental animals. We examined effects of melatonin on cognitive deficits, neuronal damage, cell proliferation, neuroblast differentiation and neuronal maturation in the mouse dentate gyrus after cotreatment of scopolamine (anticholinergic agent) and melatonin. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally injected for 2 and/or 4 weeks to 8-week-old mice. Scopolamine treatment induced significant cognitive deficits 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly improved spatial learning and short-term memory impairments. Two and 4 weeks after scopolamine treatment, neurons were not damaged/dead in the dentate gyrus, in addition, no neuronal damage/death was shown after cotreatment of scopolamine and melatonin. Ki67 (a marker for cell proliferation)- and doublecortin (a marker for neuroblast differentiation)-positive cells were significantly decreased in the dentate gyrus 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly increased Ki67- and doublecortin-positive cells compared with scopolamine-treated group. However, double immunofluorescence for NeuN/BrdU, which indicates newly-generated mature neurons, did not show double-labeled cells (adult neurogenesis) in the dentate gyrus 2 and 4 weeks after cotreatment of scopolamine and melatonin. Our results suggest that melatonin treatment recovers scopolamine-induced spatial learning and short-term memory impairments and restores or increases scopolamine-induced decrease of cell proliferation and neuroblast differentiation, but does not lead to adult neurogenesis (maturation of neurons) in the mouse dentate gyrus following scopolamine treatment.

  8. [Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

    Science.gov (United States)

    Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

    2014-01-01

    The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

  9. Physiological optics, cognition and emotion: a novel look at the early work of Wilhelm Wundt.

    Science.gov (United States)

    Wassmann, Claudia

    2009-04-01

    The German physiologist Wilhelm Wundt, who later founded experimental psychology, arguably developed the first modern scientific conception of emotion. In the first edition of Vorlesungen über die Menschen- und Thierseele (Lectures on human and animal psychology), which was published in 1863, Wundt tried to establish that emotions were essential parts of rational thought. In fact, he considered them unconscious steps of decision-making that were implied in all processes of conscious thought. His early work deserves attention not only because it is the attempt to conceptualize cognition and emotion strictly from a neural point of view but also because it represents the very foundation of the debate about the nature of emotion that revolved around William James' theory of emotion during the 1890s. However, this aspect of his work is little known because scholars who have analyzed Wundt's work focused on his late career. Furthermore, historical analysis interpreted Wundt's work within a philosophical framework, rather than placing it in the context of German medical and physiological research in which it belongs. In addition, Wundt's early works are hardly available to an English speaking audience because they were never translated.

  10. Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats.

    Science.gov (United States)

    Li, Fang; Yan, Chao-Qun; Lin, Li-Ting; Li, Hui; Zeng, Xiang-Hong; Liu, Yi; Du, Si-Qi; Zhu, Wen; Liu, Cun-Zhi

    2015-04-28

    Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P area in any of the groups (P > 0.05). These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.

  11. Sleep and athletic performance: the effects of sleep loss on exercise performance, and physiological and cognitive responses to exercise.

    Science.gov (United States)

    Fullagar, Hugh H K; Skorski, Sabrina; Duffield, Rob; Hammes, Daniel; Coutts, Aaron J; Meyer, Tim

    2015-02-01

    Although its true function remains unclear, sleep is considered critical to human physiological and cognitive function. Equally, since sleep loss is a common occurrence prior to competition in athletes, this could significantly impact upon their athletic performance. Much of the previous research has reported that exercise performance is negatively affected following sleep loss; however, conflicting findings mean that the extent, influence, and mechanisms of sleep loss affecting exercise performance remain uncertain. For instance, research indicates some maximal physical efforts and gross motor performances can be maintained. In comparison, the few published studies investigating the effect of sleep loss on performance in athletes report a reduction in sport-specific performance. The effects of sleep loss on physiological responses to exercise also remain equivocal; however, it appears a reduction in sleep quality and quantity could result in an autonomic nervous system imbalance, simulating symptoms of the overtraining syndrome. Additionally, increases in pro-inflammatory cytokines following sleep loss could promote immune system dysfunction. Of further concern, numerous studies investigating the effects of sleep loss on cognitive function report slower and less accurate cognitive performance. Based on this context, this review aims to evaluate the importance and prevalence of sleep in athletes and summarises the effects of sleep loss (restriction and deprivation) on exercise performance, and physiological and cognitive responses to exercise. Given the equivocal understanding of sleep and athletic performance outcomes, further research and consideration is required to obtain a greater knowledge of the interaction between sleep and performance.

  12. Cognitive and physiological responses in humans exposed to a TETRA base station signal in relation to perceived electromagnetic hypersensitivity.

    Science.gov (United States)

    Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

    2012-01-01

    Terrestrial Trunked Radio (TETRA) technology ("Airwave") has led to public concern because of its potential interference with electrical activity in the brain. The present study is the first to examine whether acute exposure to a TETRA base station signal has an impact on cognitive functioning and physiological responses. Participants were exposed to a 420 MHz TETRA signal at a power flux density of 10 mW/m(2) as well as sham (no signal) under double-blind conditions. Fifty-one people who reported a perceived sensitivity to electromagnetic fields as well as 132 controls participated in a double-blind provocation study. Forty-eight sensitive and 132 control participants completed all three sessions. Measures of short-term memory, working memory, and attention were administered while physiological responses (blood volume pulse, heart rate, skin conductance) were monitored. After applying exclusion criteria based on task performance for each aforementioned cognitive measure, data were analyzed for 36, 43, and 48 sensitive participants for these respective tasks and, likewise, 107,125, and 129 controls. We observed no differences in cognitive performance between sham and TETRA exposure in either group; physiological response also did not differ between the exposure conditions. These findings are similar to previous double-blind studies with other mobile phone signals (900-2100 MHz), which could not establish any clear evidence that mobile phone signals affect health or cognitive function. Copyright © 2011 Wiley Periodicals, Inc.

  13. A real-time hybrid neuron network for highly parallel cognitive systems.

    Science.gov (United States)

    Christiaanse, Gerrit Jan; Zjajo, Amir; Galuzzi, Carlo; van Leuken, Rene

    2016-08-01

    For comprehensive understanding of how neurons communicate with each other, new tools need to be developed that can accurately mimic the behaviour of such neurons and neuron networks under `real-time' constraints. In this paper, we propose an easily customisable, highly pipelined, neuron network design, which executes optimally scheduled floating-point operations for maximal amount of biophysically plausible neurons per FPGA family type. To reduce the required amount of resources without adverse effect on the calculation latency, a single exponent instance is used for multiple neuron calculation operations. Experimental results indicate that the proposed network design allows the simulation of up to 1188 neurons on Virtex7 (XC7VX550T) device in brain real-time yielding a speed-up of x12.4 compared to the state-of-the art.

  14. Curcuma treatment prevents cognitive deficit and alteration of neuronal morphology in the limbic system of aging rats.

    Science.gov (United States)

    Vidal, Blanca; Vázquez-Roque, Rubén A; Gnecco, Dino; Enríquez, Raúl G; Floran, Benjamin; Díaz, Alfonso; Flores, Gonzalo

    2017-03-01

    Curcuma is a natural compound that has shown neuroprotective properties, and has been reported to prevent aging and improve memory. While the mechanism(s) underlying these effects are unclear, they may be related to increases in neural plasticity. Morphological changes have been reported in neuronal dendrites in the limbic system in animals and elderly humans with cognitive impairment. In this regard, there is a need to use alternative therapies that delay the onset of morphologies and behavioral characteristics of aging. Therefore, the objective of this study was to evaluate the effect of curcuma on cognitive processes and dendritic morphology of neurons in the prefrontal cortex (PFC), the CA1 and CA3 regions of the dorsal hippocampus, the dentate gyrus, and the basolateral amygdala (BLA) of aged rats. 18-month-old rats were administered curcuma (100 mg/kg) daily for 60 days. After treatment, recognition memory was assessed using the novel object recognition test. Curcuma-treated rats showed a significant increase in the exploration quotient. Dendritic morphology was assessed by Golgi-Cox staining and followed by Sholl analysis. Curcuma-treated rats showed a significant increase in dendritic spine density and dendritic length in pyramidal neurons of the PFC, the CA1 and CA3, and the BLA. The preservation of dendritic morphology was positively correlated with cognitive improvements. Our results suggest that curcuma induces modification of dendritic morphology in the aforementioned regions. These changes may explain how curcuma slows the aging process that has already begun in these animals, preventing deterioration in neuronal morphology of the limbic system and recognition memory. © 2016 Wiley Periodicals, Inc.

  15. Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer's Disease.

    Science.gov (United States)

    Li, Jinze; Ma, Xiaowei; Wang, Yu; Chen, Chengjuan; Hu, Min; Wang, Linlin; Fu, Junmin; Shi, Gaona; Zhang, Dongming; Zhang, Tiantai

    2018-01-01

    Neuroinflammatory reactions mediated by microglia and astrocytes have been shown to play a key role in early progression of Alzheimer's disease (AD). Increased evidences have demonstrated that neurons exacerbate local inflammatory reactions by producing inflammatory mediators and act as an important participant in the pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural product that is part of a class of novel non-steroidal anti-inflammatory drugs (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic effects on arthritis-induced mice and suppressed the activation of glial cells. In the current study, we investigated the effects of MSL on cognitive function and neuronal protection induced by amyloid-beta peptides (Aβ) and explored potential underlying mechanisms involved. Amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of MSL through behavioral testing and neuronal degenerative changes. In addition, copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to determine the transduction of cyclooxygenase (COX) and mitogen-activated protein kinase (MAPK) pathways. Our results indicated that at an early stage, MSL treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice. Moreover, in an in vitro AD model, MSL treatment protected injured cells by increasing cell viability, improving mitochondrial dysfunction, and decreasing oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N-terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly demonstrated cognitive preservation by protecting neurons via a pleiotropic anti-inflammatory effect in the context of AD-associated deficits. Therefore, early treatment of anti-inflammatory therapy may be an effective strategy for treating AD.

  16. Acoustic Measures of Voice and Physiologic Measures of Autonomic Arousal during Speech as a Function of Cognitive Load.

    Science.gov (United States)

    MacPherson, Megan K; Abur, Defne; Stepp, Cara E

    2017-07-01

    This study aimed to determine the relationship among cognitive load condition and measures of autonomic arousal and voice production in healthy adults. A prospective study design was conducted. Sixteen healthy young adults (eight men, eight women) produced a sentence containing an embedded Stroop task in each of two cognitive load conditions: congruent and incongruent. In both conditions, participants said the font color of the color words instead of the word text. In the incongruent condition, font color differed from the word text, creating an increase in cognitive load relative to the congruent condition in which font color and word text matched. Three physiologic measures of autonomic arousal (pulse volume amplitude, pulse period, and skin conductance response amplitude) and four acoustic measures of voice (sound pressure level, fundamental frequency, cepstral peak prominence, and low-to-high spectral energy ratio) were analyzed for eight sentence productions in each cognitive load condition per participant. A logistic regression model was constructed to predict the cognitive load condition (congruent or incongruent) using subject as a categorical predictor and the three autonomic measures and four acoustic measures as continuous predictors. It revealed that skin conductance response amplitude, cepstral peak prominence, and low-to-high spectral energy ratio were significantly associated with cognitive load condition. During speech produced under increased cognitive load, healthy young adults show changes in physiologic markers of heightened autonomic arousal and acoustic measures of voice quality. Future work is necessary to examine these measures in older adults and individuals with voice disorders. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  17. Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1.

    Science.gov (United States)

    Light, Alan R; Hughen, Ronald W; Zhang, Jie; Rainier, Jon; Liu, Zhuqing; Lee, Jeewoo

    2008-09-01

    The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate.

  18. Is rivastigmine safe as pretreatment against nerve agents poisoning? A pharmacological, physiological and cognitive assessment in healthy young adult volunteers.

    Science.gov (United States)

    Lavon, Ophir; Eisenkraft, Arik; Blanca, Merav; Raveh, Lily; Ramaty, Erez; Krivoy, Amir; Atsmon, Jacob; Grauer, Ettie; Brandeis, Rachel

    2015-07-01

    Rivastigmine, a reversible cholinesterase inhibitor, approved as a remedy in Alzheimer's disease, was suggested as pretreatment against nerve agents poisoning. We evaluated the pharmacokinetic, pharmacodynamic, physiologic, cognitive and emotional effects of repeated rivastigmine in young healthy male adults, in a double blind, placebo controlled crossover trial. Three groups completed 3 treatment periods: 0, 1.5 and 3mg twice a day, for a total of 5 intakes. Parameters monitored were: vital signs, ECG, laboratory tests, sialometry, visual accommodation, inspiratory peak flow, and cognitive function tests. Adverse reactions were mild. Peak blood levels and peak cholinesterase inhibition increased with repeated intakes, and high variability and non-linear pharmacokinetics were demonstrated. In addition, two cognitive functions were affected (perceptual speed and dynamic tracking). The complicated pharmacological profile and the high inter-personal variability limit the potential use of rivastigmine as pretreatment for war fighters and first responders. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Iron overload accelerates neuronal amyloid-β production and cognitive impairment in transgenic mice model of Alzheimer's disease.

    Science.gov (United States)

    Becerril-Ortega, Javier; Bordji, Karim; Fréret, Thomas; Rush, Travis; Buisson, Alain

    2014-10-01

    Iron dyshomeostasis is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD); yet, its mechanism is not well understood. Here, we investigated the AD-related mechanism(s) of iron-sulfate exposure in vitro and in vivo, using cultured primary cortical neurons and APP/PS1 AD-model mice, respectively. In both systems, we observed iron-induced disruptions of amyloid precursor protein (APP) processing, neuronal signaling, and cognitive behavior. Iron overload increased production of amyloidogenic KPI-APP and amyloid beta. Further, this APP misprocessing was blocked by MK-801 in vitro, suggesting the effect was N-methyl-D-aspartate receptor (NMDAR) dependent. Calcium imaging confirmed that 24 hours iron exposure led to disrupted synaptic signaling by augmenting GluN2B-containing NMDAR expression-GluN2B messenger RNA and protein levels were increased and promoting excessing extrasynaptic NMDAR signaling. The disrupted GluN2B expression was concurrent with diminished expression of the splicing factors, sc35 and hnRNPA1. In APP/PS1 mice, chronic iron treatment led to hastened progression of cognitive impairment with the novel object recognition discrimination index, revealing a deficit at the age of 4 months, concomitant with augmented GluN2B expression. Together, these data suggest iron-induced APP misprocessing and hastened cognitive decline occur through inordinate extrasynaptic NMDAR activation. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Reduced activation in the mirror neuron system during a virtual social cognition task in euthymic bipolar disorder.

    Science.gov (United States)

    Kim, Eosu; Jung, Young-Chul; Ku, Jeonghun; Kim, Jae-Jin; Lee, Hyeongrae; Kim, So Young; Kim, Sun I; Cho, Hyun-Sang

    2009-11-13

    Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others' emotional expression. Relative to normal controls, BD patients showed reduced activations in the 'mirror neuron system', including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients.

  1. Getting from neuron to checkmark: Models and methods in cognitive survey research

    NARCIS (Netherlands)

    Holleman, B.C.; Murre, J.M.J.

    2008-01-01

    Since the 1980s much work has been done in the field of Cognitive Survey Research. In an interdisciplinary endeavour, survey methodologists and cognitive psychologists (as well as social psychologists and linguists) have worked to unravel the cognitive processes underlying survey responses: to

  2. Effects of U.S. Navy Diver Training on Physiological Parameters, Time of Useful Consciousness and Cognitive Performance During Periods of Normobaric Hypoxia

    Science.gov (United States)

    2014-04-01

    TRAINING ON PHYSIOLOGICAL PARAMETERS, TIME OF USEFULL CONSCIOUSNESS, AND COGNITIVE PERFORMANCE DURING PERIODS OF NORMOBARIC HYPOXIA...Sato, Y. Watanabe, "Time of Usefull Consciousness Determination in Aircrew Members with Rerference to Prior Altitude Chamber Experience and Age

  3. The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions

    Directory of Open Access Journals (Sweden)

    Ayumu eInutsuka

    2013-03-01

    Full Text Available The hypothalamus monitors body homeostasis and regulates various behaviors such as feeding, thermogenesis, and sleeping. Orexins (also known as hypocretins were identified as endogenous ligands for two orphan G-protein-coupled receptors in the lateral hypothalamic area. They were initially recognized as regulators of feeding behavior, but they are mainly regarded as key modulators of the sleep/wakefulness cycle. Orexins activate orexin neurons, monoaminergic and cholinergic neurons in the hypothalamus/brainstem regions, to maintain a long, consolidated awake period. Anatomical studies of neural projections from/to orexin neurons and phenotypic characterization of transgenic mice revealed various roles for orexin neurons in the coordination of emotion, energy homeostasis, reward system, and arousal. For example, orexin neurons are regulated by peripheral metabolic cues, including ghrelin, leptin, and glucose concentration. This suggests that they may provide a link between energy homeostasis and arousal states. A link between the limbic system and orexin neurons might be important for increasing vigilance during emotional stimuli. Orexins are also involved in reward systems and the mechanisms of drug addiction. These findings suggest that orexin neurons sense the outer and inner environment of the body and maintain the proper wakefulness level of animals for survival. This review discusses the mechanism by which orexins maintain sleep/wakefulness states and how this mechanism relates to other systems that regulate emotion, reward, and energy homeostasis.

  4. Morphological and Physiological Interactions Between GnRH3 and Hypocretin/Orexin Neuronal Systems in Zebrafish (Danio rerio).

    Science.gov (United States)

    Zhao, Yali; Singh, Chanpreet; Prober, David A; Wayne, Nancy L

    2016-10-01

    GnRH neurons integrate internal and external cues to control sexual maturation and fertility. Homeostasis of energy balance and food intake correlates strongly with the status of reproduction. Neuropeptides secreted by the hypothalamus involved in modulating energy balance and feeding may play additional roles in the regulation of reproduction. Hypocretin (Hcrt) (also known as orexin) is one such peptide, primarily controlling sleep/wakefulness, food intake, and reward processing. There is a growing body of evidence indicating that Hcrt/orexin (Hcrt) modulates reproduction through interacting with the hypothalamo-pituitary-gonadal axis in mammals. To explore potential morphological and functional interactions between the GnRH and Hcrt neuronal systems, we employed a variety of experimental approaches including confocal imaging, immunohistochemistry, and electrophysiology in transgenic zebrafish, in which fluorescent proteins are genetically expressed in GnRH3 and Hcrt neurons. Our imaging data revealed close apposition and direct connection between GnRH3 and Hcrt neuronal systems in the hypothalamus during larval development through adulthood. Furthermore, the Hcrt receptor (HcrtR) is expressed in GnRH3 neurons. Electrophysiological data revealed a reversible inhibitory effect of Hcrt on GnRH3 neuron electrical activity, which was blocked by the HcrtR antagonist almorexant. In addition, Hcrt had no effect on the electrical activity of GnRH3 neurons in the HcrtR null mutant zebrafish (HcrtR -/- ). Our findings demonstrate a close anatomical and functional relationship between Hcrt and GnRH neuronal systems in zebrafish. It is the first demonstration of a link between neuronal circuits controlling sleeping/arousal/feeding and reproduction in zebrafish, an important animal model for investigating the molecular genetics of development.

  5. The Role of Flipped Learning in Managing the Cognitive Load of a Threshold Concept in Physiology

    Science.gov (United States)

    Akkaraju, Shylaja

    2016-01-01

    To help students master challenging, threshold concepts in physiology, I used the flipped learning model in a human anatomy and physiology course with very encouraging results in terms of student motivation, preparedness, engagement, and performance. The flipped learning model was enhanced by pre-training and formative assessments that provided…

  6. Neurocognitive poetics: methods and models for investigating the neuronal and cognitive-affective bases of literature reception.

    Science.gov (United States)

    Jacobs, Arthur M

    2015-01-01

    A long tradition of research including classical rhetoric, esthetics and poetics theory, formalism and structuralism, as well as current perspectives in (neuro)cognitive poetics has investigated structural and functional aspects of literature reception. Despite a wealth of literature published in specialized journals like Poetics, however, still little is known about how the brain processes and creates literary and poetic texts. Still, such stimulus material might be suited better than other genres for demonstrating the complexities with which our brain constructs the world in and around us, because it unifies thought and language, music and imagery in a clear, manageable way, most often with play, pleasure, and emotion (Schrott and Jacobs, 2011). In this paper, I discuss methods and models for investigating the neuronal and cognitive-affective bases of literary reading together with pertinent results from studies on poetics, text processing, emotion, or neuroaesthetics, and outline current challenges and future perspectives.

  7. A neuronal model of a global workspace in effortful cognitive tasks.

    Science.gov (United States)

    Dehaene, S; Kerszberg, M; Changeux, J P

    1998-11-24

    A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.

  8. Physiological Reactivity to Cognitive Stressors: Variations by Age and Socioeconomic Status

    Science.gov (United States)

    Neupert, Shevaun D.; Miller, Lisa M. Soederberg; Lachman, Margie E.

    2006-01-01

    The present study focused on age and SES differences in stress reactivity in response to cognitively challenging tasks. Specifically, we assessed within-person trajectories of cortisol, a steroid hormone released by the adrenal gland in response to stressors, before, during, and after exposure to cognitively challenging tasks. We extend the…

  9. TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation

    Directory of Open Access Journals (Sweden)

    Belarbi Karim

    2012-01-01

    Full Text Available Abstract Background Chronic neuroinflammation is a hallmark of several neurological disorders associated with cognitive loss. Activated microglia and secreted factors such as tumor necrosis factor (TNF-α are key mediators of neuroinflammation and may contribute to neuronal dysfunction. Our study was aimed to evaluate the therapeutic potential of a novel analog of thalidomide, 3,6'-dithiothalidomide (DT, an agent with anti-TNF-α activity, in a model of chronic neuroinflammation. Methods Lipopolysaccharide or artificial cerebrospinal fluid was infused into the fourth ventricle of three-month-old rats for 28 days. Starting on day 29, animals received daily intraperitoneal injections of DT (56 mg/kg/day or vehicle for 14 days. Thereafter, cognitive function was assessed by novel object recognition, novel place recognition and Morris water maze, and animals were euthanized 25 min following water maze probe test evaluation. Results Chronic LPS-infusion was characterized by increased gene expression of the proinflammatory cytokines TNF-α and IL-1β in the hippocampus. Treatment with DT normalized TNF-α levels back to control levels but not IL-1β. Treatment with DT attenuated the expression of TLR2, TLR4, IRAK1 and Hmgb1, all genes involved in the TLR-mediated signaling pathway associated with classical microglia activation. However DT did not impact the numbers of MHC Class II immunoreactive cells. Chronic neuroinflammation impaired novel place recognition, spatial learning and memory function; but it did not impact novel object recognition. Importantly, treatment with DT restored cognitive function in LPS-infused animals and normalized the fraction of hippocampal neurons expressing the plasticity-related immediate-early gene Arc. Conclusion Our data demonstrate that the TNF-α synthesis inhibitor DT can significantly reverse hippocampus-dependent cognitive deficits induced by chronic neuroinflammation. These results suggest that TNF-α is a

  10. Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons.

    Science.gov (United States)

    Noble, Emily E; Mavanji, Vijayakumar; Little, Morgan R; Billington, Charles J; Kotz, Catherine M; Wang, ChuanFeng

    2014-10-01

    Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for 7 weeks of exercise intervention. Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (pdiet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. Published by Elsevier Inc.

  11. Comparison of a Mirror Neuron System among Elders with Mild Cognitive Impairment, Alzheimer's Disease, and No Disease

    International Nuclear Information System (INIS)

    Rattanachayoto, P.; Tritanon, O.; Laothamatas, J.; Sungkarat, W.

    2012-01-01

    Alzheimer's disease (AD) is the most common cause of dementia. There are lots of old people suffering from the disease. Mild cognitive impairment (MCI) is a transitional state between normal aging and dementia. An individual with MCI has an increased risk of developing AD. The mirror neuron system (MNS), activated during the observation and execution of actions, has been linked with cognitive processes.The objective of this study is to examine the MNS abnormalities in elders with MCI and AD. Ninety-two subjects (5 MCI,7 mild AD, and 80 cognitively normal) were studied by using functional magnetic resonance imaging (fMRI). In the fMRI experiment, subjects were asked to observe a video showing hand movement (tearing a piece of paper) and a control condition (observing a fixation point).The image data were analyzed using SPM2 (Statistical Parametric Mapping).There were significant activations of bilateral inferior frontal lobule and inferior parietal lobule due to the observation of hand movement.The brain activations of the normal group were statistical significant greater than those in the MCI and mild AD groups.There was no significant difference between the MCI and mild AD groups. Elders with MCI and mild AD had fewer MNS activations than the normal controls, suggesting that the dysfunction of MNS may underlie cognitive impairments in MCI and AD patients.These findings imply that fMRI is sufficiently sensitive to detect MNS changes occurring in MCI and AD.

  12. Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients.

    Directory of Open Access Journals (Sweden)

    Márcio Silveira Corrêa

    Full Text Available Older familial caregivers of Alzheimer's disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers.The cognitive measures of 17 young (31-58 years and 18 old (63-84 years caregivers and of 17 young (37-57 years and 18 old (62-84 years non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF in serum.Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups.Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.

  13. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    Science.gov (United States)

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Ginseng Rb fraction protects glia, neurons and cognitive function in a rat model of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Kangning Xu

    Full Text Available The loss and injury of neurons play an important role in the onset of various neurodegenerative diseases, while both microgliosis and astrocyte loss or dysfunction are significant causes of neuronal degeneration. Previous studies have suggested that an extract enriched panaxadiol saponins from ginseng has more neuroprotective potential than the total saponins of ginseng. The present study investigated whether a fraction of highly purified panaxadiol saponins (termed as Rb fraction was protective for both glia and neurons, especially GABAergic interneurons, against kainic acid (KA-induced excitotoxicity in rats. Rats received Rb fraction at 30 mg/kg (i.p., 40 mg/kg (i.p. or saline followed 40 min later by an intracerebroventricular injection of KA. Acute hippocampal injury was determined at 48 h after KA, and impairment of hippocampus-dependent learning and memory as well as delayed neuronal injury was determined 16 to 21 days later. KA injection produced significant acute hippocampal injuries, including GAD67-positive GABAergic interneuron loss in CA1, paralbumin (PV-positive GABAergic interneuron loss, pyramidal neuron degeneration and astrocyte damage accompanied with reactive microglia in both CA1 and CA3 regions of the hippocampus. There was also a delayed loss of GAD67-positive interneurons in CA1, CA3, hilus and dentate gyrus. Microgliosis also became more severe 21 days later. Accordingly, KA injection resulted in hippocampus-dependent spatial memory impairment. Interestingly, the pretreatment with Rb fraction at 30 or 40 mg/kg significantly protected the pyramidal neurons and GABAergic interneurons against KA-induced acute excitotoxicity and delayed injury. Rb fraction also prevented memory impairments and protected astrocytes from KA-induced acute excitotoxicity. Additionally, microglial activation, especially the delayed microgliosis, was inhibited by Rb fraction. Overall, this study demonstrated that Rb fraction protected both

  15. Role of the mitochondrial sodium/calcium exchanger in neuronal physiology and in the pathogenesis of neurological diseases.

    Science.gov (United States)

    Castaldo, P; Cataldi, M; Magi, S; Lariccia, V; Arcangeli, S; Amoroso, S

    2009-01-12

    In neurons, as in other excitable cells, mitochondria extrude Ca(2+) ions from their matrix in exchange with cytosolic Na(+) ions. This exchange is mediated by a specific transporter located in the inner mitochondrial membrane, the mitochondrial Na(+)/Ca(2+) exchanger (NCX(mito)). The stoichiometry of NCX(mito)-operated Na(+)/Ca(2+) exchange has been the subject of a long controversy, but evidence of an electrogenic 3 Na(+)/1 Ca(2+) exchange is increasing. Although the molecular identity of NCX(mito) is still undetermined, data obtained in our laboratory suggest that besides the long-sought and as yet unfound mitochondrial-specific NCX, the three isoforms of plasmamembrane NCX can contribute to NCX(mito) in neurons and astrocytes. NCX(mito) has a role in controlling neuronal Ca(2+) homeostasis and neuronal bioenergetics. Indeed, by cycling the Ca(2+) ions captured by mitochondria back to the cytosol, NCX(mito) determines a shoulder in neuronal [Ca(2+)](c) responses to neurotransmitters and depolarizing stimuli which may then outlast stimulus duration. This persistent NCX(mito)-dependent Ca(2+) release has a role in post-tetanic potentiation, a form of short-term synaptic plasticity. By controlling [Ca(2+)](m) NCX(mito) regulates the activity of the Ca(2+)-sensitive enzymes pyruvate-, alpha-ketoglutarate- and isocitrate-dehydrogenases and affects the activity of the respiratory chain. Convincing experimental evidence suggests that supraphysiological activation of NCX(mito) contributes to neuronal cell death in the ischemic brain and, in epileptic neurons coping with seizure-induced ion overload, reduces the ability to reestablish normal ionic homeostasis. These data suggest that NCX(mito) could represent an important target for the development of new neurological drugs.

  16. Physiological Aβ Concentrations Produce a More Biomimetic Representation of the Alzheimer's Disease Phenotype in iPSC Derived Human Neurons.

    Science.gov (United States)

    Berry, Bonnie J; Smith, Alec S T; Long, Christopher J; Martin, Candace C; Hickman, James J

    2018-05-22

    Alzheimer's disease (AD) is characterized by slow, progressive neurodegeneration leading to severe neurological impairment, but current drug development efforts are limited by the lack of robust, human-based disease models. Amyloid-β (Aβ) is known to play an integral role in AD progression as it has been shown to interfere with neurological function. However, studies into AD pathology commonly apply Aβ to neurons for short durations at nonphysiological concentrations to induce an exaggerated dysfunctional phenotype. Such methods are unlikely to elucidate early stage disease dysfunction, when treatment is still possible, since damage to neurons by these high concentrations is extensive. In this study, we investigated chronic, pathologically relevant Aβ oligomer concentrations to induce an electrophysiological phenotype that is more representative of early AD progression compared to an acute high-dose application in human cortical neurons. The high, acute oligomer dose resulted in severe neuronal toxicity as well as upregulation of tau and phosphorylated tau. Chronic, low-dose treatment produced significant functional impairment without increased cell death or accumulation of tau protein. This in vitro phenotype more closely mirrors the status of early stage neural decline in AD pathology and could provide a valuable tool to further understanding of early stage AD pathophysiology and for screening potential therapeutic compounds.

  17. An efficient deletion mutant packaging system for defective herpes simplex virus vectors: Potential applications to human gene therapy and neuronal physiology

    International Nuclear Information System (INIS)

    Geller, A.I.; Keyomarsi, K.; Bryan, J.; Pardee, A.B.

    1990-01-01

    The authors have previously described a defective herpes simplex virus (HSV-1) vector system that permits that introduction of virtually any gene into nonmitotic cells. pHSVlac, the prototype vector, stably expresses Escherichia coli β-galactosidase from a constitutive promoter in many human cell lines, in cultured rat neurons from throughout the nervous system, and in cells in the adult rat brain. HSV-1 vectors expressing other genes may prove useful for studying neuronal physiology or performing human gene therapy for neurological diseases, such as Parkinson disease or brain tumors. A HSV-1 temperature-sensitive (ts) mutant, ts K, has been used as helper virus; ts mutants revert to wild type. In contrast, HSV-1 deletion mutants essentially cannot revert to wild type; therefore, use of a deletion mutant as helper virus might permit human gene therapy with HSV-1 vectors. They now report an efficient packaging system for HSV-1 VECTORS USING A DELETION MUTANT, d30EBA, as helper virus; virus is grown on the complementing cell line M64A. pHSVlac virus prepared using the deletion mutant packaging system stably expresses β-galactosidase in cultured rat sympathetic neurons and glia. Both D30EBA and ts K contain a mutation in the IE3 gene of HSV-1 strain 17 and have the same phenotype; therefore, changing the helper virus from ts K to D30EBA does not alter the host range or other properties of the HSV-1 vector system

  18. Hypothalamic-Pituitary-Adrenal Axis Physiology and Cognitive Control of Behavior in Stress Inoculated Monkeys

    Science.gov (United States)

    Parker, Karen J.; Buckmaster, Christine L.; Lindley, Steven E.; Schatzberg, Alan F.; Lyons, David M.

    2012-01-01

    Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated…

  19. The role of stress mindset in shaping cognitive, emotional, and physiological responses to challenging and threatening stress.

    Science.gov (United States)

    Crum, Alia J; Akinola, Modupe; Martin, Ashley; Fath, Sean

    2017-07-01

    Prior research suggests that altering situation-specific evaluations of stress as challenging versus threatening can improve responses to stress. The aim of the current study was to explore whether cognitive, physiological and affective stress responses can be altered independent of situation-specific evaluations by changing individuals' mindsets about the nature of stress in general. Using a 2 × 2 design, we experimentally manipulated stress mindset using multi-media film clips orienting participants (N = 113) to either the enhancing or debilitating nature of stress. We also manipulated challenge and threat evaluations by providing positive or negative feedback to participants during a social stress test. Results revealed that under both threat and challenge stress evaluations, a stress-is-enhancing mindset produced sharper increases in anabolic ("growth") hormones relative to a stress-is-debilitating mindset. Furthermore, when the stress was evaluated as a challenge, a stress-is-enhancing mindset produced sharper increases in positive affect, heightened attentional bias towards positive stimuli, and greater cognitive flexibility, whereas a stress-is-debilitating mindset produced worse cognitive and affective outcomes. These findings advance stress management theory and practice by demonstrating that a short manipulation designed to generate a stress-is-enhancing mindset can improve responses to both challenging and threatening stress.

  20. Physiological roles of CNS muscarinic receptors gained from knockout mice

    DEFF Research Database (Denmark)

    Thomsen, Morgane; Sørensen, Gunnar; Dencker, Ditte

    2017-01-01

    receptors modulating neuronal activity and neurotransmitter release in many brain regions, shaping neuronal plasticity, and affecting functions ranging from motor and sensory function to cognitive processes. As gene targeting technology evolves including the use of conditional, cell type specific strains......, knockout mice are likely to continue to provide valuable insights into brain physiology and pathophysiology, and advance the development of new medications for a range of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and addictions, as well as non-opioid analgesics...

  1. ApoB100/LDLR-/- hypercholesterolaemic mice as a model for mild cognitive impairment and neuronal damage.

    Directory of Open Access Journals (Sweden)

    Carlos Ramírez

    Full Text Available Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD. Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR] of human familial hypercholesterolaemia (FH. From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100 levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing and impairment of the episodic-like memory (determined by the integrated memory test. This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline.

  2. ESC-Derived Basal Forebrain Cholinergic Neurons Ameliorate the Cognitive Symptoms Associated with Alzheimer’s Disease in Mouse Models

    Directory of Open Access Journals (Sweden)

    Wei Yue

    2015-11-01

    Full Text Available Degeneration of basal forebrain cholinergic neurons (BFCNs is associated with cognitive impairments of Alzheimer’s disease (AD, implying that BFCNs hold potentials in exploring stem cell-based replacement therapy for AD. However, studies on derivation of BFCNs from embryonic stem cells (ESCs are limited, and the application of ESC-derived BFCNs remains to be determined. Here, we report on differentiation approaches for directing both mouse and human ESCs into mature BFCNs. These ESC-derived BFCNs exhibit features similar to those of their in vivo counterparts and acquire appropriate functional properties. After transplantation into the basal forebrain of AD model mice, ESC-derived BFCN progenitors predominantly differentiate into mature cholinergic neurons that functionally integrate into the endogenous basal forebrain cholinergic projection system. The AD mice grafted with mouse or human BFCNs exhibit improvements in learning and memory performances. Our findings suggest a promising perspective of ESC-derived BFCNs in the development of stem cell-based therapies for treatment of AD.

  3. Reactivity to Social Stress in Subclinical Social Anxiety: Emotional Experience, Cognitive Appraisals, Behavior, and Physiology

    OpenAIRE

    Crişan, Liviu G.; Vulturar, Romana; Miclea, Mircea; Miu, Andrei C.

    2016-01-01

    Recent research indicates that subclinical social anxiety is associated with dysfunctions at multiple psychological and biological levels, in a manner that seems reminiscent of social anxiety disorder (SAD). This study aimed to describe multidimensional responses to laboratory-induced social stress in an analog sample selected for social anxiety symptoms. State anxiety, cognitive biases related to negative social evaluation, speech anxiety behaviors, and cortisol reactivity were assessed in t...

  4. Cognitive disorganization in hippocampus: a physiological model of the disorganization in psychosis

    Czech Academy of Sciences Publication Activity Database

    Olypher, Andrej Vadimovich; Klement, Daniel; Fenton, André Antonio

    2006-01-01

    Roč. 26, č. 1 (2006), s. 158-168 ISSN 0270-6474 R&D Projects: GA MŠk(CZ) LC554 Grant - others:European Commission(XE) QLG3-CT-1999-00192 Institutional research plan: CEZ:AV0Z5011922 Keywords : cognitive disorganization * reversible lesion * parasitic attractor Subject RIV: FH - Neurology Impact factor: 7.453, year: 2006

  5. The effects of extended nap periods on cognitive, physiological and subjective responses under simulated night shift conditions.

    Science.gov (United States)

    Davy, Jonathan; Göbel, Matthias

    2018-02-01

    Extended nap opportunities have been effective in maintaining alertness in the context of extended night shifts (+12 h). However, there is limited evidence of their efficacy during 8-h shifts. Thus, this study explored the effects of extended naps on cognitive, physiological and perceptual responses during four simulated, 8-h night shifts. In a laboratory setting, 32 participants were allocated to one of three conditions. All participants completed four consecutive, 8-h night shifts, with the arrangements differing by condition. The fixed night condition worked from 22h00 to 06h00, while the nap early group worked from 20h00 to 08h00 and napped between 00h00 and 03h20. The nap late group worked from 00h00 to 12h00 and napped between 04h00 and 07h20. Nap length was limited to 3 hours and 20 minutes. Participants performed a simple beading task during each shift, while also completing six to eight test batteries roughly every 2 h. During each shift, six test batteries were completed, in which the following measures were taken. Performance indicators included beading output, eye accommodation time, choice reaction time, visual vigilance, simple reaction time, processing speed and object recognition, working memory, motor response time and tracking performance. Physiological measures included heart rate and tympanic temperature, whereas subjective sleepiness and reported sleep length and quality while outside the laboratory constituted the self reported measures. Both naps reduced subjective sleepiness but did not alter the circadian and homeostatic-related changes in cognitive and physiological measures, relative to the fixed night condition. Additionally, there was evidence of sleep inertia following each nap, which resulted in transient reductions in certain perceptual cognitive performance measures. The present study suggested that there were some benefits associated with including an extended nap during 8-h night shifts. However, the effects of sleep inertia

  6. From Neurons to Brainpower: Cognitive Neuroscience and Brain-Based Learning

    Science.gov (United States)

    Phillips, Janet M.

    2005-01-01

    We have learned more about the brain in the past five years than the previous 100. Neuroimaging, lesion studies, and animal studies have revealed the intricate inner workings of the brain and learning. Synaptogenesis, pruning, sensitive periods, and plasticity have all become accepted concepts of cognitive neuroscience that are now being applied…

  7. Evidence supporting a role for astrocytes in the regulation of cognitive flexibility and neuronal oscillations through the Ca2+ binding protein S100β.

    Science.gov (United States)

    Brockett, Adam T; Kane, Gary A; Monari, Patrick K; Briones, Brandy A; Vigneron, Pierre-Antoine; Barber, Gabriela A; Bermudez, Andres; Dieffenbach, Uma; Kloth, Alexander D; Buschman, Timothy J; Gould, Elizabeth

    2018-01-01

    The medial prefrontal cortex (mPFC) is important for cognitive flexibility, the ability to switch between two task-relevant dimensions. Changes in neuronal oscillations and alterations in the coupling across frequency ranges have been correlated with attention and cognitive flexibility. Here we show that astrocytes in the mPFC of adult male Sprague Dawley rats, participate in cognitive flexibility through the astrocyte-specific Ca2+ binding protein S100β, which improves cognitive flexibility and increases phase amplitude coupling between theta and gamma oscillations. We further show that reduction of astrocyte number in the mPFC impairs cognitive flexibility and diminishes delta, alpha and gamma power. Conversely, chemogenetic activation of astrocytic intracellular Ca2+ signaling in the mPFC enhances cognitive flexibility, while inactivation of endogenous S100β among chemogenetically activated astrocytes in the mPFC prevents this improvement. Collectively, our work suggests that astrocytes make important contributions to cognitive flexibility and that they do so by releasing a Ca2+ binding protein which in turn enhances coordinated neuronal oscillations.

  8. Fear versus humor: the impact of sensation seeking on physiological, cognitive, and emotional responses to antialcohol abuse messages.

    Science.gov (United States)

    Lee, Moon J; Shin, Mija

    2011-01-01

    This study investigates the differences in physiological, cognitive, and emotional responses to existing emotional antialcohol abuse advertisements (fear vs. humor appeal) between high and low sensation seekers. A 2 (Message Type) x 2 (Sensation-Seeking Tendency) x 4 (Message Repetition) mixed-model experiment with repeated measures was conducted with 71 college students. The results, based on self-reports, indicated that fear messages generated more interest and perceived danger of excessive drinking regardless of sensation-seeking tendency, whereas humorous messages were rated as more likeable than fear messages, and the difference was bigger among low sensation seekers than among high sensation seekers. One interesting finding was that for both fear and humor appeals, low sensation seekers showed greater emotional responses (greater corrugators activities and greater zygomatic activities) than high sensation seekers overall. The implications of the current study as well as suggestions for future study were discussed.

  9. Mind and body: concepts of human cognition, physiology and false belief in children with autism or typical development.

    Science.gov (United States)

    Peterson, Candida C

    2005-08-01

    This study examined theory of mind (ToM) and concepts of human biology (eyes, heart, brain, lungs and mind) in a sample of 67 children, including 25 high functioning children with autism (age 6-13), plus age-matched and preschool comparison groups. Contrary to Baron-Cohen [1989, Journal of Autism and Developmental Disorders, 19(4), 579-600], most children with autism correctly understood the functions of the brain (84%) and the mind (64%). Their explanations were predominantly mentalistic. They outperformed typically developing preschoolers in understanding inner physiological (heart, lungs) and cognitive (brain, mind) systems, and scored as high as age-matched typical children. Yet, in line with much previous ToM research, most children with autism (60%) failed false belief, and their ToM performance was unrelated to their understanding of. human biology. Results were discussed in relation to neurobiological and social-experiential accounts of the ToM deficit in autism.

  10. Discrete emotions predict changes in cognition, judgment, experience, behavior, and physiology: a meta-analysis of experimental emotion elicitations.

    Science.gov (United States)

    Lench, Heather C; Flores, Sarah A; Bench, Shane W

    2011-09-01

    Our purpose in the present meta-analysis was to examine the extent to which discrete emotions elicit changes in cognition, judgment, experience, behavior, and physiology; whether these changes are correlated as would be expected if emotions organize responses across these systems; and which factors moderate the magnitude of these effects. Studies (687; 4,946 effects, 49,473 participants) were included that elicited the discrete emotions of happiness, sadness, anger, and anxiety as independent variables with adults. Consistent with discrete emotion theory, there were (a) moderate differences among discrete emotions; (b) differences among discrete negative emotions; and (c) correlated changes in behavior, experience, and physiology (cognition and judgment were mostly not correlated with other changes). Valence, valence-arousal, and approach-avoidance models of emotion were not as clearly supported. There was evidence that these factors are likely important components of emotion but that they could not fully account for the pattern of results. Most emotion elicitations were effective, although the efficacy varied with the emotions being compared. Picture presentations were overall the most effective elicitor of discrete emotions. Stronger effects of emotion elicitations were associated with happiness versus negative emotions, self-reported experience, a greater proportion of women (for elicitations of happiness and sadness), omission of a cover story, and participants alone versus in groups. Conclusions are limited by the inclusion of only some discrete emotions, exclusion of studies that did not elicit discrete emotions, few available effect sizes for some contrasts and moderators, and the methodological rigor of included studies. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  11. Selective serotonergic excitation of callosal projection neurons

    Directory of Open Access Journals (Sweden)

    Daniel eAvesar

    2012-03-01

    Full Text Available Serotonin (5-HT acting as a neurotransmitter in the cerebral cortex is critical for cognitive function, yet how 5-HT regulates information processing in cortical circuits is not well understood. We tested the serotonergic responsiveness of layer 5 pyramidal neurons (L5PNs of the mouse medial prefrontal cortex (mPFC, and found 3 distinct response types: long-lasting 5-HT1A (1A receptor-dependent inhibitory responses (84% of L5PNs, 5-HT2A (2A receptor-dependent excitatory responses (9%, and biphasic responses in which 2A-dependent excitation followed brief inhibition (5%. Relative to 5-HT-inhibited neurons, those excited by 5-HT had physiological properties characteristic of callosal/commissural (COM neurons that project to the contralateral cortex. We tested whether serotonergic responses in cortical pyramidal neurons are correlated with their axonal projection pattern using retrograde fluorescent labeling of COM and corticopontine-projecting (CPn neurons. 5-HT generated excitatory or biphasic responses in all 5-HT-responsive layer 5 COM neurons. Conversely, CPn neurons were universally inhibited by 5-HT. Serotonergic excitation of COM neurons was blocked by the 2A antagonist MDL 11939, while serotonergic inhibition of CPn neurons was blocked by the 1A antagonist WAY 100635, confirming a role for these two receptor subtypes in regulating pyramidal neuron activity. Selective serotonergic excitation of COM neurons was not layer-specific, as COM neurons in layer 2/3 were also selectively excited by 5-HT relative to their non-labeled pyramidal neuron neighbors. Because neocortical 2A receptors are implicated in the etiology and pathophysiology of schizophrenia, we propose that COM neurons may represent a novel cellular target for intervention in psychiatric disease.

  12. Chewing Gum: Cognitive Performance, Mood, Well-Being, and Associated Physiology

    Science.gov (United States)

    Allen, Andrew P.; Smith, Andrew P.

    2015-01-01

    Recent evidence has indicated that chewing gum can enhance attention, as well as promoting well-being and work performance. Four studies (two experiments and two intervention studies) examined the robustness of and mechanisms for these effects. Study 1 investigated the acute effect of gum on mood in the absence of task performance. Study 2 examined the effect of rate and force of chewing on mood and attention performance. Study 3 assessed the effects of chewing gum during one working day on well-being and performance, as well as postwork mood and cognitive performance. In Study 4, performance and well-being were reported throughout the workday and at the end of the day, and heart rate and cortisol were measured. Under experimental conditions, gum was associated with higher alertness regardless of whether performance tasks were completed and altered sustained attention. Rate of chewing and subjective force of chewing did not alter mood but had some limited effects on attention. Chewing gum during the workday was associated with higher productivity and fewer cognitive problems, raised cortisol levels in the morning, and did not affect heart rate. The results emphasise that chewing gum can attenuate reductions in alertness, suggesting that chewing gum enhances worker performance. PMID:26075253

  13. Chewing Gum: Cognitive Performance, Mood, Well-Being, and Associated Physiology

    Directory of Open Access Journals (Sweden)

    Andrew P. Allen

    2015-01-01

    Full Text Available Recent evidence has indicated that chewing gum can enhance attention, as well as promoting well-being and work performance. Four studies (two experiments and two intervention studies examined the robustness of and mechanisms for these effects. Study 1 investigated the acute effect of gum on mood in the absence of task performance. Study 2 examined the effect of rate and force of chewing on mood and attention performance. Study 3 assessed the effects of chewing gum during one working day on well-being and performance, as well as postwork mood and cognitive performance. In Study 4, performance and well-being were reported throughout the workday and at the end of the day, and heart rate and cortisol were measured. Under experimental conditions, gum was associated with higher alertness regardless of whether performance tasks were completed and altered sustained attention. Rate of chewing and subjective force of chewing did not alter mood but had some limited effects on attention. Chewing gum during the workday was associated with higher productivity and fewer cognitive problems, raised cortisol levels in the morning, and did not affect heart rate. The results emphasise that chewing gum can attenuate reductions in alertness, suggesting that chewing gum enhances worker performance.

  14. Chewing gum: cognitive performance, mood, well-being, and associated physiology.

    Science.gov (United States)

    Allen, Andrew P; Smith, Andrew P

    2015-01-01

    Recent evidence has indicated that chewing gum can enhance attention, as well as promoting well-being and work performance. Four studies (two experiments and two intervention studies) examined the robustness of and mechanisms for these effects. Study 1 investigated the acute effect of gum on mood in the absence of task performance. Study 2 examined the effect of rate and force of chewing on mood and attention performance. Study 3 assessed the effects of chewing gum during one working day on well-being and performance, as well as postwork mood and cognitive performance. In Study 4, performance and well-being were reported throughout the workday and at the end of the day, and heart rate and cortisol were measured. Under experimental conditions, gum was associated with higher alertness regardless of whether performance tasks were completed and altered sustained attention. Rate of chewing and subjective force of chewing did not alter mood but had some limited effects on attention. Chewing gum during the workday was associated with higher productivity and fewer cognitive problems, raised cortisol levels in the morning, and did not affect heart rate. The results emphasise that chewing gum can attenuate reductions in alertness, suggesting that chewing gum enhances worker performance.

  15. Cognitive dysfunction in hereditary spastic paraplegias and other motor neuron disorders

    Directory of Open Access Journals (Sweden)

    Ingrid Faber

    Full Text Available ABSTRACT Hereditary spastic paraplegia (HSP is a diverse group of single-gene disorders that share the predominant clinical feature of progressive lower limb spasticity and weakness. More than 70 different genetic subtypes have been described and all modes of inheritance are possible. Intellectual dysfunction in HSP is frequent in recessive forms but rare in dominant families. It may manifest by either mental retardation and/or cognitive decline. The latter may be subtle, restricted to executive dysfunction or may evolve to severe dementia. The cognitive profile is thought to depend largely on the genetic subtype of HSP, although wide phenotypic variability within the same genetic subtype and also within the same family can be found.

  16. Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.

    Science.gov (United States)

    Takeda, A; Suzuki, M; Tempaku, M; Ohashi, K; Tamano, H

    2015-09-24

    Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. The effect of a new therapy for children with tics targeting underlying cognitive, behavioral and physiological processes

    Directory of Open Access Journals (Sweden)

    Julie B. Leclerc

    2016-08-01

    Full Text Available Tourette disorder (TD is characterized by motor and vocal tics and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder Facotik to a consecutive case series of children aged 8-12 years. The Facotik therapy was adapted from the adult Cognitive and Psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive-behavioral and physiological processes against which the tic occurs rather than only addressing the tic behavior. The Facotik therapy lasted 12-14 weeks. Each week 90-minute session contained 20 minutes of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population and seven cases completed therapy and post-treatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem post treatment. The results confirm the conclusion of a previous pilot study which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches which target tics specifically.

  18. The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes.

    Science.gov (United States)

    Leclerc, Julie B; O'Connor, Kieron P; J-Nolin, Gabrielle; Valois, Philippe; Lavoie, Marc E

    2016-01-01

    Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8-12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive-behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12-14 weeks. Each week 90-min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically.

  19. Cognitive phase transitions in the cerebral cortex enhancing the neuron doctrine by modeling neural fields

    CERN Document Server

    Kozma, Robert

    2016-01-01

    This intriguing book was born out of the many discussions the authors had in the past 10 years about the role of scale-free structure and dynamics in producing intelligent behavior in brains. The microscopic dynamics of neural networks is well described by the prevailing paradigm based in a narrow interpretation of the neuron doctrine. This book broadens the doctrine by incorporating the dynamics of neural fields, as first revealed by modeling with differential equations (K-sets).  The book broadens that approach by application of random graph theory (neuropercolation). The book concludes with diverse commentaries that exemplify the wide range of mathematical/conceptual approaches to neural fields. This book is intended for researchers, postdocs, and graduate students, who see the limitations of network theory and seek a beachhead from which to embark on mesoscopic and macroscopic neurodynamics.

  20. Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Ginsberg, Stephen D; Malek-Ahmadi, Michael H; Alldred, Melissa J; Che, Shaoli; Elarova, Irina; Chen, Yinghua; Jeanneteau, Freddy; Kranz, Thorsten M; Chao, Moses V; Counts, Scott E; Mufson, Elliott J

    2017-09-09

    Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections. Gene expression levels were correlated with cognitive test scores and AD neuropathology criteria. We found a significant downregulation of several neurotrophin genes (e.g., Gdnf, Ngfb, and Ntf4) in CA1 pyramidal neurons in MCI compared to NCI and AD subjects. In addition, the neurotrophin receptor transcripts TrkB and TrkC were decreased in MCI and AD compared to NCI. Regional hippocampal dissections also revealed select neurotrophic gene dysfunction providing evidence for vulnerability within the hippocampus proper during the progression of dementia. Downregulation of several neurotrophins of the NGF family and cognate neurotrophin receptor (TrkA, TrkB, and TrkC) genes correlated with antemortem cognitive measures including the Mini-Mental State Exam (MMSE), a composite global cognitive score (GCS), and Episodic, Semantic, and Working Memory, Perceptual Speed, and Visuospatial domains. Significant correlations were found between select neurotrophic expression downregulation and neuritic plaques (NPs) and neurofibrillary tangles (NFTs), but not diffuse plaques (DPs). These data suggest that dysfunction of neurotrophin signaling complexes have profound negative sequelae within vulnerable hippocampal cell types, which play a role in mnemonic and executive dysfunction

  1. Panax ginseng extract attenuates neuronal injury and cognitive deficits in rats with vascular dementia induced by chronic cerebral hypoperfusion

    Directory of Open Access Journals (Sweden)

    Jun-De Zhu

    2018-01-01

    Full Text Available Panax ginseng is a slow-growing perennial plant. Panax ginseng extract has numerous biological activities, including antitumor, anti-inflammatory and antistress activities. Panax ginseng extract also has a cognition-enhancing effect in rats with alcohol-induced memory impairment. In this study, we partially occluded the bilateral carotid arteries in the rat to induce chronic cerebral hypoperfusion, a well-known model of vascular dementia. The rats were then intragastrically administered 50 or 100 mg/kg Panax ginseng extract. Morris water maze and balance beam tests were used to evaluate memory deficits and motor function, respectively. Protein quantity was used to evaluate cholinergic neurons. Immunofluorescence staining was used to assess the number of glial fibrillary acidic protein-positive cells. Western blot assay was used to evaluate protein levels of vascular endothelial growth factor, basic fibroblast growth factor, Bcl-2 and Bax. Treatment with Panax ginseng extract for 8 weeks significantly improved behavioral function and increased neuronal density and VEGF and bFGF protein expression in the hippocampal CA3 area. Furthermore, Panax ginseng extract reduced the number of glial fibrillary acidic protein-immunoreactive cells, and it decreased apoptosis by upregulating Bcl-2 and downregulating Bax protein expression. The effect of Panax ginseng extract was dose-dependent and similar to that of nimodipine, a commonly used drug for the treatment of vascular dementia. These findings suggest that Panax ginseng extract is neuroprotective against vascular dementia induced by chronic cerebral hypoperfusion, and therefore might have therapeutic potential for preventing and treating the disease.

  2. Physiological and cognitive mediators for the association between self-reported depressed mood and impaired choice stepping reaction time in older people.

    NARCIS (Netherlands)

    Kvelde, T.; Pijnappels, M.A.G.M.; Delbaere, K.; Close, J.C.; Lord, S.R.

    2010-01-01

    Background. The aim of the study was to use path analysis to test a theoretical model proposing that the relationship between self-reported depressed mood and choice stepping reaction time (CSRT) is mediated by psychoactive medication use, physiological performance, and cognitive ability.A total of

  3. Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition

    Science.gov (United States)

    Daitch, Amy L.; Foster, Brett L.; Schrouff, Jessica; Rangarajan, Vinitha; Kaşikçi, Itır; Gattas, Sandra; Parvizi, Josef

    2016-01-01

    Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain. PMID:27821758

  4. Biomonitoring of physiological status and cognitive performance of underway submariners undergoing a novel watch-standing schedule

    Science.gov (United States)

    Duplessis, C. A.; Cullum, M. E.; Crepeau, L. J.

    2005-05-01

    Submarine watch-standers adhere to a 6 hour-on, 12 hour-off (6/12) watch-standing schedule, yoking them to an 18-hr day, engendering circadian desynchronization and chronic sleep deprivation. Moreover, the chronic social crowding, shift work, and confinement of submarine life provide additional stressors known to correlate with elevated secretory immunoglobulin A (sIgA) and cortisol levels, reduced performance, immunologic dysfunction, malignancies, infections, gastrointestinal illness, coronary disease, anxiety, and depression. We evaluated an alternative, compressed, fixed work schedule designed to enhance circadian rhythm entrainment, sleep hygiene, performance, and health on 10 underway submariners, who followed the alternative and 6/12 schedules for approximately 2 weeks each. We measured subjects" sleep, cognitive performance, and salivary biomarker levels. Pilot analysis of the salivary data on one subject utilizing ELISA suggests elevated biomarker levels of stress. Average PM cortisol levels were 0.2 μg/L (normal range: nondetectable - 0.15 μg/L), and mean sIgA levels were 562 μg/ml (normal range: 100-500 μg/ml). Future research exploiting real-time salivary bioassays, via fluorescent polarimetry technology, identified by the Office of Naval Research (ONR) as a future Naval requirement, allows researchers to address correlations between stress-induced elaboration of salivary biomarkers with physiological and performance decrements, thereby fostering insight into the underway submariner"s psychoimmunological status. This may help identify strategies that enhance resilience to stressors. Specifically, empirically-based modeling can identify optimal watch-standing schedules and stress-mitigating procedures -- within the operational constraints of the submarine milieu and the mission --that foster improved circadian entrainment and reduced stress reactivity, enhancing physiological health, operational performance, safety, and job satisfaction.

  5. Cognitive behavioral stress management effects on psychosocial and physiological adaptation in women undergoing treatment for breast cancer.

    Science.gov (United States)

    Antoni, Michael H; Lechner, Suzanne; Diaz, Alain; Vargas, Sara; Holley, Heather; Phillips, Kristin; McGregor, Bonnie; Carver, Charles S; Blomberg, Bonnie

    2009-07-01

    A diagnosis of breast cancer and treatment are psychologically stressful events, particularly over the first year after diagnosis. Women undergo many demanding and anxiety-arousing treatments such as surgery, radiation and chemotherapy. Psychosocial interventions that promote psychosocial adaptation to these challenges may modulate physiological processes (neuroendocrine and immune) that are relevant for health outcomes in breast cancer patients. Women with Stages 1-3 breast cancer recruited 4-8 weeks after surgery were randomized to either a 10-week group-based cognitive behavioral stress management (CBSM) intervention or a 1-day psychoeducational control group and completed questionnaires and late afternoon blood samples at study entry and 6 and 12 months after assignment to experimental condition. Of 128 women initially providing psychosocial questionnaire and blood samples at study entry, 97 provided complete data for anxiety measures and cortisol analysis at all time points, and immune assays were run on a subset of 85 of these women. Those assigned to a 10-week group-based CBSM intervention evidenced better psychosocial adaptation (lower reported cancer-specific anxiety and interviewer-rated general anxiety symptoms) and physiological adaptation (lower cortisol, greater Th1 cytokine [interleukin-2 and interferon-gamma] production and IL-2:IL-4 ratio) after their adjuvant treatment compared to those in the control group. Effects on psychosocial adaptation indicators and cortisol appeared to hold across the entire 12-month observation period. Th1 cytokine regulation changes held only over the initial 6-month period. This intervention may have facilitated a "recovery or maintenance" of Th1 cytokine regulation during or after the adjuvant therapy period. Behavioral interventions that address dysregulated neuroendocrine function could play a clinically significant role in optimizing host immunologic resistance during a vulnerable period.

  6. Analysis of neuron-astrocyte metabolic cooperation in the brain of db/db mice with cognitive decline using 13C NMR spectroscopy.

    Science.gov (United States)

    Zheng, Hong; Zheng, Yongquan; Wang, Dan; Cai, Aimin; Lin, Qiuting; Zhao, Liangcai; Chen, Minjiang; Deng, Mingjie; Ye, Xinjian; Gao, Hongchang

    2017-01-01

    Type 2 diabetes has been linked to cognitive impairment, but its potential metabolic mechanism is still unclear. The present study aimed to explore neuron-astrocyte metabolic cooperation in the brain of diabetic (db/db, BKS.Cg-m +/+ Leprdb/J) mice with cognitive decline using 13 C NMR technique in combination with intravenous [2- 13 C]-acetate and [3- 13 C]-lactate infusions. We found that the 13 C-enrichment from [2- 13 C]-acetate into tricarboxylic acid cycle intermediate, succinate, was significantly decreased in db/db mice with cognitive decline compared with wild-type (WT, C57BLKS/J) mice, while an opposite result was obtained after [3- 13 C]-lactate infusion. Relative to WT mice, db/db mice with cognitive decline had significantly lower 13 C labeling percentages in neurotransmitters including glutamine, glutamate, and γ-aminobutyric acid after [2- 13 C]-acetate infusion. However, [3- 13 C]-lactate resulted in increased 13 C-enrichments in neurotransmitters in db/db mice with cognitive decline. This may indicate that the disturbance of neurotransmitter metabolism occurred during the development of cognitive decline. In addition, a reduction in 13 C-labeling of lactate and an increase in gluconeogenesis were found from both labeled infusions in db/db mice with cognitive decline. Therefore, our results suggest that the development of cognitive decline in type 2 diabetes may be implicated to an unbalanced metabolism in neuron-astrocyte cooperation and an enhancement of gluconeogenesis. © The Author(s) 2016.

  7. The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes

    Science.gov (United States)

    Leclerc, Julie B.; O’Connor, Kieron P.; J.-Nolin, Gabrielle; Valois, Philippe; Lavoie, Marc E.

    2016-01-01

    Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8–12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive–behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12–14 weeks. Each week 90-min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically. PMID:27563292

  8. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Wang, Dongmei; Yan, Junqiang; Chen, Jing; Wu, Wenlan; Zhu, Xiaoying; Wang, Yong

    2015-10-01

    The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5% in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5% increase in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin

  9. Representation of pheromones, interspecific signals, and plant odors in higher olfactory centers; mapping physiologically identified antennal-lobe projection neurons in the male heliothine moth

    Directory of Open Access Journals (Sweden)

    Xin-Cheng eZhao

    2014-10-01

    Full Text Available In the primary olfactory centre of the moth brain, for example, a few enlarged glomeruli situated dorsally, at the entrance of the antennal nerve, are devoted to information about female-produced substances whereas a set of more numerous ordinary glomeruli receives input about general odorants. Heliothine moths are particularly suitable for studying central chemosensory mechanisms not only because of their anatomically separated systems for plant odours and pheromones but also due to their use of female-produced substances in communication across the species. Thus, the male-specific system of heliothine moths includes two sub arrangements, one ensuring attraction and mating behavior by carrying information about pheromones released by conspecifics, and the other reproductive isolation via signal information emitted from heterospecifics. Based on previous tracing experiments, a general chemotopic organization of the male-specific glomeruli has been demonstrated in a number of heliothine species. As compared to the well explored organization of the moth antennal lobe, demonstrating a non-overlapping representation of the biologically relevant stimuli, less is known about the neural arrangement residing at the following synaptic level, i.e. the mushroom body calyces and the lateral horn. In the study presented here, we have labelled physiologically characterized antennal-lobe projection neurons in males of the two heliothine species, Heliothis virescens and Helicoverpa assulta, for the purpose of mapping their target regions in the protocerebrum. In order to compare the representation of plant odours, pheromones, and interspecific signals in the higher brain regions of each species, we have created standard brain atlases and registered three-dimensional models of distinct uniglomerular projection neuron types into the relevant atlas.

  10. Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.

    Science.gov (United States)

    Feng, Xiaodong; Yang, Shanli; Liu, Jiao; Huang, Jia; Peng, Jun; Lin, Jiumao; Tao, Jing; Chen, Lidian

    2013-05-01

    Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor‑κB (NF-κB)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post‑stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-κB signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-κB activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-κB pathway. Collectively, our findings suggest that inhibition of NF-κB‑mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.

  11. Brains are not just neurons. Comment on “Toward a computational framework for cognitive biology: Unifying approaches from cognitive neuroscience and comparative cognition” by Fitch

    Science.gov (United States)

    Huber, Ludwig

    2014-09-01

    This comment addresses the first component of Fitch's framework: the computational power of single neurons [3]. Although I agree that traditional models of neural computation have vastly underestimated the computational power of single neurons, I am hesitant to follow him completely. The exclusive focus on neurons is likely to underestimate the importance of other cells in the brain. In the last years, two such cell types have received appropriate attention by neuroscientists: interneurons and glia. Interneurons are small, tightly packed cells involved in the control of information processing in learning and memory. Rather than transmitting externally (like motor or sensory neurons), these neurons process information within internal circuits of the brain (therefore also called 'relay neurons'). Some specialized interneuron subtypes temporally regulate the flow of information in a given cortical circuit during relevant behavioral events [4]. In the human brain approx. 100 billion interneurons control information processing and are implicated in disorders such as epilepsy and Parkinson's.

  12. Methyl Salicylate Lactoside Protects Neurons Ameliorating Cognitive Disorder Through Inhibiting Amyloid Beta-Induced Neuroinflammatory Response in Alzheimer’s Disease

    Science.gov (United States)

    Li, Jinze; Ma, Xiaowei; Wang, Yu; Chen, Chengjuan; Hu, Min; Wang, Linlin; Fu, Junmin; Shi, Gaona; Zhang, Dongming; Zhang, Tiantai

    2018-01-01

    Neuroinflammatory reactions mediated by microglia and astrocytes have been shown to play a key role in early progression of Alzheimer’s disease (AD). Increased evidences have demonstrated that neurons exacerbate local inflammatory reactions by producing inflammatory mediators and act as an important participant in the pathogenesis of AD. Methyl salicylate lactoside (MSL) is an isolated natural product that is part of a class of novel non-steroidal anti-inflammatory drugs (NSAID). In our previous studies, we demonstrated that MSL exhibited therapeutic effects on arthritis-induced mice and suppressed the activation of glial cells. In the current study, we investigated the effects of MSL on cognitive function and neuronal protection induced by amyloid-beta peptides (Aβ) and explored potential underlying mechanisms involved. Amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice were used to evaluate the effects of MSL through behavioral testing and neuronal degenerative changes. In addition, copper-injured APP Swedish mutation overexpressing SH-SY5Y cells were used to determine the transduction of cyclooxygenase (COX) and mitogen-activated protein kinase (MAPK) pathways. Our results indicated that at an early stage, MSL treatment ameliorated cognitive impairment and neurodegeneration in APP/PS1 mice. Moreover, in an in vitro AD model, MSL treatment protected injured cells by increasing cell viability, improving mitochondrial dysfunction, and decreasing oxidative damage. In addition, MSL inhibited the phosphorylated level of c-Jun N-terminal kinase (JNK) and p38 MAPK, and suppressed the expression of COX-1/2. As a novel NSAIDs and used for the treatment in early stage of AD, MSL clearly demonstrated cognitive preservation by protecting neurons via a pleiotropic anti-inflammatory effect in the context of AD-associated deficits. Therefore, early treatment of anti-inflammatory therapy may be an effective strategy for treating AD. PMID:29636677

  13. Coping with preoperative anxiety in cesarean section: physiological, cognitive, and emotional effects of listening to favorite music.

    Science.gov (United States)

    Kushnir, Jonathan; Friedman, Ahuva; Ehrenfeld, Mally; Kushnir, Talma

    2012-06-01

    Listening to music has a stress-reducing effect in surgical procedures. The effects of listening to music immediately before a cesarean section have not been studied. The objective of this study was to assess the effects of listening to selected music while waiting for a cesarean section on emotional reactions, on cognitive appraisal of the threat of surgery, and on stress-related physiological reactions. A total of 60 healthy women waiting alone to undergo an elective cesarean section for medical reasons only were randomly assigned either to an experimental or a control group. An hour before surgery they reported mood, and threat perception. Vital signs were assessed by a nurse. The experimental group listened to preselected favorite music for 40 minutes, and the control group waited for the operation without music. At the end of this period, all participants responded to a questionnaire assessing mood and threat perception, and the nurse measured vital signs. Women who listened to music before a cesarean section had a significant increase in positive emotions and a significant decline in negative emotions and perceived threat of the situation when compared with women in the control group, who exhibited a decline in positive emotions, an increase in the perceived threat of the situation, and had no change in negative emotions. Women who listened to music also exhibited a significant reduction in systolic blood pressure compared with a significant increase in diastolic blood pressure and respiratory rate in the control group. Listening to favorite music immediately before a cesarean section may be a cost-effective, emotion-focused coping strategy. (BIRTH 39:2 June 2012). © 2012, Copyright the Authors Journal compilation © 2012, Wiley Periodicals, Inc.

  14. Relating normalization to neuronal populations across cortical areas.

    Science.gov (United States)

    Ruff, Douglas A; Alberts, Joshua J; Cohen, Marlene R

    2016-09-01

    Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. Copyright © 2016 the American Physiological Society.

  15. Short-term exposure to mobile phone base station signals does not affect cognitive functioning or physiological measures in individuals who report sensitivity to electromagnetic fields and controls.

    Science.gov (United States)

    Eltiti, Stacy; Wallace, Denise; Ridgewell, Anna; Zougkou, Konstantina; Russo, Riccardo; Sepulveda, Francisco; Fox, Elaine

    2009-10-01

    Individuals who report sensitivity to electromagnetic fields often report cognitive impairments that they believe are due to exposure to mobile phone technology. Previous research in this area has revealed mixed results, however, with the majority of research only testing control individuals. Two studies using control and self-reported sensitive participants found inconsistent effects of mobile phone base stations on cognitive functioning. The aim of the present study was to clarify whether short-term (50 min) exposure at 10 mW/m(2) to typical Global System for Mobile Communication (GSM) and Universal Mobile Telecommunications System (UMTS) base station signals affects attention, memory, and physiological endpoints in sensitive and control participants. Data from 44 sensitive and 44 matched-control participants who performed the digit symbol substitution task (DSST), digit span task (DS), and a mental arithmetic task (MA), while being exposed to GSM, UMTS, and sham signals under double-blind conditions were analyzed. Overall, cognitive functioning was not affected by short-term exposure to either GSM or UMTS signals in the current study. Nor did exposure affect the physiological measurements of blood volume pulse (BVP), heart rate (HR), and skin conductance (SC) that were taken while participants performed the cognitive tasks.

  16. [Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

    Science.gov (United States)

    Indo, Yasuhiro

    2015-05-01

    Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

  17. Cognitive and physiological effects of an "energy drink": an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions.

    Science.gov (United States)

    Scholey, Andrew B; Kennedy, David O

    2004-11-01

    Both glucose and caffeine can improve aspects of cognitive performance and, in the case of caffeine, mood. There are few studies investigating the effects of the two substances in combination. We assessed the mood, cognitive and physiological effects of a soft drink containing caffeine and glucose as well as flavouring levels of herbal extracts. The effects of different drink fractions were also evaluated. Using a randomised, double-blind, balanced, five-way crossover design, 20 participants who were overnight fasted and caffeine-deprived received 250 ml drinks containing 37.5 g glucose; 75 mg caffeine; ginseng and ginkgo biloba at flavouring levels; a whole drink (containing all these substances) or a placebo (vehicle). Participants were assessed in each drink condition, separated by a 7-day wash-out period. Cognitive, psychomotor and mood assessment took place immediately prior to the drink then 30 min thereafter. The primary outcome measures included five aspects of cognitive performance from the Cognitive Drug Research assessment battery. Mood, heart rate and blood glucose levels were also monitored. Compared with placebo, the whole drink resulted in significantly improved performance on "secondary memory" and "speed of attention" factors. There were no other cognitive or mood effects. This pattern of results would not be predicted from the effects of glucose and caffeine in isolation, either as seen here or from the literature addressing the effects of the substances in isolation. These data suggest that there is some degree of synergy between the cognition-modulating effects of glucose and caffeine which merits further investigation.

  18. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  19. The political left rolls with the good and the political right confronts the bad: connecting physiology and cognition to preferences

    Science.gov (United States)

    Dodd, Michael D.; Balzer, Amanda; Jacobs, Carly M.; Gruszczynski, Michael W.; Smith, Kevin B.; Hibbing, John R.

    2012-01-01

    We report evidence that individual-level variation in people's physiological and attentional responses to aversive and appetitive stimuli are correlated with broad political orientations. Specifically, we find that greater orientation to aversive stimuli tends to be associated with right-of-centre and greater orientation to appetitive (pleasing) stimuli with left-of-centre political inclinations. These findings are consistent with recent evidence that political views are connected to physiological predispositions but are unique in incorporating findings on variation in directed attention that make it possible to understand additional aspects of the link between the physiological and the political. PMID:22271780

  20. The challenge of non-invasive cognitive physiology of the human brain: how to negotiate the irrelevant background noise without spoiling the recorded data through electronic averaging.

    Science.gov (United States)

    Tomberg, C; Desmedt, J E

    1999-07-29

    Brain mechanisms involved in selective attention in humans can be studied by measures of regional blood flow and metabolism (by positron emission tomography) which help identify the various locations with enhanced activities over a period of time of seconds. The physiological measures provided by scalp-recorded brain electrical potentials have a better resolution (milliseconds) and can reveal the actual sequences of distinct neural events and their precise timing. We studied selective attention to sensory inputs from fingers because the brain somatic representations are deployed over the brain convexity under the scalp thereby making it possible to assess distinct stages of cortical processing and representation through their characteristic scalp topographies. In the electrical response to a finger input attended by the subject, the well-known P300 manifests a widespread inhibitory mechanism which is released after a target stimulus has been identified. P300 is preceded by distinct cognitive electrogeneses such as P40, P100 and N140 which can be differentiated from the control (obligatory) profile by superimposition or electronic subtraction. The first cortical response N20 is stable across conditions, suggesting that the first afferent thalamocortical volley is not affected by selective attention. At the next stage of modality-specific cortex in which the sensory features are processed and represented, responses were enhanced (cognitive P40) only a very few milliseconds after arrival of the afferent volley at the cortex, thus documenting a remarkable precocity of attention gain control in the somatic modality. The physiology of selective attention also provides useful cues in relation to non-target inputs which the subject must differentiate in order to perform the task. When having to tell fingers apart, the brain strategy for non-target fingers is not to inhibit or filter them out, but rather to submit their input to several processing operations that are

  1. Effect of Task-Correlated Physiological Fluctuations and Motion in 2D and 3D Echo-Planar Imaging in a Higher Cognitive Level fMRI Paradigm.

    Science.gov (United States)

    Ladstein, Jarle; Evensmoen, Hallvard R; Håberg, Asta K; Kristoffersen, Anders; Goa, Pål E

    2016-01-01

    To compare 2D and 3D echo-planar imaging (EPI) in a higher cognitive level fMRI paradigm. In particular, to study the link between the presence of task-correlated physiological fluctuations and motion and the fMRI contrast estimates from either 2D EPI or 3D EPI datasets, with and without adding nuisance regressors to the model. A signal model in the presence of partly task-correlated fluctuations is derived, and predictions for contrast estimates with and without nuisance regressors are made. Thirty-one healthy volunteers were scanned using 2D EPI and 3D EPI during a virtual environmental learning paradigm. In a subgroup of 7 subjects, heart rate and respiration were logged, and the correlation with the paradigm was evaluated. FMRI analysis was performed using models with and without nuisance regressors. Differences in the mean contrast estimates were investigated by analysis-of-variance using Subject, Sequence, Day, and Run as factors. The distributions of group level contrast estimates were compared. Partially task-correlated fluctuations in respiration, heart rate and motion were observed. Statistically significant differences were found in the mean contrast estimates between the 2D EPI and 3D EPI when using a model without nuisance regressors. The inclusion of nuisance regressors for cardiorespiratory effects and motion reduced the difference to a statistically non-significant level. Furthermore, the contrast estimate values shifted more when including nuisance regressors for 3D EPI compared to 2D EPI. The results are consistent with 3D EPI having a higher sensitivity to fluctuations compared to 2D EPI. In the presence partially task-correlated physiological fluctuations or motion, proper correction is necessary to get expectation correct contrast estimates when using 3D EPI. As such task-correlated physiological fluctuations or motion is difficult to avoid in paradigms exploring higher cognitive functions, 2D EPI seems to be the preferred choice for higher

  2. Experimental modification of interpretation bias about animal fear in young children: effects on cognition, avoidance behavior, anxiety vulnerability, and physiological responding.

    Science.gov (United States)

    Lester, Kathryn J; Field, Andy P; Muris, Peter

    2011-01-01

    This study investigated the effects of experimentally modifying interpretation biases for children's cognitions, avoidance behavior, anxiety vulnerability, and physiological responding. Sixty-seven children (6-11 years) were randomly assigned to receive a positive or negative interpretation bias modification procedure to induce interpretation biases toward or away from threat about ambiguous situations involving Australian marsupials. Children rapidly learned to select outcomes of ambiguous situations, which were congruent with their assigned condition. Furthermore, following positive modification, children's threat biases about novel ambiguous situations significantly decreased, whereas threat biases significantly increased after negative modification. In response to a stress-evoking behavioral avoidance test, positive modification attenuated behavioral avoidance compared to negative modification. However, no significant effects of bias modification on anxiety vulnerability or physiological responses to this stress-evoking Behavioral Avoidance Task were observed.

  3. Baby, you light-up my face: culture-general physiological responses to infants and culture-specific cognitive judgements of adults.

    Directory of Open Access Journals (Sweden)

    Gianluca Esposito

    Full Text Available Infants universally elicit in adults a set of solicitous behaviors that are evolutionarily important for the survival of the species. However, exposure, experience, and prejudice appear to govern adults' social choice and ingroup attitudes towards other adults. In the current study, physiological arousal and behavioral judgments were assessed while adults processed unfamiliar infant and adult faces of ingroup vs. outgroup members in two contrasting cultures, Japan and Italy. Physiological arousal was investigated using the novel technique of infrared thermography and behavioral judgments using ratings. We uncovered a dissociation between physiological and behavioral responses. At the physiological level, both Japanese and Italian adults showed significant activation (increase of facial temperature for both ingroup and outgroup infant faces. At the behavioral level, both Japanese and Italian adults showed significant preferences for ingroup adults. Arousal responses to infants appear to be mediated by the autonomic nervous system and are not dependent on direct caregiving exposure, but behavioral responses appear to be mediated by higher-order cognitive processing based on social acceptance and cultural exposure.

  4. Effects of Dietary Nitrate Supplementation on Physiological Responses, Cognitive Function, and Exercise Performance at Moderate and Very-High Simulated Altitude

    Directory of Open Access Journals (Sweden)

    Oliver M. Shannon

    2017-06-01

    Full Text Available Purpose: Nitric oxide (NO bioavailability is reduced during acute altitude exposure, contributing toward the decline in physiological and cognitive function in this environment. This study evaluated the effects of nitrate (NO3− supplementation on NO bioavailability, physiological and cognitive function, and exercise performance at moderate and very-high simulated altitude.Methods:Ten males (mean (SD: V˙O2max: 60.9 (10.1 ml·kg−1·min−1 rested and performed exercise twice at moderate (~14.0% O2; ~3,000 m and twice at very-high (~11.7% O2; ~4,300 m simulated altitude. Participants ingested either 140 ml concentrated NO3−-rich (BRJ; ~12.5 mmol NO3− or NO3−-deplete (PLA; 0.01 mmol NO3− beetroot juice 2 h before each trial. Participants rested for 45 min in normobaric hypoxia prior to completing an exercise task. Exercise comprised a 45 min walk at 30% V˙O2max and a 3 km time-trial (TT, both conducted on a treadmill at a 10% gradient whilst carrying a 10 kg backpack to simulate altitude hiking. Plasma nitrite concentration ([NO2−], peripheral oxygen saturation (SpO2, pulmonary oxygen uptake (V˙O2, muscle and cerebral oxygenation, and cognitive function were measured throughout.Results: Pre-exercise plasma [NO2−] was significantly elevated in BRJ compared with PLA (p = 0.001. Pulmonary V˙O2 was reduced (p = 0.020, and SpO2 was elevated (p = 0.005 during steady-state exercise in BRJ compared with PLA, with similar effects at both altitudes. BRJ supplementation enhanced 3 km TT performance relative to PLA by 3.8% [1,653.9 (261.3 vs. 1718.7 (213.0 s] and 4.2% [1,809.8 (262.0 vs. 1,889.1 (203.9 s] at 3,000 and 4,300 m, respectively (p = 0.019. Oxygenation of the gastrocnemius was elevated during the TT consequent to BRJ (p = 0.011. The number of false alarms during the Rapid Visual Information Processing Task tended to be lower with BRJ compared with PLA prior to altitude exposure (p = 0.056. Performance in all other cognitive tasks

  5. What neuromodulation and lesion studies tell us about the function of the mirror neuron system and embodied cognition

    NARCIS (Netherlands)

    Keysers, Christian; Paracampo, Riccardo; Gazzola, V.

    2018-01-01

    We review neuromodulation and lesion studies that address how activations in the mirror neuron system contribute to our perception of observed actions. Past reviews showed disruptions of this parieto-premotor network impair imitation and goal and kinematic processing. Recent studies bring five new

  6. Non-Smoker Exposure to Secondhand Cannabis Smoke II: Effect of Room Ventilation on the Physiological, Subjective, and Behavioral/Cognitive Effects

    Science.gov (United States)

    Herrmann, Evan S.; Cone, Edward J; Mitchell, John M.; Bigelow, George E.; LoDico, Charles; Flegel, Ron; Vandrey, Ryan

    2015-01-01

    Introduction Cannabis is the most widely used illicit drug. Many individuals are incidentally exposed to secondhand cannabis smoke, but little is known about the effects of this exposure. This report examines the physiological, subjective, and behavioral/cognitive effects of secondhand cannabis exposure, and the influence of room ventilation on these effects. Methods Non-cannabis-using individuals were exposed to secondhand cannabis smoke from six individuals smoking cannabis (11.3% THC) ad libitum in a specially constructed chamber for one hour. Chamber ventilation was experimentally manipulated so that participants were exposed under unventilated conditions or with ventilation at a rate of 11 air exchanges/hour. Physiological, subjective and behavioral/cognitive measures of cannabis exposure assessed after exposure sessions were compared to baseline measures. Results Exposure to secondhand cannabis smoke under unventilated conditions produced detectable cannabinoid levels in blood and urine, minor increases in heart rate, mild to moderate self-reported sedative drug effects, and impaired performance on the Digit Symbol Substitution Task (DSST). One urine specimen tested positive at using a 50 ng/mL cut-off and several specimens were positive at 20 ng/mL. Exposure under ventilated conditions resulted in much lower blood cannabinoid levels, and did not produce sedative drug effects, impairments in performance, or positive urine screen results. Conclusions Room ventilation has a pronounced effect on exposure to secondhand cannabis smoke. Under extreme, unventilated conditions, secondhand cannabis smoke exposure can produce detectable levels of THC in blood and urine, minor physiological and subjective drug effects, and minor impairment on a task requiring psychomotor ability and working memory. PMID:25957157

  7. Physiological and brain activity after a combined cognitive behavioral treatment plus video game therapy for emotional regulation in bulimia nervosa: a case report.

    Science.gov (United States)

    Fagundo, Ana Beatriz; Via, Esther; Sánchez, Isabel; Jiménez-Murcia, Susana; Forcano, Laura; Soriano-Mas, Carles; Giner-Bartolomé, Cristina; Santamaría, Juan J; Ben-Moussa, Maher; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Lems, Peter; Cardoner, Narcís; Menchón, Jose M; de la Torre, Rafael; Fernandez-Aranda, Fernando

    2014-08-12

    PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances.

  8. Non-smoker exposure to secondhand cannabis smoke II: Effect of room ventilation on the physiological, subjective, and behavioral/cognitive effects.

    Science.gov (United States)

    Herrmann, Evan S; Cone, Edward J; Mitchell, John M; Bigelow, George E; LoDico, Charles; Flegel, Ron; Vandrey, Ryan

    2015-06-01

    Cannabis is the most widely used illicit drug. Many individuals are incidentally exposed to secondhand cannabis smoke, but little is known about the effects of this exposure. This report examines the physiological, subjective, and behavioral/cognitive effects of secondhand cannabis exposure, and the influence of room ventilation on these effects. Non-cannabis-using individuals were exposed to secondhand cannabis smoke from six individuals smoking cannabis (11.3% THC) ad libitum in a specially constructed chamber for 1h. Chamber ventilation was experimentally manipulated so that participants were exposed under unventilated conditions or with ventilation at a rate of 11 air exchanges/h. Physiological, subjective and behavioral/cognitive measures of cannabis exposure assessed after exposure sessions were compared to baseline measures. Exposure to secondhand cannabis smoke under unventilated conditions produced detectable cannabinoid levels in blood and urine, minor increases in heart rate, mild to moderate self-reported sedative drug effects, and impaired performance on the digit symbol substitution task (DSST). One urine specimen tested positive at using a 50 ng/ml cut-off and several specimens were positive at 20 ng/ml. Exposure under ventilated conditions resulted in much lower blood cannabinoid levels, and did not produce sedative drug effects, impairments in performance, or positive urine screen results. Room ventilation has a pronounced effect on exposure to secondhand cannabis smoke. Under extreme, unventilated conditions, secondhand cannabis smoke exposure can produce detectable levels of THC in blood and urine, minor physiological and subjective drug effects, and minor impairment on a task requiring psychomotor ability and working memory. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Physiological and Brain Activity After a Combined Cognitive Behavioral Treatment Plus Video Game Therapy for Emotional Regulation in Bulimia Nervosa: A Case Report

    Science.gov (United States)

    Fagundo, Ana Beatriz; Via, Esther; Sánchez, Isabel; Jiménez-Murcia, Susana; Forcano, Laura; Soriano-Mas, Carles; Giner-Bartolomé, Cristina; Santamaría, Juan J; Ben-Moussa, Maher; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Lems, Peter; Cardoner, Narcís; Menchón, Jose M; de la Torre, Rafael

    2014-01-01

    Background PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. Objective The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Methods Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Results Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. Conclusions These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances. PMID:25116416

  10. Physiological and behavioral indices of emotion dysregulation as predictors of outcome from cognitive behavioral therapy and acceptance and commitment therapy for anxiety.

    Science.gov (United States)

    Davies, Carolyn D; Niles, Andrea N; Pittig, Andre; Arch, Joanna J; Craske, Michelle G

    2015-03-01

    Identifying for whom and under what conditions a treatment is most effective is an essential step toward personalized medicine. The current study examined pre-treatment physiological and behavioral variables as predictors and moderators of outcome in a randomized clinical trial comparing cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for anxiety disorders. Sixty individuals with a DSM-IV defined principal anxiety disorder completed 12 sessions of either CBT or ACT. Baseline physiological and behavioral variables were measured prior to entering treatment. Self-reported anxiety symptoms were assessed at pre-treatment, post-treatment, and 6- and 12-month follow-up from baseline. Higher pre-treatment heart rate variability was associated with worse outcome across ACT and CBT. ACT outperformed CBT for individuals with high behavioral avoidance. Subjective anxiety levels during laboratory tasks did not predict or moderate treatment outcome. Due to small sample sizes of each disorder, disorder-specific predictors were not tested. Future research should examine these predictors in larger samples and across other outcome variables. Lower heart rate variability was identified as a prognostic indicator of overall outcome, whereas high behavioral avoidance was identified as a prescriptive indicator of superior outcome from ACT versus CBT. Investigation of pre-treatment physiological and behavioral variables as predictors and moderators of outcome may help guide future treatment-matching efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. High-level cognition in phobics: Abstract anticipatory memory is associated with the attenuation of physiological reactivity to threat.

    NARCIS (Netherlands)

    Kindt, M.; Brosschot, J.F.; Boiten, F.

    1999-01-01

    Investigated whether the cognitive processing of threat in anxious individuals is dominated by abstract anticipatory memory, and whether this abstract memory mode is related to the incomplete activation of the fear network. Activation of the fear network was assessed during phobic exposure, as

  12. Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice.

    Science.gov (United States)

    Gu, G; Zhang, W; Li, M; Ni, J; Wang, P

    2015-04-16

    The ability to selectively control the differentiation of neural stem cells (NSCs) into cholinergic neurons in vivo would be an important step toward cell replacement therapy. First, green fluorescent protein (GFP)-NSCs were induced to differentiate into cholinergic neuron-like cells (CNLs) with retinoic acid (RA) pre-induction followed by nerve growth factor (NGF) induction. Then, these CNLs were transplanted into bilateral hippocampus of APP/PS1 transgenic mice. Behavioral parameters showed by Morris water maze (MWM) tests and the percentages of GFP-labeled cholinergic neurons of CNL transplanted mice were compared with those of controls. Brain levels of choline acetyltransferase (ChAT) mRNA and proteins were analyzed by quantitative real-time PCR and Western blotting, ChAT activity and acetylcholine (ACh) concentration were also evaluated by ChAT activity and ACh concentration assay kits. Immunofluorescence analysis showed that 80.3±1.5% NSCs differentiated into CNLs after RA pre-induction followed by NGF induction in vitro. Three months after transplantation, 82.4±6.3% CNLs differentiated into cholinergic neurons in vivo. APP/PS1 mice transplanted with CNLs showed a significant improvement in learning and memory ability compared with control groups at different time points. Furthermore, CNLs transplantation dramatically increased in the expressions of ChAT mRNA and protein, as well ChAT activity and ACh concentration in APP/PS1 mice. Our findings support the prospect of using NSC-derived CNLs in developing therapies for Alzheimer's disease (AD). Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Changes of Functional and Directed Resting-State Connectivity Are Associated with Neuronal Oscillations, ApoE Genotype and Amyloid Deposition in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Lars Michels

    2017-09-01

    Full Text Available The assessment of effects associated with cognitive impairment using electroencephalography (EEG power mapping allows the visualization of frequency-band specific local changes in oscillatory activity. In contrast, measures of coherence and dynamic source synchronization allow for the study of functional and effective connectivity, respectively. Yet, these measures have rarely been assessed in parallel in the context of mild cognitive impairment (MCI and furthermore it has not been examined if they are related to risk factors of Alzheimer’s disease (AD such as amyloid deposition and apolipoprotein ε4 (ApoE allele occurrence. Here, we investigated functional and directed connectivities with Renormalized Partial Directed Coherence (RPDC in 17 healthy controls (HC and 17 participants with MCI. Participants underwent ApoE-genotyping and Pittsburgh compound B positron emission tomography (PiB-PET to assess amyloid deposition. We observed lower spectral source power in MCI in the alpha and beta bands. Coherence was stronger in HC than MCI across different neuronal sources in the delta, theta, alpha, beta and gamma bands. The directed coherence analysis indicated lower information flow between fronto-temporal (including the hippocampus sources and unidirectional connectivity in MCI. In MCI, alpha and beta RPDC showed an inverse correlation to age and gender; global amyloid deposition was inversely correlated to alpha coherence, RPDC and beta and gamma coherence. Furthermore, the ApoE status was negatively correlated to alpha coherence and RPDC, beta RPDC and gamma coherence. A classification analysis of cognitive state revealed the highest accuracy using EEG power, coherence and RPDC as input. For this small but statistically robust (Bayesian power analyses sample, our results suggest that resting EEG related functional and directed connectivities are sensitive to the cognitive state and are linked to ApoE and amyloid burden.

  14. Total Lignans of Schisandra chinensis Ameliorates Aβ1-42-Induced Neurodegeneration with Cognitive Impairment in Mice and Primary Mouse Neuronal Cells.

    Directory of Open Access Journals (Sweden)

    Xu Zhao

    Full Text Available Lignan compounds extracted from Schisandra chinensis (Turcz. Baill. have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease. This study was designed to investigate the effects of total lignans of Schisandra chinensis (TLS on cognitive function and neurodegeneration in the model of AD induced by Aβ1-42 in vivo and in vitro. It was found that intragastric infusion with TLS (50 and 200 mg/kg to Aβ1-42-induced mice significantly increased the number of avoidances in the shuttle-box test and swimming time in the target quadrant in the Morris water maze test. TLS at dose of 200 mg/kg significantly restored the activities of total antioxidant capacity (T-AOC, as well as the level of malondialdehyde (MDA both in the hippocampus and cerebral cortex in mice. Results of histopathological examination indicated that TLS noticeably ameliorated the neurodegeneration in the hippocampus in mice. On the other hand, TLS (100 μM could protect the Aβ1-42-induced primary mouse neuronal cells by blocking the decrease of mitochondrial membrane potential (MMP, change the expressions of Bcl-2 (important regulator in the mitochondria apoptosis pathway. Moreover, TLS also decreased the activity of β-secretase 1 (BACE1, crucial protease contributes to the hydrolysis of amyloid precursor protein (APP, and inhibited the expression of JKN/p38, which involved in the MAPKs signaling pathways in both mice and primary mouse neuronal cells. In summary, TLS might protect against cognitive deficits and neurodegeneration by releasing the damage of oxidative stress, inhibiting the expression of BACE1 and the MAPKs inflammatory signaling pathways.

  15. Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.

    Science.gov (United States)

    McDonough, Patrick M; Prigozhina, Natalie L; Basa, Ranor C B; Price, Jeffrey H

    2017-07-01

    Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days. Kinetic Image Cytometry™ (KIC™) methods were developed to quantify spontaneously occurring intracellular calcium transients representing the activity of the neurons, and high-content analysis (HCA) methods were developed to quantify the expression, colocalization, and puncta formed by synaptic proteins (postsynaptic density protein-95 [PSD-95] and presynaptic protein Synapsin-1 [Syn-1]). As quantified by KIC, FSK increased the occurrence and synchronization of the calcium transients indicating stimulatory effects on RHN activity, whereas TAM had inhibitory effects. As quantified by HCA, FSK also increased PSD-95 puncta and PSD-95:Syn-1 colocalization, whereas ES increased the puncta of both PSD-95 and Syn-1 with little effect on colocalization. The estrogen receptor antagonist FUL also increased PSD-95 puncta. In contrast, TAM reduced Syn-1 and PSD-95:Syn-1 colocalization, consistent with its inhibitory effects on the calcium transients. Thus TAM reduced activity and synapse formation by the RHNs, which may relate to the ability of this agent to cause PCCI. The results illustrate that KIC and HCA can be used to quantify neurotoxic and neuroprotective effects of chemicals in RHNs to investigate mechanisms and potential therapeutics for PCCI.

  16. Differential effects of common variants in SCN2A on general cognitive ability, brain physiology, and messenger RNA expression in schizophrenia cases and control individuals.

    Science.gov (United States)

    Dickinson, Dwight; Straub, Richard E; Trampush, Joey W; Gao, Yuan; Feng, Ningping; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L; Kolachana, Bhaskar; Hashimoto, Ryota; Takeda, Masatoshi; Baum, Graham L; Rujescu, Dan; Callicott, Joseph H; Hyde, Thomas M; Berman, Karen F; Kleinman, Joel E; Weinberger, Daniel R

    2014-06-01

    One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation. To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals. Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals. We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts. The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 × 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide

  17. Physiological Acoustics

    Science.gov (United States)

    Young, Eric D.

    The analysis of physiological sound in the peripheral auditory system solves three important problems. First, sound energy impinging on the head must be captured and presented to the transduction apparatus in the ear as a suitable mechanical signal; second, this mechanical signal needs to be transduced into a neural representation that can be used by the brain; third, the resulting neural representation needs to be analyzed by central neurons to extract information useful to the animal. This chapter provides an overview of some aspects of the first two of these processes. The description is entirely focused on the mammalian auditory system, primarily on human hearing and on the hearing of a few commonly used laboratory animals (mainly rodents and carnivores). Useful summaries of non-mammalian hearing are available [1]. Because of the large size of the literature, review papers are referenced wherever possible.

  18. Effects of chewing gum on cognitive function, mood and physiology in stressed and non-stressed volunteers.

    Science.gov (United States)

    Smith, Andrew

    2010-02-01

    Recent research suggests that chewing gum may improve aspects of cognitive function and mood. There is also evidence suggesting that chewing gum reduces stress. It is important, therefore, to examine these two areas and to determine whether contextual factors (chewing habit, type of gum, and personality) modify such effects. The aims of the present study were: (i) to determine whether chewing gum improved mood and mental performance; (ii) to determine whether chewing gum had benefits in stressed individuals; and (iii) to determine whether chewing habit, type of gum and level of anxiety modified the effects of gum. A cross-over study involving 133 volunteers was carried out. Each volunteer carried out a test session when they were chewing gum and without gum, with order of gum conditions counterbalanced across subjects. Baseline sessions were conducted prior to each test session. Approximately half of the volunteers were tested in 75 dBA noise (the stress condition) and the rest in quiet. Volunteers were stratified on chewing habit and anxiety level. Approximately, half of the volunteers were given mint gum and half fruit gum. The volunteers rated their mood at the start and end of each session and had their heart rate monitored over the session. Saliva samples were taken to allow cortisol levels (good indicator of alertness and stress) to be assayed. During the session, volunteers carried out tasks measuring a range of cognitive functions (aspects of memory, selective and sustained attention, psychomotor speed and accuracy). Chewing gum was associated with greater alertness and a more positive mood. Reaction times were quicker in the gum condition, and this effect became bigger as the task became more difficult. Chewing gum also improved selective and sustained attention. Heart rate and cortisol levels were higher when chewing which confirms the alerting effect of chewing gum. Overall, the results suggest that chewing gum produces a number of benefits that are

  19. Neuron-microglia interactions in mental health disorders: 'For better, and for worse'

    Directory of Open Access Journals (Sweden)

    Eric S Wohleb

    2016-11-01

    Full Text Available Persistent cognitive and behavioral symptoms that characterize many mental health disorders arise from impaired neuroplasticity in several key corticolimbic brain regions. Recent evidence suggest that reciprocal neuron-microglia interactions shape neuroplasticity during physiological conditions, implicating microglia in the neurobiology of mental health disorders. Neuron-microglia interactions are modulated by several molecular and cellular pathways and dysregulation of these pathways often have neurobiological consequences, including aberrant neuronal responses and microglia activation. The interactions between neurons and microglia have implications for mental health disorders as rodent stress models cause concomitant neuronal dystrophy and alterations in microglia morphology and function. In this context, functional changes in microglia may be indicative of an immune state termed parainflammation in which tissue-resident macrophages (i.e., microglia respond to malfunctioning cells by initiating modest inflammation in an attempt to restore homeostasis. Thus, aberrant neuronal activity and release of damage-associated signals during repeated stress exposure may contribute to functional changes in microglia and resultant parainflammation. Furthermore, accumulating evidence shows that uncoupling neuron-microglia interactions may contribute to altered neuroplasticity and associated anxiety- or depressive-like behaviors. Additional work shows that microglia have varied phenotypes in specific brain regions, which may underlie divergent neuroplasticity observed in corticolimbic structures following stress exposure. These findings indicate that neuron-microglia interactions are critical mediators of the interface between adaptive, homeostatic neuronal function and the neurobiology of mental health disorders.

  20. Predicting athletic performance with self-confidence and somatic and cognitive anxiety as a function of motor and physiological requirements in six sports.

    Science.gov (United States)

    Taylor, J

    1987-03-01

    The purpose of the present study is to examine the ability of certain psychological attributes to predict performance in six National Collegiate Athletic Association Division I collegiate sports. Eighty-four athletes from the varsity sports teams of cross country running, alpine and nordic skiing, tennis, basketball, and track and field at the University of Colorado completed a questionnaire adapted from Martens (1977; Martens et al., 1983) that measured their trait levels of self-confidence (Bandura, 1977), somatic anxiety, and cognitive anxiety (Martens, 1977; Martens et al., 1983). In addition, at three to six competitions during the season, the members of the cross country running and tennis teams filled out a state measure (Martens et al., 1983) of the three attributes from one to two hours prior to the competition. Following each competition, subjective and objective ratings of performance were obtained, and, for all sports, coaches' ratings of performance and an overall seasonal team ranking were determined as seasonal performance measures. The sports were dichotomized along motor and physiological dimensions. Results indicate that all three psychological attributes were significant predictors of performance in both fine motor, anaerobic sports and gross motor, aerobic sports. Further, clear differences in these relationships emerged as a function of the dichotomization. In addition, unexpected sex differences emerged. The findings are discussed relative to prior research and their implications for future research.

  1. Imitation, mirror neurons and autism

    OpenAIRE

    Williams, Justin H.G.; Whiten, Andrew; Suddendorf, Thomas; Perrett, David I.

    2001-01-01

    Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show ac...

  2. The Neuronal Ceroid-Lipofuscinoses

    Science.gov (United States)

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  3. The human cerebellum: a review of physiologic neuroanatomy.

    Science.gov (United States)

    Roostaei, Tina; Nazeri, Arash; Sahraian, Mohammad Ali; Minagar, Alireza

    2014-11-01

    The cerebellum resides in the posterior cranial fossa dorsal to the brainstem and has diverse connections to the cerebrum, brain stem, and spinal cord. It is anatomically and physiologically divided into distinct functional compartments and is composed of highly regular arrays of neuronal units, each sharing the same basic cerebellar microcircuitry. Its circuitry is critically involved in motor control and motor learning, and its role in nonmotor cognitive and affective functions is becoming increasingly recognized. This article describes the cerebellar gross and histologic neuroanatomy in relation to its function, and the relevance of cerebellar circuitry and firing patterns to motor learning. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Injection of Aβ1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew.

    Science.gov (United States)

    Lin, Na; Xiong, Liu-Lin; Zhang, Rong-Ping; Zheng, Hong; Wang, Lei; Qian, Zhong-Yi; Zhang, Piao; Chen, Zhi-Wei; Gao, Fa-Bao; Wang, Ting-Hua

    2016-05-01

    Alzheimer's disease (AD) can incur significant health care costs to the patient, their families, and society; furthermore, effective treatments are limited, as the mechanisms of AD are not fully understood. This study utilized twelve adult male tree shrews (TS), which were randomly divided into PBS and amyloidbetapeptide1-40 (Aβ1-40) groups. AD model was established via an intracerebroventricular (icv) injection of Aβ1-40 after being incubated for 4 days at 37 °C. Behavioral, pathophysiological and molecular changes were evaluated by hippocampal-dependent tasks, magnetic resonance imaging (MRI), silver staining, hematoxylin-eosin (HE) staining, TUNEL assay and gene sequencing, respectively. At 4 weeks post-injection, as compared with the PBS group, in Aβ1-40 injected animals: cognitive impairments happened, and the hippocampus had atrophied indicated by MRI findings; meanwhile, HE staining showed the cells of the CA3 and DG were significantly thinner and smaller. The average number of cells in the DG, but not the CA3, was also significantly reduced; furthermore, silver staining revealed neurotic plaques and neurofibrillary tangles (NFTs) in the hippocampi; TUNEL assay showed many cells exhibited apoptosis, which was associated with downregulated BCL-2/BCL-XL-associated death promoter (Bad), inhibitor of apoptosis protein (IAP), Cytochrome c (CytC) and upregulated tumor necrosis factor receptor 1 (TNF-R1); lastly, gene sequencing reported a total of 924 mobilized genes, among which 13 of the downregulated and 19 of the upregulated genes were common to the AD pathway. The present study not only established AD models in TS, but also reported on the underlying mechanism involved in neuronal apoptosis associated with multiple gene expression.

  5. Brain signal variability differentially affects cognitive flexibility and cognitive stability

    NARCIS (Netherlands)

    Armbruster-Genç, D.J.N.; Ültzhöffer, K.; Fiebach, C.J.

    2016-01-01

    Recent research yielded the intriguing conclusion that, in healthy adults, higher levels of variability in neuronal processes are beneficial for cognitive functioning. Beneficial effects of variability in neuronal processing can also be inferred from neurocomputational theories of working memory,

  6. CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice.

    Science.gov (United States)

    Vingtdeux, Valérie; Chang, Eric H; Frattini, Stephen A; Zhao, Haitian; Chandakkar, Pallavi; Adrien, Leslie; Strohl, Joshua J; Gibson, Elizabeth L; Ohmoto, Makoto; Matsumoto, Ichiro; Huerta, Patricio T; Marambaud, Philippe

    2016-04-12

    CALHM1 is a cell surface calcium channel expressed in cerebral neurons. CALHM1 function in the brain remains unknown, but recent results showed that neuronal CALHM1 controls intracellular calcium signaling and cell excitability, two mechanisms required for synaptic function. Here, we describe the generation of Calhm1 knockout (Calhm1(-/-)) mice and investigate CALHM1 role in neuronal and cognitive functions. Structural analysis revealed that Calhm1(-/-) brains had normal regional and cellular architecture, and showed no evidence of neuronal or synaptic loss, indicating that CALHM1 deficiency does not affect brain development or brain integrity in adulthood. However, Calhm1(-/-) mice showed a severe impairment in memory flexibility, assessed in the Morris water maze, and a significant disruption of long-term potentiation without alteration of long-term depression, measured in ex vivo hippocampal slices. Importantly, in primary neurons and hippocampal slices, CALHM1 activation facilitated the phosphorylation of NMDA and AMPA receptors by protein kinase A. Furthermore, neuronal CALHM1 activation potentiated the effect of glutamate on the expression of c-Fos and C/EBPβ, two immediate-early gene markers of neuronal activity. Thus, CALHM1 controls synaptic activity in cerebral neurons and is required for the flexible processing of memory in mice. These results shed light on CALHM1 physiology in the mammalian brain.

  7. Oscillating from Neurosecretion to Multitasking Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    David R. Grattan

    2016-04-01

    Full Text Available In this issue of Cell Reports, Stagkourakis et al. (2016 report that oscillating hypothalamic TIDA neurons, previously thought to be simple neurosecretory neurons controlling pituitary prolactin secretion, control dopamine output via autoregulatory mechanisms and thus could potentially regulate other physiologically important hypothalamic neuronal circuits.

  8. Stress-related exhaustion disorder--clinical manifestation of burnout? A review of assessment methods, sleep impairments, cognitive disturbances, and neuro-biological and physiological changes in clinical burnout.

    Science.gov (United States)

    Grossi, Giorgio; Perski, Aleksander; Osika, Walter; Savic, Ivanka

    2015-12-01

    The aim of this paper was to provide an overview of the literature on clinically significant burnout, focusing on its assessment, associations with sleep disturbances, cognitive impairments, as well as neurobiological and physiological correlates. Fifty-nine English language articles and six book chapters were included. The results indicate that exhaustion disorder (ED), as described in the Swedish version of the International Classification of Diseases, seems to be the most valid clinical equivalent of burnout. The data supports the notion that sleep impairments are causative and maintaining factors for this condition. Patients with clinical burnout/ED suffer from cognitive impairments in the areas of memory and executive functioning. The studies on neuro-biological mechanisms have reported functional uncoupling of networks relating the limbic system to the pre-frontal cortex, and decreased volumes of structures within the basal ganglia. Although there is a growing body of literature on the physiological correlates of clinical burnout/ED, there is to date no biomarker for this condition. More studies on the role of sleep disturbances, cognitive impairments, and neurobiological and physiological correlates in clinical burnout/ED are warranted. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  9. From physiological psychology to psychological physiology: Postnonclassical approach to ethnocultural phenomena.

    Directory of Open Access Journals (Sweden)

    Asmolov, A.G.

    2015-07-01

    Full Text Available In modern science, along with the “classic” and “non-classical” approach to solving fundamental and applied problems, there is an actively developing “postnonclassical” research paradigm. This renovation of general scientific methodology has been accompanied by the emergence of new experimental technologies and new scientific research directions based on them. “Social psychophysiology” is one such direction. It is formed within the frame of postnonclassical methodology at the intersection of neuroscience and psychology. This work is devoted to the analytical review of the methods, achievements and prospects of contemporary social neuroscience and social psychophysiology studying brain structures that are specifically related to the implementation of social forms of behavior and intercultural communication. Physiological studies of brain activity during social interaction processes, which are simulated using virtual reality environments, are analyzed, and the physiological approach to the study of the brain mechanisms associated with social perception, social cognition and social behavior is used. Along with the analysis of psychophysiological studies of the mechanisms of social perception and social cognition, we discuss the theories of “Brain Reading” and “Theory of Mind” and the underlying data concerning “Gnostic neurons recognition of persons and recognition of emotional facial expressions”, “mirror neurons”, “emotional resonance” and “cognitive resonance”. Particular emphasis is placed on the discussion of a fundamentally new trend in the study of the relationship between the brain and culture (i.e., “cultural neuroscience”. Related to this connection, the following topics are raised: physiological mechanisms protecting the “individual distance” in communication between members of a personified community, psychophysiological approaches to the study of cross-cultural differences, physiological

  10. Nasal Physiology

    Science.gov (United States)

    ... Caregivers Contact ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... Patient Education About this Website Font Size + - Home > ANATOMY > Nasal Physiology Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy ...

  11. The biophysics of neuronal growth

    International Nuclear Information System (INIS)

    Franze, Kristian; Guck, Jochen

    2010-01-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  12. Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

    Science.gov (United States)

    Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

    2017-11-17

    The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Augmenting cognition by neuronal oscillations

    NARCIS (Netherlands)

    Horschig, J.M.; Zumer, J.; Bahramisharif, A.

    2014-01-01

    Cortical oscillations have been shown to represent fundamental functions of a working brain, e.g., communication, stimulus binding, error monitoring, and inhibition, and are directly linked to behavior. Recent studies intervening with these oscillations have demonstrated effective modulation of both

  14. Phospholipase A2 – nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment

    OpenAIRE

    Hermann, Petra M.; Watson, Shawn N.; Wildering, Willem C.

    2014-01-01

    TThe aging brain can undergo a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative disea...

  15. Focusing on neuronal cell-type specific mechanisms for brain circuit organization, function and dysfunction

    Institute of Scientific and Technical Information of China (English)

    Lu Li

    2017-01-01

    Mammalian brain circuits consist of dynamically interconnected neurons with characteristic morphology, physiology, connectivity and genetics which are often called neuronal cell types. Neuronal cell types have been considered as building blocks of brain circuits, but knowledge of how neuron types or subtypes connect to and interact with each other to perform neural computation is still lacking. Such mechanistic insights are critical not only to our understanding of normal brain functions, such as perception, motion and cognition, but also to brain disorders including Alzheimer's disease, Schizophrenia and epilepsy, to name a few. Thus it is necessary to carry out systematic and standardized studies on neuronal cell-type specific mechanisms for brain circuit organization and function, which will provide good opportunities to bridge basic and clinical research. Here based on recent technology advancements, we discuss the strategy to target and manipulate specific populations of neuronsin vivo to provide unique insights on how neuron types or subtypes behave, interact, and generate emergent properties in a fully connected brain network. Our approach is highlighted by combining transgenic animal models, targeted electrophysiology and imaging with robotics, thus complete and standardized mapping ofin vivo properties of genetically defined neuron populations can be achieved in transgenic mouse models, which will facilitate the development of novel therapeutic strategies for brain disorders.

  16. Modulation of firing and synaptic transmission of serotonergic neurons by intrinsic G protein-coupled receptors and ion channels

    Directory of Open Access Journals (Sweden)

    Takashi eMaejima

    2013-05-01

    Full Text Available Serotonergic neurons project to virtually all regions of the CNS and are consequently involved in many critical physiological functions such as mood, sexual behavior, feeding, sleep/wake cycle, memory, cognition, blood pressure regulation, breathing and reproductive success. Therefore serotonin release and serotonergic neuronal activity have to be precisely controlled and modulated by interacting brain circuits to adapt to specific emotional and environmental states. We will review the current knowledge about G protein-coupled receptors and ion channels involved in the regulation of serotonergic system, how their regulation is modulating the intrinsic activity of serotonergic neurons and its transmitter release and will discuss the latest methods for controlling the modulation of serotonin release and intracellular signaling in serotonergic neurons in vitro and in vivo.

  17. Physiology of neuronal-glial networking

    Czech Academy of Sciences Publication Activity Database

    Verkhratsky, Alexei

    2010-01-01

    Roč. 57, č. 4 (2010), s. 332-343 ISSN 0197-0186 Institutional research plan: CEZ:AV0Z50390703 Keywords : Glia * Astrocytes * Glutamate receptors Subject RIV: FH - Neurology Impact factor: 3.601, year: 2010

  18. Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer's Disease.

    Science.gov (United States)

    Kwakowsky, Andrea; Milne, Michael R; Waldvogel, Henry J; Faull, Richard L

    2016-12-17

    The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer's disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer's disease.

  19. Human physiology in space

    Science.gov (United States)

    Vernikos, J.

    1996-01-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  20. Imitation, mirror neurons and autism.

    Science.gov (United States)

    Williams, J H; Whiten, A; Suddendorf, T; Perrett, D I

    2001-06-01

    Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.

  1. Rice Physiology

    Science.gov (United States)

    P.A. Counce; Davidi R. Gealy; Shi-Jean Susana Sung

    2002-01-01

    Physiology occurs tn physical space through chemical reactions constrained by anatomy and morphology, yet guided by genetics. Physiology has been called the logic of life. Genes encode structural and fimcdonal proteins. These proteins are subsequently processed to produce enzymes that direct and govern the biomechanical processes involved in the physiology of the...

  2. Opposite effects of low and high doses of Abeta42 on electrical network and neuronal excitability in the rat prefrontal cortex.

    Science.gov (United States)

    Wang, Yun; Zhang, Guangping; Zhou, Hongwei; Barakat, Amey; Querfurth, Henry

    2009-12-21

    Changes in neuronal synchronization have been found in patients and animal models of Alzheimer's disease (AD). Synchronized behaviors within neuronal networks are important to such complex cognitive processes as working memory. The mechanisms behind these changes are not understood but may involve the action of soluble beta-amyloid (Abeta) on electrical networks. In order to determine if Abeta can induce changes in neuronal synchronization, the activities of pyramidal neurons were recorded in rat prefrontal cortical (PFC) slices under calcium-free conditions using multi-neuron patch clamp technique. Electrical network activities and synchronization among neurons were significantly inhibited by low dose Abeta42 (1 nM) and initially by high dose Abeta42 (500 nM). However, prolonged application of high dose Abeta42 resulted in network activation and tonic firing. Underlying these observations, we discovered that prolonged application of low and high doses of Abeta42 induced opposite changes in action potential (AP)-threshold and after-hyperpolarization (AHP) of neurons. Accordingly, low dose Abeta42 significantly increased the AP-threshold and deepened the AHP, making neurons less excitable. In contrast, high dose Abeta42 significantly reduced the AP-threshold and shallowed the AHP, making neurons more excitable. These results support a model that low dose Abeta42 released into the interstitium has a physiologic feedback role to dampen electrical network activity by reducing neuronal excitability. Higher concentrations of Abeta42 over time promote supra-synchronization between individual neurons by increasing their excitability. The latter may disrupt frontal-based cognitive processing and in some cases lead to epileptiform discharges.

  3. Opposite effects of low and high doses of Abeta42 on electrical network and neuronal excitability in the rat prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Yun Wang

    Full Text Available Changes in neuronal synchronization have been found in patients and animal models of Alzheimer's disease (AD. Synchronized behaviors within neuronal networks are important to such complex cognitive processes as working memory. The mechanisms behind these changes are not understood but may involve the action of soluble beta-amyloid (Abeta on electrical networks. In order to determine if Abeta can induce changes in neuronal synchronization, the activities of pyramidal neurons were recorded in rat prefrontal cortical (PFC slices under calcium-free conditions using multi-neuron patch clamp technique. Electrical network activities and synchronization among neurons were significantly inhibited by low dose Abeta42 (1 nM and initially by high dose Abeta42 (500 nM. However, prolonged application of high dose Abeta42 resulted in network activation and tonic firing. Underlying these observations, we discovered that prolonged application of low and high doses of Abeta42 induced opposite changes in action potential (AP-threshold and after-hyperpolarization (AHP of neurons. Accordingly, low dose Abeta42 significantly increased the AP-threshold and deepened the AHP, making neurons less excitable. In contrast, high dose Abeta42 significantly reduced the AP-threshold and shallowed the AHP, making neurons more excitable. These results support a model that low dose Abeta42 released into the interstitium has a physiologic feedback role to dampen electrical network activity by reducing neuronal excitability. Higher concentrations of Abeta42 over time promote supra-synchronization between individual neurons by increasing their excitability. The latter may disrupt frontal-based cognitive processing and in some cases lead to epileptiform discharges.

  4. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  5. Neuronal avalanches and learning

    International Nuclear Information System (INIS)

    Arcangelis, Lucilla de

    2011-01-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  6. Transgenic miR132 alters neuronal spine density and impairs novel object recognition memory.

    Directory of Open Access Journals (Sweden)

    Katelin F Hansen

    2010-11-01

    Full Text Available Inducible gene expression plays a central role in neuronal plasticity, learning, and memory, and dysfunction of the underlying molecular events can lead to severe neuronal disorders. In addition to coding transcripts (mRNAs, non-coding microRNAs (miRNAs appear to play a role in these processes. For instance, the CREB-regulated miRNA miR132 has been shown to affect neuronal structure in an activity-dependent manner, yet the details of its physiological effects and the behavioral consequences in vivo remain unclear. To examine these questions, we employed a transgenic mouse strain that expresses miR132 in forebrain neurons. Morphometric analysis of hippocampal neurons revealed that transgenic miR132 triggers a marked increase in dendritic spine density. Additionally, miR132 transgenic mice exhibited a decrease in the expression of MeCP2, a protein implicated in Rett Syndrome and other disorders of mental retardation. Consistent with these findings, miR132 transgenic mice displayed significant deficits in novel object recognition. Together, these data support a role for miR132 as a regulator of neuronal structure and function, and raise the possibility that dysregulation of miR132 could contribute to an array of cognitive disorders.

  7. Advances in 3D neuronal cell culture

    NARCIS (Netherlands)

    Frimat, Jean Philippe; Xie, Sijia; Bastiaens, Alex; Schurink, Bart; Wolbers, Floor; Den Toonder, Jaap; Luttge, Regina

    2015-01-01

    In this contribution, the authors present our advances in three-dimensional (3D) neuronal cell culture platform technology contributing to controlled environments for microtissue engineering and analysis of cellular physiological and pathological responses. First, a micromachined silicon sieving

  8. Trafficking of neuronal calcium channels

    Czech Academy of Sciences Publication Activity Database

    Weiss, Norbert; Zamponi, G. W.

    2017-01-01

    Roč. 1, č. 1 (2017), č. článku NS20160003. ISSN 2059-6553 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * neuron * trafficing Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) http://www.neuronalsignaling.org/content/1/1/NS20160003

  9. Neurochemical differences between target-specific populations of rat dorsal raphe projection neurons.

    Science.gov (United States)

    Prouty, Eric W; Chandler, Daniel J; Waterhouse, Barry D

    2017-11-15

    Serotonin (5-HT)-containing neurons in the dorsal raphe (DR) nucleus project throughout the forebrain and are implicated in many physiological processes and neuropsychiatric disorders. Diversity among these neurons has been characterized in terms of their neurochemistry and anatomical organization, but a clear sense of whether these attributes align with specific brain functions or terminal fields is lacking. DR 5-HT neurons can co-express additional neuroactive substances, increasing the potential for individualized regulation of target circuits. The goal of this study was to link DR neurons to a specific functional role by characterizing cells according to both their neurotransmitter expression and efferent connectivity; specifically, cells projecting to the medial prefrontal cortex (mPFC), a region implicated in cognition, emotion, and responses to stress. Following retrograde tracer injection, brainstem sections from Sprague-Dawley rats were immunohistochemically stained for markers of serotonin, glutamate, GABA, and nitric oxide (NO). 98% of the mPFC-projecting serotonergic neurons co-expressed the marker for glutamate, while the markers for NO and GABA were observed in 60% and less than 1% of those neurons, respectively. To identify potential target-specific differences in co-transmitter expression, we also characterized DR neurons projecting to a visual sensory structure, the lateral geniculate nucleus (LGN). The proportion of serotonergic neurons co-expressing NO was greater amongst cells targeting the mPFC vs LGN (60% vs 22%). The established role of 5-HT in affective disorders and the emerging role of NO in stress signaling suggest that the impact of 5-HT/NO co-localization in DR neurons that regulate mPFC circuit function may be clinically relevant. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Zhen-Yi Hong

    2015-08-01

    Full Text Available SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson’s disease and Alzheimer’s disease (AD. In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1 double-transgenic mice without affecting amyloid-β (Aβ burden. In addition, decreases in cAMP-response element-binding protein (CREB phosphorylation, brain-derived neurotrophic factor (BDNF and tropomyosin-related kinase B (TrkB phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  11. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice.

    Science.gov (United States)

    Hong, Zhen-Yi; Yu, Shuang-Shuang; Wang, Zhi-Jun; Zhu, Yi-Zhun

    2015-08-07

    SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1) double-transgenic mice without affecting amyloid-β (Aβ) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  12. A Longitudinal Study of Cognition, Proton MR Spectroscopy and Synaptic and Neuronal Pathology in Aging Wild-type and AβPPswe-PS1dE9 Mice

    Science.gov (United States)

    Jansen, Diane; Zerbi, Valerio; Janssen, Carola I. F.; Dederen, Pieter J. W. C.; Mutsaers, Martina P. C.; Hafkemeijer, Anne; Janssen, Anna-Lena; Nobelen, Cindy L. M.; Veltien, Andor; Asten, Jack J.; Heerschap, Arend; Kiliaan, Amanda J.

    2013-01-01

    Proton magnetic resonance spectroscopy (1H MRS) is a valuable tool in Alzheimer’s disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel 1H MRS at 7 Tesla, in the brains of AβPPSswe-PS1dE9 and wild-type mice at 8 and 12 months of age. Furthermore, we wanted to determine whether alterations in hippocampal metabolite levels coincided with behavioral changes, cognitive decline and neuropathological features, to gain a better understanding of the underlying neurodegenerative processes. Moreover, correlation analyses were performed in the 12-month-old AβPP-PS1 animals with the hippocampal amyloid-β deposition, TBS-T soluble Aβ levels and high-molecular weight Aβ aggregate levels to gain a better understanding of the possible involvement of Aβ in neurochemical and behavioral changes, cognitive decline and neuropathological features in AβPP-PS1 transgenic mice. Our results show that at 8 months of age AβPPswe-PS1dE9 mice display behavioral and cognitive changes compared to age-matched wild-type mice, as determined in the open field and the (reverse) Morris water maze. However, there were no variations in hippocampal metabolite levels at this age. AβPP-PS1 mice at 12 months of age display more severe behavioral and cognitive impairment, which coincided with alterations in hippocampal metabolite levels that suggest reduced neuronal integrity. Furthermore, correlation analyses suggest a possible role of Aβ in inflammatory processes, synaptic dysfunction and impaired neurogenesis. PMID:23717459

  13. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

    Science.gov (United States)

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

  14. The assessment of neural injury following open heart surgery by physiological tremor analysis.

    Science.gov (United States)

    Németh, Adám; Hejjel, László; Ajtay, Zénó; Kellényi, Lóránd; Solymos, Andor; Bártfai, Imre; Kovács, Norbert; Lenkey, Zsófia; Cziráki, Attila; Szabados, Sándor

    2013-02-21

    The appearance of post-operative cognitive dysfunction as a result of open heart surgery has been proven by several studies. Focal and/or sporadic neuron damage emerging in the central nervous system may not only appear as cognitive dysfunction, but might strongly influence features of physiological tremor. We investigated 110 patients (age: 34-73 years; 76 male, 34 female; 51 coronary artery bypass grafting (CABG), 25 valve replacement, 25 combined open heart surgery, 9 off-pump CABG) before surgery and after open-heart surgery on the 3(rd) to 5(th) post-operative day. The assessment of the physiological tremor analysis was performed with our newly developed equipment based on the Analog Devices ADXL 320 JPC integrated accelerometer chip. Recordings were stored on a PC and spectral analysis was performed by fast Fourier transformation (FFT). We compared power integrals in the 1-4 Hz, 4-8 Hz and 8-12 Hz frequency ranges and these were statistically assessed by the Wilcoxon rank correlation test. We found significant changes in the power spectrum of physiological tremor. The spectrum in the 8-12 Hz range (neuronal oscillation) decreased and a shift was recognised to the lower spectrum (p open heart surgery.

  15. Neuronal coherence and its functional role in communication between neurons

    NARCIS (Netherlands)

    Zeitler-Geurds, M.

    2010-01-01

    Neuronal oscillations are observed in many brain areas in various frequency bands. Each of the frequency bands is associated with a particular functional role. Gamma oscillations (30-80 Hz) are thought to be related to cognitive tasks like memory and attention and possibly also involved in the

  16. Administration of PBN (N-tert-butyl-alfa-phenylnitrone) during status epilepticus reduces neuronal injury, improves cognitive functions but enhances epileptogenesis in immature rats

    Czech Academy of Sciences Publication Activity Database

    Kubová, Hana; Folbergrová, Jaroslava; Otáhal, Jakub; Mareš, Pavel

    2007-01-01

    Roč. 59, Suppl. 1 (2007), s. 10-10 ISSN 1734-1140. [Day of neuropsychopharmacology /16./. 06.09.2007-08.09.2007, Wroclaw] Institutional research plan: CEZ:AV0Z50110509 Keywords : PBN * status epilepticus * immature rats Subject RIV: ED - Physiology

  17. Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons.

    Science.gov (United States)

    Vila-Luna, S; Cabrera-Isidoro, S; Vila-Luna, L; Juárez-Díaz, I; Bata-García, J L; Alvarez-Cervera, F J; Zapata-Vázquez, R E; Arankowsky-Sandoval, G; Heredia-López, F; Flores, G; Góngora-Alfaro, J L

    2012-01-27

    Chronic caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer's disease. Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive decline that male Wistar rats experience from young (≈3 months) to middle age (≈10 months). When animals were young they were evaluated at weekly intervals in three tests: motor activity habituation in the open field (30-min sessions at the same time on consecutive days), continuous spontaneous alternation in the Y-maze (8 min), and elevated plus-maze (5 min). Afterward, rats from the same litter were randomly assigned either to a caffeine-treated group (n=13) or a control group (n=11), which received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were ≈4 months old, and lasted for 6 months. Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal, a time period that is far in excess for the full excretion of a caffeine dose in this species. Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining. Compared with controls, we found that middle-aged rats that had chronically consumed low doses of caffeine (1) maintained their locomotor habituation during the second consecutive day exposure to the open field (an index of non-associative learning), (2) maintained their exploratory drive to complete the conventional minimum of nine arm visits required to calculate the alternation performance in the Y-maze in a greater proportion, (3) maintained their alternation percentage above chance level (an index of working memory), and (4) did not increase the anxiety indexes assessed by measuring the time spent in the open arms of the elevated plus maze. In addition, morphometric analysis of hippocampal neurons revealed that dendritic branching (90-140 μm from the soma), length of 4th and 5th order branches, total dendritic length, and spine density in distal dendritic branches were greater in

  18. Firing dynamics of an autaptic neuron

    International Nuclear Information System (INIS)

    Wang Heng-Tong; Chen Yong

    2015-01-01

    Autapses are synapses that connect a neuron to itself in the nervous system. Previously, both experimental and theoretical studies have demonstrated that autaptic connections in the nervous system have a significant physiological function. Autapses in nature provide self-delayed feedback, thus introducing an additional timescale to neuronal activities and causing many dynamic behaviors in neurons. Recently, theoretical studies have revealed that an autapse provides a control option for adjusting the response of a neuron: e.g., an autaptic connection can cause the electrical activities of the Hindmarsh–Rose neuron to switch between quiescent, periodic, and chaotic firing patterns; an autapse can enhance or suppress the mode-locking status of a neuron injected with sinusoidal current; and the firing frequency and interspike interval distributions of the response spike train can also be modified by the autapse. In this paper, we review recent studies that showed how an autapse affects the response of a single neuron. (topical review)

  19. Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

    Science.gov (United States)

    Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

    2014-01-01

    The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

  20. Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

    Directory of Open Access Journals (Sweden)

    Petra Maria Hermann

    2014-12-01

    Full Text Available TThe aging brain can undergo a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (peroxidation of membrane lipids and activation of phospholipase A2 (PLA2 enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the Biology of cognitive aging we (1 portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and (2 recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

  1. Promoting brain health through exercise and diet in older adults: a physiological perspective

    Science.gov (United States)

    Pialoux, Vincent; Corbett, Dale; Drogos, Lauren; Erickson, Kirk I.; Eskes, Gail A.

    2016-01-01

    Abstract The rise in incidence of age‐related cognitive impairment is a global health concern. Ageing is associated with a number of changes in the brain that, collectively, contribute to the declines in cognitive function observed in older adults. Structurally, the ageing brain atrophies as white and grey matter volumes decrease. Oxidative stress and inflammation promote endothelial dysfunction thereby hampering cerebral perfusion and thus delivery of energy substrates and nutrients. Further, the development of amyloid plaques and neurofibrillary tangles contributes to neuronal loss. Of interest, there are substantial inter‐individual differences in the degree to which these physical and functional changes impact upon cognitive function as we grow older. This review describes how engaging in physical activity and cognitive activities and adhering to a Mediterranean style diet promote ‘brain health’. From a physiological perspective, we discuss the effects of these modifiable lifestyle behaviours on the brain, and how some recent human trials are beginning to show some promise as to the effectiveness of lifestyle behaviours in combating cognitive impairment. Moreover, we propose that these lifestyle behaviours, through numerous mechanisms, serve to increase brain, cerebrovascular and cognitive reserve, thereby preserving and enhancing cognitive function for longer. PMID:27524792

  2. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  3. Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease

    Science.gov (United States)

    Kwakowsky, Andrea; Milne, Michael R.; Waldvogel, Henry J.; Faull, Richard L.

    2016-01-01

    The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease. PMID:27999310

  4. Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Andrea Kwakowsky

    2016-12-01

    Full Text Available The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2 on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease.

  5. Effects of violent video games on aggressive behavior, aggressive cognition, aggressive affect, physiological arousal, and prosocial behavior: a meta-analytic review of the scientific literature.

    Science.gov (United States)

    Anderson, C A; Bushman, B J

    2001-09-01

    Research on exposure to television and movie violence suggests that playing violent video games will increase aggressive behavior. A metaanalytic review of the video-game research literature reveals that violent video games increase aggressive behavior in children and young adults. Experimental and nonexperimental studies with males and females in laboratory and field settings support this conclusion. Analyses also reveal that exposure to violent video games increases physiological arousal and aggression-related thoughts and feelings. Playing violent video games also decreases prosocial behavior.

  6. High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

    Science.gov (United States)

    Brückner, Melanie; Lasarzik, Irina; Jahn-Eimermacher, Antje; Peetz, Dirk; Werner, Christian; Engelhard, Kristin; Thal, Serge C

    2013-09-13

    Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. The effect of partial agonist of serotonin-1A receptor on cognitive functions in animal model of schizophrenia

    OpenAIRE

    Antošová, Eliška

    2011-01-01

    Serotoin is a neurotransmitter participating in regulation of many physiologic fuctions. Main serotogenous neurons can be found in nukleus raphe of the brain stem. Nucleus raphe inervates many areas of the brain including the cerebal cortex and hipocampus. These structures are important for controling of higher cognitive functions. 5HT1A receptor is one of many subtypes of serotonin receptors and its activation inhibits iniciating of the action potencials. 5HT1A receptor is expressed presynap...

  8. Orexin neurons receive glycinergic innervations.

    Directory of Open Access Journals (Sweden)

    Mari Hondo

    Full Text Available Glycine, a nonessential amino-acid that acts as an inhibitory neurotransmitter in the central nervous system, is currently used as a dietary supplement to improve the quality of sleep, but its mechanism of action is poorly understood. We confirmed the effects of glycine on sleep/wakefulness behavior in mice when administered peripherally. Glycine administration increased non-rapid eye movement (NREM sleep time and decreased the amount and mean episode duration of wakefulness when administered in the dark period. Since peripheral administration of glycine induced fragmentation of sleep/wakefulness states, which is a characteristic of orexin deficiency, we examined the effects of glycine on orexin neurons. The number of Fos-positive orexin neurons markedly decreased after intraperitoneal administration of glycine to mice. To examine whether glycine acts directly on orexin neurons, we examined the effects of glycine on orexin neurons by patch-clamp electrophysiology. Glycine directly induced hyperpolarization and cessation of firing of orexin neurons. These responses were inhibited by a specific glycine receptor antagonist, strychnine. Triple-labeling immunofluorescent analysis showed close apposition of glycine transporter 2 (GlyT2-immunoreactive glycinergic fibers onto orexin-immunoreactive neurons. Immunoelectron microscopic analysis revealed that GlyT2-immunoreactive terminals made symmetrical synaptic contacts with somata and dendrites of orexin neurons. Double-labeling immunoelectron microscopy demonstrated that glycine receptor alpha subunits were localized in the postsynaptic membrane of symmetrical inhibitory synapses on orexin neurons. Considering the importance of glycinergic regulation during REM sleep, our observations suggest that glycine injection might affect the activity of orexin neurons, and that glycinergic inhibition of orexin neurons might play a role in physiological sleep regulation.

  9. Physiological parameters

    International Nuclear Information System (INIS)

    Natera, E.S.

    1998-01-01

    The physiological characteristics of man depend on the intake, metabolism and excretion of stable elements from food, water, and air. The physiological behavior of natural radionuclides and radionuclides from nuclear weapons testing and from the utilization of nuclear energy is believed to follow the pattern of stable elements. Hence information on the normal physiological processes occurring in the human body plays an important role in the assessment of the radiation dose received by man. Two important physiological parameters needed for internal dose determination are the pulmonary function and the water balance. In the Coordinated Research Programme on the characterization of Asian population, five participants submitted data on these physiological characteristics - China, India, Japan, Philippines and Viet Nam. During the CRP, data on other pertinent characteristics such as physical and dietary were simultaneously being collected. Hence, the information on the physiological characteristics alone, coming from the five participants were not complete and are probably not sufficient to establish standard values for the Reference Asian Man. Nonetheless, the data collected is a valuable contribution to this research programme

  10. Electromagnetic radiation-2450 MHz exposure causes cognition ...

    Indian Academy of Sciences (India)

    83

    Electromagnetic radiation-2450 MHz exposure causes cognition deficit with mitochondrial. 1 ... decrease in levels of acetylcholine, and increase in activity of acetyl ...... neuronal apoptosis and cognitive disturbances in sevoflurane or propofol ...

  11. Mirror neurons and language in schizophrenia

    OpenAIRE

    Bendová, Marie

    2016-01-01

    Mirror neurons are a specific kind of visuomotor neurons that are involved in action execution and also in action perception. The mirror mechanism is linked to a variety of complex psychological functions such as social-cognitive functions and language. People with schizophrenia have often difficulties both in mirror neuron system and in language skills. In the first part of our research we studied the connectivity of mirror neuron areas (such as IFG, STG, PMC, SMC and so on) by fMRI in resti...

  12. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  13. Physiological slowing and upregulation of inhibition in cortex are correlated with behavioral deficits in protein malnourished rats.

    Directory of Open Access Journals (Sweden)

    Rahul Chaudhary

    Full Text Available Protein malnutrition during early development has been correlated with cognitive and learning disabilities in children, but the neuronal deficits caused by long-term protein deficiency are not well understood. We exposed rats from gestation up to adulthood to a protein-deficient (PD diet, to emulate chronic protein malnutrition in humans. The offspring exhibited significantly impaired performance on the 'Gap-crossing' (GC task after reaching maturity, a behavior that has been shown to depend on normal functioning of the somatosensory cortex. The physiological state of the somatosensory cortex was examined to determine neuronal correlates of the deficits in behavior. Extracellular multi-unit recording from layer 4 (L4 neurons that receive direct thalamocortical inputs and layers 2/3 (L2/3 neurons that are dominated by intracortical connections in the whisker-barrel cortex of PD rats exhibited significantly low spontaneous activity and depressed responses to whisker stimulation. L4 neurons were more severely affected than L2/3 neurons. The response onset was significantly delayed in L4 cells. The peak response latency of L4 and L2/3 neurons was delayed significantly. In L2/3 and L4 of the barrel cortex there was a substantial increase in GAD65 (112% over controls and much smaller increase in NMDAR1 (12-20%, suggesting enhanced inhibition in the PD cortex. These results show that chronic protein deficiency negatively affects both thalamo-cortical and cortico-cortical transmission during somatosensory information processing. The findings support the interpretation that sustained protein deficiency interferes with features of cortical sensory processing that are likely to underlie the cognitive impairments reported in humans who have suffered from prolonged protein deficiency.

  14. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  15. Mathematical physiology

    CERN Document Server

    Sneyd, James

    2009-01-01

    There has been a long history of interaction between mathematics and physiology. This book looks in detail at a wide selection of mathematical models in physiology, showing how physiological problems can be formulated and studied mathematically, and how such models give rise to interesting and challenging mathematical questions. With its coverage of many recent models it gives an overview of the field, while many older models are also discussed, to put the modern work in context. In this second edition the coverage of basic principles has been expanded to include such topics as stochastic differential equations, Markov models and Gibbs free energy, and the selection of models has also been expanded to include some of the basic models of fluid transport, respiration/perfusion, blood diseases, molecular motors, smooth muscle, neuroendrocine cells, the baroreceptor loop, turboglomerular oscillations, blood clotting and the retina. Owing to this extensive coverage, the second edition is published in two volumes. ...

  16. Physiological pseudomyopia.

    Science.gov (United States)

    Jones, R

    1990-08-01

    Objective refraction through plus fogging lenses and base-in prisms revealed that normally accommodation is not completely relaxed when the stimulus to accommodation is zero. The myopic shift in the refractive error due to this focus error of accommodation was defined as physiological pseudomyopia. Two previously established features of accommodation are responsible for this behavior: (1) accommodation acts as a proportional control system for steady-state responses; and (2) the rest focus of accommodation is nonzero. It is proposed that the hyperopic shift in refraction observed in cycloplegia is the result of elimination of physiological pseudomyopia.

  17. Neurochemical pathways that converge on thalamic trigeminovascular neurons: potential substrate for modulation of migraine by sleep, food intake, stress and anxiety.

    Directory of Open Access Journals (Sweden)

    Rodrigo Noseda

    Full Text Available Dynamic thalamic regulation of sensory signals allows the cortex to adjust better to rapidly changing behavioral, physiological and environmental demands. To fulfill this role, thalamic neurons must themselves be subjected to constantly changing modulatory inputs that originate in multiple neurochemical pathways involved in autonomic, affective and cognitive functions. Our overall goal is to define an anatomical framework for conceptualizing how a 'decision' is made on whether a trigeminovascular thalamic neuron fires, for how long, and at what frequency. To begin answering this question, we determine which neuropeptides/neurotransmitters are in a position to modulate thalamic trigeminovascular neurons. Using a combination of in-vivo single-unit recording, juxtacellular labeling with tetramethylrhodamine dextran (TMR and in-vitro immunohistochemistry, we found that thalamic trigeminovascular neurons were surrounded by high density of axons containing biomarkers of glutamate, GABA, dopamine and serotonin; moderate density of axons containing noradrenaline and histamine; low density of axons containing orexin and melanin concentrating hormone (MCH; but not axons containing CGRP, serotonin 1D receptor, oxytocin or vasopressin. In the context of migraine, the findings suggest that the transmission of headache-related nociceptive signals from the thalamus to the cortex may be modulated by opposing forces (i.e., facilitatory, inhibitory that are governed by continuous adjustments needed to keep physiological, behavioral, cognitive and emotional homeostasis.

  18. Exercise physiology

    DEFF Research Database (Denmark)

    Kiens, Bente; Richter, Erik; Wojtaszewski, Jørgen

    2014-01-01

    The passing of Professor Bengt Saltin on September 12, 2014 truly marks the end of an era. As editor of the Journal of Applied Physiology and one of Bengt’s many collaborators and colleagues, I wanted the Journal to celebrate his many seminal contributions by means of an Editorial. Professor Bent...

  19. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

    Science.gov (United States)

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

    2015-05-19

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

  20. Protocol for culturing low density pure rat hippocampal neurons supported by mature mixed neuron cultures.

    Science.gov (United States)

    Yang, Qian; Ke, Yini; Luo, Jianhong; Tang, Yang

    2017-02-01

    primary hippocampal neuron cultures allow for subcellular morphological dissection, easy access to drug treatment and electrophysiology analysis of individual neurons, and is therefore an ideal model for the study of neuron physiology. While neuron and glia mixed cultures are relatively easy to prepare, pure neurons are particular hard to culture at low densities which are suitable for morphology studies. This may be due to a lack of neurotrophic factors such as brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and Glial cell line-derived neurotrophic factor (GDNF). In this study we used a two step protocol in which neuron-glia mixed cultures were initially prepared for maturation to support the growth of young neurons plated at very low densities. Our protocol showed that neurotrophic support resulted in physiologically functional hippocampal neurons with larger cell body, increased neurite length and decreased branching and complexity compared to cultures prepared using a conventional method. Our protocol provides a novel way to culture highly uniformed hippocampal neurons for acquiring high quality, neuron based data. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release.

    Science.gov (United States)

    Rau, Andrew R; Hentges, Shane T

    2017-08-02

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these

  2. Functional magnetic resonance imaging study of neuronal activation during cognitive tasks related to frontal lobe functions in patients with obsessive-compulsive disorder

    International Nuclear Information System (INIS)

    Koizumi, Hazuki

    2010-01-01

    Previous neurological studies and brain activation studies using functional magnetic resonance imaging (f-MRI) have suggested frontal lobe dysfunctions in patients with obsessive-compulsive disorder (OCD). However, no f-MRI study has used cognitive tasks reflecting fluency of ideas and memory related to frontal lobe functions. The purposes of this study are to assess the neuropsychological examinations and brain activities of OCD patients using f-MRI, as well as, to investigate the relationship between the severity of obsessive-compulsive symptoms and frontal lobe functions. The subjects were 22 right-handed persons consisting of 11 outpatients who had received a diagnosis of OCD based on diagnostic and statistical manual of mental disorders-fourth edition (DMS-IV) and age- and sex-matched 11 healthy controls. All subjects were examined using Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Wechsler Adult Intelligence Scale-3 rd edition (WAIS-III), Wisconsin Card Sorting Test (WCST), Modified Stroop Test (MST), Verbal Fluency Test (VFT), Idea Fluency Test (IFT), and Rey-Auditory Verbal Learning Test (RAVLT). The brain activities were measured with f-MRI during three cognitive tasks; Task 1: idea generation (IFT), Task 2: word generation (VFT), and Task 3: remembrance of words (RAVLT). The block design was used in the trials, in which rest and activating tasks were alternated for five times in each task. The neuropsychological examinations revealed significant differences in the numbers of categories achieved and total errors in WCST, times of Part I in MST, scores of VFT and IFT, and the results of RAVLT between the OCD patients and healthy controls. Using functional brain imaging with f-MRI, noticeable activations were found in the superior, middle, inferior frontal gyri, and the cingulate gyrus during all tasks in both the OCD and control groups. The OCD patients had significantly higher activation in the cingulate gyrus than normal controls during Task 1 (IFT

  3. Environmental physiology

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Summaries of research projects conducted during 1978 and 1979 are presented. Subject areas include: the effects of environmental pollutants on homeostasis of the hematopoietic system; pollutant effects on steroid metabolism; pollutant effects on pulmonary macrophages; effects of toxic gases on lung cells; the development of immunological methods for assessing lung damage at the cellular level; the response of erythropoietin concentration to various physiological changes; and the study of actinide metabolism in monkey skeletons

  4. Cholinergic modulation of cognitive processing: insights drawn from computational models

    Directory of Open Access Journals (Sweden)

    Ehren L Newman

    2012-06-01

    Full Text Available Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm play a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers.

  5. Nitric oxide: a physiologic messenger.

    Science.gov (United States)

    Lowenstein, C J; Dinerman, J L; Snyder, S H

    1994-02-01

    To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.

  6. Selective visual attention to drive cognitive brain machine interfaces: from concepts to neurofeedback and rehabilitation applications

    Directory of Open Access Journals (Sweden)

    Elaine eAstrand

    2014-08-01

    Full Text Available Brain Machine Interfaces (BMI using motor cortical activity to drive an external effector like a screen cursor or a robotic arm have seen enormous success and proven their great rehabilitation potential. An emerging parallel effort is now directed to BMIs controlled by endogenous cognitive activity, also called cognitive BMIs. While more challenging, this approach opens new dimensions to the rehabilitation of cognitive disorders. In the present work, we focus on BMIs driven by visuospatial attention signals and we provide a critical review of these studies in the light of the accumulated knowledge about the psychophysics, anatomy and neurophysiology of visual spatial attention. Importantly, we provide a unique comparative overview of the several studies, ranging from noninvasive to invasive human and non-human primates studies, that decode attention-related information from ongoing neuronal activity. We discuss these studies in the light of the challenges attention-driven cognitive BMIs have to face. In a second part of the review, we discuss past and current attention-based neurofeedback studies, describing both the covert effects of neurofeedback onto neuronal activity and its overt behavioral effects. Importantly, we compare neurofeedback studies based on the amplitude of cortical activity to studies based on the enhancement of cortical information content. Last, we discuss several lines of future research and applications for attention-driven cognitive BCIs, including the rehabilitation of cognitive deficits, restored communication in locked-in patients, and open-field applications for enhanced cognition in normal subjects. The core motivation of this work is the key idea that the improvement of current cognitive BMIs for therapeutic and open field applications needs to be grounded in a proper interdisciplinary understanding of the physiology of the cognitive function of interest, be it spatial attention, working memory or any other

  7. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  8. Triple-aspect monism: physiological, mental unconscious and conscious aspects of brain activity.

    Science.gov (United States)

    Pereira, Alfredo

    2014-06-01

    Brain activity contains three fundamental aspects: (a) The physiological aspect, covering all kinds of processes that involve matter and/or energy; (b) the mental unconscious aspect, consisting of dynamical patterns (i.e., frequency, amplitude and phase-modulated waves) embodied in neural activity. These patterns are variously operated (transmitted, stored, combined, matched, amplified, erased, etc), forming cognitive and emotional unconscious processes and (c) the mental conscious aspect, consisting of feelings experienced in the first-person perspective and cognitive functions grounded in feelings, as memory formation, selection of the focus of attention, voluntary behavior, aesthetical appraisal and ethical judgment. Triple-aspect monism (TAM) is a philosophical theory that provides a model of the relation of the three aspects. Spatially distributed neuronal dendritic potentials generate amplitude-modulated waveforms transmitted to the extracellular medium and adjacent astrocytes, prompting the formation of large waves in the astrocyte network, which are claimed to both integrate distributed information and instantiate feelings. According to the valence of the feeling, the large wave feeds back on neuronal synapses, modulating (reinforcing or depressing) cognitive and behavioral functions.

  9. Mirror Neurons from Associative Learning

    OpenAIRE

    Catmur, Caroline; Press, Clare; Heyes, Cecilia

    2016-01-01

    Mirror neurons fire both when executing actions and observing others perform similar actions. Their sensorimotor matching properties have generally been considered a genetic adaptation for social cognition; however, in the present chapter we argue that the evidence in favor of this account is not compelling. Instead we present evidence supporting an alternative account: that mirror neurons’ matching properties arise from associative learning during individual development. Notably, this proces...

  10. Occupational physiology

    CERN Document Server

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  11. Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function.

    Science.gov (United States)

    Vannini, Eleonora; Olimpico, Francesco; Middei, Silvia; Ammassari-Teule, Martine; de Graaf, Erik L; McDonnell, Liam; Schmidt, Gudula; Fabbri, Alessia; Fiorentini, Carla; Baroncelli, Laura; Costa, Mario; Caleo, Matteo

    2016-12-01

    Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle- and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. "Is all the stuff about neurons necessary?" The development of lay summaries to disseminate findings from the Newcastle Cognitive Function after Stroke (COGFAST) study.

    Science.gov (United States)

    Barnfield, Sarah; Pitts, Alison Clara; Kalaria, Raj; Allan, Louise; Tullo, Ellen

    2017-01-01

    Why did we do this study? It can be difficult for scientists to communicate their research findings to the public. This is partly due to the complexity of translating scientific language into words that the public understand. Further, it may be hard for the public to find out about and locate information about research studies. We aimed to adapt some scientific articles about the links between dementia and stroke into lay summaries to be displayed online for the general public. How did we do it? We collaborated with five people from a volunteer organisation, VOICENorth. They took part in two group discussions about studies reporting on the link between dementia and stroke, and selected four studies to translate into lay summaries and display on a website. We discussed the layout and language of the summaries and made adaptations to make them more understandable to the general public. What did we find? We were able to work with members of the public to translate research findings into lay summaries suitable for a general audience. We made changes to language and layout including the use of 'question and answer' style layouts, the addition of a reference list of scientific terms, and removing certain words. What does this mean? Working with members of the public is a realistic way to create resources that improve the accessibility of research findings to the wider public. Background Scientific research is often poorly understood by the general public and difficult for them to access. This presents a major barrier to disseminating and translating research findings. Stroke and dementia are both major public health issues, and research has shown lifestyle measures help to prevent them. This project aimed to select a series of studies from the Newcastle Cognitive Function after Stroke cohort (COGFAST) and create lay summaries comprehensible and accessible to the public. Methods We used a focus group format to collaborate with five members of the public to review COGFAST

  13. A Simple Picaxe Microcontroller Pulse Source for Juxtacellular Neuronal Labelling.

    Science.gov (United States)

    Verberne, Anthony J M

    2016-10-19

    Juxtacellular neuronal labelling is a method which allows neurophysiologists to fill physiologically-identified neurons with small positively-charged marker molecules. Labelled neurons are identified by histochemical processing of brain sections along with immunohistochemical identification of neuropeptides, neurotransmitters, neurotransmitter transporters or biosynthetic enzymes. A microcontroller-based pulser circuit and associated BASIC software script is described for incorporation into the design of a commercially-available intracellular electrometer for use in juxtacellular neuronal labelling. Printed circuit board construction has been used for reliability and reproducibility. The current design obviates the need for a separate digital pulse source and simplifies the juxtacellular neuronal labelling procedure.

  14. Timing control by redundant inhibitory neuronal circuits

    Energy Technology Data Exchange (ETDEWEB)

    Tristan, I., E-mail: itristan@ucsd.edu; Rulkov, N. F.; Huerta, R.; Rabinovich, M. [BioCircuits Institute, University of California, San Diego, La Jolla, California 92093-0402 (United States)

    2014-03-15

    Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model.

  15. Chromatin Regulation of Neuronal Maturation and Plasticity.

    Science.gov (United States)

    Gallegos, David A; Chan, Urann; Chen, Liang-Fu; West, Anne E

    2018-05-01

    Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss how mechanisms of chromatin regulation help to orchestrate the transcriptional programs that underlie the maturation of developing neurons and the plasticity of adult neurons. We review how chromatin regulation acts locally to modulate the expression of specific genes and more broadly to coordinate gene expression programs during transitions between cellular states. These data highlight the importance of epigenetic transcriptional mechanisms in postmitotic neurons. We suggest areas where emerging methods may advance understanding in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Timing control by redundant inhibitory neuronal circuits

    International Nuclear Information System (INIS)

    Tristan, I.; Rulkov, N. F.; Huerta, R.; Rabinovich, M.

    2014-01-01

    Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model

  17. A map of taste neuron projections in the Drosophila CNS

    Indian Academy of Sciences (India)

    2014-07-08

    Jul 8, 2014 ... information that they represent. The extensive ... physiology and behaviour in the wild type and in these mutants .... taste information is processed in the CNS. 2. ..... gene affecting the specificity of the chemosensory neurons of.

  18. Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting.

    Science.gov (United States)

    Morozova, Ekaterina O; Myroshnychenko, Maxym; Zakharov, Denis; di Volo, Matteo; Gutkin, Boris; Lapish, Christopher C; Kuznetsov, Alexey

    2016-10-01

    In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca 2+ ) concentration, thus reducing the Ca 2+ -dependent potassium (K + ) current. In this way, the GABA-mediated hyperpolarization replaces Ca 2+ -dependent K + current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally. Copyright © 2016 the American Physiological Society.

  19. Spectral fingerprints of large-scale neuronal interactions

    NARCIS (Netherlands)

    Siegel, M.; Donner, T.H.; Engel, A.K.

    2012-01-01

    Cognition results from interactions among functionally specialized but widely distributed brain regions; however, neuroscience has so far largely focused on characterizing the function of individual brain regions and neurons therein. Here we discuss recent studies that have instead investigated the

  20. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

    OpenAIRE

    Merkle, Florian T.; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F.

    2015-01-01

    Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin...

  1. Space Physiology within an Exercise Physiology Curriculum

    Science.gov (United States)

    Carter, Jason R.; West, John B.

    2013-01-01

    Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of…

  2. Mirror neurons: functions, mechanisms and models.

    Science.gov (United States)

    Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael A

    2013-04-12

    Mirror neurons for manipulation fire both when the animal manipulates an object in a specific way and when it sees another animal (or the experimenter) perform an action that is more or less similar. Such neurons were originally found in macaque monkeys, in the ventral premotor cortex, area F5 and later also in the inferior parietal lobule. Recent neuroimaging data indicate that the adult human brain is endowed with a "mirror neuron system," putatively containing mirror neurons and other neurons, for matching the observation and execution of actions. Mirror neurons may serve action recognition in monkeys as well as humans, whereas their putative role in imitation and language may be realized in human but not in monkey. This article shows the important role of computational models in providing sufficient and causal explanations for the observed phenomena involving mirror systems and the learning processes which form them, and underlines the need for additional circuitry to lift up the monkey mirror neuron circuit to sustain the posited cognitive functions attributed to the human mirror neuron system. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Where do mirror neurons come from?

    Science.gov (United States)

    Heyes, Cecilia

    2010-03-01

    Debates about the evolution of the 'mirror neuron system' imply that it is an adaptation for action understanding. Alternatively, mirror neurons may be a byproduct of associative learning. Here I argue that the adaptation and associative hypotheses both offer plausible accounts of the origin of mirror neurons, but the associative hypothesis has three advantages. First, it provides a straightforward, testable explanation for the differences between monkeys and humans that have led some researchers to question the existence of a mirror neuron system. Second, it is consistent with emerging evidence that mirror neurons contribute to a range of social cognitive functions, but do not play a dominant, specialised role in action understanding. Finally, the associative hypothesis is supported by recent data showing that, even in adulthood, the mirror neuron system can be transformed by sensorimotor learning. The associative account implies that mirror neurons come from sensorimotor experience, and that much of this experience is obtained through interaction with others. Therefore, if the associative account is correct, the mirror neuron system is a product, as well as a process, of social interaction. (c) 2009 Elsevier Ltd. All rights reserved.

  4. Zolpidem Reduces Hippocampal Neuronal Activity in Freely Behaving Mice: A Large Scale Calcium Imaging Study with Miniaturized Fluorescence Microscope

    Science.gov (United States)

    Berdyyeva, Tamara; Otte, Stephani; Aluisio, Leah; Ziv, Yaniv; Burns, Laurie D.; Dugovic, Christine; Yun, Sujin; Ghosh, Kunal K.; Schnitzer, Mark J.; Lovenberg, Timothy; Bonaventure, Pascal

    2014-01-01

    Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal’s state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼65%) significantly decreasing the rate of calcium transients, and a small subset (3%) showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders. PMID:25372144

  5. Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large scale calcium imaging study with miniaturized fluorescence microscope.

    Directory of Open Access Journals (Sweden)

    Tamara Berdyyeva

    Full Text Available Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65% significantly decreasing the rate of calcium transients, and a small subset (3% showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

  6. Numbers, Neurons and Tides, Oh My!

    Science.gov (United States)

    Ortiz, Mary Theresa

    2006-01-01

    Mathematical applications to biology are presented in Anatomy & Physiology, General and Marine Biology. Body measurements and anatomical terminology are integrated, and problems involving neuron conduction speed, red blood cells, hemoglobin and glomerular filtration presented. General Biology applications include trans-membrane potential and…

  7. Managing Brain Extracellular K(+) during Neuronal Activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Stoica, Anca; MacAulay, Nanna

    2016-01-01

    characteristics required to fulfill their distinct physiological roles in clearance of K(+) from the extracellular space in the face of neuronal activity. Understanding the nature, impact and effects of the various Na(+)/K(+)-ATPase isoform combinations in K(+) management in the central nervous system might...... understanding of the pathological events occurring during disease....

  8. Modulation of neuronal network activity with ghrelin

    NARCIS (Netherlands)

    Stoyanova, Irina; Rutten, Wim; le Feber, Jakob

    2012-01-01

    Ghrelin is a neuropeptide regulating multiple physiological processes, including high brain functions such as learning and memory formation. However, the effect of ghrelin on network activity patterns and developments has not been studied yet. Therefore, we used dissociated cortical neurons plated

  9. Physiological Indicators of Workload in a Remotely Piloted Aircraft Simulation

    Science.gov (United States)

    2015-10-01

    cognitive workload. That is, both cognitive underload and overload can negatively impact performance (Young & Stanton, 2002). One solution to...Report contains color. 14. ABSTRACT Toward preventing performance decrements associated with mental overload in remotely piloted aircraft (RPA...operations, the current research investigated the feasibility of using physiological measures to assess cognitive workload. Two RPA operators were

  10. Behavioral Modulation by Spontaneous Activity of Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    Toshiharu Ichinose

    2017-12-01

    Full Text Available Dopamine modulates a variety of animal behaviors that range from sleep and learning to courtship and aggression. Besides its well-known phasic firing to natural reward, a substantial number of dopamine neurons (DANs are known to exhibit ongoing intrinsic activity in the absence of an external stimulus. While accumulating evidence points at functional implications for these intrinsic “spontaneous activities” of DANs in cognitive processes, a causal link to behavior and its underlying mechanisms has yet to be elucidated. Recent physiological studies in the model organism Drosophila melanogaster have uncovered that DANs in the fly brain are also spontaneously active, and that this activity reflects the behavioral/internal states of the animal. Strikingly, genetic manipulation of basal DAN activity resulted in behavioral alterations in the fly, providing critical evidence that links spontaneous DAN activity to behavioral states. Furthermore, circuit-level analyses have started to reveal cellular and molecular mechanisms that mediate or regulate spontaneous DAN activity. Through reviewing recent findings in different animals with the major focus on flies, we will discuss potential roles of this physiological phenomenon in directing animal behaviors.

  11. Endocannabinoids mediate neuron-astrocyte communication.

    Science.gov (United States)

    Navarrete, Marta; Araque, Alfonso

    2008-03-27

    Cannabinoid receptors play key roles in brain function, and cannabinoid effects in brain physiology and drug-related behavior are thought to be mediated by receptors present in neurons. Neuron-astrocyte communication relies on the expression by astrocytes of neurotransmitter receptors. Yet, the expression of cannabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication remain largely unknown. We show that hippocampal astrocytes express CB1 receptors that upon activation lead to phospholipase C-dependent Ca2+ mobilization from internal stores. These receptors are activated by endocannabinoids released by neurons, increasing astrocyte Ca2+ levels, which stimulate glutamate release that activates NMDA receptors in pyramidal neurons. These results demonstrate the existence of endocannabinoid-mediated neuron-astrocyte communication, revealing that astrocytes are targets of cannabinoids and might therefore participate in the physiology of cannabinoid-related addiction. They also reveal the existence of an endocannabinoid-glutamate signaling pathway where astrocytes serve as a bridge for nonsynaptic interneuronal communication.

  12. Drawing on student knowledge in human anatomy and physiology

    Science.gov (United States)

    Slominski, Tara Nicole

    Prior to instruction, students may have developed alternative conceptions about the mechanics behind human physiology. To help students re-shape these ideas into correct reasoning, the faulty characteristics reinforcing the alternative conceptions need to made explicit. This study used student-generated drawings to expose alternative conceptions Human Anatomy and Physiology students had prior to instruction on neuron physiology. Specifically, we investigated how students thought about neuron communication across a synapse (n=355) and how neuron activity can be modified (n=311). When asked to depict basic communication between two neurons, at least 80% of students demonstrated incorrect ideas about synaptic transmission. When targeting spatial and temporal summation, only eleven students (3.5%) were able to accurately depict at least one form of summation. In response to both drawing questions, student drawings revealed multiple alternative conceptions that resulted in a deeper analysis and characterization of the wide variation of student ideas.

  13. The Hypocretin/Orexin Neuronal Networks in Zebrafish.

    Science.gov (United States)

    Elbaz, Idan; Levitas-Djerbi, Talia; Appelbaum, Lior

    2017-01-01

    The hypothalamic Hypocretin/Orexin (Hcrt) neurons secrete two Hcrt neuropeptides. These neurons and peptides play a major role in the regulation of feeding, sleep wake cycle, reward-seeking, addiction, and stress. Loss of Hcrt neurons causes the sleep disorder narcolepsy. The zebrafish has become an attractive model to study the Hcrt neuronal network because it is a transparent vertebrate that enables simple genetic manipulation, imaging of the structure and function of neuronal circuits in live animals, and high-throughput monitoring of behavioral performance during both day and night. The zebrafish Hcrt network comprises ~16-60 neurons, which similar to mammals, are located in the hypothalamus and widely innervate the brain and spinal cord, and regulate various fundamental behaviors such as feeding, sleep, and wakefulness. Here we review how the zebrafish contributes to the study of the Hcrt neuronal system molecularly, anatomically, physiologically, and pathologically.

  14. Coupling Perception with Actions via Mirror Neurons

    Czech Academy of Sciences Publication Activity Database

    Wiedermann, Jiří

    č. 55 (2003), s. 11-12 ISSN 0926-4981 R&D Projects: GA ČR GA201/02/1456 Institutional research plan: AV0Z1030915 Keywords : mirror neurons * cognitive agents * neural nets Subject RIV: BA - General Mathematics http://www.ercim.eu/publication/Ercim_News/enw55/wiedermann.html

  15. Unbroken Mirror Neurons in Autism Spectrum Disorders

    Science.gov (United States)

    Fan, Yang-Teng; Decety, Jean; Yang, Chia-Yen; Liu, Ji-Lin; Cheng, Yawei

    2010-01-01

    Background: The "broken mirror" theory of autism, which proposes that a dysfunction of the human mirror neuron system (MNS) is responsible for the core social and cognitive deficits in individuals with autism spectrum disorders (ASD), has received considerable attention despite weak empirical evidence. Methods: In this electroencephalographic…

  16. Autoimmunity as a Driving Force of Cognitive Evolution

    Directory of Open Access Journals (Sweden)

    Serge Nataf

    2017-10-01

    Full Text Available In the last decades, increasingly robust experimental approaches have formally demonstrated that autoimmunity is a physiological process involved in a large range of functions including cognition. On this basis, the recently enunciated “brain superautoantigens” theory proposes that autoimmunity has been a driving force of cognitive evolution. It is notably suggested that the immune and nervous systems have somehow co-evolved and exerted a mutual selection pressure benefiting to both systems. In this two-way process, the evolutionary-determined emergence of neurons expressing specific immunogenic antigens (brain superautoantigens has exerted a selection pressure on immune genes shaping the T-cell repertoire. Such a selection pressure on immune genes has translated into the emergence of a finely tuned autoimmune T-cell repertoire that promotes cognition. In another hand, the evolutionary-determined emergence of brain-autoreactive T-cells has exerted a selection pressure on neural genes coding for brain superautoantigens. Such a selection pressure has translated into the emergence of a neural repertoire (defined here as the whole of neurons, synapses and non-neuronal cells involved in cognitive functions expressing brain superautoantigens. Overall, the brain superautoantigens theory suggests that cognitive evolution might have been primarily driven by internal cues rather than external environmental conditions. Importantly, while providing a unique molecular connection between neural and T-cell repertoires under physiological conditions, brain superautoantigens may also constitute an Achilles heel responsible for the particular susceptibility of Homo sapiens to “neuroimmune co-pathologies” i.e., disorders affecting both neural and T-cell repertoires. These may notably include paraneoplastic syndromes, multiple sclerosis as well as autism, schizophrenia and neurodegenerative diseases. In the context of this theoretical frame, a specific

  17. Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    2015-06-01

    Conclusion: DMH cholinergic neurons directly send efferent signals to sympathetic premotor neurons in the Rpa. Elevated cholinergic input to this area reduces BAT activity through activation of M2 mAChRs on serotonergic neurons. Therefore, the direct DMHACh–Rpa5-HT pathway may mediate physiological heat-defense responses to elevated environmental temperature.

  18. Memory deficits with intact cognitive control in the methylazoxymethanol acetate (MAM) exposure model of neurodevelopmental insult.

    Science.gov (United States)

    O'Reilly, Kally C; Perica, Maria I; Fenton, André A

    2016-10-01

    Cognitive impairments are amongst the most debilitating deficits of schizophrenia and the best predictor of functional outcome. Schizophrenia is hypothesized to have a neurodevelopmental origin, making animal models of neurodevelopmental insult important for testing predictions that early insults will impair cognitive function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17 display morphological, physiological and behavioral abnormalities relevant to schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We examined brain activity in MAM rats by histochemically assessing cytochrome oxidase enzyme activity, a metabolic marker of neuronal activity. To assess cognition, we used a hippocampus-dependent two-frame active place avoidance paradigm to examine learning and spatial memory, as well as cognitive control and flexibility using the same environment and evaluating the same set of behaviors. We confirmed that adult MAM rats have altered hippocampal morphology and brain function, and that they are hyperactive in an open field. The latter likely indicates MAM rats have a sensorimotor gating deficit that is common to many animal models used for schizophrenia research. On first inspection, cognitive control seems impaired in MAM rats, indicated by more errors during the two-frame active place avoidance task. Because MAM rats are hyperactive throughout place avoidance training, we considered the possibility that the hyperlocomotion may account for the apparent cognitive deficits. These deficits were reduced on the basis of measures of cognitive performance that account for motor activity differences. However, though other aspects of memory are intact, the ability of MAM rats to express trial-to-trial memory is delayed compared to control rats. These findings suggest that spatial learning and cognitive abilities are largely intact, that the most prominent cognitive deficit is specific to acquiring memory in the MAM

  19. Activating mitochondrial function and haemoglobin expression with EH-201, an inducer of erythropoietin in neuronal cells, reverses memory impairment.

    Science.gov (United States)

    Horng, Lin-Yea; Hsu, Pei-Lun; Chen, Li-Wen; Tseng, Wang-Zou; Hsu, Kai-Tin; Wu, Chia-Ling; Wu, Rong-Tsun

    2015-10-01

    Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood-brain barrier, we tested EH-201 (2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury. The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201. EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

  20. Activation of different neural precursor populations in the adult hippocampus: does this lead to new neurons with discrete functions?

    Science.gov (United States)

    Jhaveri, Dhanisha J; Taylor, Chanel J; Bartlett, Perry F

    2012-07-01

    Resident populations of stem and precursor cells drive the production of new neurons in the adult hippocampus. Recent discoveries have highlighted that a large proportion of these precursor cells are in fact quiescent and can be activated by distinct neuronal activity under both normal physiological and pathological conditions. As growing evidence indicates that newborn neurons play a critical role in cognitive functions such as learning and memory and in mood regulation, it is paramount that we obtain a better understanding of how the reservoirs of stem and precursor cells are maintained and activated. In this review, we critically examine the roles of key molecular mechanisms that have been shown to regulate hippocampal precursor cells, especially their activation. We believe that understanding the mechanistic details of the activity-driven regulation of precursor cells will equip us with the ability to develop tailored strategies to trigger the generation of new neurons, thereby improving the functional outcomes in various neurological and psychiatric conditions. Copyright © 2012 Wiley Periodicals, Inc.

  1. Mirror neurons: from origin to function.

    Science.gov (United States)

    Cook, Richard; Bird, Geoffrey; Catmur, Caroline; Press, Clare; Heyes, Cecilia

    2014-04-01

    This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively observes a similar action performed by another agent. It is widely believed that mirror neurons are a genetic adaptation for action understanding; that they were designed by evolution to fulfill a specific socio-cognitive function. In contrast, we argue that mirror neurons are forged by domain-general processes of associative learning in the course of individual development, and, although they may have psychological functions, they do not necessarily have a specific evolutionary purpose or adaptive function. The evidence supporting this view shows that (1) mirror neurons do not consistently encode action "goals"; (2) the contingency- and context-sensitive nature of associative learning explains the full range of mirror neuron properties; (3) human infants receive enough sensorimotor experience to support associative learning of mirror neurons ("wealth of the stimulus"); and (4) mirror neurons can be changed in radical ways by sensorimotor training. The associative account implies that reliable information about the function of mirror neurons can be obtained only by research based on developmental history, system-level theory, and careful experimentation.

  2. Biophysical properties and computational modeling of calcium spikes in serotonergic neurons of the dorsal raphe nucleus.

    Science.gov (United States)

    Tuckwell, Henry C

    2013-06-01

    Serotonergic neurons of the dorsal raphe nuclei, with their extensive innervation of nearly the whole brain have important modulatory effects on many cognitive and physiological processes. They play important roles in clinical depression and other psychiatric disorders. In order to quantify the effects of serotonergic transmission on target cells it is desirable to construct computational models and to this end these it is necessary to have details of the biophysical and spike properties of the serotonergic neurons. Here several basic properties are reviewed with data from several studies since the 1960s to the present. The quantities included are input resistance, resting membrane potential, membrane time constant, firing rate, spike duration, spike and afterhyperpolarization (AHP) amplitude, spike threshold, cell capacitance, soma and somadendritic areas. The action potentials of these cells are normally triggered by a combination of sodium and calcium currents which may result in autonomous pacemaker activity. We here analyse the mechanisms of high-threshold calcium spikes which have been demonstrated in these cells the presence of TTX (tetrodotoxin). The parameters for calcium dynamics required to give calcium spikes are quite different from those for regular spiking which suggests the involvement of restricted parts of the soma-dendritic surface as has been found, for example, in hippocampal neurons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation.

    Science.gov (United States)

    Fröhlich, Dominik; Kuo, Wen Ping; Frühbeis, Carsten; Sun, Jyh-Jang; Zehendner, Christoph M; Luhmann, Heiko J; Pinto, Sheena; Toedling, Joern; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

    2014-09-26

    Exosomes are small membranous vesicles of endocytic origin that are released by almost every cell type. They exert versatile functions in intercellular communication important for many physiological and pathological processes. Recently, exosomes attracted interest with regard to their role in cell-cell communication in the nervous system. We have shown that exosomes released from oligodendrocytes upon stimulation with the neurotransmitter glutamate are internalized by neurons and enhance the neuronal stress tolerance. Here, we demonstrate that oligodendroglial exosomes also promote neuronal survival during oxygen-glucose deprivation, a model of cerebral ischaemia. We show the transfer from oligodendrocytes to neurons of superoxide dismutase and catalase, enzymes which are known to help cells to resist oxidative stress. Additionally, we identify various effects of oligodendroglial exosomes on neuronal physiology. Electrophysiological analysis using in vitro multi-electrode arrays revealed an increased firing rate of neurons exposed to oligodendroglial exosomes. Moreover, gene expression analysis and phosphorylation arrays uncovered differentially expressed genes and altered signal transduction pathways in neurons after exosome treatment. Our study thus provides new insight into the broad spectrum of action of oligodendroglial exosomes and their effects on neuronal physiology. The exchange of extracellular vesicles between neural cells may exhibit remarkable potential to impact brain performance. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  4. The mirror neuron system and the consequences of its dysfunction.

    Science.gov (United States)

    Iacoboni, Marco; Dapretto, Mirella

    2006-12-01

    The discovery of premotor and parietal cells known as mirror neurons in the macaque brain that fire not only when the animal is in action, but also when it observes others carrying out the same actions provides a plausible neurophysiological mechanism for a variety of important social behaviours, from imitation to empathy. Recent data also show that dysfunction of the mirror neuron system in humans might be a core deficit in autism, a socially isolating condition. Here, we review the neurophysiology of the mirror neuron system and its role in social cognition and discuss the clinical implications of mirror neuron dysfunction.

  5. Magnocellular Neurons and Posterior Pituitary Function.

    Science.gov (United States)

    Brown, Colin H

    2016-09-15

    The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  6. Cognitive effort: A neuroeconomic approach

    Science.gov (United States)

    Braver, Todd S.

    2015-01-01

    Cognitive effort has been implicated in numerous theories regarding normal and aberrant behavior and the physiological response to engagement with demanding tasks. Yet, despite broad interest, no unifying, operational definition of cognitive effort itself has been proposed. Here, we argue that the most intuitive and epistemologically valuable treatment is in terms of effort-based decision-making, and advocate a neuroeconomics-focused research strategy. We first outline psychological and neuroscientific theories of cognitive effort. Then we describe the benefits of a neuroeconomic research strategy, highlighting how it affords greater inferential traction than do traditional markers of cognitive effort, including self-reports and physiologic markers of autonomic arousal. Finally, we sketch a future series of studies that can leverage the full potential of the neuroeconomic approach toward understanding the cognitive and neural mechanisms that give rise to phenomenal, subjective cognitive effort. PMID:25673005

  7. Insights into the role of neuronal glucokinase.

    Science.gov (United States)

    De Backer, Ivan; Hussain, Sufyan S; Bloom, Stephen R; Gardiner, James V

    2016-07-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. Copyright © 2016 the American Physiological Society.

  8. Zebrafish transgenic constructs label specific neurons in Xenopus laevis spinal cord and identify frog V0v spinal neurons.

    Science.gov (United States)

    Juárez-Morales, José L; Martinez-De Luna, Reyna I; Zuber, Michael E; Roberts, Alan; Lewis, Katharine E

    2017-09-01

    A correctly functioning spinal cord is crucial for locomotion and communication between body and brain but there are fundamental gaps in our knowledge of how spinal neuronal circuitry is established and functions. To understand the genetic program that regulates specification and functions of this circuitry, we need to connect neuronal molecular phenotypes with physiological analyses. Studies using Xenopus laevis tadpoles have increased our understanding of spinal cord neuronal physiology and function, particularly in locomotor circuitry. However, the X. laevis tetraploid genome and long generation time make it difficult to investigate how neurons are specified. The opacity of X. laevis embryos also makes it hard to connect functional classes of neurons and the genes that they express. We demonstrate here that Tol2 transgenic constructs using zebrafish enhancers that drive expression in specific zebrafish spinal neurons label equivalent neurons in X. laevis and that the incorporation of a Gal4:UAS amplification cassette enables cells to be observed in live X. laevis tadpoles. This technique should enable the molecular phenotypes, morphologies and physiologies of distinct X. laevis spinal neurons to be examined together in vivo. We have used an islet1 enhancer to label Rohon-Beard sensory neurons and evx enhancers to identify V0v neurons, for the first time, in X. laevis spinal cord. Our work demonstrates the homology of spinal cord circuitry in zebrafish and X. laevis, suggesting that future work could combine their relative strengths to elucidate a more complete picture of how vertebrate spinal cord neurons are specified, and function to generate behavior. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1007-1020, 2017. © 2017 Wiley Periodicals, Inc.

  9. Neurochemistry of bulbospinal presympathetic neurons of the medulla oblongata.

    Science.gov (United States)

    Stornetta, Ruth L

    2009-11-01

    This review focuses on presympathetic neurons in the medulla oblongata including the adrenergic cell groups C1-C3 in the rostral ventrolateral medulla and the serotonergic, GABAergic and glycinergic neurons in the ventromedial medulla. The phenotypes of these neurons including colocalized neuropeptides (e.g., neuropeptide Y, enkephalin, thyrotropin-releasing hormone, substance P) as well as their relative anatomical location are considered in relation to predicting their function in control of sympathetic outflow, in particular the sympathetic outflows controlling blood pressure and thermoregulation. Several explanations are considered for how the neuroeffectors coexisting in these neurons might be functioning, although their exact purpose remains unknown. Although there is abundant data on potential neurotransmitters and neuropeptides contained in the presympathetic neurons, we are still unable to predict function and physiology based solely on the phenotype of these neurons.

  10. Tinbergen on mirror neurons

    Science.gov (United States)

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology—the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible ‘best explanation’ for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of ‘survival value’, should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding—or another social cognitive function—by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories. PMID:24778376

  11. Tinbergen on mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.

  12. Neuronal Migration Disorders

    Science.gov (United States)

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  13. Motor Neuron Diseases

    Science.gov (United States)

    ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...

  14. From sensation to cognition.

    Science.gov (United States)

    Mesulam, M M

    1998-06-01

    Sensory information undergoes extensive associative elaboration and attentional modulation as it becomes incorporated into the texture of cognition. This process occurs along a core synaptic hierarchy which includes the primary sensory, upstream unimodal, downstream unimodal, heteromodal, paralimbic and limbic zones of the cerebral cortex. Connections from one zone to another are reciprocal and allow higher synaptic levels to exert a feedback (top-down) influence upon earlier levels of processing. Each cortical area provides a nexus for the convergence of afferents and divergence of efferents. The resultant synaptic organization supports parallel as well as serial processing, and allows each sensory event to initiate multiple cognitive and behavioural outcomes. Upstream sectors of unimodal association areas encode basic features of sensation such as colour, motion, form and pitch. More complex contents of sensory experience such as objects, faces, word-forms, spatial locations and sound sequences become encoded within downstream sectors of unimodal areas by groups of coarsely tuned neurons. The highest synaptic levels of sensory-fugal processing are occupied by heteromodal, paralimbic and limbic cortices, collectively known as transmodal areas. The unique role of these areas is to bind multiple unimodal and other transmodal areas into distributed but integrated multimodal representations. Transmodal areas in the midtemporal cortex, Wernicke's area, the hippocampal-entorhinal complex and the posterior parietal cortex provide critical gateways for transforming perception into recognition, word-forms into meaning, scenes and events into experiences, and spatial locations into targets for exploration. All cognitive processes arise from analogous associative transformations of similar sets of sensory inputs. The differences in the resultant cognitive operation are determined by the anatomical and physiological properties of the transmodal node that acts as the critical

  15. Reciprocal cholinergic and GABAergic modulation of the small ventrolateral pacemaker neurons of Drosophila's circadian clock neuron network.

    Science.gov (United States)

    Lelito, Katherine R; Shafer, Orie T

    2012-04-01

    The relatively simple clock neuron network of Drosophila is a valuable model system for the neuronal basis of circadian timekeeping. Unfortunately, many key neuronal classes of this network are inaccessible to electrophysiological analysis. We have therefore adopted the use of genetically encoded sensors to address the physiology of the fly's circadian clock network. Using genetically encoded Ca(2+) and cAMP sensors, we have investigated the physiological responses of two specific classes of clock neuron, the large and small ventrolateral neurons (l- and s-LN(v)s), to two neurotransmitters implicated in their modulation: acetylcholine (ACh) and γ-aminobutyric acid (GABA). Live imaging of l-LN(v) cAMP and Ca(2+) dynamics in response to cholinergic agonist and GABA application were well aligned with published electrophysiological data, indicating that our sensors were capable of faithfully reporting acute physiological responses to these transmitters within single adult clock neuron soma. We extended these live imaging methods to s-LN(v)s, critical neuronal pacemakers whose physiological properties in the adult brain are largely unknown. Our s-LN(v) experiments revealed the predicted excitatory responses to bath-applied cholinergic agonists and the predicted inhibitory effects of GABA and established that the antagonism of ACh and GABA extends to their effects on cAMP signaling. These data support recently published but physiologically untested models of s-LN(v) modulation and lead to the prediction that cholinergic and GABAergic inputs to s-LN(v)s will have opposing effects on the phase and/or period of the molecular clock within these critical pacemaker neurons.

  16. Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons.

    Science.gov (United States)

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2017-04-01

    Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN) has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices. Selective photoactivation of orexin fibers elicited short-latency postsynaptic currents in all SPNs tested ( n = 34). These light-triggered responses were heterogeneous, with a majority being excitatory glutamatergic responses (59%) and a minority of inhibitory GABAergic (35%) and mixed glutamatergic and GABAergic currents (6%). Both glutamatergic and GABAergic responses were present in the presence of tetrodotoxin and 4-aminopyridine, suggesting a monosynaptic connection between orexin neurons and SPNs. In addition to generating postsynaptic responses, photostimulation facilitated action potential firing in SPNs (current clamp configuration). Glutamatergic, but not GABAergic, postsynaptic currents were diminished by application of the orexin receptor antagonist almorexant, indicating orexin release facilitates glutamatergic neurotransmission in this pathway. This work identifies a neuronal circuit by which orexin neurons likely exert sympathoexcitatory control of cardiovascular function. NEW & NOTEWORTHY This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not

  17. Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

    Science.gov (United States)

    Dufourny, Laurence; Lomet, Didier

    2017-12-01

    Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Bidirectional Microglia-Neuron Communication in the Healthy Brain

    Directory of Open Access Journals (Sweden)

    Ukpong B. Eyo

    2013-01-01

    Full Text Available Unlike other resident neural cells that are of neuroectodermal origin, microglia are resident neural cells of mesodermal origin. Traditionally recognized for their immune functions during disease, new roles are being attributed to these cells in the development and maintenance of the central nervous system (CNS including specific communication with neurons. In this review, we highlight some of the recent findings on the bidirectional interaction between neurons and microglia. We discuss these interactions along two lines. First, we review data that suggest that microglial activity is modulated by neuronal signals, focusing on evidence that (i neurons are capable of regulating microglial activation state and influence basal microglial activities; (ii classic neurotransmitters affect microglial behavior; (iii chemotactic signals attract microglia during acute neuronal injury. Next, we discuss some of the recent data on how microglia signal to neurons. Signaling mechanisms include (i direct physical contact of microglial processes with neuronal elements; (ii microglial regulation of neuronal synapse and circuit by fractalkine, complement, and DAP12 signaling. In addition, we discuss the use of microglial depletion strategies in studying the role of microglia in neuronal development and synaptic physiology. Deciphering the mechanisms of bidirectional microglial-neuronal communication provides novel insights in understanding microglial function in both the healthy and diseased brain.

  19. The role of GABA in the regulation of GnRH neurons

    Directory of Open Access Journals (Sweden)

    Miho eWatanabe

    2014-11-01

    Full Text Available Gonadotropin-releasing hormone (GnRH neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction.

  20. Two distinct populations of projection neurons in the rat lateral parafascicular thalamic nucleus and their cholinergic responsiveness.

    Science.gov (United States)

    Beatty, J A; Sylwestrak, E L; Cox, C L

    2009-08-04

    The lateral parafascicular nucleus (lPf) is a member of the intralaminar thalamic nuclei, a collection of nuclei that characteristically provides widespread projections to the neocortex and basal ganglia and is associated with arousal, sensory, and motor functions. Recently, lPf neurons have been shown to possess different characteristics than other cortical-projecting thalamic relay neurons. We performed whole cell recordings from lPf neurons using an in vitro rat slice preparation and found two distinct neuronal subtypes that were differentiated by distinct morphological and physiological characteristics: diffuse and bushy. Diffuse neurons, which had been previously described, were the predominant neuronal subtype (66%). These neurons had few, poorly-branching, extended dendrites, and rarely displayed burst-like action potential discharge, a ubiquitous feature of thalamocortical relay neurons. Interestingly, we discovered a smaller population of bushy neurons (34%) that shared similar morphological and physiological characteristics with thalamocortical relay neurons of primary sensory thalamic nuclei. In contrast to other thalamocortical relay neurons, activation of muscarinic cholinergic receptors produced a membrane hyperpolarization via activation of M(2) receptors in most lPf neurons (60%). In a minority of lPf neurons (33%), muscarinic agonists produced a membrane depolarization via activation of predominantly M(3) receptors. The muscarinic receptor-mediated actions were independent of lPf neuronal subtype (i.e. diffuse or bushy neurons); however the cholinergic actions were correlated with lPf neurons with different efferent targets. Retrogradely-labeled lPf neurons from frontal cortical fluorescent bead injections primarily consisted of bushy type lPf neurons (78%), but more importantly, all of these neurons were depolarized by muscarinic agonists. On the other hand, lPf neurons labeled by striatal injections were predominantly hyperpolarized by muscarinic

  1. Axonal regeneration and neuronal function are preserved in motor neurons lacking ß-actin in vivo.

    Directory of Open Access Journals (Sweden)

    Thomas R Cheever

    2011-03-01

    Full Text Available The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA, suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo.

  2. Energy-efficient neural information processing in individual neurons and neuronal networks.

    Science.gov (United States)

    Yu, Lianchun; Yu, Yuguo

    2017-11-01

    Brains are composed of networks of an enormous number of neurons interconnected with synapses. Neural information is carried by the electrical signals within neurons and the chemical signals among neurons. Generating these electrical and chemical signals is metabolically expensive. The fundamental issue raised here is whether brains have evolved efficient ways of developing an energy-efficient neural code from the molecular level to the circuit level. Here, we summarize the factors and biophysical mechanisms that could contribute to the energy-efficient neural code for processing input signals. The factors range from ion channel kinetics, body temperature, axonal propagation of action potentials, low-probability release of synaptic neurotransmitters, optimal input and noise, the size of neurons and neuronal clusters, excitation/inhibition balance, coding strategy, cortical wiring, and the organization of functional connectivity. Both experimental and computational evidence suggests that neural systems may use these factors to maximize the efficiency of energy consumption in processing neural signals. Studies indicate that efficient energy utilization may be universal in neuronal systems as an evolutionary consequence of the pressure of limited energy. As a result, neuronal connections may be wired in a highly economical manner to lower energy costs and space. Individual neurons within a network may encode independent stimulus components to allow a minimal number of neurons to represent whole stimulus characteristics efficiently. This basic principle may fundamentally change our view of how billions of neurons organize themselves into complex circuits to operate and generate the most powerful intelligent cognition in nature. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. A possible new mechanism for the control of miRNA expression in neurons.

    Science.gov (United States)

    Kinjo, Erika Reime; Higa, Guilherme Shigueto Vilar; de Sousa, Erica; Casado, Otávio Augusto Nocera; Damico, Marcio Vinicius; Britto, Luiz Roberto G; Kihara, Alexandre Hiroaki

    2013-10-01

    The control of gene expression by miRNAs has been widely investigated in different species and cell types. Following a probabilistic rather than a deterministic regimen, the action of these short nucleotide sequences on specific genes depends on intracellular concentration, which in turn reflects the balance between biosynthesis and degradation. Recent studies have described the involvement of XRN2, an exoribonuclease, in miRNA degradation and PAPD4, an atypical poly(A) polymerase, in miRNA stability. Herein, we examined the expression of XRN2 and PAPD4 in developing and adult rat hippocampi. Combining bioinformatics and real-time PCR, we demonstrated that XRN2 and PAPD4 expression is regulated by the uncorrelated action of transcription factors, resulting in distinct gene expression profiles during development. Analyses of nuclei position and nestin labeling revealed that both proteins progressively accumulated during neuronal differentiation, and that they are weakly expressed in immature neurons and absent in glial and endothelial cells. Despite the differences in subcellular localization, both genes were concurrently identified within identical neuronal subpopulations, including specific inhibitory interneurons. Thus, we cope with a singular circumstance in biology: an almost complete intersected expression of functional-opposed genes, reinforcing that their antagonistically driven actions on miRNAs "make sense" if simultaneously present at the same cells. Considering that the transcriptome in the nervous system is finely tuned to physiological processes, it was remarkable that miRNA stability-related genes were concurrently identified in neurons that play essential roles in cognitive functions such as memory and learning. In summary, this study reveals a possible new mechanism for the control of miRNA expression. © 2013 Elsevier Inc. All rights reserved.

  4. Neuro-cognition and social-cognition: application to exercise rehabilitation

    OpenAIRE

    Kim, Sooyeon

    2013-01-01

    The discovery of mirror neurons has been recognized as one of the major developments in neuroscience, with possible implications for the explanation of many important cognitive functions, including action and perception understanding, imitation, and empathy. In the mirror neuron system, action observation, imitation, and empathy are represented in the same basic motor circuit as action execution. The present paper presents basic neurophysiological findings about mirror neuron system and discu...

  5. Impairment of the nerve growth factor pathway driving amyloid accumulation in cholinergic neurons: the incipit of the Alzheimer′s disease story?

    Directory of Open Access Journals (Sweden)

    Viviana Triaca

    2016-01-01

    Full Text Available The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor (NGF alterations in sporadic Alzheimer′s disease (AD, an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons (BFCN, is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neurotrophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario: NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the septo-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment (MCI and its progression toward AD.

  6. Mirror Neurons and Mirror-Touch Synesthesia.

    Science.gov (United States)

    Linkovski, Omer; Katzin, Naama; Salti, Moti

    2016-05-30

    Since mirror neurons were introduced to the neuroscientific community more than 20 years ago, they have become an elegant and intuitive account for different cognitive mechanisms (e.g., empathy, goal understanding) and conditions (e.g., autism spectrum disorders). Recently, mirror neurons were suggested to be the mechanism underlying a specific type of synesthesia. Mirror-touch synesthesia is a phenomenon in which individuals experience somatosensory sensations when seeing someone else being touched. Appealing as it is, careful delineation is required when applying this mechanism. Using the mirror-touch synesthesia case, we put forward theoretical and methodological issues that should be addressed before relying on the mirror-neurons account. © The Author(s) 2016.

  7. Imitation, empathy, and mirror neurons.

    Science.gov (United States)

    Iacoboni, Marco

    2009-01-01

    There is a convergence between cognitive models of imitation, constructs derived from social psychology studies on mimicry and empathy, and recent empirical findings from the neurosciences. The ideomotor framework of human actions assumes a common representational format for action and perception that facilitates imitation. Furthermore, the associative sequence learning model of imitation proposes that experience-based Hebbian learning forms links between sensory processing of the actions of others and motor plans. Social psychology studies have demonstrated that imitation and mimicry are pervasive, automatic, and facilitate empathy. Neuroscience investigations have demonstrated physiological mechanisms of mirroring at single-cell and neural-system levels that support the cognitive and social psychology constructs. Why were these neural mechanisms selected, and what is their adaptive advantage? Neural mirroring solves the "problem of other minds" (how we can access and understand the minds of others) and makes intersubjectivity possible, thus facilitating social behavior.

  8. Cellular Links between Neuronal Activity and Energy Homeostasis

    OpenAIRE

    Shetty, Pavan K.; Galeffi, Francesca; Turner, Dennis A.

    2012-01-01

    Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which lea...

  9. Neuronal network analyses: premises, promises and uncertainties

    OpenAIRE

    Parker, David

    2010-01-01

    Neuronal networks assemble the cellular components needed for sensory, motor and cognitive functions. Any rational intervention in the nervous system will thus require an understanding of network function. Obtaining this understanding is widely considered to be one of the major tasks facing neuroscience today. Network analyses have been performed for some years in relatively simple systems. In addition to the direct insights these systems have provided, they also illustrate some of the diffic...

  10. Dicer maintains the identity and function of proprioceptive sensory neurons.

    Science.gov (United States)

    O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer; Zhang, Haihan; Shima, Yasuyuki; Ladle, David R; Nelson, Sacha B

    2017-03-01

    RNAs are crucially important for maintaining proprioception. Additionally, this study hints at the larger question of how neurons maintain their functional and molecular specificity. Copyright © 2017 the American Physiological Society.

  11. Topological schemas of cognitive maps and spatial learning

    Directory of Open Access Journals (Sweden)

    Andrey eBabichev

    2016-03-01

    Full Text Available Spatial navigation in mammals is based on building a mental representation of their environment---a cognitive map. However, both the nature of this cognitive map and its underpinning in neural structures and activity remains vague. A key difficulty is that these maps are collective, emergent phenomena that cannot be reduced to a simple combination of inputs provided by individual neurons. In this paper we suggest computational frameworks for integrating the spiking signals of individual cells into a spatial map, which we call schemas. We provide examples of four schemas defined by different types of topological relations that may be neurophysiologically encoded in the brain and demonstrate that each schema provides its own large-scale characteristics of the environment---the schema integrals. Moreover, we find that, in all cases, these integrals are learned at a rate which is faster than the rate of complete training of neural networks. Thus, the proposed schema framework differentiates between the cognitive aspect of spatial learning and the physiological aspect at the neural network level.

  12. Topological Schemas of Cognitive Maps and Spatial Learning.

    Science.gov (United States)

    Babichev, Andrey; Cheng, Sen; Dabaghian, Yuri A

    2016-01-01

    Spatial navigation in mammals is based on building a mental representation of their environment-a cognitive map. However, both the nature of this cognitive map and its underpinning in neural structures and activity remains vague. A key difficulty is that these maps are collective, emergent phenomena that cannot be reduced to a simple combination of inputs provided by individual neurons. In this paper we suggest computational frameworks for integrating the spiking signals of individual cells into a spatial map, which we call schemas. We provide examples of four schemas defined by different types of topological relations that may be neurophysiologically encoded in the brain and demonstrate that each schema provides its own large-scale characteristics of the environment-the schema integrals. Moreover, we find that, in all cases, these integrals are learned at a rate which is faster than the rate of complete training of neural networks. Thus, the proposed schema framework differentiates between the cognitive aspect of spatial learning and the physiological aspect at the neural network level.

  13. Neuron-astrocyte signaling is preserved in the aging brain.

    Science.gov (United States)

    Gómez-Gonzalo, Marta; Martin-Fernandez, Mario; Martínez-Murillo, Ricardo; Mederos, Sara; Hernández-Vivanco, Alicia; Jamison, Stephanie; Fernandez, Ana P; Serrano, Julia; Calero, Pilar; Futch, Hunter S; Corpas, Rubén; Sanfeliu, Coral; Perea, Gertrudis; Araque, Alfonso

    2017-04-01

    Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca 2+ elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown. We have investigated the existence and properties of astrocyte-neuron signaling in physiologically and pathologically aging mouse hippocampal and cortical slices at different lifetime points (0.5 to 20 month-old animals). We found that astrocytes preserved their ability to express spontaneous and neurotransmitter-dependent intracellular Ca 2+ signals from juvenile to aging brains. Likewise, resting levels of gliotransmission, assessed by neuronal NMDAR activation by glutamate released from astrocytes, were largely preserved with similar properties in all tested age groups, but DHPG-induced gliotransmission was reduced in aged mice. In contrast, gliotransmission was enhanced in the APP/PS1 mouse model of Alzheimer's disease, indicating a dysregulation of astrocyte-neuron signaling in pathological conditions. Disruption of the astrocytic IP 3 R2 mediated-signaling, which is required for neurotransmitter-induced astrocyte Ca 2+ signals and gliotransmission, boosted the progression of amyloid plaque deposits and synaptic plasticity impairments in APP/PS1 mice at early stages of the disease. Therefore, astrocyte-neuron interaction is a fundamental signaling, largely conserved in the adult and aging brain of healthy animals, but it is altered in Alzheimer's disease, suggesting that dysfunctions of astrocyte Ca 2+ physiology may contribute to this neurodegenerative disease. GLIA 2017 GLIA 2017;65:569-580. © 2017 Wiley

  14. [Behavioral-cognitive disorders due to chronic exposure to industrial and environmental toxic substances].

    Science.gov (United States)

    Mangone, Carlos A; Genovese, Osvaldo; Abel, Carlos

    2006-01-01

    A review of neurotoxics is made, given the low tendency to investigate for chronic exposure to environmental and industrial potential central nervous system toxic substances (heavy metals, insecticides, organic solvents and carbon monoxide) in the history of a patient consulting for behavioral - cognitive complains, and considering the potential overturn of the disease if a correct diagnosis and early treatment is made. to determine the onset of the cognitive - behavioral features, presentation pattern, diagnosis and treatment of such neurotoxics (NT). systematized search in Cochrane and Medline reviews, Embase and Lilacs. chronic exposure to neurotoxics can produce personality changes (sleeping problems, excitation, depression, delusions and hallucinations) as well as cognitive problems (memory, learning, language and cognitive reaction problems). NT may cause changes in the neuron morphology and its sub cellular structures, affecting its normal biochemistry and physiology (proteins and neurotransmitters synthesis). The clinical history, diagnosis and treatment of each neurotoxic are discussed. The NT must be taken in consideration among the possible different etiologies when a patient with a bizarre behavioral cognitive syndrome is examined.

  15. Physiological models of the lateral superior olive.

    Directory of Open Access Journals (Sweden)

    Go Ashida

    2017-12-01

    Full Text Available In computational biology, modeling is a fundamental tool for formulating, analyzing and predicting complex phenomena. Most neuron models, however, are designed to reproduce certain small sets of empirical data. Hence their outcome is usually not compatible or comparable with other models or datasets, making it unclear how widely applicable such models are. In this study, we investigate these aspects of modeling, namely credibility and generalizability, with a specific focus on auditory neurons involved in the localization of sound sources. The primary cues for binaural sound localization are comprised of interaural time and level differences (ITD/ILD, which are the timing and intensity differences of the sound waves arriving at the two ears. The lateral superior olive (LSO in the auditory brainstem is one of the locations where such acoustic information is first computed. An LSO neuron receives temporally structured excitatory and inhibitory synaptic inputs that are driven by ipsi- and contralateral sound stimuli, respectively, and changes its spike rate according to binaural acoustic differences. Here we examine seven contemporary models of LSO neurons with different levels of biophysical complexity, from predominantly functional ones ('shot-noise' models to those with more detailed physiological components (variations of integrate-and-fire and Hodgkin-Huxley-type. These models, calibrated to reproduce known monaural and binaural characteristics of LSO, generate largely similar results to each other in simulating ITD and ILD coding. Our comparisons of physiological detail, computational efficiency, predictive performances, and further expandability of the models demonstrate (1 that the simplistic, functional LSO models are suitable for applications where low computational costs and mathematical transparency are needed, (2 that more complex models with detailed membrane potential dynamics are necessary for simulation studies where sub-neuronal

  16. Chewing Over Physiology Integration

    Science.gov (United States)

    Abdulkader, Fernando; Azevedo-Martins, Anna Karenina; de Arcisio Miranda, Manoel; Brunaldi, Kellen

    2005-01-01

    An important challenge for both students and teachers of physiology is to integrate the differentareas in which physiological knowledge is didactically divided. In developing countries, such an issue is even more demanding, because budget restrictions often affect the physiology program with laboratory classes being the first on the list when it…

  17. Plant Physiology in Greenhouses

    NARCIS (Netherlands)

    Heuvelink, E.; Kierkels, T.

    2015-01-01

    Since 2004 Ep Heuvelink and Tijs Kierkels have been writing a continuing series of plant physiology articles for the Dutch horticultural journal Onder Glas and the international edition In Greenhouses. The book Plant Physiology in Greenhouses consists of 50 of their plant physiology articles. The

  18. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells.

    Science.gov (United States)

    Merkle, Florian T; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F

    2015-02-15

    Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a 'self-patterning' strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases. © 2015. Published by The Company of Biologists Ltd.

  19. Multistability in a neuron model with extracellular potassium dynamics

    Science.gov (United States)

    Wu, Xing-Xing; Shuai, J. W.

    2012-06-01

    Experiments show a primary role of extracellular potassium concentrations in neuronal hyperexcitability and in the generation of epileptiform bursting and depolarization blocks without synaptic mechanisms. We adopt a physiologically relevant hippocampal CA1 neuron model in a zero-calcium condition to better understand the function of extracellular potassium in neuronal seizurelike activities. The model neuron is surrounded by interstitial space in which potassium ions are able to accumulate. Potassium currents, Na+-K+ pumps, glial buffering, and ion diffusion are regulatory mechanisms of extracellular potassium. We also consider a reduced model with a fixed potassium concentration. The bifurcation structure and spiking frequency of the two models are studied. We show that, besides hyperexcitability and bursting pattern modulation, the potassium dynamics can induce not only bistability but also tristability of different firing patterns. Our results reveal the emergence of the complex behavior of multistability due to the dynamical [K+]o modulation on neuronal activities.

  20. A Simple Picaxe Microcontroller Pulse Source for Juxtacellular Neuronal Labelling †

    Science.gov (United States)

    Verberne, Anthony J. M.

    2016-01-01

    Juxtacellular neuronal labelling is a method which allows neurophysiologists to fill physiologically-identified neurons with small positively-charged marker molecules. Labelled neurons are identified by histochemical processing of brain sections along with immunohistochemical identification of neuropeptides, neurotransmitters, neurotransmitter transporters or biosynthetic enzymes. A microcontroller-based pulser circuit and associated BASIC software script is described for incorporation into the design of a commercially-available intracellular electrometer for use in juxtacellular neuronal labelling. Printed circuit board construction has been used for reliability and reproducibility. The current design obviates the need for a separate digital pulse source and simplifies the juxtacellular neuronal labelling procedure. PMID:28952589

  1. Cognitive Changes

    Science.gov (United States)

    ... are here Home › Non-Movement Symptoms › Cognitive Changes Cognitive Changes Some people with Parkinson’s disease (PD) experience mild cognitive impairment. Feelings of distraction or disorganization can accompany ...

  2. Doppler radar physiological sensing

    CERN Document Server

    Lubecke, Victor M; Droitcour, Amy D; Park, Byung-Kwon; Singh, Aditya

    2016-01-01

    Presents a comprehensive description of the theory and practical implementation of Doppler radar-based physiological monitoring. This book includes an overview of current physiological monitoring techniques and explains the fundamental technology used in remote non-contact monitoring methods. Basic radio wave propagation and radar principles are introduced along with the fundamentals of physiological motion and measurement. Specific design and implementation considerations for physiological monitoring radar systems are then discussed in detail. The authors address current research and commercial development of Doppler radar based physiological monitoring for healthcare and other applications.

  3. Reelin secreted by GABAergic neurons regulates glutamate receptor homeostasis.

    Directory of Open Access Journals (Sweden)

    Cecilia Gonzalez Campo

    Full Text Available BACKGROUND: Reelin is a large secreted protein of the extracellular matrix that has been proposed to participate to the etiology of schizophrenia. During development, reelin is crucial for the correct cytoarchitecture of laminated brain structures and is produced by a subset of neurons named Cajal-Retzius. After birth, most of these cells degenerate and reelin expression persists in postnatal and adult brain. The phenotype of neurons that bind secreted reelin and whether the continuous secretion of reelin is required for physiological functions at postnatal stages remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Combining immunocytochemical and pharmacological approaches, we first report that two distinct patterns of reelin expression are present in cultured hippocampal neurons. We show that in hippocampal cultures, reelin is secreted by GABAergic neurons displaying an intense reelin immunoreactivity (IR. We demonstrate that secreted reelin binds to receptors of the lipoprotein family on neurons with a punctate reelin IR. Secondly, using calcium imaging techniques, we examined the physiological consequences of reelin secretion blockade. Blocking protein secretion rapidly and reversibly changes the subunit composition of N-methyl-D-aspartate glutamate receptors (NMDARs to a predominance of NR2B-containing NMDARs. Addition of recombinant or endogenously secreted reelin rescues the effects of protein secretion blockade and reverts the fraction of NR2B-containing NMDARs to control levels. Therefore, the continuous secretion of reelin is necessary to control the subunit composition of NMDARs in hippocampal neurons. CONCLUSIONS/SIGNIFICANCE: Our data show that the heterogeneity of reelin immunoreactivity correlates with distinct functional populations: neurons synthesizing and secreting reelin and/or neurons binding reelin. Furthermore, we show that continuous reelin secretion is a strict requirement to maintain the composition of NMDARs. We propose

  4. Dehydration: physiology, assessment, and performance effects.

    Science.gov (United States)

    Cheuvront, Samuel N; Kenefick, Robert W

    2014-01-01

    This article provides a comprehensive review of dehydration assessment and presents a unique evaluation of the dehydration and performance literature. The importance of osmolality and volume are emphasized when discussing the physiology, assessment, and performance effects of dehydration. The underappreciated physiologic distinction between a loss of hypo-osmotic body water (intracellular dehydration) and an iso-osmotic loss of body water (extracellular dehydration) is presented and argued as the single most essential aspect of dehydration assessment. The importance of diagnostic and biological variation analyses to dehydration assessment methods is reviewed and their use in gauging the true potential of any dehydration assessment method highlighted. The necessity for establishing proper baselines is discussed, as is the magnitude of dehydration required to elicit reliable and detectable osmotic or volume-mediated compensatory physiologic responses. The discussion of physiologic responses further helps inform and explain our analysis of the literature suggesting a ≥ 2% dehydration threshold for impaired endurance exercise performance mediated by volume loss. In contrast, no clear threshold or plausible mechanism(s) support the marginal, but potentially important, impairment in strength, and power observed with dehydration. Similarly, the potential for dehydration to impair cognition appears small and related primarily to distraction or discomfort. The impact of dehydration on any particular sport skill or task is therefore likely dependent upon the makeup of the task itself (e.g., endurance, strength, cognitive, and motor skill). © 2014 American Physiological Society.

  5. Cognitive Challenges

    Science.gov (United States)

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Cognitive Challenges Approximately 45% to 60% of individuals with TSC develop cognitive challenges (intellectual disabilities), although the degree of intellectual ...

  6. Development of realtime cognitive state estimator

    International Nuclear Information System (INIS)

    Takahashi, Makoto; Kitamura, Masashi; Yoshikaea, Hidekazu

    2004-01-01

    The realtime cognitive state estimator based on the set of physiological measures has been developed in order to provide valuable information on the human behavior during the interaction through the Man-Machine Interface. The artificial neural network has been adopted to categorize the cognitive states by using the qualitative physiological data pattern as the inputs. The laboratory experiments, in which the subjects' cognitive states were intentionally controlled by the task presented, were performed to obtain training data sets for the neural network. The developed system has been shown to be capable of estimating cognitive state with higher accuracy and realtime estimation capability has also been confirmed through the data processing experiments. (author)

  7. Thalamic physiology of intentional essential tremor is more like cerebellar tremor than postural essential tremor

    OpenAIRE

    Zakaria, R; Lenz, FA; Hua, S; Avin, BH; Liu, CC; Mari, Z

    2013-01-01

    The neuronal physiological correlates of clinical heterogeneity in human essential tremor are unknown. We now test the hypothesis that thalamic neuronal and EMG activities during intention essential tremor are similar to those of the intention tremor which is characteristic of cerebellar lesions. Thalamic neuronal firing was studied in a cerebellar relay nucleus (ventral intermediate, Vim) and in a pallidal relay nucleus (ventral oral posterior, Vop) during stereotactic surgery for the treatm...

  8. Estimation of the neuronal activation using fMRI data: An observer-based approach

    KAUST Repository

    Laleg-Kirati, Taous-Meriem; Arabi, Hossein; Tadjine, Mohamed; Zayane, Chadia

    2013-01-01

    This paper deals with the estimation of the neuronal activation and some unmeasured physiological information using the Blood Oxygenation Level Dependent (BOLD) signal measured using functional Magnetic Resonance Imaging (fMRI). We propose to use

  9. Physiological Based Simulator Fidelity Design Guidance

    Science.gov (United States)

    Schnell, Thomas; Hamel, Nancy; Postnikov, Alex; Hoke, Jaclyn; McLean, Angus L. M. Thom, III

    2012-01-01

    The evolution of the role of flight simulation has reinforced assumptions in aviation that the degree of realism in a simulation system directly correlates to the training benefit, i.e., more fidelity is always better. The construct of fidelity has several dimensions, including physical fidelity, functional fidelity, and cognitive fidelity. Interaction of different fidelity dimensions has an impact on trainee immersion, presence, and transfer of training. This paper discusses research results of a recent study that investigated if physiological-based methods could be used to determine the required level of simulator fidelity. Pilots performed a relatively complex flight task consisting of mission task elements of various levels of difficulty in a fixed base flight simulator and a real fighter jet trainer aircraft. Flight runs were performed using one forward visual channel of 40 deg. field of view for the lowest level of fidelity, 120 deg. field of view for the middle level of fidelity, and unrestricted field of view and full dynamic acceleration in the real airplane. Neuro-cognitive and physiological measures were collected under these conditions using the Cognitive Avionics Tool Set (CATS) and nonlinear closed form models for workload prediction were generated based on these data for the various mission task elements. One finding of the work described herein is that simple heart rate is a relatively good predictor of cognitive workload, even for short tasks with dynamic changes in cognitive loading. Additionally, we found that models that used a wide range of physiological and neuro-cognitive measures can further boost the accuracy of the workload prediction.

  10. Kappe neurons, a novel population of olfactory sensory neurons

    OpenAIRE

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons ar...

  11. Cognitive Reserve and Alzheimer's Disease Biomarkers Are Independent Determinants of Cognition

    Science.gov (United States)

    Vemuri, Prashanthi; Weigand, Stephen D.; Przybelski, Scott A.; Knopman, David S.; Smith, Glenn E.; Trojanowski, John Q.; Shaw, Leslie M.; Decarli, Charlie S.; Carmichael, Owen; Bernstein, Matt A.; Aisen, Paul S.; Weiner, Michael; Petersen, Ronald C.; Jack, Clifford R., Jr.

    2011-01-01

    The objective of this study was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer's disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury…

  12. Eph receptors and ephrins in neuron-astrocyte communication at synapses.

    Science.gov (United States)

    Murai, Keith K; Pasquale, Elena B

    2011-11-01

    Neuron-glia communication is essential for regulating the properties of synaptic connections in the brain. Astrocytes, in particular, play a critical and complex role in synapse development, maintenance, and plasticity. Likewise, neurons reciprocally influence astrocyte physiology. However, the molecular signaling events that enable astrocytes and neurons to effectively communicate with each other are only partially defined. Recent findings have revealed that Eph receptor tyrosine kinases and ephrins play an important role in contact-dependent neuron-glia communication at synapses. Upon binding, these two families of cell surface-associated proteins trigger bidirectional signaling events that regulate the structural and physiological properties of both neurons and astrocytes. This review will focus on the emerging role of Eph receptors and ephrins in neuron-astrocyte interaction at synapses and discuss implications for synaptic plasticity, behavior, and disease. Copyright © 2011 Wiley-Liss, Inc.

  13. Cognitive consilience: Primate non-primary neuroanatomical circuits underlying cognition

    Directory of Open Access Journals (Sweden)

    Soren Van Hout Solari

    2011-12-01

    Full Text Available Interactions between the cerebral cortex, thalamus, and basal ganglia form the basis ofcognitive information processing in the mammalian brain. Understanding the principles ofneuroanatomical organization in these structures is critical to understanding the functions theyperform and ultimately how the human brain works. We have manually distilled and synthesizedhundreds of primate neuroanatomy facts into a single interactive visualization. The resultingpicture represents the fundamental neuroanatomical blueprint upon which cognitive functionsmust be implemented. Within this framework we hypothesize and detail 7 functional circuitscorresponding to psychological perspectives on the brain: consolidated long-term declarativememory, short-term declarative memory, working memory/information processing, behavioralmemory selection, behavioral memory output, cognitive control, and cortical information flow regulation. Each circuit is described in terms of distinguishable neuronal groups including thecerebral isocortex (9 pyramidal neuronal groups, parahippocampal gyrus and hippocampus,thalamus (4 neuronal groups, basal ganglia (7 neuronal groups, metencephalon, basal forebrainand other subcortical nuclei. We focus on neuroanatomy related to primate non-primary corticalsystems to elucidate the basis underlying the distinct homotypical cognitive architecture. To dis-play the breadth of this review, we introduce a novel method of integrating and presenting datain multiple independent visualizations: an interactive website (www.cognitiveconsilience.comand standalone iPhone and iPad applications. With these tools we present a unique, annotatedview of neuroanatomical consilience (integration of knowledge.

  14. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  15. Spinal cord: motor neuron diseases.

    Science.gov (United States)

    Rezania, Kourosh; Roos, Raymond P

    2013-02-01

    Spinal cord motor neuron diseases affect lower motor neurons in the ventral horn. This article focuses on the most common spinal cord motor neuron disease, amyotrophic lateral sclerosis, which also affects upper motor neurons. Also discussed are other motor neuron diseases that only affect the lower motor neurons. Despite the identification of several genes associated with familial amyotrophic lateral sclerosis, the pathogenesis of this complex disease remains elusive. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Cannabinoid mitigation of neuronal morphological change important to development and learning: insight from a zebra finch model of psychopharmacology.

    Science.gov (United States)

    Soderstrom, Ken; Gilbert, Marcoita T

    2013-03-19

    Normal CNS development proceeds through late-postnatal stages of adolescent development. The activity-dependence of this development underscores the significance of CNS-active drug exposure prior to completion of brain maturation. Exogenous modulation of signaling important in regulating normal development is of particular concern. This mini-review presents a summary of the accumulated behavioral, physiological and biochemical evidence supporting such a key regulatory role for endocannabinoid signaling during late-postnatal CNS development. Our focus is on the data obtained using a unique zebra finch model of developmental psychopharmacology. This animal has allowed investigation of neuronal morphological effects essential to establishment and maintenance of neural circuitry, including processes related to synaptogenesis and dendritic spine dynamics. Altered neurophysiology that follows exogenous cannabinoid exposure during adolescent development has the potential to persistently alter cognition, learning and memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin

    OpenAIRE

    Wang, Qian; Liu, Chen; Uchida, Aki; Chuang, Jen-Chieh; Walker, Angela; Liu, Tiemin; Osborne-Lawrence, Sherri; Mason, Brittany L.; Mosher, Christina; Berglund, Eric D.; Elmquist, Joel K.; Zigman, Jeffrey M.

    2014-01-01

    The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreERT2 transgenic mouse model that allows spatiotemporally-controlled re-expression of physiologi...

  18. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Xuemei Shi

    2017-11-01

    Conclusions: We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity.

  19. Walk like me, talk like me. The connection between mirror neurons and autism spectrum disorder.

    Science.gov (United States)

    Saffin, Jillian M; Tohid, Hassaan

    2016-04-01

    Understanding social cognition has become a hallmark in deciphering autism spectrum disorder. Neurobiological theories are taking precedence in causation studies as researchers look to abnormalities in brain development as the cause of deficits in social behavior, cognitive processes, and language. Following their discovery in the 1990s, mirror neurons have become a dominant theory for that the mirror neuron system may play a critical role in the pathophysiology of various symptoms of autism. Over the decades, the theory has evolved from the suggestion of a broken mirror neuron system to impairments in mirror neuron circuitry. The mirror neuron system has not gained total support due to inconsistent findings; a comprehensive analysis of the growing body of research could shed light on the benefits, or the disadvantage of continuing to study mirror neurons and their connection to autism.

  20. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  1. Expression of diverse neuropeptide cotransmitters by identified motor neurons in Aplysia

    International Nuclear Information System (INIS)

    Church, P.J.; Lloyd, P.E.

    1991-01-01

    Neuropeptide synthesis was determined for individual identified ventral-cluster neurons in the buccal ganglia of Aplysia. Each of these cells was shown to be a motor neuron that innervates buccal muscles that generate biting and swallowing movements during feeding. Individual neurons were identified by a battery of physiological criteria and stained with intracellular injection of a vital dye, and the ganglia were incubated in 35S-methionine. Peptide synthesis was determined by measuring labeled peptides in extracts from individually dissected neuronal cell bodies analyzed by HPLC. Previously characterized peptides found to be synthesized included buccalin, FMRFamide, myomodulin, and the 2 small cardioactive peptides (SCPs). Each of these neuropeptides has been shown to modulate buccal muscle responses to motor neuron stimulation. Two other peptides were found to be synthesized in individual motor neurons. One peptide, which was consistently observed in neurons that also synthesized myomodulin, is likely to be the recently sequenced myomodulin B. The other peptide was observed in a subset of the neurons that synthesize FMRFamide. While identified motor neurons consistently synthesized the same peptide(s), neurons that innervate the same muscle often express different peptides. Neurons that synthesized the SCPs also contained SCP-like activity, as determined by snail heart bioassay. Our results indicate that every identified motor neuron synthesizes a subset of these methionine-containing peptides, and that several neurons consistently synthesize peptides that are likely to be processed from multiple precursors

  2. Sleep-Active Neurons: Conserved Motors of Sleep

    Science.gov (United States)

    Bringmann, Henrik

    2018-01-01

    Sleep is crucial for survival and well-being. This behavioral and physiological state has been studied in all major genetically accessible model animals, including rodents, fish, flies, and worms. Genetic and optogenetic studies have identified several neurons that control sleep, making it now possible to compare circuit mechanisms across species. The “motor” of sleep across animal species is formed by neurons that depolarize at the onset of sleep to actively induce this state by directly inhibiting wakefulness. These sleep-inducing neurons are themselves controlled by inhibitory or activating upstream pathways, which act as the “drivers” of the sleep motor: arousal inhibits “sleep-active” neurons whereas various sleep-promoting “tiredness” pathways converge onto sleep-active neurons to depolarize them. This review provides the first overview of sleep-active neurons across the major model animals. The occurrence of sleep-active neurons and their regulation by upstream pathways in both vertebrate and invertebrate species suggests that these neurons are general and ancient components that evolved early in the history of nervous systems. PMID:29618588

  3. Nutrient-dependent increased dendritic arborization of somatosensory neurons.

    Science.gov (United States)

    Watanabe, Kaori; Furumizo, Yuki; Usui, Tadao; Hattori, Yukako; Uemura, Tadashi

    2017-01-01

    Suboptimal nutrition imposes developmental constraints on infant animals, which marshal adaptive responses to eventually become mature adults. Such responses are mounted at multiple levels from systemic to cellular. At the cellular level, the underlying mechanisms of cell proliferation control have been intensively studied. However, less is known about how growth of postmitotic and morphologically complex cells, such as neurons, is controlled by nutritional status. We address this question using Class I and Class IV dendritic arborization neurons in Drosophila larvae. Class IV neurons have been shown to sense nociceptive thermal, mechanical and light stimuli, whereas Class I neurons are proprioceptors. We reared larvae on diets with different protein and carbohydrate content throughout larval stages and examined how morphologies of Class I or Class IV neurons were affected. Dendritic arbors of Class IV neurons became more complex when larvae were reared on a low-yeast diet, which contains lower amounts of amino acids and other ingredients, compared to a high-yeast diet. In contrast, such low-yeast-dependent hyperarborization was not seen in Class I neurons. The physiological and metabolic implications of the hyperarborization phenotype are discussed in relation to a recent hypothesis that Class IV neurons sense protein-deficient stress and to our characterization of how the dietary yeast contents impacted larval metabolism. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  4. Prenatal Ontogeny as a Susceptibility Period for Cortical GABA Neuron Disturbances in Schizophrenia

    OpenAIRE

    Volk, David W.; Lewis, David A.

    2013-01-01

    Cognitive deficits in schizophrenia have been linked to disturbances in GABA neurons in the prefrontal cortex. Furthermore, cognitive deficits in schizophrenia appear well before the onset of psychosis and have been reported to be present during early childhood and even during the first year of life. Taken together, these data raise the following question: Does the disease process that produces abnormalities in prefrontal GABA neurons in schizophrenia begin prenatally and disrupt the ontogeny...

  5. Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

    OpenAIRE

    Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

    2015-01-01

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cog...

  6. Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights.

    Science.gov (United States)

    Heeley, Nicholas; Kirwan, Peter; Darwish, Tamana; Arnaud, Marion; Evans, Mark L; Merkle, Florian T; Reimann, Frank; Gribble, Fiona M; Blouet, Clemence

    2018-04-01

    Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration. A neurochemically diverse subset of both mouse and human hypothalamic neurons responded rapidly to l-leucine. Consistent with l-leucine's anorexigenic role, we found that 25% of mouse MBH POMC neurons were activated by l-leucine. 10% of MBH NPY neurons were inhibited by l-leucine, and leucine rapidly reduced AGRP secretion, providing a mechanism for the rapid leucine-induced inhibition of foraging behavior in rodents. Surprisingly, none of the candidate mechanisms previously implicated in hypothalamic leucine sensing (K ATP channels, mTORC1 signaling, amino-acid decarboxylation) were involved in the acute activity changes produced by l-leucine. Instead, our data indicate that leucine-induced neuronal activation involves a plasma membrane Ca 2+ channel, whereas leucine-induced neuronal inhibition is mediated by inhibition of a store-operated Ca 2+ current. A subset of neurons in the mediobasal hypothalamus rapidly respond to physiological changes in extracellular leucine concentration. Leucine can produce both increases and decreases in neuronal Ca 2+ concentrations in a neurochemically-diverse group of neurons, including some POMC and NPY/AGRP neurons. Our data reveal that leucine can signal through novel mechanisms to rapidly

  7. Proton- and ammonium- sensing by histaminergic neurons controlling wakefulness.

    Directory of Open Access Journals (Sweden)

    Yvgenij eYanovsky

    2012-04-01

    Full Text Available Orexinergic and histaminergic neurons in the posterior hypothalamus are involved in the control of arousal. Extracellular levels of acid /CO2 are fundamental physicochemical signals controlling wakefulness and breathing. Acidification excites orexinergic neurons like the chemosensory neurons in the brain stem. Hypercapnia induces c-Fos expression, a marker for increased neuronal activity, in the rat histaminergic tuberomamillary nucleus (TMN, but the mechanisms of this excitation are unknown. Acid-sensing ion channels (ASICs are gated by protons and also by ammonium. Recordings in rat brain slices revealed now that acidification within the physiological range (pH from 7.3 to 7.0 as well as ammonium chloride (5mM excite histaminergic neurons. We detected variable combinations of 4 known types of ASICs in single TMN neurons, along with the pharmacological properties of pH-induced current. At pH 7.0 however, activation of ASICs in TMN neurons was negligible. Block of type I metabotropic glutamate receptors abolished proton- but not ammonium- induced excitation. Mouse TMN neurons were identified within a novel HDC-Cre transgenic reporter mouse line. In contrast to the rat these lacked pH 7.0-induced excitation and showed only a minimal response to the mGluR I agonist DHPG (0.5µM. Ammonium-induced excitation was similar in mouse and rat. Thus glutamate, which is released by glial cells and orexinergic axons amplifies CO2/acid-induced arousal through the recruitment of the histaminergic system in rat but not in mouse. These results are relevant for the understanding of neuronal mechanisms controlling H+/CO2-induced arousal in hepatic encephalopathy and obstructive sleep apnoea. The new HDC-Cre mouse model will be a useful tool for studying the physiological and pathophysiological roles of the histaminergic system.

  8. Spatially tuned normalization explains attention modulation variance within neurons.

    Science.gov (United States)

    Ni, Amy M; Maunsell, John H R

    2017-09-01

    area can be largely explained by between-neuron differences in normalization strength. Here we demonstrate that attention modulation size varies within neurons as well and that this variance is largely explained by within-neuron differences in normalization strength. We provide a new spatially tuned normalization model that explains this broad range of observed normalization and attention effects. Copyright © 2017 the American Physiological Society.

  9. Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function.

    Science.gov (United States)

    Spencer, William C; Deneris, Evan S

    2017-01-01

    The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling

  10. Differential labelling of retinal neurones by 3H-2-deoxyglucose

    International Nuclear Information System (INIS)

    Basinger, S.F.; Gordon, W.C.; Lam, D.M.K.

    1979-01-01

    The use of tritium-labelled 2-deoxyglucose in combination with plastic embedding is reported to produce stimulus dependent labelling at cellular level in the isolated goldfish retina. The results suggest that the use of tritium in place of the more usual 14 C labelled tracer is advantageous in studying the physiology and functional connections of retinal neurones. (U.K.)

  11. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  12. The mirror neuron system.

    Science.gov (United States)

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

    Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

  13. Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

    Directory of Open Access Journals (Sweden)

    Erik eHrabovszky

    2013-09-01

    Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

  14. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

    Science.gov (United States)

    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects. Copyright © 2012 S. Karger AG, Basel.

  15. Sleep and cognition.

    Science.gov (United States)

    Deak, Maryann C; Stickgold, Robert

    2010-07-01

    Sleep is a complex physiologic state, the importance of which has long been recognized. Lack of sleep is detrimental to humans and animals. Over the past decade, an important link between sleep and cognitive processing has been established. Sleep plays an important role in consolidation of different types of memory and contributes to insightful, inferential thinking. While the mechanism by which memories are processed in sleep remains unknown, several experimental models have been proposed. This article explores the link between sleep and cognition by reviewing (1) the effects of sleep deprivation on cognition, (2) the influence of sleep on consolidation of declarative and non-declarative memory, and (3) some proposed models of how sleep facilitates memory consolidation in sleep. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  16. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture*

    Science.gov (United States)

    Mauceri, Daniela; Hagenston, Anna M.; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar

    2015-01-01

    Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. PMID:26231212

  17. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture.

    Science.gov (United States)

    Mauceri, Daniela; Hagenston, Anna M; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar

    2015-09-18

    Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Modeling the Development of Goal-Specificity in Mirror Neurons.

    Science.gov (United States)

    Thill, Serge; Svensson, Henrik; Ziemke, Tom

    2011-12-01

    Neurophysiological studies have shown that parietal mirror neurons encode not only actions but also the goal of these actions. Although some mirror neurons will fire whenever a certain action is perceived (goal-independently), most will only fire if the motion is perceived as part of an action with a specific goal. This result is important for the action-understanding hypothesis as it provides a potential neurological basis for such a cognitive ability. It is also relevant for the design of artificial cognitive systems, in particular robotic systems that rely on computational models of the mirror system in their interaction with other agents. Yet, to date, no computational model has explicitly addressed the mechanisms that give rise to both goal-specific and goal-independent parietal mirror neurons. In the present paper, we present a computational model based on a self-organizing map, which receives artificial inputs representing information about both the observed or executed actions and the context in which they were executed. We show that the map develops a biologically plausible organization in which goal-specific mirror neurons emerge. We further show that the fundamental cause for both the appearance and the number of goal-specific neurons can be found in geometric relationships between the different inputs to the map. The results are important to the action-understanding hypothesis as they provide a mechanism for the emergence of goal-specific parietal mirror neurons and lead to a number of predictions: (1) Learning of new goals may mostly reassign existing goal-specific neurons rather than recruit new ones; (2) input differences between executed and observed actions can explain observed corresponding differences in the number of goal-specific neurons; and (3) the percentage of goal-specific neurons may differ between motion primitives.

  19. Regulation of gonadotropin-releasing hormone neurons by glucose

    Science.gov (United States)

    Roland, Alison V.; Moenter, Suzanne M.

    2011-01-01

    Reproduction is influenced by energy balance, but the physiological pathways mediating their relationship have not been fully elucidated. As the central regulators of fertility, gonadotropin-releasing hormone (GnRH) neurons integrate numerous physiological signals, including metabolic cues. Circulating glucose levels regulate GnRH release and may in part mediate the effects of negative energy balance on fertility. Existing evidence suggests that neural pathways originating in the hindbrain, as well as in the hypothalamic feeding nuclei, transmit information concerning glucose availability to GnRH neurons. Here we review recent evidence suggesting that GnRH neurons may directly sense changes in glucose availability by a mechanism involving adenosine monophosphate-activated protein kinase (AMPK). These findings expand our understanding of how metabolic signaling in the brain regulates reproduction. PMID:21855365

  20. Advances in physiological computing

    CERN Document Server

    Fairclough, Stephen H

    2014-01-01

    This edited collection will provide an overview of the field of physiological computing, i.e. the use of physiological signals as input for computer control. It will cover a breadth of current research, from brain-computer interfaces to telemedicine.

  1. Phun Week: Understanding Physiology

    Science.gov (United States)

    Limson, Mel; Matyas, Marsha Lakes

    2009-01-01

    Topics such as sports, exercise, health, and nutrition can make the science of physiology relevant and engaging for students. In addition, many lessons on these topics, such as those on the cardiovascular, respiratory, and digestive systems, align with national and state life science education standards. Physiology Understanding Week (PhUn…

  2. Neuron-glia metabolic coupling and plasticity.

    Science.gov (United States)

    Magistretti, Pierre J

    2006-06-01

    The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function that has provided the basis for 2-deoxyglucose-based functional imaging with positron emission tomography (PET). Astrocytes play a central role in neurometabolic coupling, and the basic mechanism involves glutamate-stimulated aerobic glycolysis; the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and processing via glycolysis, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. An operational model, the 'astrocyte-neuron lactate shuttle', is supported experimentally by a large body of evidence, which provides a molecular and cellular basis for interpreting data obtained from functional brain imaging studies. In addition, this neuron-glia metabolic coupling undergoes plastic adaptations in parallel with adaptive mechanisms that characterize synaptic plasticity. Thus, distinct subregions of the hippocampus are metabolically active at different time points during spatial learning tasks, suggesting that a type of metabolic plasticity, involving by definition neuron-glia coupling, occurs during learning. In addition, marked variations in the expression of genes involved in glial glycogen metabolism are observed during the sleep-wake cycle, with in particular a marked induction of expression of the gene encoding for protein targeting to glycogen (PTG) following sleep deprivation. These data suggest that glial metabolic plasticity is likely to be concomitant with synaptic plasticity.

  3. Taurine Biosynthesis by Neurons and Astrocytes*

    Science.gov (United States)

    Vitvitsky, Victor; Garg, Sanjay K.; Banerjee, Ruma

    2011-01-01

    The physiological roles of taurine, a product of cysteine degradation and one of the most abundant amino acids in the body, remain elusive. Taurine deficiency leads to heart dysfunction, brain development abnormalities, retinal degradation, and other pathologies. The taurine synthetic pathway is proposed to be incomplete in astrocytes and neurons, and metabolic cooperation between these cell types is reportedly needed to complete the pathway. In this study, we analyzed taurine synthesis capability as reported by incorporation of radioactivity from [35S]cysteine into taurine, in primary murine astrocytes and neurons, and in several transformed cell lines (human (SH-SY5Y) and murine (N1E-115) neuroblastoma, human astrocytoma (U-87MG and 1321 N1), and rat glioma (C6)). Extensive incorporation of radioactivity from [35S]cysteine into taurine was observed in rat glioma cells as well as in primary mouse astrocytes and neurons, establishing the presence of an intact taurine synthesis pathway in these cells. Interestingly, exposure of cells to cysteine or cysteamine resulted in elevated intracellular hypotaurine without a corresponding increase in taurine levels, suggesting that oxidation of hypotaurine limits taurine synthesis in cells. Consistent with its role as an organic osmolyte, taurine synthesis was stimulated under hypertonic conditions in neurons. PMID:21778230

  4. Postnatal Gene Therapy Improves Spatial Learning Despite the Presence of Neuronal Ectopia in a Model of Neuronal Migration Disorder

    Directory of Open Access Journals (Sweden)

    Huaiyu Hu

    2016-11-01

    Full Text Available Patients with type II lissencephaly, a neuronal migration disorder with ectopic neurons, suffer from severe mental retardation, including learning deficits. There is no effective therapy to prevent or correct the formation of neuronal ectopia, which is presumed to cause cognitive deficits. We hypothesized that learning deficits were not solely caused by neuronal ectopia and that postnatal gene therapy could improve learning without correcting the neuronal ectopia formed during fetal development. To test this hypothesis, we evaluated spatial learning of cerebral cortex-specific protein O-mannosyltransferase 2 (POMT2, an enzyme required for O-mannosyl glycosylation knockout mice and compared to the knockout mice that were injected with an adeno-associated viral vector (AAV encoding POMT2 into the postnatal brains with Barnes maze. The data showed that the knockout mice exhibited reduced glycosylation in the cerebral cortex, reduced dendritic spine density on CA1 neurons, and increased latency to the target hole in the Barnes maze, indicating learning deficits. Postnatal gene therapy restored functional glycosylation, rescued dendritic spine defects, and improved performance on the Barnes maze by the knockout mice even though neuronal ectopia was not corrected. These results indicate that postnatal gene therapy improves spatial learning despite the presence of neuronal ectopia.

  5. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia

    Science.gov (United States)

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-01-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that—against general belief—neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress. PMID:24569689

  6. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia.

    Science.gov (United States)

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-06-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that-against general belief-neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress.

  7. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  8. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  9. Cell-Specific Cholinergic Modulation of Excitability of Layer 5B Principal Neurons in Mouse Auditory Cortex

    Science.gov (United States)

    Joshi, Ankur; Kalappa, Bopanna I.; Anderson, Charles T.

    2016-01-01

    The neuromodulator acetylcholine (ACh) is crucial for several cognitive functions, such as perception, attention, and learning and memory. Whereas, in most cases, the cellular circuits or the specific neurons via which ACh exerts its cognitive effects remain unknown, it is known that auditory cortex (AC) neurons projecting from layer 5B (L5B) to the inferior colliculus, corticocollicular neurons, are required for cholinergic-mediated relearning of sound localization after occlusion of one ear. Therefore, elucidation of the effects of ACh on the excitability of corticocollicular neurons will bridge the cell-specific and cognitive properties of ACh. Because AC L5B contains another class of neurons that project to the contralateral cortex, corticocallosal neurons, to identify the cell-specific mechanisms that enable corticocollicular neurons to participate in sound localization relearning, we investigated the effects of ACh release on both L5B corticocallosal and corticocollicular neurons. Using in vitro electrophysiology and optogenetics in mouse brain slices, we found that ACh generated nicotinic ACh receptor (nAChR)-mediated depolarizing potentials and muscarinic ACh receptor (mAChR)-mediated hyperpolarizing potentials in AC L5B corticocallosal neurons. In corticocollicular neurons, ACh release also generated nAChR-mediated depolarizing potentials. However, in contrast to the mAChR-mediated hyperpolarizing potentials in corticocallosal neurons, ACh generated prolonged mAChR-mediated depolarizing potentials in corticocollicular neurons. These prolonged depolarizing potentials generated persistent firing in corticocollicular neurons, whereas corticocallosal neurons lacking mAChR-mediated depolarizing potentials did not show persistent firing. We propose that ACh-mediated persistent firing in corticocollicular neurons may represent a critical mechanism required for learning-induced plasticity in AC. SIGNIFICANCE STATEMENT Acetylcholine (ACh) is crucial for cognitive

  10. The Effects of Motor Neurone Disease on Language: Further Evidence

    Science.gov (United States)

    Bak, Thomas H.; Hodges, John R.

    2004-01-01

    It might sound surprising that Motor Neurone Disease (MND), regarded still by many as the very example of a neurodegenerative disease affecting selectively the motor system and sparing the sensory functions as well as cognition, can have a significant influence on language. In this article we hope to demonstrate that language dysfunction is not…

  11. Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia

    Science.gov (United States)

    Takeuchi, Koichi; Yang, Yupeng; Takayasu, Yukihiro; Gertner, Michael; Hwang, Jee-Yeon; Aromolaran, Kelly; Bennett, Michael V.L.; Zukin, R. Suzanne

    2015-01-01

    Global ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global ischemia is not clear. Here we show that long term estradiol treatment initiated 14 days prior to global ischemia in ovariectomized female rats acts via the IGF-1 receptor to protect the functional integrity of CA1 neurons. Global ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global ischemia. Estradiol-induced rescue of LTP requires the IGF-1 receptor, but not the classical estrogen receptors (ER)-α or β. These findings support a model whereby estradiol acts via the IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global ischemia. PMID:25463028

  12. Using Electroencephalography to Measure Cognitive Load

    Science.gov (United States)

    Antonenko, Pavlo; Paas, Fred; Grabner, Roland; van Gog, Tamara

    2010-01-01

    Application of physiological methods, in particular electroencephalography (EEG), offers new and promising approaches to educational psychology research. EEG is identified as a physiological index that can serve as an online, continuous measure of cognitive load detecting subtle fluctuations in instantaneous load, which can help explain effects of…

  13. Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons.

    Science.gov (United States)

    Inutsuka, Ayumu; Inui, Azusa; Tabuchi, Sawako; Tsunematsu, Tomomi; Lazarus, Michael; Yamanaka, Akihiro

    2014-10-01

    Orexin neurons in the hypothalamus regulate energy homeostasis by coordinating various physiological responses. Past studies have shown the role of the orexin peptide itself; however, orexin neurons contain not only orexin but also other neurotransmitters such as glutamate and dynorphin. In this study, we examined the physiological role of orexin neurons in feeding behavior and metabolism by pharmacogenetic activation and chronic ablation. We generated novel orexin-Cre mice and utilized Cre-dependent adeno-associated virus vectors to express Gq-coupled modified GPCR, hM3Dq or diphtheria toxin fragment A in orexin neurons. By intraperitoneal injection of clozapine-N oxide in orexin-Cre mice expressing hM3Dq in orexin neurons, we could selectively manipulate the activity of orexin neurons. Pharmacogenetic stimulation of orexin neurons simultaneously increased locomotive activity, food intake, water intake and the respiratory exchange ratio (RER). Elevation of blood glucose levels and RER persisted even after locomotion and feeding behaviors returned to basal levels. Accordantly, 83% ablation of orexin neurons resulted in decreased food and water intake, while 70% ablation had almost no effect on these parameters. Our results indicate that orexin neurons play an integral role in regulation of both feeding behavior and metabolism. This regulation is so robust that greater than 80% of orexin neurons were ablated before significant changes in feeding behavior emerged. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Neuronal regulation of homeostasis by nutrient sensing.

    Science.gov (United States)

    Lam, Tony K T

    2010-04-01

    In type 2 diabetes and obesity, the homeostatic control of glucose and energy balance is impaired, leading to hyperglycemia and hyperphagia. Recent studies indicate that nutrient-sensing mechanisms in the body activate negative-feedback systems to regulate energy and glucose homeostasis through a neuronal network. Direct metabolic signaling within the intestine activates gut-brain and gut-brain-liver axes to regulate energy and glucose homeostasis, respectively. In parallel, direct metabolism of nutrients within the hypothalamus regulates food intake and blood glucose levels. These findings highlight the importance of the central nervous system in mediating the ability of nutrient sensing to maintain homeostasis. Futhermore, they provide a physiological and neuronal framework by which enhancing or restoring nutrient sensing in the intestine and the brain could normalize energy and glucose homeostasis in diabetes and obesity.

  15. Gestural coupling and social cognition

    DEFF Research Database (Denmark)

    Michael, John; Krueger, Joel William

    2012-01-01

    Social cognition researchers have become increasingly interested in the ways that behavioral, physiological, and neural coupling facilitate social interaction and interpersonal understanding. We distinguish two ways of conceptualizing the role of such coupling processes in social cognition: strong...... an essential enabling feature for social interaction and interpersonal understanding more generally and thus ought to exhibit severe deficits in these areas. We challenge SI's prediction and show how MS cases offer compelling reasons for instead adopting MI's pluralistic model of social interaction...... and interpersonal understanding. We conclude that investigations of coupling processes within social interaction should inform rather than marginalize or eliminate investigation of higher-level individual cognition...

  16. Predicting of Physiological Changes through Personality Traits and Decision Making Styles

    Directory of Open Access Journals (Sweden)

    Saeed Imani

    2016-12-01

    Full Text Available Background and Objective: One of the important concepts of social psychology is cognitive dissonance. When our practice is in conflict with our previous attitudes often change our attitude so that we will operate in concert with; this is cognitive dissonance. The aim of this study was evaluation of relation between decision making styles, personality traits and physiological components of cognitive dissonance and also offering a statistical model about them.Materials and Methods: In this correlation study, 130 students of Elmi-Karbordi University of Safadasht were invited and they were asked to complete Scott & Bruce Decision-Making Styles Questionnaire and Gray-Wilson Personality Questionnaire. Before and after distributing those questionnaires, their physiological conditions were receded. Cognitive dissonance was induced by writing about reducing amount of budget which deserved to orphans and rating the reduction of interest of lovely character that ignore his or her fans. Data analysis conducted through regression and multi vitiate covariance.Results: There were correlation between cognitive styles (Avoidant, dependent, logical and intuitive and also personality variables (Flight and Approach, active avoidance, Fight and Extinction with cognitive dissonance. The effect of cognitive (decision making styles and personality variables on physiological components was mediate indirectly through cognitive dissonance, in levels of P=0.01 and P=0.05 difference, was significant. Conclusion: Decision making styles and personality traits are related to cognitive dissonance and its physiological components, and also predict physiological components of cognitive dissonance.

  17. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  18. Genetic deficiency of GABA differentially regulates respiratory and non-respiratory motor neuron development.

    Directory of Open Access Journals (Sweden)

    Matthew J Fogarty

    Full Text Available Central nervous system GABAergic and glycinergic synaptic activity switches from postsynaptic excitation to inhibition during the stage when motor neuron numbers are being reduced, and when synaptic connections are being established onto and by motor neurons. In mice this occurs between embryonic (E day 13 and birth (postnatal day 0. Our previous work on mice lacking glycinergic transmission suggested that altered motor neuron activity levels correspondingly regulated motor neuron survival and muscle innervation for all respiratory and non respiratory motor neuron pools, during this period of development [1]. To determine if GABAergic transmission plays a similar role, we quantified motor neuron number and the extent of muscle innervation in four distinct regions of the brain stem and spinal cord; hypoglossal, phrenic, brachial and lumbar motor pools, in mice lacking the enzyme GAD67. These mice display a 90% drop in CNS GABA levels ( [2]; this study. For respiratory-based motor neurons (hypoglossal and phrenic motor pools, we have observed significant drops in motor neuron number (17% decline for hypoglossal and 23% decline for phrenic and muscle innervations (55% decrease. By contrast for non-respiratory motor neurons of the brachial lateral motor column, we have observed an increase in motor neuron number (43% increase and muscle innervations (99% increase; however for more caudally located motor neurons within the lumbar lateral motor column, we observed no change in either neuron number or muscle innervation. These results show in mice lacking physiological levels of GABA, there are distinct regional changes in motor neuron number and muscle innervation, which appear to be linked to their physiological function and to their rostral-caudal position within the developing spinal cord. Our results also suggest that for more caudal (lumbar regions of the spinal cord, the effect of GABA is less influential on motor neuron development compared to

  19. Synaptic communication between neurons and NG2+ cells.

    Science.gov (United States)

    Paukert, Martin; Bergles, Dwight E

    2006-10-01

    Chemical synaptic transmission provides the basis for much of the rapid signaling that occurs within neuronal networks. However, recent studies have provided compelling evidence that synapses are not used exclusively for communication between neurons. Physiological and anatomical studies indicate that a distinct class of glia known as NG2(+) cells also forms direct synaptic junctions with both glutamatergic and GABAergic neurons. Glutamatergic signaling can influence intracellular Ca(2+) levels in NG2(+) cells by activating Ca(2+) permeable AMPA receptors, and these inputs can be potentiated through high frequency stimulation. Although the significance of this highly differentiated form of communication remains to be established, these neuro-glia synapses might enable neurons to influence rapidly the behavior of this ubiquitous class of glial progenitors.

  20. Microfluidic Neurons, a New Way in Neuromorphic Engineering?

    Directory of Open Access Journals (Sweden)

    Timothée Levi

    2016-08-01

    Full Text Available This article describes a new way to explore neuromorphic engineering, the biomimetic artificial neuron using microfluidic techniques. This new device could replace silicon neurons and solve the issues of biocompatibility and power consumption. The biological neuron transmits electrical signals based on ion flow through their plasma membrane. Action potentials are propagated along axons and represent the fundamental electrical signals by which information are transmitted from one place to another in the nervous system. Based on this physiological behavior, we propose a microfluidic structure composed of chambers representing the intra and extracellular environments, connected by channels actuated by Quake valves. These channels are equipped with selective ion permeable membranes to mimic the exchange of chemical species found in the biological neuron. A thick polydimethylsiloxane (PDMS membrane is used to create the Quake valve membrane. Integrated electrodes are used to measure the potential difference between the intracellular and extracellular environments: the membrane potential.

  1. Rac1 regulates neuronal polarization through the WAVE complex

    DEFF Research Database (Denmark)

    Tahirovic, Sabina; Hellal, Farida; Neukirchen, Dorothee

    2010-01-01

    the physiological function of Rac1 in neuronal development, we have generated a conditional knock-out mouse, in which Rac1 is ablated in the whole brain. Rac1-deficient cerebellar granule neurons, which do not express other Rac isoforms, showed impaired neuronal migration and axon formation both in vivo...... and in vitro. In addition, Rac1 ablation disrupts lamellipodia formation in growth cones. The analysis of Rac1 effectors revealed the absence of the Wiskott-Aldrich syndrome protein (WASP) family verprolin-homologous protein (WAVE) complex from the plasma membrane of knock-out growth cones. Loss of WAVE...... function inhibited axon growth, whereas overexpression of a membrane-tethered WAVE mutant partially rescued axon growth in Rac1-knock-out neurons. In addition, pharmacological inhibition of the WAVE complex effector Arp2/3 also reduced axon growth. We propose that Rac1 recruits the WAVE complex...

  2. Language comprehension warps the mirror neuron system

    Directory of Open Access Journals (Sweden)

    Noah eZarr

    2013-12-01

    Full Text Available Is the mirror neuron system (MNS used in language understanding? According to embodied accounts of language comprehension, understanding sentences describing actions makes use of neural mechanisms of action control, including the MNS. Consequently, repeatedly comprehending sentences describing similar actions should induce adaptation of the MNS thereby warping its use in other cognitive processes such as action recognition and prediction. To test this prediction, participants read blocks of multiple sentences where each sentence in the block described transfer of objects in a direction away or toward the reader. Following each block, adaptation was measured by having participants predict the end-point of videotaped actions. The adapting sentences disrupted prediction of actions in the same direction, but a only for videos of biological motion, and b only when the effector implied by the language (e.g., the hand matched the videos. These findings are signatures of the mirror neuron system.

  3. [Effect of intermittent hypoxia of sleep apnea on embryonic rat cortical neurons in vitro].

    Science.gov (United States)

    Zhang, Chanjuan; Li, Yanzhong; Wang, Yan

    2015-05-01

    To investigate the effects of different pattens of intermittent hypoxia on the activity and apoptosis of primary cultured rat embryonic cortical neurons, and to evaluate the role of intermittent hypoxia in the mechanism of obstructive sleep syndrom induced cognitive function loss. The embryonic cerebral cortical neurons were cultured in vitro and were identified by immunofluorescence. Cultured neurons were randomly divided into intermittent hypoxia group, intermittent normal oxygen group, persistent hypoxia group and the control group, and intermittent hypoxia group was divided into five subgroups according to different frequency and time-bound. Neurons were exposed in different modes of hypoxia. MTT colorimetry was used to detect the viability of the neurons, and DAPI colorated measurement was used to calculate the percentages of neuron apoptosis. There were significantly different effects between all subgroups of intermittent hypoxia and the continued hypoxia group on neuronal activity and apoptosis (P Intermittent hypoxia groups with different frequency and time had no difference in neuronal activity and apoptosis (P > 0.05). The effect of intermittent hypoxia was more serious than that of continued hypoxia on neuronal activity and apoptosis; The impact of intermittent hypoxia on neuronal activity and apoptosis may be an important factor in obstructive sleep apnea related cognitive impairment.

  4. Assessing neuronal networks: understanding Alzheimer's disease.

    LENUS (Irish Health Repository)

    Bokde, Arun L W

    2012-02-01

    Findings derived from neuroimaging of the structural and functional organization of the human brain have led to the widely supported hypothesis that neuronal networks of temporally coordinated brain activity across different regional brain structures underpin cognitive function. Failure of integration within a network leads to cognitive dysfunction. The current discussion on Alzheimer\\'s disease (AD) argues that it presents in part a disconnection syndrome. Studies using functional magnetic resonance imaging, positron emission tomography and electroencephalography demonstrate that synchronicity of brain activity is altered in AD and correlates with cognitive deficits. Moreover, recent advances in diffusion tensor imaging have made it possible to track axonal projections across the brain, revealing substantial regional impairment in fiber-tract integrity in AD. Accumulating evidence points towards a network breakdown reflecting disconnection at both the structural and functional system level. The exact relationship among these multiple mechanistic variables and their contribution to cognitive alterations and ultimately decline is yet unknown. Focused research efforts aimed at the integration of both function and structure hold great promise not only in improving our understanding of cognition but also of its characteristic progressive metamorphosis in complex chronic neurodegenerative disorders such as AD.

  5. Loss of MeCP2 From Forebrain Excitatory Neurons Leads to Cortical Hyperexcitation and Seizures

    Science.gov (United States)

    Zhang, Wen; Peterson, Matthew; Beyer, Barbara; Frankel, Wayne N.

    2014-01-01

    Mutations of MECP2 cause Rett syndrome (RTT), a neurodevelopmental disorder leading to loss of motor and cognitive functions, impaired social interactions, and seizure at young ages. Defects of neuronal circuit development and function are thought to be responsible for the symptoms of RTT. The majority of RTT patients show recurrent seizures, indicating that neuronal hyperexcitation is a common feature of RTT. However, mechanisms underlying hyperexcitation in RTT are poorly understood. Here we show that deletion of Mecp2 from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. Selective deletion of Mecp2 from excitatory but not inhibitory neurons in the forebrain reduces GABAergic transmission in layer 5 pyramidal neurons in the prefrontal and somatosensory cortices. Loss of MeCP2 from cortical excitatory neurons reduces the number of GABAergic synapses in the cortex, and enhances the excitability of layer 5 pyramidal neurons. Using single-cell deletion of Mecp2 in layer 2/3 pyramidal neurons, we show that GABAergic transmission is reduced in neurons without MeCP2, but is normal in neighboring neurons with MeCP2. Together, these results suggest that MeCP2 in cortical excitatory neurons plays a critical role in the regulation of GABAergic transmission and cortical excitability. PMID:24523563

  6. Sleep for cognitive enhancement

    Directory of Open Access Journals (Sweden)

    Susanne eDiekelmann

    2014-04-01

    Full Text Available Sleep is essential for effective cognitive functioning. Loosing even a few hours of sleep can have detrimental effects on a wide variety of cognitive processes such as attention, language, reasoning, decision making, learning and memory. While sleep is necessary to ensure normal healthy cognitive functioning, it can also enhance performance beyond the boundaries of the normal condition. This article discusses the enhancing potential of sleep, mainly focusing on the domain of learning and memory. Sleep is known to facilitate the consolidation of memories learned before sleep as well as the acquisition of new memories to be learned after sleep. According to a widely held model this beneficial effect of sleep relies on the neuronal reactivation of memories during sleep that is associated with sleep-specific brain oscillations (slow oscillations, spindles, ripples as well as a characteristic neurotransmitter milieu. Recent research indicates that memory processing during sleep can be boosted by (i cueing memory reactivation during sleep, (ii stimulating sleep-specific brain oscillations, and (iii targeting specific neurotransmitter systems pharmacologically. Olfactory and auditory cues can be used, for example, to increase reactivation of associated memories during post-learning sleep. Intensifying neocortical slow oscillations (the hallmark of slow wave sleep by electrical or auditory stimulation and modulating specific neurotransmitters such as noradrenaline and glutamate likewise facilitates memory processing during sleep. With this evidence in mind, this article concludes by discussing different methodological caveats and ethical issues that should be considered when thinking about using sleep for cognitive enhancement in everyday applications.

  7. Novel transcriptional networks regulated by CLOCK in human neurons.

    Science.gov (United States)

    Fontenot, Miles R; Berto, Stefano; Liu, Yuxiang; Werthmann, Gordon; Douglas, Connor; Usui, Noriyoshi; Gleason, Kelly; Tamminga, Carol A; Takahashi, Joseph S; Konopka, Genevieve

    2017-11-01

    The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks is driven by hub genes with human-specific patterns of expression. These data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function. © 2017 Fontenot et al.; Published by Cold Spring Harbor Laboratory Press.

  8. The neuronal identity bias behind neocortical GABAergic plasticity.

    Science.gov (United States)

    Allene, Camille; Lourenço, Joana; Bacci, Alberto

    2015-09-01

    In the neocortex, different types of excitatory and inhibitory neurons connect to one another following a detailed blueprint, defining functionally-distinct subnetworks, whose activity and modulation underlie complex cognitive functions. We review the cell-autonomous plasticity of perisomatic inhibition onto principal excitatory neurons. We propose that the tendency of different cortical layers to exhibit depression or potentiation of perisomatic inhibition is dictated by the specific identities of principal neurons (PNs). These are mainly defined by their projection targets and by their preference to be innervated by specific perisomatic-targeting basket cell types. Therefore, principal neurons responsible for relaying information to subcortical nuclei are differentially inhibited and show specific forms of plasticity compared to other PNs that are specialized in more associative functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Prevention of hypoglycemia-induced neuronal death by minocycline

    Science.gov (United States)

    2012-01-01

    Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced neuronal death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for neuronal death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, neuronal death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients. PMID:22998689

  10. Neuromorphic cognitive systems a learning and memory centered approach

    CERN Document Server

    Yu, Qiang; Hu, Jun; Tan Chen, Kay

    2017-01-01

    This book presents neuromorphic cognitive systems from a learning and memory-centered perspective. It illustrates how to build a system network of neurons to perform spike-based information processing, computing, and high-level cognitive tasks. It is beneficial to a wide spectrum of readers, including undergraduate and postgraduate students and researchers who are interested in neuromorphic computing and neuromorphic engineering, as well as engineers and professionals in industry who are involved in the design and applications of neuromorphic cognitive systems, neuromorphic sensors and processors, and cognitive robotics. The book formulates a systematic framework, from the basic mathematical and computational methods in spike-based neural encoding, learning in both single and multi-layered networks, to a near cognitive level composed of memory and cognition. Since the mechanisms for integrating spiking neurons integrate to formulate cognitive functions as in the brain are little understood, studies of neuromo...

  11. Respiratory signaling of locus coeruleus neurons during hypercapnic acidosis in the bullfrog, Lithobates catesbeianus.

    Science.gov (United States)

    Santin, J M; Hartzler, L K

    2013-02-01

    The locus coeruleus (LC) in the brainstem senses alterations in CO(2)/pH and influences ventilatory adjustments that restore blood gas values to starting levels in bullfrogs (Lithobates catesbeianus). We hypothesized that neurons of the bullfrog LC are sensitive to changes in CO(2)/pH and that chemosensitive responses are intrinsic to individual neurons. In addition, we hypothesized putative respiratory control neurons of the bullfrog LC would be stimulated by hypercapnic acidosis within physiological ranges of P(CO(2))/pH. 84% of LC neurons depolarized and increased firing rates during exposure to hypercapnic acidosis (HA). A pH dose response curve shows LC neurons from bullfrogs increase firing rates during physiologically relevant CO(2)/pH changes. With chemical synapses blocked, half of chemosensitive neurons lost sensitivity to HA; however, gap junction blockade did not alter chemosensitive responses. Intrinsically chemosensitive neurons increased input resistance during HA. These data demonstrate that majority of neurons within the bullfrog LC elicit robust firing responses during physiological ΔCO(2)/pH, likely enabling adjustment of acid-base balance through breathing. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Proton- and ammonium-sensing by histaminergic neurons controlling wakefulness.

    Science.gov (United States)

    Yanovsky, Yevgenij; Zigman, Jeffrey M; Kernder, Anna; Bein, Alisa; Sakata, Ichiro; Osborne-Lawrence, Sherri; Haas, Helmut L; Sergeeva, Olga A

    2012-01-01

    The histaminergic neurons in the tuberomamillary nucleus (TMN) of the posterior hypothalamus are involved in the control of arousal. These neurons are sensitive to hypercapnia as has been shown in experiments examining c-Fos expression, a marker for increased neuronal activity. We investigated the mechanisms through which TMN neurons respond to changes in extracellular levels of acid/CO(2). Recordings in rat brain slices revealed that acidification within the physiological range (pH from 7.4 to 7.0), as well as ammonium chloride (5 mM), excite histaminergic neurons. This excitation is significantly reduced by antagonists of type I metabotropic glutamate receptors and abolished by benzamil, an antagonist of acid-sensing ion channels (ASICs) and Na(+)/Ca(2+) exchanger, or by ouabain which blocks Na(+)/K(+) ATPase. We detected variable combinations of 4 known types of ASICs in single TMN neurons, and observed activation of ASICs in single dissociated TMN neurons only at pH lower than 7.0. Thus, glutamate, which is known to be released by glial cells and orexinergic neurons, amplifies the acid/CO(2)-induced activation of TMN neurons. This amplification demands the coordinated function of metabotropic glutamate receptors, Na(+)/Ca(2+) exchanger and Na(+)/K(+) ATPase. We also developed a novel HDC-Cre transgenic reporter mouse line in which histaminergic TMN neurons can be visualized. In contrast to the rat, the mouse histaminergic neurons lacked the pH 7.0-induced excitation and displayed only a minimal response to the mGluR I agonist DHPG (0.5 μM). On the other hand, ammonium-induced excitation was similar in mouse and rat. These results are relevant for the understanding of the neuronal mechanisms controlling acid/CO(2)-induced arousal in hepatic encephalopathy and obstructive sleep apnoea. Moreover, the new HDC-Cre mouse model will be a useful tool for studying the physiological and pathophysiological roles of the histaminergic system.

  13. Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

    Science.gov (United States)

    Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

    2015-11-18

    Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. [Frontiers in Live Bone Imaging Researches. In vivo imaging of neuron and glia].

    Science.gov (United States)

    Wake, Hiroaki; Kato, Daisuke

    2015-06-01

    Glial cells originate the Greek word'glue'had traditionally been only thought as supporting cells for neurons. Because glial cells are electrically non-excitable, neuroscience researchers have focused on elucidation of excitable cell properties, neuron. Recent advanced optical methods lead us to observe glial structure, motility and their function in normal physiological conditions. These approaches let us to know that they are not just the supporting cells for neuron but could receive signal from neurons through receptors for neurotransmitters and to regulate neuronal functions, thus modulating behavior phenotype. Such studies also suggest that glial cells are highly dynamic and actively maintain brain homeostasis. Here, we review physiological function of glial cells through a new perspective clarified by innovations of imaging technology including two-photon microscope.

  15. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

    Science.gov (United States)

    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

  16. In search for a gold-standard procedure to count motor neurons in the spinal cord.

    Science.gov (United States)

    Ferrucci, Michela; Lazzeri, Gloria; Flaibani, Marina; Biagioni, Francesca; Cantini, Federica; Madonna, Michele; Bucci, Domenico; Limanaqi, Fiona; Soldani, Paola; Fornai, Francesco

    2018-03-14

    Counting motor neurons within the spinal cord and brainstem represents a seminal step to comprehend the anatomy and physiology of the final common pathway sourcing from the CNS. Motor neuron loss allows to assess the severity of motor neuron disorders while providing a tool to assess disease modifying effects. Counting motor neurons at first implies gold standard identification methods. In fact, motor neurons may occur within mixed nuclei housing a considerable amount of neurons other than motor neurons. In the present review, we analyse various approaches to count motor neurons emphasizing both the benefits and bias of each protocol. A special emphasis is placed on discussing automated stereology. When automated stereology does not take into account site-specificity and does not distinguish between heterogeneous neuronal populations, it may confound data making such a procedure a sort of "guide for the perplex". Thus, if on the one hand automated stereology improves our ability to quantify neuronal populations, it may also hide false positives/negatives in neuronal counts. For instance, classic staining for antigens such as SMI-32, SMN and ChAT, which are routinely considered to be specific for motor neurons, may also occur in other neuronal types of the spinal cord. Even site specificity within Lamina IX may be misleading due to neuronal populations having a size and shape typical of motor neurons. This is the case of spinal border cells, which often surpass the border of Lamina VII and intermingle with motor neurons of Lamina IX. The present article discusses the need to join automated stereology with a dedicated knowledge of each specific neuroanatomical setting.

  17. Brain Signal Variability Differentially Affects Cognitive Flexibility and Cognitive Stability.

    Science.gov (United States)

    Armbruster-Genç, Diana J N; Ueltzhöffer, Kai; Fiebach, Christian J

    2016-04-06

    Recent research yielded the intriguing conclusion that, in healthy adults, higher levels of variability in neuronal processes are beneficial for cognitive functioning. Beneficial effects of variability in neuronal processing can also be inferred from neurocomputational theories of working memory, albeit this holds only for tasks requiring cognitive flexibility. However, cognitive stability, i.e., the ability to maintain a task goal in the face of irrelevant distractors, should suffer under high levels of brain signal variability. To directly test this prediction, we studied both behavioral and brain signal variability during cognitive flexibility (i.e., task switching) and cognitive stability (i.e., distractor inhibition) in a sample of healthy human subjects and developed an efficient and easy-to-implement analysis approach to assess BOLD-signal variability in event-related fMRI task paradigms. Results show a general positive effect of neural variability on task performance as assessed by accuracy measures. However, higher levels of BOLD-signal variability in the left inferior frontal junction area result in reduced error rate costs during task switching and thus facilitate cognitive flexibility. In contrast, variability in the same area has a detrimental effect on cognitive stability, as shown in a negative effect of variability on response time costs during distractor inhibition. This pattern was mirrored at the behavioral level, with higher behavioral variability predicting better task switching but worse distractor inhibition performance. Our data extend previous results on brain signal variability by showing a differential effect of brain signal variability that depends on task context, in line with predictions from computational theories. Recent neuroscientific research showed that the human brain signal is intrinsically variable and suggested that this variability improves performance. Computational models of prefrontal neural networks predict differential

  18. Reproduction, physiology and biochemistry

    Science.gov (United States)

    This chapter summarizes fundamental knowledge and recent discoveries about the reproduction, physiology and biochemistry of plant-parasitic nematodes. Various types of reproduction are reviewed, including sexual reproduction and mitotic and meiotic parthenogenesis. Although much is known about the p...

  19. Endogenous Pyrogen Physiology.

    Science.gov (United States)

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  20. [Mirror neurons: from anatomy to pathophysiological and therapeutic implications].

    Science.gov (United States)

    Mathon, B

    2013-04-01

    Mirror neurons are a special class of neurons discovered in the 1990s. They respond when we perform an action and also when we see someone else perform that action. They play a role in the pathophysiology of some neuropsychiatric diseases. Mirror neurons have been identified in humans: in Broca's area and the inferior parietal cortex. Their responses are qualitative and selective depending on the observed action. Emotions (including disgust) and empathy seem to operate according to a mirror mechanism. Indeed, the mirror system allows us to encode the sensory experience and to simulate the emotional state of others. This results in our improved identification of the emotions in others. Additionally, mirror neurons can encode an observed action in motor stimuli and allow its reproduction; thus, they are involved in imitation and learning. Current studies are assessing the role of mirror neurons in the pathopysiology of social-behavior disorders, including autism and schizophrenia. Understanding this mirror system will allow us to develop psychotherapy practices based on empathic resonance between the patient and the therapist. Also, some authors report that a passive rehabilitation technique, based on stimulation of the mirror-neuron system, has a beneficial effect in the treatment of patients with post-stroke motor deficits. Mirror neurons are an anatomical entity that enables improved understanding of behavior and emotions, and serves as a base for developing new cognitive therapies. Additional studies are needed to clarify the exact role of this neuronal system in social cognition and its role in the development of some neuropsychiatric diseases. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. Determination of relevant neuron-neuron connections for neural prosthetics using time-delayed mutual information: tutorial and preliminary results.

    Science.gov (United States)

    Taghva, Alexander; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W

    2012-12-01

    Identification of functional dependence among neurons is a necessary component in both the rational design of neural prostheses as well as in the characterization of network physiology. The objective of this article is to provide a tutorial for neurosurgeons regarding information theory, specifically time-delayed mutual information, and to compare time-delayed mutual information, an information theoretic quantity based on statistical dependence, with cross-correlation, a commonly used metric for this task in a preliminary analysis of rat hippocampal neurons. Spike trains were recorded from rats performing delayed nonmatch-to-sample task using an array of electrodes surgically implanted into the hippocampus of each hemisphere of the brain. In addition, spike train simulations of positively correlated neurons, negatively correlated neurons, and neurons correlated by nonlinear functions were generated. These were evaluated by time-delayed mutual information (MI) and cross-correlation. Application of time-delayed MI to experimental data indicated the optimal bin size for information capture in the CA3-CA1 system was 40 ms, which may provide some insight into the spatiotemporal nature of encoding in the rat hippocampus. On simulated data, time-delayed MI showed peak values at appropriate time lags in positively correlated, negatively correlated, and complexly correlated data. Cross-correlation showed peak and troughs with positively correlated and negatively correlated data, but failed to capture some higher order correlations. Comparison of time-delayed MI to cross-correlation in identification of functionally dependent neurons indicates that the methods are not equivalent. Time-delayed MI appeared to capture some interactions between CA3-CA1 neurons at physiologically plausible time delays missed by cross-correlation. It should be considered as a method for identification of functional dependence between neurons and may be useful in the development of neural

  2. Biophysics and cell physiology

    International Nuclear Information System (INIS)

    Mazur, P.

    1975-01-01

    Progress is reported on research activities in the fields of physiology and low-temperature biology of mammalian embryos; effects of sub-zero temperatures on eggs and embryos of sea urchins; survival of frozen-thawed human red cells; effects of radiation on physiology of Escherichia coli; transfer of triplet electronic energy in dinucleotides; effects of x radiation on DNA degradation; energy deposition by neutrons; photosynthesis; excision repair of uv-induced pyrimidine dimers in DNA of plant cells

  3. Physiology of Ramadan fasting

    OpenAIRE

    Shokoufeh Bonakdaran

    2016-01-01

    Considering the emphasis of Islam on the importance of fasting, Muslims attempt to fast from dawn until sunset during the holy month of Ramadan. Fasting is associated with several benefits for normal and healthy individuals. However, it could pose high risks to the health of diabetic patients due to certain physiological changes. This study aimed to compare the physiological changes associated with fasting in healthy individuals and diabetic patients during Ramadan. Furthermore, we reviewed t...

  4. Reconciling genetic evolution and the associative learning account of mirror neurons through data-acquisition mechanisms.

    Science.gov (United States)

    Lotem, Arnon; Kolodny, Oren

    2014-04-01

    An associative learning account of mirror neurons should not preclude genetic evolution of its underlying mechanisms. On the contrary, an associative learning framework for cognitive development should seek heritable variation in the learning rules and in the data-acquisition mechanisms that construct associative networks, demonstrating how small genetic modifications of associative elements can give rise to the evolution of complex cognition.

  5. Personalized physiological medicine.

    Science.gov (United States)

    Ince, Can

    2017-12-28

    This paper introduces the concept of personalized physiological medicine that is specifically directed at the needs of the critically ill patient. This differs from the conventional view of personalized medicine, characterized by biomarkers and gene profiling, instead focusing on time-variant changes in the pathophysiology and regulation of various organ systems and their cellular and subcellular constituents. I propose that personalized physiological medicine is composed of four pillars relevant to the critically ill patient. Pillar 1 is defined by the frailty and fitness of the patient and their physiological reserve to cope with the stress of critical illness and therapy. Pillar 2 involves monitoring of the key physiological variables of the different organ systems and their response to disease and therapy. Pillar 3 concerns the evaluation of the success of resuscitation by assessment of the hemodynamic coherence between the systemic and microcirculation and parenchyma of the organ systems. Finally, pillar 4 is defined by the integration of the physiological and clinical data into a time-learning adaptive model of the patient to provide feedback about the function of organ systems and to guide and assess the response to disease and therapy. I discuss each pillar and describe the challenges to research and development that will allow the realization of personalized physiological medicine to be practiced at the bedside for critically ill patients.

  6. ALS and other motor neuron diseases.

    Science.gov (United States)

    Tiryaki, Ezgi; Horak, Holli A

    2014-10-01

    This review describes the most common motor neuron disease, ALS. It discusses the diagnosis and evaluation of ALS and the current understanding of its pathophysiology, including new genetic underpinnings of the disease. This article also covers other motor neuron diseases, reviews how to distinguish them from ALS, and discusses their pathophysiology. In this article, the spectrum of cognitive involvement in ALS, new concepts about protein synthesis pathology in the etiology of ALS, and new genetic associations will be covered. This concept has changed over the past 3 to 4 years with the discovery of new genes and genetic processes that may trigger the disease. As of 2014, two-thirds of familial ALS and 10% of sporadic ALS can be explained by genetics. TAR DNA binding protein 43 kDa (TDP-43), for instance, has been shown to cause frontotemporal dementia as well as some cases of familial ALS, and is associated with frontotemporal dysfunction in ALS. The anterior horn cells control all voluntary movement: motor activity, respiratory, speech, and swallowing functions are dependent upon signals from the anterior horn cells. Diseases that damage the anterior horn cells, therefore, have a profound impact. Symptoms of anterior horn cell loss (weakness, falling, choking) lead patients to seek medical attention. Neurologists are the most likely practitioners to recognize and diagnose damage or loss of anterior horn cells. ALS, the prototypical motor neuron disease, demonstrates the impact of this class of disorders. ALS and other motor neuron diseases can represent diagnostic challenges. Neurologists are often called upon to serve as a "medical home" for these patients: coordinating care, arranging for durable medical equipment, and leading discussions about end-of-life care with patients and caregivers. It is important for neurologists to be able to identify motor neuron diseases and to evaluate and treat patients affected by them.

  7. Kappe neurons, a novel population of olfactory sensory neurons.

    Science.gov (United States)

    Ahuja, Gaurav; Bozorg Nia, Shahrzad; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  8. Spontaneous Cognition and Epistemic Agency in the Cognitive Niche

    Science.gov (United States)

    Fabry, Regina E.

    2018-01-01

    According to Thomas Metzinger, many human cognitive processes in the waking state are spontaneous and are deprived of the experience of epistemic agency. He considers mind wandering as a paradigm example of our recurring loss of epistemic agency. I will enrich this view by extending the scope of the concept of epistemic agency to include cases of depressive rumination and creative cognition, which are additional types of spontaneous cognition. Like mind wandering, they are characterized by unique phenomenal and functional properties that give rise to varying degrees of epistemic agency. The main claim of this paper will be that the experience of being an epistemic agent within a certain time frame is a relational phenomenon that emerges from the organism’s capacity to interact with its cognitive niche. To explore this relation, I develop a new framework that integrates phenomenological considerations on epistemic agency with a functional account of the reciprocal coupling of the embodied organism with its cognitive niche. This account rests upon dynamical accounts of strong embodied and embedded cognition and recent work on cognitive niche construction. Importantly, epistemic agency and organism-niche coupling are gradual phenomena ranging from weak to strong realizations. The emerging framework will be employed to analyze mind wandering, depressive rumination, and creative cognition as well as their commonalities and differences. Mind wandering and depressive rumination are cases of weak epistemic agency and organism-niche coupling. However, there are also important phenomenological, functional, and neuronal differences. In contrast, creative cognition is a case of strong epistemic agency and organism-niche coupling. By providing a phenomenological and functional analysis of these distinct types of spontaneous cognition, we can gain a better understanding of the importance of organism-niche interaction for the realization of epistemic agency.

  9. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

  10. Histological and functional benefit following transplantation of motor neuron progenitors to the injured rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Sharyn L Rossi

    2010-07-01

    Full Text Available Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit.In order to investigate the amenability of the injured adult spinal cord to motor neuron differentiation, we transplanted spinal cord injured animals with a high purity population of human motor neuron progenitors (hMNP derived from human embryonic stem cells (hESCs. In vitro, hMNPs displayed characteristic motor neuron-specific markers, a typical electrophysiological profile, functionally innervated human or rodent muscle, and secreted physiologically active growth factors that caused neurite branching and neuronal survival. hMNP transplantation into cervical SCI sites in adult rats resulted in suppression of intracellular signaling pathways associated with SCI pathogenesis, which correlated with greater endogenous neuronal survival and neurite branching. These neurotrophic effects were accompanied by significantly enhanced performance on all parameters of the balance beam task, as compared to controls. Interestingly, hMNP transplantation resulted in survival, differentiation, and site-specific integration of hMNPs distal to the SCI site within ventral horns, but hMNPs near the SCI site reverted to a neuronal progenitor state, suggesting an environmental deficiency for neuronal maturation associated with SCI.These findings underscore the barriers imposed on neuronal differentiation of transplanted cells by the gliogenic nature of the injured spinal cord, and the physiological relevance of transplant-derived neurotrophic support to functional recovery.

  11. Auditory DUM neurons in a bush-cricket: A filter bank for carrier frequency.

    Science.gov (United States)

    Lefebvre, Paule Chloé; Seifert, Marvin; Stumpner, Andreas

    2018-05-01

    In bush-crickets the first stage of central auditory processing occurs in the prothoracic ganglion. About 15 to 50 different auditory dorsal unpaired median neurons (DUM neurons) exist but they have not been studied in any detail. These DUM neurons may be classified into seven different morphological types, although, there is only limited correlation between morphology and physiological responses. Ninety seven percent of the stained neurons were local, 3% were intersegmental. About 90% project nearly exclusively into the auditory neuropile, and 45% into restricted areas therein. Lateral extensions overlap with the axons of primary auditory sensory neurons close to their branching point. DUM neurons are typically tuned to frequencies covering the range between 2 and 50 kHz and thereby may establish a filter bank for carrier frequency. Less than 10% of DUM neurons have their branches in adjacent and more posterior regions of the auditory neuropile and are mostly tuned to low frequencies, less sensitive than the other types and respond to vibration. Thirty five percent of DUM show indications of inhibition, either through reduced responses at higher intensities, or by hyperpolarizing responses to sound. Most DUM neurons produce phasic spike responses preferably at higher intensities. Spikes may be elicited by intracellular current injection. Preliminary data suggest that auditory DUM neurons have GABA as transmitter and therefore may inhibit other auditory interneurons. From all known local auditory neurons, only DUM neurons have frequency specific responses which appear suited for local processing relevant for acoustic communication in bush crickets. © 2018 Wiley Periodicals, Inc.

  12. Network feedback regulates motor output across a range of modulatory neuron activity.

    Science.gov (United States)

    Spencer, Robert M; Blitz, Dawn M

    2016-06-01

    Modulatory projection neurons alter network neuron synaptic and intrinsic properties to elicit multiple different outputs. Sensory and other inputs elicit a range of modulatory neuron activity that is further shaped by network feedback, yet little is known regarding how the impact of network feedback on modulatory neurons regulates network output across a physiological range of modulatory neuron activity. Identified network neurons, a fully described connectome, and a well-characterized, identified modulatory projection neuron enabled us to address this issue in the crab (Cancer borealis) stomatogastric nervous system. The modulatory neuron modulatory commissural neuron 1 (MCN1) activates and modulates two networks that generate rhythms via different cellular mechanisms and at distinct frequencies. MCN1 is activated at rates of 5-35 Hz in vivo and in vitro. Additionally, network feedback elicits MCN1 activity time-locked to motor activity. We asked how network activation, rhythm speed, and neuron activity levels are regulated by the presence or absence of network feedback across a physiological range of MCN1 activity rates. There were both similarities and differences in responses of the two networks to MCN1 activity. Many parameters in both networks were sensitive to network feedback effects on MCN1 activity. However, for most parameters, MCN1 activity rate did not determine the extent to which network output was altered by the addition of network feedback. These data demonstrate that the influence of network feedback on modulatory neuron activity is an important determinant of network output and feedback can be effective in shaping network output regardless of the extent of network modulation. Copyright © 2016 the American Physiological Society.

  13. Physiological arousal in processing recognition information

    Directory of Open Access Journals (Sweden)

    Guy Hochman

    2010-07-01

    Full Text Available The recognition heuristic (RH; Goldstein and Gigerenzer, 2002 suggests that, when applicable, probabilistic inferences are based on a noncompensatory examination of whether an object is recognized or not. The overall findings on the processes that underlie this fast and frugal heuristic are somewhat mixed, and many studies have expressed the need for considering a more compensatory integration of recognition information. Regardless of the mechanism involved, it is clear that recognition has a strong influence on choices, and this finding might be explained by the fact that recognition cues arouse affect and thus receive more attention than cognitive cues. To test this assumption, we investigated whether recognition results in a direct affective signal by measuring physiological arousal (i.e., peripheral arterial tone in the established city-size task. We found that recognition of cities does not directly result in increased physiological arousal. Moreover, the results show that physiological arousal increased with increasing inconsistency between recognition information and additional cue information. These findings support predictions derived by a compensatory Parallel Constraint Satisfaction model rather than predictions of noncompensatory models. Additional results concerning confidence ratings, response times, and choice proportions further demonstrated that recognition information and other cognitive cues are integrated in a compensatory manner.

  14. Journal of Gravitational Physiology, Volume 12, Number 1

    Science.gov (United States)

    Fuller, Charles A. (Editor); Cogoli, Augusto (Editor); Hargens, Alan R. (Editor); Smith, Arthur H. (Editor)

    2005-01-01

    The following topics were covered: System Specificity in Responsiveness to Intermittent -Gx Gravitation during Simulated Microgravity in Rats; A Brief Overview of Animal Hypergravity Studies; Neurovestibular Adaptation to Short Radius Centrifugation; Effect of Artificial Gravity with Exercise Load by Using Short-Arm Centrifuge with Bicycle Ergometer as a Countermeasure Against Disused Osteoporosis; Perception of Body Vertical in Microgravity during Parabolic Flight; Virtual Environment a Behavioral and Countermeasure Tool for Assisted Gesture in Weightlessness: Experiments during Parabolic Flight; Artificial Gravity: Physiological Perspectives for Long-Term Space Exploration; Comparison of the Effects of DL-threo-Beta-Benzyloxyaspartate on the Glutamate Release from Synaptosomes before and after Exposure of Rats to Artificial Gravity; Do Perception and Postrotatory Vestibulo-Ocular Reflex Share the Same Gravity Reference?; Vestibular Adaptation to Changing Gravity Levels and the Orientation of Listing's Plane; Compound Mechanism Hypothesis on +Gz - Induced Brain Injury and Dysfunction of Learning and Memory; Environmental Challenge Impairs Prefrontal Brain Functions; Effect of 6-Days of Support Withdrawal on Characteristics of Balance Function; Hypergravity-Induced Changes of Neuronal Activities in CA1 Region of Rat Hippocampus; Audiological Findings in Antiorthostatic Position Modelling Microgravitation; Investigating Human Cognitive Performance during Spaceflight; The Relevance of the Minimization of Torque Exchange with the Environment in Weightlessness is Confirmed by Asimulation Study; Characteristics of the Eyes Pursuit Function during Readaptation to Terrestrial Gravity after Prolonged Flights Aboard the International Space Station; Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects; Structural Reappraisal of Dendritic Tree of Cerebellar Purkinje Cell for Novel Functional Modeling of Elementary Sensorimotor Adaptive

  15. Neuronal Migration and Neuronal Migration Disorder in Cerebral Cortex

    OpenAIRE

    SUN, Xue-Zhi; TAKAHASHI, Sentaro; GUI, Chun; ZHANG, Rui; KOGA, Kazuo; NOUYE, Minoru; MURATA, Yoshiharu

    2002-01-01

    Neuronal cell migration is one of the most significant features during cortical development. After final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. Neuronal migration is guided by radial glial fibers and also needs proper receptors, ligands, and other unknown extracellular factors, requests local signaling (e.g. some emitted by the Cajal-Retz...

  16. The neuronal correlates of mirror illusion in children with spastic hemiparesis: a study with functional magnetic resonance imaging.

    Science.gov (United States)

    Weisstanner, Christian; Saxer, Stefanie; Wiest, Roland; Kaelin-Lang, Alain; Newman, Christopher J; Steinlin, Maja; Grunt, Sebastian

    2017-03-21

    To investigate the neuronal activation pattern underlying the effects of mirror illusion in children/adolescents with normal motor development and in children/adolescents with hemiparesis and preserved contralateral corticospinal organisation. The type of cortical reorganisation was classified according to results of transcranial magnetic stimulation. Only subjects with congenital lesions and physiological contralateral cortical reorganisation were included. Functional magnetic resonance imaging was performed to investigate neuronal activation patterns with and without a mirror box. Each test consisted of a unimanual and a bimanual motor task. Seven children/adolescents with congenital hemiparesis (10-20 years old, three boys and four girls) and seven healthy subjects (8-17 years old, four boys and three girls) participated in this study. In the bimanual experiment, children with hemiparesis showed a significant effect of the mirror illusion (phemiparesis leads to activation of brain areas involved in visual conflict detection and cognitive control to resolve this conflict. This effect is observed only in bimanual training. We consider that for mirror therapy in children and adolescents with hemiparesis a bimanual approach is more suitable than a unimanual approach.

  17. Changes in prefrontal neuronal activity after learning to perform a spatial working memory task.

    Science.gov (United States)

    Qi, Xue-Lian; Meyer, Travis; Stanford, Terrence R; Constantinidis, Christos

    2011-12-01

    The prefrontal cortex is considered essential for learning to perform cognitive tasks though little is known about how the representation of stimulus properties is altered by learning. To address this issue, we recorded neuronal activity in monkeys before and after training on a task that required visual working memory. After the subjects learned to perform the task, we observed activation of more prefrontal neurons and increased activity during working memory maintenance. The working memory-related increase in firing rate was due mostly to regular-spiking putative pyramidal neurons. Unexpectedly, the selectivity of neurons for stimulus properties and the ability of neurons to discriminate between stimuli decreased as the information about stimulus properties was apparently present in neural firing prior to training and neuronal selectivity degraded after training in the task. The effect was robust and could not be accounted for by differences in sampling sites, selection of neurons, level of performance, or merely the elapse of time. The results indicate that, in contrast to the effects of perceptual learning, mastery of a cognitive task degrades the apparent stimulus selectivity as neurons represent more abstract information related to the task. This effect is countered by the recruitment of more neurons after training.

  18. Mirror neurons and the social nature of language: the neural exploitation hypothesis.

    Science.gov (United States)

    Gallese, Vittorio

    2008-01-01

    This paper discusses the relevance of the discovery of mirror neurons in monkeys and of the mirror neuron system in humans to a neuroscientific account of primates' social cognition and its evolution. It is proposed that mirror neurons and the functional mechanism they underpin, embodied simulation, can ground within a unitary neurophysiological explanatory framework important aspects of human social cognition. In particular, the main focus is on language, here conceived according to a neurophenomenological perspective, grounding meaning on the social experience of action. A neurophysiological hypothesis--the "neural exploitation hypothesis"--is introduced to explain how key aspects of human social cognition are underpinned by brain mechanisms originally evolved for sensorimotor integration. It is proposed that these mechanisms were later on adapted as new neurofunctional architecture for thought and language, while retaining their original functions as well. By neural exploitation, social cognition and language can be linked to the experiential domain of action.

  19. Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates

    Science.gov (United States)

    Raghanti, Mary Ann; Conley, Tiffini; Sudduth, Jessica; Erwin, Joseph M.; Stimpson, Cheryl D.; Hof, Patrick R.; Sherwood, Chet C.

    2012-01-01

    We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system. PMID:23042407

  20. Learning Recruits Neurons Representing Previously Established Associations in the Corvid Endbrain.

    Science.gov (United States)

    Veit, Lena; Pidpruzhnykova, Galyna; Nieder, Andreas

    2017-10-01

    Crows quickly learn arbitrary associations. As a neuronal correlate of this behavior, single neurons in the corvid endbrain area nidopallium caudolaterale (NCL) change their response properties during association learning. In crows performing a delayed association task that required them to map both familiar and novel sample pictures to the same two choice pictures, NCL neurons established a common, prospective code for associations. Here, we report that neuronal tuning changes during learning were not distributed equally in the recorded population of NCL neurons. Instead, such learning-related changes relied almost exclusively on neurons which were already encoding familiar associations. Only in such neurons did behavioral improvements during learning of novel associations coincide with increasing selectivity over the learning process. The size and direction of selectivity for familiar and newly learned associations were highly correlated. These increases in selectivity for novel associations occurred only late in the delay period. Moreover, NCL neurons discriminated correct from erroneous trial outcome based on feedback signals at the end of the trial, particularly in newly learned associations. Our results indicate that task-relevant changes during association learning are not distributed within the population of corvid NCL neurons but rather are restricted to a specific group of association-selective neurons. Such association neurons in the multimodal cognitive integration area NCL likely play an important role during highly flexible behavior in corvids.

  1. Early Visual Cortex as a Multiscale Cognitive Blackboard

    NARCIS (Netherlands)

    Roelfsema, Pieter R.; de Lange, Floris P.

    2016-01-01

    Neurons in early visual cortical areas not only represent incoming visual information but are also engaged by higher level cognitive processes, including attention, working memory, imagery, and decision-making. Are these cognitive effects an epiphenomenon or are they functionally relevant for these

  2. Early visual cortex as a multiscale cognitive blackboard.

    NARCIS (Netherlands)

    Roelfsema, P.R.; De Lange, Floris

    2016-01-01

    Neurons in early visual cortical areas not only represent incoming visual information but are also engaged by higher level cognitive processes, including attention, working memory, imagery, and decision-making. Are these cognitive effects an epiphenomenon or are they functionally relevant for these

  3. Neuronal Activation After Prolonged Immobilization: Do the Same or Different Neurons Respond to a Novel Stressor?

    Science.gov (United States)

    Marín-Blasco, Ignacio; Muñoz-Abellán, Cristina; Andero, Raül; Nadal, Roser; Armario, Antonio

    2018-04-01

    Despite extensive research on the impact of emotional stressors on brain function using immediate-early genes (e.g., c-fos), there are still important questions that remain unanswered such as the reason for the progressive decline of c-fos expression in response to prolonged stress and the neuronal populations activated by different stressors. This study tackles these 2 questions by evaluating c-fos expression in response to 2 different emotional stressors applied sequentially, and performing a fluorescent double labeling of c-Fos protein and c-fos mRNA on stress-related brain areas. Results were complemented with the assessment of the hypothalamic-pituitary-adrenal axis activation. We showed that the progressive decline of c-fos expression could be related to 2 differing mechanisms involving either transcriptional repression or changes in stimulatory inputs. Moreover, the neuronal populations that respond to the different stressors appear to be predominantly separated in high-level processing areas (e.g., medial prefrontal cortex). However, in low-hierarchy areas (e.g., paraventricular nucleus of the hypothalamus) neuronal populations appear to respond unspecifically. The data suggest that the distinct physiological and behavioral consequences of emotional stressors, and their implication in the development of psychopathologies, are likely to be closely associated with neuronal populations specifically activated by each stressor.

  4. Plant Physiology and Development

    DEFF Research Database (Denmark)

    Taiz, Lincoln; Zeiger, Eduardo; Møller, Ian Max

    Throughout its twenty-two year history, the authors of Plant Physiology have continually updated the book to incorporate the latest advances in plant biology and implement pedagogical improvements requested by adopters. This has made Plant Physiology the most authoritative, comprehensive......, and widely used upper-division plant biology textbook. In the Sixth Edition, the Growth and Development section (Unit III) has been reorganized and expanded to present the complete life cycle of seed plants from germination to senescence. In recognition of this enhancement, the text has been renamed Plant...... Physiology and Development. As before, Unit III begins with updated chapters on Cell Walls and Signals and Signal Transduction. The latter chapter has been expanded to include a discussion of major signaling molecules, such as calcium ions and plant hormones. A new, unified chapter entitled Signals from...

  5. A multisensory centrifugal neuron in the olfactory pathway of heliothine moths

    DEFF Research Database (Denmark)

    Zhao, Xin-Cheng; Pfuhl, Gerit; Surlykke, Annemarie

    2013-01-01

    fine processes in the dorsomedial region of the protocerebrum and extensive neuronal branches with blebby terminals in all glomeruli of the antennal lobe. Its soma is located dorsally of the central body close to the brain midline. Mass-fills of antennal-lobe connections with protocerebral regions...... showed that the centrifugal neuron is, in each brain hemisphere, one within a small group of neurons having their somata clustered. In both species the neuron was excited during application of non-odorant airborne signals, including transient sound pulses of broad bandwidth and air velocity changes....... Additional responses to odors were recorded from the neuron in Heliothis virescens. The putative biological significance of the centrifugal antennal-lobe neuron is discussed with regard to its morphological and physiological properties. In particular, a possible role in multisensory processes underlying...

  6. Deleterious effects of neuronal accumulation of glycogen in flies and mice.

    Science.gov (United States)

    Duran, Jordi; Tevy, María Florencia; Garcia-Rocha, Mar; Calbó, Joaquim; Milán, Marco; Guinovart, Joan J

    2012-08-01

    Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form of GS to force neuronal accumulation of glycogen. We present evidence that the progressive accumulation of glycogen in mouse and Drosophila neurons leads to neuronal loss, locomotion defects and reduced lifespan. Our results highlight glycogen accumulation in neurons as a direct cause of neurodegeneration. Copyright © 2012 EMBO Molecular Medicine.

  7. Data on isoaspartylation of neuronal ELAVL proteins

    Directory of Open Access Journals (Sweden)

    Mario A. Pulido

    2016-12-01

    Full Text Available This article contains experimental data examining the propensity of neuronal ELAVL proteins to become isoaspartylated. The data are related to the article “Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4” (M.A. Pulido, M.K. DerHartunian, Z. Qin, E.M. Chung, D.S. Kang, A.W. Woodham, J.A. Tsou, R. Klooster, O. Akbari, L. Wang, W.M. Kast, S.V. Liu, J.J.G.M. Verschuuren, D.W. Aswad, I.A. Laird-Offringa, 2016 [1], in which it was reported that the N-terminal region of recombinant human ELAVL4 protein, incubated under physiological conditions, acquires a type of highly immunogenic protein damage. Here, we present Western blot analysis data generated by using an affinity-purified polyclonal rabbit antibody (raised against an N-terminal ELAVL4 isoaspartyl-converted peptide to probe recombinant protein fragments of the other three members of the ELAVL family: the highly homologous neuronal ELAVL2 (HuB and ELAVL3 (HuC, and the much less homologous ubiquitously expressed ELAVL1 (HuR.

  8. Motor cognition-motor semantics: action perception theory of cognition and communication.

    Science.gov (United States)

    Pulvermüller, Friedemann; Moseley, Rachel L; Egorova, Natalia; Shebani, Zubaida; Boulenger, Véronique

    2014-03-01

    A new perspective on cognition views cortical cell assemblies linking together knowledge about actions and perceptions not only as the vehicles of integrated action and perception processing but, furthermore, as a brain basis for a wide range of higher cortical functions, including attention, meaning and concepts, sequences, goals and intentions, and even communicative social interaction. This article explains mechanisms relevant to mechanistic action perception theory, points to concrete neuronal circuits in brains along with artificial neuronal network simulations, and summarizes recent brain imaging and other experimental data documenting the role of action perception circuits in cognition, language and communication. © 2013 Published by Elsevier Ltd.

  9. Neuronal nets in robotics

    International Nuclear Information System (INIS)

    Jimenez Sanchez, Raul

    1999-01-01

    The paper gives a generic idea of the solutions that the neuronal nets contribute to the robotics. The advantages and the inconveniences are exposed that have regarding the conventional techniques. It also describe the more excellent applications as the pursuit of trajectories, the positioning based on images, the force control or of the mobile robots management, among others

  10. Cognitive Control Signals in Posterior Cingulate Cortex

    Directory of Open Access Journals (Sweden)

    Benjamin eHayden

    2010-12-01

    Full Text Available Efficiently shifting between tasks is a central function of cognitive control. The role of the default network—a constellation of areas with high baseline activity that declines during task performance—in cognitive control remains poorly understood. We hypothesized that task switching demands cognitive control to shift the balance of processing towards the external world, and therefore predicted that switching between the two tasks would require suppression of activity of neurons within the CGp. To test this idea, we recorded the activity of single neurons in posterior cingulate cortex (CGp, a central node in the default network, in monkeys performing two interleaved tasks. As predicted, we found that basal levels of neuronal activity were reduced following a switch from one task to another and gradually returned to pre-switch baseline on subsequent trials. We failed to observe these effects in lateral intraparietal cortex (LIP, part of the dorsal fronto-parietal cortical attention network directly connected to CGp. These findings indicate that suppression of neuronal activity in CGp facilitates cognitive control, and suggest that activity in the default network reflects processes that directly compete with control processes elsewhere in the brain..

  11. Visual cognition

    Energy Technology Data Exchange (ETDEWEB)

    Pinker, S.

    1985-01-01

    This book consists of essays covering issues in visual cognition presenting experimental techniques from cognitive psychology, methods of modeling cognitive processes on computers from artificial intelligence, and methods of studying brain organization from neuropsychology. Topics considered include: parts of recognition; visual routines; upward direction; mental rotation, and discrimination of left and right turns in maps; individual differences in mental imagery, computational analysis and the neurological basis of mental imagery: componental analysis.

  12. Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

    Science.gov (United States)

    Benn, Abigail; Barker, Gareth R I; Stuart, Sarah A; Roloff, Eva V L; Teschemacher, Anja G; Warburton, E Clea; Robinson, Emma S J

    2016-05-04

    Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance. These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement. Copyright © 2016 Benn et al.

  13. Corazonin neurons function in sexually dimorphic circuitry that shape behavioral responses to stress in Drosophila.

    Directory of Open Access Journals (Sweden)

    Yan Zhao

    Full Text Available All organisms are confronted with dynamic environmental changes that challenge homeostasis, which is the operational definition of stress. Stress produces adaptive behavioral and physiological responses, which, in the Metazoa, are mediated through the actions of various hormones. Based on its associated phenotypes and its expression profiles, a candidate stress hormone in Drosophila is the corazonin neuropeptide. We evaluated the potential roles of corazonin in mediating stress-related changes in target behaviors and physiologies through genetic alteration of corazonin neuronal excitability. Ablation of corazonin neurons confers resistance to metabolic, osmotic, and oxidative stress, as measured by survival. Silencing and activation of corazonin neurons lead to differential lifespan under stress, and these effects showed a strong dependence on sex. Additionally, altered corazonin neuron physiology leads to fundamental differences in locomotor activity, and these effects were also sex-dependent. The dynamics of altered locomotor behavior accompanying stress was likewise altered in flies with altered corazonin neuronal function. We report that corazonin transcript expression is altered under starvation and osmotic stress, and that triglyceride and dopamine levels are equally impacted in corazonin neuronal alterations and these phenotypes similarly show significant sexual dimorphisms. Notably, these sexual dimorphisms map to corazonin neurons. These results underscore the importance of central peptidergic processing within the context of stress and place corazonin signaling as a critical feature of neuroendocrine events that shape stress responses and may underlie the inherent sexual dimorphic differences in stress responses.

  14. Cognitive Readiness

    National Research Council Canada - National Science Library

    Morrison, John

    2002-01-01

    Cognitive readiness is described as the mental preparation an individual needs to establish and sustain competent performance in the complex and unpredictable environment of modern military operations...

  15. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  16. [Chewing and cognitive function].

    Science.gov (United States)

    Hirano, Yoshiyuki; Onozuka, Minoru

    2014-01-01

    Chewing does not only crush food to aid swallowing and digestion; it also helps to relieve stress and regulate cognitive functions, including alertness and executive function. It is well known that chewing gum is used for sleepiness prevention during work, learning, and driving. In addition, it has been shown in the elderly that a decrease in the number of residual teeth is related to dementia onset. These findings suggest a link between chewing and maintaining memory and attention. Recently, many studies regarding the effects of chewing on memory and attention were conducted using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). When a working memory task was used, the middle frontal gyrus in the dorsolateral prefrontal cortex showed greater activation in addition to producing higher alertness after chewing. Furthermore, using an attentional network test, reaction time shortened, and the anterior cingulate cortex and left frontal gyrus were both activated for the executive network. From these results, it is suggested that chewing elevates alertness, consequently leading to improvements in cognitive performance. In this review, we introduce findings concerning the effects of chewing on cognitive performance, and discuss the neuronal mechanisms underlying these effects.

  17. Dynamical analysis of Parkinsonian state emulated by hybrid Izhikevich neuron models

    Science.gov (United States)

    Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Li, Huiyan; Loparo, Kenneth A.; Fietkiewicz, Chris

    2015-11-01

    Computational models play a significant role in exploring novel theories to complement the findings of physiological experiments. Various computational models have been developed to reveal the mechanisms underlying brain functions. Particularly, in the development of therapies to modulate behavioral and pathological abnormalities, computational models provide the basic foundations to exhibit transitions between physiological and pathological conditions. Considering the significant roles of the intrinsic properties of the globus pallidus and the coupling connections between neurons in determining the firing patterns and the dynamical activities of the basal ganglia neuronal network, we propose a hypothesis that pathological behaviors under the Parkinsonian state may originate from combined effects of intrinsic properties of globus pallidus neurons and synaptic conductances in the whole neuronal network. In order to establish a computational efficient network model, hybrid Izhikevich neuron model is used due to its capacity of capturing the dynamical characteristics of the biological neuronal activities. Detailed analysis of the individual Izhikevich neuron model can assist in understanding the roles of model parameters, which then facilitates the establishment of the basal ganglia-thalamic network model, and contributes to a further exploration of the underlying mechanisms of the Parkinsonian state. Simulation results show that the hybrid Izhikevich neuron model is capable of capturing many of the dynamical properties of the basal ganglia-thalamic neuronal network, such as variations of the firing rates and emergence of synchronous oscillations under the Parkinsonian condition, despite the simplicity of the two-dimensional neuronal model. It may suggest that the computational efficient hybrid Izhikevich neuron model can be used to explore basal ganglia normal and abnormal functions. Especially it provides an efficient way of emulating the large-scale neuron network

  18. Iso-α-acids, bitter components of beer, prevent obesity-induced cognitive decline.

    Science.gov (United States)

    Ayabe, Tatsuhiro; Ohya, Rena; Kondo, Keiji; Ano, Yasuhisa

    2018-03-19

    Dementia and cognitive decline have become worldwide public health problems, and it was recently reported that life-style related diseases and obesity are key risk factors in dementia. Iso-α-acids, hop-derived bitter components of beer, have been reported to have various physiological functions via activation of peroxisome proliferator-activated receptor γ. In this report, we demonstrated that daily intake of iso-α-acids suppresses inflammations in the hippocampus and improves cognitive decline induced by high fat diet (HFD). Body weight, epididymal fat weight, and plasma triglyceride levels were increased in HFD-fed mice, and significantly decreased in iso-α-acids supplemented HFD-fed mice. HFD feeding enhances the production of inflammatory cytokines and chemokines, such as TNF-α, which was significantly suppressed by iso-α-acids administration. HFD-induced neuroinflammation caused lipid peroxidation, neuronal loss, and atrophy in hippocampus, and those were not observed in iso-α-acids-treated mice. Furthermore, iso-α-acids intake significantly improved cognitive decline induced by HFD-feeding. Iso-α-acids are food derived components that suppressing both lipid accumulation and brain inflammation, thus iso-α-acids might be beneficial for the risk of dementia increased by obesity and lifestyle-related diseases.

  19. Nigerian Journal of Physiological Sciences

    African Journals Online (AJOL)

    Nigerian Journal of Physiological Sciences (Niger. J. Physiol. Sci.) is a biannual publication of the Physiological Society of Nigeria. It covers diverse areas of research in physiological sciences, publishing reviews in current research areas and original laboratory and clinical research in physiological sciences. Other websites ...

  20. Cognitive anthropology is a cognitive science.

    Science.gov (United States)

    Boster, James S

    2012-07-01

    Cognitive anthropology contributes to cognitive science as a complement to cognitive psychology. The chief threat to its survival has not been rejection by other cognitive scientists but by other cultural anthropologists. It will remain a part of cognitive science as long as cognitive anthropologists research, teach, and publish. Copyright © 2012 Cognitive Science Society, Inc.

  1. Do dorsal raphe 5-HT neurons encode "beneficialness"?

    Science.gov (United States)

    Luo, Minmin; Li, Yi; Zhong, Weixin

    2016-11-01

    The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) affects numerous behavioral and physiological processes. Drugs that alter 5-HT signaling treat several major psychiatric disorders and may lead to widespread abuse. The dorsal raphe nucleus (DRN) in the midbrain provides a majority of 5-HT for the forebrain. The importance of 5-HT signaling propels the search for a general theoretical framework under which the diverse functions of the DRN 5-HT neurons can be interpreted and additional therapeutic solutions may be developed. However, experimental data so far support several seeming irreconcilable theories, suggesting that 5-HT neurons mediate behavioral inhibition, aversive processing, or reward signaling. Here, we review recent progresses and propose that DRN 5-HT neurons encode "beneficialness" - how beneficial the current environmental context represents for an individual. Specifically, we speculate that the activity of these neurons reflects the possible net benefit of the current context as determined by p·R-C, in which p indicates reward probability, R the reward value, and C the cost. Through the widespread projections of these neurons to the forebrain, the beneficialness signal may reconfigure neural circuits to bias perception, boost positive emotions, and switch behavioral choices. The "beneficialness" hypothesis can explain many conflicting observations, and at the same time raises new questions. We suggest additional experiments that will help elucidate the exact computational functions of the DRN 5-HT neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Subfornical organ neurons integrate cardiovascular and metabolic signals.

    Science.gov (United States)

    Cancelliere, Nicole M; Ferguson, Alastair V

    2017-02-01

    The subfornical organ (SFO) is a critical circumventricular organ involved in the control of cardiovascular and metabolic homeostasis. Despite the plethora of circulating signals continuously sensed by the SFO, studies investigating how these signals are integrated are lacking. In this study, we use patch-clamp techniques to investigate how the traditionally classified "cardiovascular" hormone ANG II, "metabolic" hormone CCK and "metabolic" signal glucose interact and are integrated in the SFO. Sequential bath application of CCK (10 nM) and ANG (10 nM) onto dissociated SFO neurons revealed that 63% of responsive SFO neurons depolarized to both CCK and ANG; 25% depolarized to ANG only; and 12% hyperpolarized to CCK only. We next investigated the effects of glucose by incubating and recording neurons in either hypoglycemic, normoglycemic, or hyperglycemic conditions and comparing the proportions of responses to ANG ( n = 55) or CCK ( n = 83) application in each condition. A hyperglycemic environment was associated with a larger proportion of depolarizing responses to ANG ( χ 2 , P neurons excited by CCK are also excited by ANG and that glucose environment affects the responsiveness of neurons to both of these hormones, highlighting the ability of SFO neurons to integrate multiple metabolic and cardiovascular signals. These findings have important implications for this structure's role in the control of various autonomic functions during hyperglycemia. Copyright © 2017 the American Physiological Society.

  3. Neuronal oscillations with non-sinusoidal morphology produce spurious phase-to-amplitude coupling and directionality.

    Directory of Open Access Journals (Sweden)

    Diego Lozano-Soldevilla

    2016-08-01

    Full Text Available Neuronal oscillations support cognitive processing. Modern views suggest that neuronal oscillations do not only reflect coordinated activity in spatially distributed networks, but also that there is interaction between the oscillations at different frequencies. For example, invasive recordings in animals and humans have found that the amplitude of fast oscillations (> 40 Hz occur non-uniformly within the phase of slower oscillations, forming the so-called cross-frequency coupling (CFC. However, the CFC patterns be influenced by features in the signal that do not relate to underlying physiological interactions. For example, CFC estimates may be sensitive to spectral correlations due to non-sinusoidal properties of the alpha band wave morphology. To investigate this issue, we performed CFC analysis using experimental and synthetic data. The former consisted in a double-blind magnetoencephalography pharmacological study in which participants received either placebo, 0.5 mg or 1.5 mg of lorazepam (LZP; GABAergic enhancer in different experimental sessions. By recording oscillatory brain activity with during rest and working memory (WM, we were able to demonstrate that posterior alpha (8 – 12 Hz phase was coupled to beta-low gamma band (20 – 45 Hz amplitude envelope during all sessions. Importantly, bicoherence values around the harmonics of the alpha frequency were similar both in magnitude and topographic distribution to the cross-frequency coherence (CFCoh values observed in the alpha-phase to beta-low gamma coupling. In addition, despite the large CFCoh we found no significant cross-frequency directionality (CFD. Critically, simulations demonstrated that a sizable part of our empirical CFCoh between alpha and beta-low gamma coupling and the lack of CFD could be explained by two-three harmonics aligned in zero phase-lag produced by the physiologically characteristic alpha asymmetry in the amplitude of the peaks relative to the troughs

  4. Sleep physiology and sleep disorders in childhood

    Directory of Open Access Journals (Sweden)

    El Shakankiry HM

    2011-09-01

    Full Text Available Hanan M El ShakankiryKing Fahd University Hospital, Al Dammam University, Al Khobar, Kingdom of Saudi ArabiaAbstract: Sleep has long been considered as a passive phenomenon, but it is now clear that it is a period of intense brain activity involving higher cortical functions. Overall, sleep affects every aspect of a child's development, particularly higher cognitive functions. Sleep concerns are ranked as the fifth leading concern of parents. Close to one third of all children suffer from sleep disorders, the prevalence of which is increased in certain pediatric populations, such as children with special needs, children with psychiatric or medical diagnoses and children with autism or pervasive developmental disorders. The paper reviews sleep physiology and the impact, classification, and management of sleep disorders in the pediatric age group.Keywords: sleep physiology, sleep disorders, childhood, epilepsy

  5. Mesocortical dopaminergic function and human cognition

    International Nuclear Information System (INIS)

    Weinberger, D.R.; Berman, K.F.; Chase, T.N.

    1988-01-01

    In summary, we have reviewed rCBF data in humans that suggest that mesoprefrontal dopaminergic activity is involved in human cognition. In patients with Parkinson's disease and possibly in patients with schizophrenia, prefrontal physiological activation during a cognitive task that appears to depend on prefrontal neural systems correlates positively with cognitive performance on the task and with clinical signs of dopaminergic function. It may be possible in the future to examine prefrontal dopamine metabolism directly during prefrontal cognition using positron emission tomography and tracers such as F-18 DOPA. 21 references

  6. Adult hippocampal neurogenesis and cognitive aging

    Directory of Open Access Journals (Sweden)

    Román Darío Moreno Fernández

    2013-12-01

    Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

  7. Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment.

    Directory of Open Access Journals (Sweden)

    Ying F Liu

    Full Text Available Cell-adhesion molecules of the immunoglobulin superfamily play critical roles in brain development, as well as in maintaining synaptic plasticity, the dysfunction of which is known to cause cognitive impairment. Recently dysfunction of KIRREL3, a synaptic molecule of the immunoglobulin superfamily, has been implicated in several neurodevelopmental conditions including intellectual disability, autism spectrum disorder, and in the neurocognitive delay associated with Jacobsen syndrome. However, the molecular mechanisms of its physiological actions remain largely unknown. Using a yeast two-hybrid screen, we found that the KIRREL3 extracellular domain interacts with brain expressed proteins MAP1B and MYO16 and its intracellular domain can potentially interact with ATP1B1, UFC1, and SHMT2. The interactions were confirmed by co-immunoprecipitation and colocalization analyses of proteins expressed in human embryonic kidney cells, mouse neuronal cells, and rat primary neuronal cells. Furthermore, we show KIRREL3 colocalization with the marker for the Golgi apparatus and synaptic vesicles. Previously, we have shown that KIRREL3 interacts with the X-linked intellectual disability associated synaptic scaffolding protein CASK through its cytoplasmic domain. In addition, we found a genomic deletion encompassing MAP1B in one patient with intellectual disability, microcephaly and seizures and deletions encompassing MYO16 in two unrelated patients with intellectual disability, autism and microcephaly. MAP1B has been previously implicated in synaptogenesis and is involved in the development of the actin-based membrane skeleton. MYO16 is expressed in hippocampal neurons and also indirectly affects actin cytoskeleton through its interaction with WAVE1 complex. We speculate KIRREL3 interacting proteins are potential candidates for intellectual disability and autism spectrum disorder. Moreover, our findings provide further insight into understanding the molecular

  8. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

  9. Subtype-Specific Corticostriatal Projection Neuron Developmental Gene Expression and Corticospinal Expression of the Paroxysmal Nonkinesigenic Dyskinesia Gene

    OpenAIRE

    Xu, Zhaoying

    2016-01-01

    The mammalian neocortex is responsible for motor control, integration of sensory information, perception, cognitive function, and consciousness. It is complex, yet highly organized, with six layers containing broad classes of excitatory projection neurons (along with interneurons) with diverse subtype and area identities. Corticostriatal projection neurons (CStrPN) are the major cortical efferent neurons connecting the cerebral cortex to the striatum of the basal ganglia, and are critically i...

  10. Simulated Exercise Physiology Laboratories.

    Science.gov (United States)

    Morrow, James R., Jr.; Pivarnik, James M.

    This book consists of a lab manual and computer disks for either Apple or IBM hardware. The lab manual serves as "tour guide" for the learner going through the various lab experiences. The manual contains definitions, proper terminology, and other basic information about physiological principles. It is organized so a step-by-step procedure may be…

  11. Physiology Flies with Time.

    Science.gov (United States)

    Sehgal, Amita

    2017-11-30

    The 2017 Nobel Prize in Medicine or Physiology has been awarded to Jeffrey Hall, Michael Rosbash, and Michael Young for elucidating molecular mechanisms of the circadian clock. From studies beginning in fruit flies, we now know that circadian regulation pervades most biological processes and has strong ties to human health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Personalized physiological medicine

    NARCIS (Netherlands)

    Ince, Can

    2017-01-01

    This paper introduces the concept of personalized physiological medicine that is specifically directed at the needs of the critically ill patient. This differs from the conventional view of personalized medicine, characterized by biomarkers and gene profiling, instead focusing on time-variant

  13. Physiological responses to hypothermia.

    Science.gov (United States)

    Wood, Thomas; Thoresen, Marianne

    2015-04-01

    Therapeutic hypothermia is the only treatment currently recommended for moderate or severe encephalopathy of hypoxic‒ischaemic origin in term neonates. Though the effects of hypothermia on human physiology have been explored for many decades, much of the data comes from animal or adult studies; the latter originally after accidental hypothermia, followed by application of controlled hypothermia after cardiac arrest or trauma, or during cardiopulmonary bypass. Though this work is informative, the effects of hypothermia on neonatal physiology after perinatal asphyxia must be considered in the context of a prolonged hypoxic insult that has already induced a number of significant physiological sequelae. This article reviews the effects of therapeutic hypothermia on respiratory, cardiovascular, and metabolic parameters, including glycaemic control and feeding requirements. The potential pitfalls of blood‒gas analysis and overtreatment of physiological changes in cardiovascular parameters are also discussed. Finally, the effects of hypothermia on drug metabolism are covered, focusing on how the pharmacokinetics, pharmacodynamics, and dosing requirements of drugs frequently used in neonatal intensive care may change during therapeutic hypothermia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. The Face of Physiology

    Directory of Open Access Journals (Sweden)

    Paul White

    2008-10-01

    Full Text Available This article explores the relationship between the physiology of the emotions and the display of character in Victorian Britain. Charles Bell and others had begun to link certain physiological functions, such as respiration, with the expression of feelings such as fear, regarding the heart and other internal organs as instruments by which the emotions were made visible. But a purely functional account of the emotions, which emerged through the development of reflex physiology during the second half of the century, would dramatically alter the nature of feelings and the means of observing them. At the same time, instinctual or acquired sympathy, which had long underpinned the accurate reading of expressions, became a problem to be surmounted by new 'objectively'. Graphic recording instruments measuring a variety of physiological functions and used with increasing frequency in clinical diagnostics became of fundamental importance for tracing the movement of feelings during the period prior to the development of cinematography. They remained, in the form of devices such as the polygraph, a crucial and controversial means of measuring affective states, beneath the potentially deceptive surface of the body.

  15. [Anatomy and physiology of sexuality].

    Science.gov (United States)

    Cour, F; Droupy, S; Faix, A; Methorst, C; Giuliano, F

    2013-07-01

    Knowledge of the physiology of male and female sexuality has advanced considerably. Initially there is always desire with its biological neuroendocrine components and its emotional field which is particularly marked in women. There is a distinction between "spontaneous" sexual desire related to intrinsic affective, cognitive stimuli, and fantasies, and "reactive" sexual desire in response to physical arousal. There are similarities between men and women concerning the activation of cerebral zones in sexual arousal contexts in laboratory conditions. The neural pathways for sexual arousal are similar between men and women, bringing into play the sympathetic centres of the thoracic and lumbar spinal cord and, at the sacral level, the parasympathetic center and the motoneurons controlling the muscular contractions of the pelviperineal striated muscles. Genital sensitivity is mainly transmitted by the pudendal nerve in both men and women. Sexual arousal in men consists of penile erection, and ejaculation accompanied with orgasm. In women, sexual arousal causes increase in blood to flow to the vagina leading to lubrication and to the vulva leading to the erection of the clitoris and vulvar hyperaemia. The orgasm which can be multiple in women is accompanied by contractions of the striated perineal muscles. Several neurotransmitters are closely involved in the control of sexuality at the central level: dopamine, ocytocin, serotonin, and peripheral: nitric oxide and noradrenaline in men, vasoactive intestinal peptide and neuropeptide Y in women. Copyright © 2012. Published by Elsevier Masson SAS.

  16. Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways.

    Science.gov (United States)

    Zhang, Jie; Niu, Na; Wang, Mingyu; McNutt, Michael A; Zhang, Donghong; Zhang, Baogang; Lu, Shijun; Liu, Yuqing; Liu, Zhihui

    2013-08-01

    Oxidative and immune attacks from the environment or microglia have been implicated in the loss of dopaminergic neurons of Parkinson's disease. The role of IgG which is an important immunologic molecule in the process of Parkinson's disease has been unclear. Evidence suggests that IgG can be produced by neurons in addition to its traditionally recognized source B lymphocytes, but its function in neurons is poorly understood. In this study, extensive expression of neuron-derived IgG was demonstrated in dopaminergic neurons of human and rat mesencephalon. With an in vitro Parkinson's disease model, we found that neuron-derived IgG can improve the survival and reduce apoptosis of dopaminergic neurons induced by 6-hydroxydopamine toxicity, and also depress the release of NO from microglia triggered by 6-hydroxydopamine. Expression of TNF-α and IL-10 in microglia was elevated to protective levels by neuron-derived IgG at a physiologic level via the FcγR I and TLR4 pathways and microglial activation could be attenuated by IgG blocking. All these data suggested that neuron-derived IgG may exert a self-protective function by activating microglia properly, and IgG may be involved in maintaining immunity homeostasis in the central nervous system and serve as an active factor under pathological conditions such as Parkinson's disease. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  17. Coordinated scaling of cortical and cerebellar numbers of neurons

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    2010-03-01

    Full Text Available While larger brains possess concertedly larger cerebral cortices and cerebella, the relative size of the cerebral cortex increases with brain size, but relative cerebellar size does not. In the absence of data on numbers of neurons in these structures, this discrepancy has been used to dispute the hypothesis that the cerebral cortex and cerebellum function and have evolved in concert and to support a trend towards neocorticalization in evolution. However, the rationale for interpreting changes in absolute and relative size of the cerebral cortex and cerebellum relies on the assumption that they reflect absolute and relative numbers of neurons in these structures across all species – an assumption that our recent studies have shown to be flawed. Here I show for the first time that the numbers of neurons in the cerebral cortex and cerebellum are directly correlated across 19 mammalian species of 4 different orders, including humans, and increase concertedly in a similar fashion both within and across the orders Eulipotyphla (Insectivora, Rodentia, Scandentia and Primata, such that on average a ratio of 3.6 neurons in the cerebellum to every neuron in the cerebral cortex is maintained across species. This coordinated scaling of cortical and cerebellar numbers of neurons provides direct evidence in favor of concerted function, scaling and evolution of these brain structures, and suggests that the common notion that equates cognitive advancement with neocortical expansion should be revisited to consider in its stead the coordinated scaling of neocortex and cerebellum as a functional ensemble.

  18. The infant mirror neuron system studied with high density EEG.

    Science.gov (United States)

    Nyström, Pär

    2008-01-01

    The mirror neuron system has been suggested to play a role in many social capabilities such as action understanding, imitation, language and empathy. These are all capabilities that develop during infancy and childhood, but the human mirror neuron system has been poorly studied using neurophysiological measures. This study measured the brain activity of 6-month-old infants and adults using a high-density EEG net with the aim of identifying mirror neuron activity. The subjects viewed both goal-directed movements and non-goal-directed movements. An independent component analysis was used to extract the sources of cognitive processes. The desynchronization of the mu rhythm in adults has been shown to be a marker for activation of the mirror neuron system and was used as a criterion to categorize independent components between subjects. The results showed significant mu desynchronization in the adult group and significantly higher ERP activation in both adults and 6-month-olds for the goal-directed action observation condition. This study demonstrate that infants as young as 6 months display mirror neuron activity and is the first to present a direct ERP measure of the mirror neuron system in infants.

  19. Avian reproductive physiology

    Science.gov (United States)

    Gee, G.F.; Gibbons, Edward F.; Durrant, Barbara S.; Demarest, Jack

    1995-01-01

    Knowledge of the many physiological factors associated with egg production , fertility, incubation, and brooding in nondomestic birds is limited. Science knows even less about reproduction in most of the 238 endangered or threatened birds. This discussion uses studies of nondomestic and, when necessary, domestic birds to describe physiological control of reproduction. Studies of the few nondomestic avian species show large variation in physiological control of reproduction. Aviculturists, in order to successfully propagate an endangered bird, must understand the bird's reproductive peculiarities. First, investigators can do studies with carefully chosen surrogate species, but eventually they need to confirm the results in the target endangered bird. Studies of reproduction in nondomestic birds increased in the last decade. Still, scientists need to do more comparative studies to understand the mechanisms that control reproduction in birds. New technologies are making it possible to study reproductive physiology of nondomestic species in less limiting ways. These technologies include telemetry to collect information without inducing stress on captives (Howey et al., 1987; Klugman, 1987), new tests for most of the humoral factors associated with reproduction, and the skill to collect small samples and manipulate birds without disrupting the physiological mechanisms (Bercovitz et al., 1985). Managers are using knowledge from these studies to improve propagation in zoological parks, private and public propagation facilities, and research institutions. Researchers need to study the control of ovulation, egg formation, and oviposition in the species of nondomestic birds that lay very few eggs in a season, hold eggs in the oviduct for longer intervals, or differ in other ways from the more thoroughly studied domestic birds. Other techniques that would enhance propagation for nondomestlc birds include tissue culture of cloned embryonic cells, cryopreservation of embryos

  20. Prototypic and Arkypallidal Neurons in the Dopamine-Intact External Globus Pallidus

    Science.gov (United States)

    Abdi, Azzedine; Mallet, Nicolas; Mohamed, Foad Y.; Sharott, Andrew; Dodson, Paul D.; Nakamura, Kouichi C.; Suri, Sana; Avery, Sophie V.; Larvin, Joseph T.; Garas, Farid N.; Garas, Shady N.; Vinciati, Federica; Morin, Stéphanie; Bezard, Erwan

    2015-01-01

    Studies in dopamine-depleted rats indicate that the external globus pallidus (GPe) contains two main types of GABAergic projection cell; so-called “prototypic” and “arkypallidal” neurons. Here, we used correlative anatomical and electrophysiological approaches in rats to determine whether and how this dichotomous organization applies to the dopamine-intact GPe. Prototypic neurons coexpressed the transcription factors Nkx2-1 and Lhx6, comprised approximately two-thirds of all GPe neurons, and were the major GPe cell type innervating the subthalamic nucleus (STN). In contrast, arkypallidal neurons expressed the transcription factor FoxP2, constituted just over one-fourth of GPe neurons, and innervated the striatum but not STN. In anesthetized dopamine-intact rats, molecularly identified prototypic neurons fired at relatively high rates and with high regularity, regardless of brain state (slow-wave activity or spontaneous activation). On average, arkypallidal neurons fired at lower rates and regularities than prototypic neurons, and the two cell types could be further distinguished by the temporal coupling of their firing to ongoing cortical oscillations. Complementing the activity differences observed in vivo, the autonomous firing of identified arkypallidal neurons in vitro was slower and more variable than that of prototypic neurons, which tallied with arkypallidal neurons displaying lower amplitudes of a “persistent” sodium current important for such pacemaking. Arkypallidal neurons also exhibited weaker driven and rebound firing compared with prototypic neurons. In conclusion, our data support the concept that a dichotomous functional organization, as actioned by arkypallidal and prototypic neurons with specialized molecular, structural, and physiological properties, is fundamental to the operations of the dopamine-intact GPe. PMID:25926446

  1. Aberrant neuronal activity-induced signaling and gene expression in a mouse model of RASopathy.

    Directory of Open Access Journals (Sweden)

    Franziska Altmüller

    2017-03-01

    Full Text Available Noonan syndrome (NS is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain. Unlike mice with a global expression of this mutation, this strain is viable and without severe systemic phenotype, but shows lower exploratory activity and reduced memory specificity, which is in line with a causal role of disturbed neuronal Ptpn11 signaling in the development of NS-linked cognitive deficits. To explore the underlying mechanisms we investigated the neuronal activity-regulated Ras signaling in brains and neuronal cultures derived from this model. We observed an altered surface expression and trafficking of synaptic glutamate receptors, which are crucial for hippocampal neuronal plasticity. Furthermore, we show that the neuronal activity-induced ERK signaling, as well as the consecutive regulation of gene expression are strongly perturbed. Microarray-based hippocampal gene expression profiling revealed profound differences in the basal state and upon stimulation of neuronal activity. The neuronal activity-dependent gene regulation was strongly attenuated in Ptpn11D61Y neurons. In silico analysis of functional networks revealed changes in the cellular signaling beyond the dysregulation of Ras/MAPK signaling that is nearly exclusively discussed in the context of NS at present. Importantly, changes in PI3K/AKT/mTOR and JAK/STAT signaling were experimentally confirmed. In summary, this study uncovers aberrant neuronal activity

  2. Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons through Overlapping but Distinct Pathways

    Directory of Open Access Journals (Sweden)

    Lewis D. Evans

    2018-03-01

    Full Text Available Summary: In Alzheimer’s disease, neurofibrillary tangle pathology appears to spread along neuronal connections, proposed to be mediated by the release and uptake of abnormal, disease-specific forms of microtubule-binding protein tau MAPT. It is currently unclear whether transfer of tau between neurons is a toxic gain-of-function process in dementia or reflects a constitutive biological process. We report two entry mechanisms for monomeric tau to human neurons: a rapid dynamin-dependent phase typical of endocytosis and a second, slower actin-dependent phase of macropinocytosis. Aggregated tau entry is independent of actin polymerization and largely dynamin dependent, consistent with endocytosis and distinct from macropinocytosis, the major route for aggregated tau entry reported for non-neuronal cells. Anti-tau antibodies abrogate monomeric tau entry into neurons, but less efficiently in the case of aggregated tau, where internalized tau carries antibody with it into neurons. These data suggest that tau entry to human neurons is a physiological process and not a disease-specific phenomenon. : In contrast with predictions that transfer of the microtubule-associated protein tau between neurons is a toxic gain-of-function process in dementia, Evans et al. show that healthy human neurons efficiently take up both normal and aggregated tau, by distinct but overlapping uptake mechanisms. Keywords: Alzheimer’s disease, frontotemporal dementia, Tau, MAPT, iPSC, endocytosis, human neurons, intracellular transport

  3. Oxytocin-receptor-expressing neurons in the parabrachial nucleus regulate fluid intake.

    Science.gov (United States)

    Ryan, Philip J; Ross, Silvano I; Campos, Carlos A; Derkach, Victor A; Palmiter, Richard D

    2017-12-01

    Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (Oxtr PBN neurons) are key regulators of fluid satiation. Chemogenetic activation of Oxtr PBN neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection. Under physiological conditions, Oxtr PBN neurons were activated by fluid satiation and hypertonic saline injection. Oxtr PBN neurons were directly innervated by oxytocin neurons in the paraventricular hypothalamus (Oxt PVH  neurons), which mildly attenuated fluid intake. Activation of neurons in the nucleus of the solitary tract substantially suppressed fluid intake and activated Oxtr PBN neurons. Our results suggest that Oxtr PBN neurons act as a key node in the fluid satiation neurocircuitry, which acts to decrease water and/or saline intake to prevent or attenuate hypervolemia and hypernatremia.

  4. Neurons for hunger and thirst transmit a negative-valence teaching signal

    Science.gov (United States)

    Gong, Rong; Magnus, Christopher J.; Yu, Yang; Sternson, Scott M.

    2015-01-01

    Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics and dynamics of two separate neuron populations that regulate energy and fluid homeostasis by using cell type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis. PMID:25915020

  5. Neuronal synchrony: peculiarity and generality.

    Science.gov (United States)

    Nowotny, Thomas; Huerta, Ramon; Rabinovich, Mikhail I

    2008-09-01

    Synchronization in neuronal systems is a new and intriguing application of dynamical systems theory. Why are neuronal systems different as a subject for synchronization? (1) Neurons in themselves are multidimensional nonlinear systems that are able to exhibit a wide variety of different activity patterns. Their "dynamical repertoire" includes regular or chaotic spiking, regular or chaotic bursting, multistability, and complex transient regimes. (2) Usually, neuronal oscillations are the result of the cooperative activity of many synaptically connected neurons (a neuronal circuit). Thus, it is necessary to consider synchronization between different neuronal circuits as well. (3) The synapses that implement the coupling between neurons are also dynamical elements and their intrinsic dynamics influences the process of synchronization or entrainment significantly. In this review we will focus on four new problems: (i) the synchronization in minimal neuronal networks with plastic synapses (synchronization with activity dependent coupling), (ii) synchronization of bursts that are generated by a group of nonsymmetrically coupled inhibitory neurons (heteroclinic synchronization), (iii) the coordination of activities of two coupled neuronal networks (partial synchronization of small composite structures), and (iv) coarse grained synchronization in larger systems (synchronization on a mesoscopic scale). (c) 2008 American Institute of Physics.

  6. Visual cognition

    Energy Technology Data Exchange (ETDEWEB)

    Pinker, S.

    1985-01-01

    This collection of research papers on visual cognition first appeared as a special issue of Cognition: International Journal of Cognitive Science. The study of visual cognition has seen enormous progress in the past decade, bringing important advances in our understanding of shape perception, visual imagery, and mental maps. Many of these discoveries are the result of converging investigations in different areas, such as cognitive and perceptual psychology, artificial intelligence, and neuropsychology. This volume is intended to highlight a sample of work at the cutting edge of this research area for the benefit of students and researchers in a variety of disciplines. The tutorial introduction that begins the volume is designed to help the nonspecialist reader bridge the gap between the contemporary research reported here and earlier textbook introductions or literature reviews.

  7. Cognitive Systems

    DEFF Research Database (Denmark)

    The tutorial will discuss the definition of cognitive systems as the possibilities to extend the current systems engineering paradigm in order to perceive, learn, reason and interact robustly in open-ended changing environments. I will also address cognitive systems in a historical perspective...... to be modeled within a limited set of predefined specifications. There will inevitably be a need for robust decisions and behaviors in novel situations that include handling of conflicts and ambiguities based on the capability and knowledge of the artificial cognitive system. Further, there is a need...... in cognitive systems include e.g. personalized information systems, sensor network systems, social dynamics system and Web2.0, and cognitive components analysis. I will use example from our own research and link to other research activities....

  8. Cognitive remission

    DEFF Research Database (Denmark)

    Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A

    2016-01-01

    BACKGROUND: Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted...... phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD....... DISCUSSION: Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal...

  9. Metabolic Agents that Enhance ATP can Improve Cognitive Functioning: A Review of the Evidence for Glucose, Oxygen, Pyruvate, Creatine, and l-Carnitine

    Directory of Open Access Journals (Sweden)

    Lauren Owen

    2011-08-01

    Full Text Available Over the past four or five decades, there has been increasing interest in the neurochemical regulation of cognition. This field received considerable attention in the 1980s, with the identification of possible cognition enhancing agents or “smart drugs”. Even though many of the optimistic claims for some agents have proven premature, evidence suggests that several metabolic agents may prove to be effective in improving and preserving cognitive performance and may lead to better cognitive aging through the lifespan. Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. There are a number of agents with the potential to improve metabolic activity. Research is now beginning to identify these various agents and delineate their potential usefulness for improving cognition in health and disease. This review provides a brief overview of the metabolic agents glucose, oxygen, pyruvate, creatine, and l-carnitine and their beneficial effects on cognitive function. These agents are directly responsible for generating ATP (adenosine triphosphate the main cellular currency of energy. The brain is the most metabolically active organ in the body and as such is particularly vulnerable to disruption of energy resources. Therefore interventions that sustain adenosine triphosphate (ATP levels may have importance for improving neuronal dysfunction and loss. Moreover, recently, it has been observed that environmental conditions and diet can affect transgenerational gene expression via epigenetic mechanisms. Metabolic agents might play a role in regulation of nutritional epigenetic effects. In summary, the reviewed metabolic agents represent a promising strategy for improving cognitive function and possibly slowing or preventing cognitive decline.

  10. The mevalonate pathway in neurons: It's not just about cholesterol.

    Science.gov (United States)

    Moutinho, Miguel; Nunes, Maria João; Rodrigues, Elsa

    2017-11-01

    Cholesterol homeostasis greatly impacts neuronal function due to the essential role of this sterol in the brain. The mevalonate (MVA) pathway leads to the synthesis of cholesterol, but also supplies cells with many other intermediary molecules crucial for neuronal function. Compelling evidence point to a model in which neurons shutdown cholesterol synthesis, and rely on a shuttle derived from astrocytes to meet their cholesterol needs. Nevertheless, several reports suggest that neurons maintain the MVA pathway active, even with sustained cholesterol supply by astrocytes. Hence, in this review we focus not on cholesterol production, but rather on the role of the MVA pathway in the synthesis of particular intermediaries, namely isoprenoids, and on their role on neuronal function. Isoprenoids act as anchors for membrane association, after being covalently bound to proteins, such as most of the small guanosine triphosphate-binding proteins, which are critical to neuronal cell function. Based on literature, on our own results, and on the analysis of public transcriptomics databases, we raise the idea that in neurons there is a shift of the MVA pathway towards the non-sterol branch, responsible for isoprenoid synthesis, in detriment to post-squalene branch, and that this is ultimately essential for synaptic activity. Nevertheless new tools that facilitate imaging and the biochemical characterization and quantification of the prenylome in neurons and astrocytes are needed to understand the regulation of isoprenoid production and protein prenylation in the brain, and to analyze its differences on diverse physiological or pathological conditions, such as aging and neurodegenerative states. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Selective neuronal vulnerability to oxidative stress in the brain

    Directory of Open Access Journals (Sweden)

    Xinkun Wang

    2010-03-01

    Full Text Available Oxidative stress (OS, caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS, plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer’s disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

  12. Differential expression of alpha-synuclein in hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Katsutoshi Taguchi

    Full Text Available α-Synuclein is the major pathological component of synucleinopathies including Parkinson's disease and dementia with Lewy bodies. Recent studies have demonstrated that α-synuclein also plays important roles in the release of synaptic vesicles and synaptic membrane recycling in healthy neurons. However, the precise relationship between the pathogenicity and physiological functions of α-synuclein remains to be elucidated. To address this issue, we investigated the subcellular localization of α-synuclein in normal and pathological conditions using primary mouse hippocampal neuronal cultures. While some neurons expressed high levels of α-synuclein in presynaptic boutons and cell bodies, other neurons either did not or only very weakly expressed the protein. These α-synuclein-negative cells were identified as inhibitory neurons by immunostaining with specific antibodies against glutamic acid decarboxylase (GAD, parvalbumin, and somatostatin. In contrast, α-synuclein-positive synapses were colocalized with the excitatory synapse marker vesicular glutamate transporter-1. This expression profile of α-synuclein was conserved in the hippocampus in vivo. In addition, we found that while presynaptic α-synuclein colocalizes with synapsin, a marker of presynaptic vesicles, it is not essential for activity-dependent membrane recycling induced by high potassium treatment. Exogenous supply of preformed fibrils generated by recombinant α-synuclein was shown to promote the formation of Lewy body (LB -like intracellular aggregates involving endogenous α-synuclein. GAD-positive neurons did not form LB-like aggregates following treatment with preformed fibrils, however, exogenous expression of human α-synuclein allowed intracellular aggregate formation in these cells. These results suggest the presence of a different mechanism for regulation of the expression of α-synuclein between excitatory and inhibitory neurons. Furthermore, α-synuclein expression

  13. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

    proteins generate forces, to the macroscopic levels where overt arm movements are vol- untarily controlled within an unpredictable environment by legions of neurons¯ring in orderly fashion. An extensive computer simulation system has been developed for this thesis, which at present contains a neural...... network scripting language for specifying arbitrary neural architectures, de¯nition ¯les for detailed spinal networks, various biologically realistic models of neurons, and dynamic synapses. Also included are structurally accurate models of intrafusal and extra-fusal muscle ¯bers and a general body...... that an explicit function may be derived which expresses the force that the spindle contractile elements must produce to exactly counter spindle unloading during muscle shortening. This information was used to calculate the corresponding "optimal" °-motoneuronal activity level. For some simple arm movement tasks...

  14. Criticality in Neuronal Networks

    Science.gov (United States)

    Friedman, Nir; Ito, Shinya; Brinkman, Braden A. W.; Shimono, Masanori; Deville, R. E. Lee; Beggs, John M.; Dahmen, Karin A.; Butler, Tom C.

    2012-02-01

    In recent years, experiments detecting the electrical firing patterns in slices of in vitro brain tissue have been analyzed to suggest the presence of scale invariance and possibly criticality in the brain. Much of the work done however has been limited in two ways: 1) the data collected is from local field potentials that do not represent the firing of individual neurons; 2) the analysis has been primarily limited to histograms. In our work we examine data based on the firing of individual neurons (spike data), and greatly extend the analysis by considering shape collapse and exponents. Our results strongly suggest that the brain operates near a tuned critical point of a highly distinctive universality class.

  15. Insulin and insulin-like growth factor receptors in the brain: physiological and pathological aspects.

    Science.gov (United States)

    Werner, Haim; LeRoith, Derek

    2014-12-01

    The involvement of insulin, the insulin-like growth factors (IGF1, IGF2) and their receptors in central nervous system development and function has been the focus of scientific interest for more than 30 years. The insulin-like peptides, both locally-produced proteins as well as those transported from the circulation into the brain via the blood-brain barrier, are involved in a myriad of biological activities. These actions include, among others, neuronal survival, neurogenes, angiogenesis, excitatory and inhibitory neurotransmission, regulation of food intake, and cognition. In recent years, a linkage between brain insulin/IGF1 and certain neuropathologies has been identified. Epidemiological studies have demonstrated a correlation between diabetes (mainly type 2) and Alzheimer׳s disease. In addition, an aberrant decline in IGF1 values was suggested to play a role in the development of Alzheimer׳s disease. The present review focuses on the expression and function of insulin, IGFs and their receptors in the brain in physiological and pathological conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  16. Evolutionary appearance of von Economo's neurons in the mammalian cerebral cortex.

    Science.gov (United States)

    Cauda, Franco; Geminiani, Giuliano Carlo; Vercelli, Alessandro

    2014-01-01

    von Economo's neurons (VENs) are large, spindle-shaped projection neurons in layer V of the frontoinsular (FI) cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months. VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the "social brain." VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain. However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the "global Workspace" architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication) between salience-related insular and cingulate and other widely separated brain areas. Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the functional magnetic resonance imaging data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and experimental

  17. Evolutionary appearance of Von Economo’s Neurons in the mammalian cerebral cortex

    Directory of Open Access Journals (Sweden)

    Franco eCauda

    2014-03-01

    Full Text Available Von Economo’s neurons (VENs are large, spindle-shaped projection neurons in layer V of the frontoinsular (FI cortex, and the anterior cingulate cortex. During human ontogenesis, the VENs can first be differentiated at late stages of gestation, and increase in number during the first eight postnatal months.VENs have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and, more recently, in the macaque. Their distribution in great apes seems to correlate with human-like social cognitive abilities and self-awareness. VENs are also found in whales, in a number of different cetaceans, and in the elephant. This phylogenetic distribution may suggest a correlation among the VENs, brain size and the social brain. VENs may be involved in the pathogenesis of specific neurological and psychiatric diseases, such as autism, callosal agenesis and schizophrenia. VENs are selectively affected in a behavioral variant of frontotemporal dementia in which empathy, social awareness and self-control are seriously compromised, thus associating VENs with the social brain.However, the presence of VENs has also been related to special functions such as mirror self-recognition. Areas containing VENs have been related to motor awareness or sense-of-knowing, discrimination between self and other, and between self and the external environment. Along this line, VENs have been related to the global Workspace architecture: in accordance the VENs have been correlated to emotional and interoceptive signals by providing fast connections (large axons = fast communication between salience-related insular and cingulate and other widely separated brain areas.Nevertheless, the lack of a characterization of their physiology and anatomical connectivity allowed only to infer their functional role based on their location and on the fMRI data. The recent finding of VENs in the anterior insula of the macaque opens the way to new insights and experimental investigatio

  18. Cognitive Effects and Sedation.

    Science.gov (United States)

    Dhingra, Lara; Ahmed, Ebtesam; Shin, Jae; Scharaga, Elyssa; Magun, Maximilian

    2015-10-01

    Cognitive effects and sedation (CES) are prevalent in chronic nonmalignant pain populations receiving long-term opioid therapy and are among the most common reasons patients discontinue opioid use. In this narrative review, we describe the phenomenology, epidemiology, mechanisms, assessment, and management of opioid-related CES. We reviewed the empirical and theoretical literature on CES in opioid-treated populations with chronic pain. Data on long-term opioid therapy (≥ 3 months in duration) in chronic nonmalignant pain patients were sought. The phenomenology of CES includes: inattention, concentration difficulties, memory deficits, psychomotor dysfunction, perceptual distortions, and executive dysfunction and somnolence, sleep disorders, and lethargy. Deficits may be caused by unrelieved pain or opioid therapy alone, or from a combination of these and other factors. Mechanisms include central nervous system effects, for example, direct toxic effects on neurons resulting in decreased consciousness; direct effects on processing and reaction resulting in cognitive or psychomotor impairment, and inhibitory effects on cholinergic activity. Pharmacological management approaches may include opioid dose reduction and rotation or psychostimulant use. Nonpharmacological approaches may include cognitive-behavioral therapy, mindfulness-based stress reduction, acupuncture, exercise, and yoga. The most prevalent CES include: memory deficits (73-81%), sleep disturbance (35-57%), and fatigue (10%). At its most severe, extreme cognitive dysfunction can result in frank delirium and decreased alertness can result in coma. Emotional distress, sleep disorders, and other comorbidities and treatments can worsen CES, particularly among the elderly. Conclusions about the neuropsychological domains affected by opioids are limited due to the heterogeneity of studies and methodological issues. Wiley Periodicals, Inc.

  19. Timing of neuron development in the rodent vestibular system

    Science.gov (United States)

    Keefe, J. R.

    1982-01-01

    The timing of cell generation (onset and duration) in the developing rat vestibular and proprioceptive systems is investigated. The results clearly indicate a defined time-span for generation of all neurons in the central nervous system nuclei studied. This cytogenetic period in both vestibular and proprioceptive sensory nuclei is determined to occur during and immediately after placentation, a potentially critical period for spaceflight exposure due to alterations in maternal physiology.

  20. Two Aspects of ASIC Function: Synaptic Plasticity and Neuronal Injury.

    Science.gov (United States)

    Huang, Yan; Jiang, Nan; Li, Jun; Ji, Yong-Hua; Xiong, Zhi-Gang; Zha, Xiang-ming

    2015-01-01

    Extracellular brain pH fluctuates in both physiological and disease conditions. The main postsynaptic proton receptor is the acid-sensing ion channels (ASICs). During the past decade, much progress has been made on protons, ASICs, and neurological disease. This review summarizes the recent progress on synaptic role of protons and our current understanding of how ASICs contribute to various types of neuronal injury in the brain. PMID:25582290

  1. Renal phosphate handling: Physiology

    Directory of Open Access Journals (Sweden)

    Narayan Prasad

    2013-01-01

    Full Text Available Phosphorus is a common anion. It plays an important role in energy generation. Renal phosphate handling is regulated by three organs parathyroid, kidney and bone through feedback loops. These counter regulatory loops also regulate intestinal absorption and thus maintain serum phosphorus concentration in physiologic range. The parathyroid hormone, vitamin D, Fibrogenic growth factor 23 (FGF23 and klotho coreceptor are the key regulators of phosphorus balance in body.

  2. Interleukin-3 prevents neuronal death induced by amyloid peptide

    Directory of Open Access Journals (Sweden)

    Otth Carola

    2007-10-01

    Full Text Available Abstract Background Interleukin-3 (IL-3 is an important glycoprotein involved in regulating biological responses such as cell proliferation, survival and differentiation. Its effects are mediated via interaction with cell surface receptors. Several studies have demonstrated the expression of IL-3 in neurons and astrocytes of the hippocampus and cortices in normal mouse brain, suggesting a physiological role of IL-3 in the central nervous system. Although there is evidence indicating that IL-3 is expressed in some neuronal populations, its physiological role in these cells is poorly known. Results In this study, we demonstrated the expression of IL-3 receptor in cortical neurons, and analyzed its influence on amyloid β (Aβ-treated cells. In these cells, IL-3 can activate at least three classical signalling pathways, Jak/STAT, Ras/MAP kinase and the PI 3-kinase. Viability assays indicated that IL-3 might play a neuroprotective role in cells treated with Aβ fibrils. It is of interest to note that our results suggest that cell survival induced by IL-3 required PI 3-kinase and Jak/STAT pathway activation, but not MAP kinase. In addition, IL-3 induced an increase of the anti-apoptotic protein Bcl-2. Conclusion Altogether these data strongly suggest that IL-3 neuroprotects neuronal cells against neurodegenerative agents like Aβ.

  3. Orexin receptor activation generates gamma band input to cholinergic and serotonergic arousal system neurons and drives an intrinsic Ca2+-dependent resonance in LDT and PPT cholinergic neurons.

    Directory of Open Access Journals (Sweden)

    Masaru eIshibashi

    2015-06-01

    Full Text Available A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT and pedunculopontine (PPT tegmental neurons and serotonergic dorsal raphe (DR neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca2+-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal targets. Since key arousal input arises from hypothalamic orexin (hypocretin neurons, we investigated whether the unusually noisy, depolarizing orexin current could provide significant gamma input to cholinergic and serotonergic neurons, and whether such input could drive Ca2+-dependent oscillations. Whole-cell recordings in brain slices were obtained from mice expressing Cre-induced fluorescence in cholinergic LDT and PPT, and serotonergic DR neurons. After first quantifying reporter expression accuracy in cholinergic and serotonergic neurons, we found that the orexin current produced significant high frequency, including gamma, input to both cholinergic and serotonergic neurons. Then, by using a dynamic clamp, we found that adding a noisy orexin conductance to cholinergic neurons induced a Ca2+-dependent resonance that peaked in the theta and alpha frequency range (4 - 14 Hz and extended up to 100 Hz. We propose that this orexin current noise and the Ca2+ dependent resonance work synergistically to boost the encoding of high-frequency synaptic inputs into action potentials and to help ensure cholinergic neurons fire during EEG activation. This activity could reinforce thalamocortical states supporting arousal, REM sleep and intracortical

  4. Circadian physiology of metabolism.

    Science.gov (United States)

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

  5. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    Science.gov (United States)

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  6. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external g