Properties of doublecortin-(DCX-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice.

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Friederike Klempin

Full Text Available The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise, also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.

Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients.

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Martinez, Hector R; Gonzalez-Garza, Maria T; Moreno-Cuevas, Jorge E; Caro, Enrique; Gutierrez-Jimenez, Eugenio; Segura, Jose J

2009-01-01

Amyotrophic lateral sclerosis (ALS) is characterized by the selective death of motor neurons. CD133(+) stem cells are known to have the capacity to differentiate into neural lineages. Stem cells may provide an alternative treatment for ALS and other neurodegenerative diseases. Five men and five women (aged 38-62 years) with confirmed ALS were included in this study. Our institutional ethics and research committees approved the protocol. After informed consent was obtained, patients underwent Hidrogen-Magnetic Resonance Imaging (H-MRI) spectroscopy and were given scores according to an ALS functional rating scale, Medical Research Council power muscle scale and daily living activities. Bone marrow was stimulated with 300 microg filgrastim subcutaneously daily for 3 days. Peripheral blood mononuclear cells were obtained after admission by leukapheresis. The cell suspension was conjugated with anti-human CD133 superparamagnetic microbeads, and linked cells were isolated in a magnetic field. The isolated cells (2.5-7.5x10(5)) were resuspended in 300 microL of the patient's cerebrospinal fluid, and implanted in motor cortexes using a Hamilton syringe. Ten patients with confirmed ALS without transplantation were used as a control group. Patients were followed up for a period of 1 year. The autologous transplantation of CD133(+) stem cells into the frontal motor cortex is a safe and well-tolerated procedure in ALS patients. The survival of treated patients was statistically higher (P=0.01) than untreated control patients. Stem-cell transplantation in the motor cortex delays ALS progression and improves quality of life.

Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.

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Bifari, Francesco; Decimo, Ilaria; Pino, Annachiara; Llorens-Bobadilla, Enric; Zhao, Sheng; Lange, Christian; Panuccio, Gabriella; Boeckx, Bram; Thienpont, Bernard; Vinckier, Stefan; Wyns, Sabine; Bouché, Ann; Lambrechts, Diether; Giugliano, Michele; Dewerchin, Mieke; Martin-Villalba, Ana; Carmeliet, Peter

2017-03-02

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2 + neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Visual Information Present in Infragranular Layers of Mouse Auditory Cortex.

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Morrill, Ryan J; Hasenstaub, Andrea R

2018-03-14

The cerebral cortex is a major hub for the convergence and integration of signals from across the sensory modalities; sensory cortices, including primary regions, are no exception. Here we show that visual stimuli influence neural firing in the auditory cortex of awake male and female mice, using multisite probes to sample single units across multiple cortical layers. We demonstrate that visual stimuli influence firing in both primary and secondary auditory cortex. We then determine the laminar location of recording sites through electrode track tracing with fluorescent dye and optogenetic identification using layer-specific markers. Spiking responses to visual stimulation occur deep in auditory cortex and are particularly prominent in layer 6. Visual modulation of firing rate occurs more frequently at areas with secondary-like auditory responses than those with primary-like responses. Auditory cortical responses to drifting visual gratings are not orientation-tuned, unlike visual cortex responses. The deepest cortical layers thus appear to be an important locus for cross-modal integration in auditory cortex. SIGNIFICANCE STATEMENT The deepest layers of the auditory cortex are often considered its most enigmatic, possessing a wide range of cell morphologies and atypical sensory responses. Here we show that, in mouse auditory cortex, these layers represent a locus of cross-modal convergence, containing many units responsive to visual stimuli. Our results suggest that this visual signal conveys the presence and timing of a stimulus rather than specifics about that stimulus, such as its orientation. These results shed light on both how and what types of cross-modal information is integrated at the earliest stages of sensory cortical processing. Copyright © 2018 the authors 0270-6474/18/382854-09$15.00/0.

Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

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Fan, Chunling; Zhang, Mengqi; Shang, Lei; Cynthia, Ngobe Akume; Li, Zhi; Yang, Zhenyu; Chen, Dan; Huang, Jufang; Xiong, Kun

2014-01-01

Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine (a marker of cell proliferation), c-Fos (a marker of cell viability) and NeuN (a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs. PMID:25206818

Automatic detection and quantitative analysis of cells in the mouse primary motor cortex

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Meng, Yunlong; He, Yong; Wu, Jingpeng; Chen, Shangbin; Li, Anan; Gong, Hui

2014-09-01

Neuronal cells play very important role on metabolism regulation and mechanism control, so cell number is a fundamental determinant of brain function. Combined suitable cell-labeling approaches with recently proposed three-dimensional optical imaging techniques, whole mouse brain coronal sections can be acquired with 1-μm voxel resolution. We have developed a completely automatic pipeline to perform cell centroids detection, and provided three-dimensional quantitative information of cells in the primary motor cortex of C57BL/6 mouse. It involves four principal steps: i) preprocessing; ii) image binarization; iii) cell centroids extraction and contour segmentation; iv) laminar density estimation. Investigations on the presented method reveal promising detection accuracy in terms of recall and precision, with average recall rate 92.1% and average precision rate 86.2%. We also analyze laminar density distribution of cells from pial surface to corpus callosum from the output vectorizations of detected cell centroids in mouse primary motor cortex, and find significant cellular density distribution variations in different layers. This automatic cell centroids detection approach will be beneficial for fast cell-counting and accurate density estimation, as time-consuming and error-prone manual identification is avoided.

Dynamic expression of calretinin in embryonic and early fetal human cortex

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Miriam eGonzalez-Gomez

2014-06-01

Full Text Available Calretinin (CR is one of the earliest neurochemical markers in human corticogenesis. In embryos from Carnegie stages (CS 17 to 23, calbindin (CB and CR stain opposite poles of the incipient cortex suggesting early regionalization: CB marks the neuroepithelium of the medial boundary of the cortex with the choroid plexus (cortical hem. By contrast, CR is confined to the subventricular zone (SVZ of the lateral and caudal ganglionic eminences at the pallial-subpallial boundary (PSB, or antihem, from where CR+/Tbr1- neurons migrate toward piriform cortex and amygdala as a component of the lateral cortical stream. At CS 19, columns of CR+ cells arise in the rostral cortex, and contribute at CS 20 to the monolayer of horizontal Tbr1+/CR+ and GAD+ cells in the preplate. At CS 21, the pioneer cortical plate appears as a radial aggregation of CR+/Tbr1+ neurons, which cover the entire future neocortex and extend the first corticofugal axons. CR expression in early human corticogenesis is thus not restricted to interneurons, but is also present in the first excitatory projection neurons of the cortex. At CS 21/22, the cortical plate is established following a lateral to medial gradient, when Tbr1+/CR- neurons settle within the pioneer cortical plate, and thus separate superficial and deep pioneer neurons. CR+ pioneer neurons disappear shortly after the formation of the cortical plate. Reelin+ Cajal-Retzius cells begin to express CR around CS21 (7/8 PCW. At CS 21-23, the CR+ SVZ at the PSB is the source of CR+ interneurons migrating into the cortical SVZ. In turn, CB+ interneurons migrate from the subpallium into the intermediate zone following the fibers of the internal capsule. Early CR+ and CB+ interneurons thus have different origins and migratory routes. CR+ cell populations in the embryonic telencephalon take part in a complex sequence of events not analyzed so far in other mammalian species, which may represent a distinctive trait of the initial steps

Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

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Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

2018-02-21

Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

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Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

2016-03-01

Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis.

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Meijer, Kim A; Eijlers, Anand J C; Geurts, Jeroen J G; Schoonheim, Menno M

2018-02-01

Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages. A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes. Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability. Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Imaging and reconstruction of cell cortex structures near the cell surface

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Jin, Luhong; Zhou, Xiaoxu; Xiu, Peng; Luo, Wei; Huang, Yujia; Yu, Feng; Kuang, Cuifang; Sun, Yonghong; Liu, Xu; Xu, Yingke

2017-11-01

Total internal reflection fluorescence microscopy (TIRFM) provides high optical sectioning capability and superb signal-to-noise ratio for imaging of cell cortex structures. The development of multi-angle (MA)-TIRFM permits high axial resolution imaging and reconstruction of cellular structures near the cell surface. Cytoskeleton is composed of a network of filaments, which are important for maintenance of cell function. The high-resolution imaging and quantitative analysis of filament organization would contribute to our understanding of cytoskeleton regulation in cell. Here, we used a custom-developed MA-TIRFM setup, together with stochastic photobleaching and single molecule localization method, to enhance the lateral resolution of TIRFM imaging to about 100 nm. In addition, we proposed novel methods to perform filament segmentation and 3D reconstruction from MA-TIRFM images. Furthermore, we applied these methods to study the 3D localization of cortical actin and microtubule structures in U373 cancer cells. Our results showed that cortical actins localize ∼ 27 nm closer to the plasma membrane when compared with microtubules. We found that treatment of cells with chemotherapy drugs nocodazole and cytochalasin B disassembles cytoskeletal network and induces the reorganization of filaments towards the cell periphery. In summary, this study provides feasible approaches for 3D imaging and analyzing cell surface distribution of cytoskeletal network. Our established microscopy platform and image analysis toolkits would facilitate the study of cytoskeletal network in cells.

Synchronous induction of detachment and reattachment of symbiotic Chlorella spp. from the cell cortex of the host Paramecium bursaria.

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Kodama, Yuuki; Fujishima, Masahiro

2013-09-01

Paramecium bursaria harbor several hundred symbiotic Chlorella spp. Each alga is enclosed in a perialgal vacuole membrane, which can attach to the host cell cortex. How the perialgal vacuole attaches beneath the host cell cortex remains unknown. High-speed centrifugation (> 1000×g) for 1min induces rapid detachment of the algae from the host cell cortex and concentrates the algae to the posterior half of the host cell. Simultaneously, most of the host acidosomes and lysosomes accumulate in the anterior half of the host cell. Both the detached algae and the dislocated acidic vesicles recover their original positions by host cyclosis within 10min after centrifugation. These recoveries were inhibited if the host cytoplasmic streaming was arrested by nocodazole. Endosymbiotic algae during the early reinfection process also show the capability of desorption after centrifugation. These results demonstrate that adhesion of the perialgal vacuole beneath the host cell cortex is repeatedly inducible, and that host cytoplasmic streaming facilitates recovery of the algal attachment. This study is the first report to illuminate the mechanism of the induction to desorb for symbiotic algae and acidic vesicles, and will contribute to the understanding of the mechanism of algal and organelle arrangements in Paramecium. Copyright © 2013 Elsevier GmbH. All rights reserved.

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory.

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Bastos, André M; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K

2018-01-30

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. Copyright © 2018 the Author(s). Published by PNAS.

A hypothesis for the evolution of the upper layers of the neocortex through co-option of the olfactory cortex developmental program.

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Federico eLuzzati

2015-05-01

Full Text Available The neocortex is unique to mammals and its evolutionary origin is still highly debated. The neocortex is generated by the dorsal pallium ventricular zone, a germinative domain that in reptiles give rise to the dorsal cortex. Whether this latter allocortical structure contains homologues of all neocortical cell types it is unclear. Recently we described a population of DCX+/Tbr1+ cells that is specifically associated with the layer II of higher order areas of both the neocortex and of the more evolutionary conserved piriform cortex. In a reptile similar cells are present in the layer II of the olfactory cortex and the DVR but not in the dorsal cortex. These data are consistent with the proposal that the reptilian dorsal cortex is homologous only to the deep layers of the neocortex while the upper layers are a mammalian innovation. Based on our observations we extended these ideas by hypothesizing that this innovation was obtained by co-opting a lateral and/or ventral pallium developmental program. Interestingly, an analysis in the Allen brain atlas revealed a striking similarity in gene expression between neocortical layers II/III and piriform cortex. We thus propose a model in which the early neocortical column originated by the superposition of the lateral olfactory and dorsal cortex. This idea is consistent with previous hypotheses that the peri-allocortex (i.e insular and perirhinal cortex may represent the more ancient neocortical part. Our model may have also interesting implications in the study of sensory processing in both neocortex and piriform cortex. The great advances in deciphering the molecular logic of the amniote pallium developmental programs will hopefully enable to directly test our hypotheses in the next future.

Deep neural networks rival the representation of primate IT cortex for core visual object recognition.

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Charles F Cadieu

2014-12-01

Full Text Available The primate visual system achieves remarkable visual object recognition performance even in brief presentations, and under changes to object exemplar, geometric transformations, and background variation (a.k.a. core visual object recognition. This remarkable performance is mediated by the representation formed in inferior temporal (IT cortex. In parallel, recent advances in machine learning have led to ever higher performing models of object recognition using artificial deep neural networks (DNNs. It remains unclear, however, whether the representational performance of DNNs rivals that of the brain. To accurately produce such a comparison, a major difficulty has been a unifying metric that accounts for experimental limitations, such as the amount of noise, the number of neural recording sites, and the number of trials, and computational limitations, such as the complexity of the decoding classifier and the number of classifier training examples. In this work, we perform a direct comparison that corrects for these experimental limitations and computational considerations. As part of our methodology, we propose an extension of "kernel analysis" that measures the generalization accuracy as a function of representational complexity. Our evaluations show that, unlike previous bio-inspired models, the latest DNNs rival the representational performance of IT cortex on this visual object recognition task. Furthermore, we show that models that perform well on measures of representational performance also perform well on measures of representational similarity to IT, and on measures of predicting individual IT multi-unit responses. Whether these DNNs rely on computational mechanisms similar to the primate visual system is yet to be determined, but, unlike all previous bio-inspired models, that possibility cannot be ruled out merely on representational performance grounds.

Playing the electric light orchestra--how electrical stimulation of visual cortex elucidates the neural basis of perception.

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Cicmil, Nela; Krug, Kristine

2015-09-19

Vision research has the potential to reveal fundamental mechanisms underlying sensory experience. Causal experimental approaches, such as electrical microstimulation, provide a unique opportunity to test the direct contributions of visual cortical neurons to perception and behaviour. But in spite of their importance, causal methods constitute a minority of the experiments used to investigate the visual cortex to date. We reconsider the function and organization of visual cortex according to results obtained from stimulation techniques, with a special emphasis on electrical stimulation of small groups of cells in awake subjects who can report their visual experience. We compare findings from humans and monkeys, striate and extrastriate cortex, and superficial versus deep cortical layers, and identify a number of revealing gaps in the 'causal map' of visual cortex. Integrating results from different methods and species, we provide a critical overview of the ways in which causal approaches have been used to further our understanding of circuitry, plasticity and information integration in visual cortex. Electrical stimulation not only elucidates the contributions of different visual areas to perception, but also contributes to our understanding of neuronal mechanisms underlying memory, attention and decision-making.

Playing the electric light orchestra—how electrical stimulation of visual cortex elucidates the neural basis of perception

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Cicmil, Nela; Krug, Kristine

2015-01-01

Vision research has the potential to reveal fundamental mechanisms underlying sensory experience. Causal experimental approaches, such as electrical microstimulation, provide a unique opportunity to test the direct contributions of visual cortical neurons to perception and behaviour. But in spite of their importance, causal methods constitute a minority of the experiments used to investigate the visual cortex to date. We reconsider the function and organization of visual cortex according to results obtained from stimulation techniques, with a special emphasis on electrical stimulation of small groups of cells in awake subjects who can report their visual experience. We compare findings from humans and monkeys, striate and extrastriate cortex, and superficial versus deep cortical layers, and identify a number of revealing gaps in the ‘causal map′ of visual cortex. Integrating results from different methods and species, we provide a critical overview of the ways in which causal approaches have been used to further our understanding of circuitry, plasticity and information integration in visual cortex. Electrical stimulation not only elucidates the contributions of different visual areas to perception, but also contributes to our understanding of neuronal mechanisms underlying memory, attention and decision-making. PMID:26240421

Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer

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Yamazaki, Yukiko; Makino, Hatsune; Hamaguchi-Hamada, Kayoko; Hamada, Shun; Sugino, Hidehiko; Kawase, Eihachiro; Miyata, Takaki; Ogawa, Masaharu; Yanagimachi, Ryuzo; Yagi, Takeshi

2001-01-01

When neural cells were collected from the entire cerebral cortex of developing mouse fetuses (15.5–17.5 days postcoitum) and their nuclei were transferred into enucleated oocytes, 5.5% of the reconstructed oocytes developed into normal offspring. This success rate was the highest among all previous mouse cloning experiments that used somatic cells. Forty-four percent of live embryos at 10.5 days postcoitum were morphologically normal when premature and early-postmitotic neural cells from the ventricular side of the cortex were used. In contrast, the majority (95%) of embryos were morphologically abnormal (including structural abnormalities in the neural tube) when postmitotic-differentiated neurons from the pial side of the cortex were used for cloning. Whereas 4.3% of embryos cloned with ventricular-side cells developed into healthy offspring, only 0.5% of those cloned with differentiated neurons in the pial side did so. These facts seem to suggest that the nuclei of neural cells in advanced stages of differentiation had lost their developmental totipotency. The underlying mechanism for this developmental limitation could be somatic DNA rearrangements in differentiating neural cells. PMID:11698647

Deep Learning Automates the Quantitative Analysis of Individual Cells in Live-Cell Imaging Experiments.

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Van Valen, David A; Kudo, Takamasa; Lane, Keara M; Macklin, Derek N; Quach, Nicolas T; DeFelice, Mialy M; Maayan, Inbal; Tanouchi, Yu; Ashley, Euan A; Covert, Markus W

2016-11-01

Live-cell imaging has opened an exciting window into the role cellular heterogeneity plays in dynamic, living systems. A major critical challenge for this class of experiments is the problem of image segmentation, or determining which parts of a microscope image correspond to which individual cells. Current approaches require many hours of manual curation and depend on approaches that are difficult to share between labs. They are also unable to robustly segment the cytoplasms of mammalian cells. Here, we show that deep convolutional neural networks, a supervised machine learning method, can solve this challenge for multiple cell types across the domains of life. We demonstrate that this approach can robustly segment fluorescent images of cell nuclei as well as phase images of the cytoplasms of individual bacterial and mammalian cells from phase contrast images without the need for a fluorescent cytoplasmic marker. These networks also enable the simultaneous segmentation and identification of different mammalian cell types grown in co-culture. A quantitative comparison with prior methods demonstrates that convolutional neural networks have improved accuracy and lead to a significant reduction in curation time. We relay our experience in designing and optimizing deep convolutional neural networks for this task and outline several design rules that we found led to robust performance. We conclude that deep convolutional neural networks are an accurate method that require less curation time, are generalizable to a multiplicity of cell types, from bacteria to mammalian cells, and expand live-cell imaging capabilities to include multi-cell type systems.

The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development

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Mariella eErrede

2014-10-01

Full Text Available This study was conducted on human developing brain by laser confocal and transmission electron microscopy to make a detailed analysis of important features of blood-brain barrier microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The blood-brain barrier status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration and before cortex lamination, with blood-brain barrier-endothelial cell markers, namely tight junction proteins (occludin and claudin-5 and influx and efflux transporters (Glut-1 and P-glycoprotein, the latter supporting evidence for functional effectiveness of the fetal blood-brain barrier. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analysed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43 were utilized as markers of radial glia cells, CD105 (endoglin as a marker of angiogenically activated endothelial cells, and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial fibres in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical vessel-specific RG fibre swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of radial glial varicosities reveals colocalization of CXCL12 with connexin Cx43, which is possibly implicated in vessel-specific chemokine signalling.

Edge Detection Based On the Characteristic of Primary Visual Cortex Cells

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Zhu, M. M.; Xu, Y. L.; Ma, H. Q.

2018-01-01

Aiming at the problem that it is difficult to balance the accuracy of edge detection and anti-noise performance, and referring to the dynamic and static perceptions of the primary visual cortex (V1) cells, a V1 cell model is established to perform edge detection. A spatiotemporal filter is adopted to simulate the receptive field of V1 simple cells, the model V1 cell is obtained after integrating the responses of simple cells by half-wave rectification and normalization, Then the natural image edge is detected by using static perception of V1 cells. The simulation results show that, the V1 model can basically fit the biological data and has the universality of biology. What’s more, compared with other edge detection operators, the proposed model is more effective and has better robustness

Isotropic actomyosin dynamics promote organization of the apical cell cortex in epithelial cells.

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Klingner, Christoph; Cherian, Anoop V; Fels, Johannes; Diesinger, Philipp M; Aufschnaiter, Roland; Maghelli, Nicola; Keil, Thomas; Beck, Gisela; Tolić-Nørrelykke, Iva M; Bathe, Mark; Wedlich-Soldner, Roland

2014-10-13

Although cortical actin plays an important role in cellular mechanics and morphogenesis, there is surprisingly little information on cortex organization at the apical surface of cells. In this paper, we characterize organization and dynamics of microvilli (MV) and a previously unappreciated actomyosin network at the apical surface of Madin-Darby canine kidney cells. In contrast to short and static MV in confluent cells, the apical surfaces of nonconfluent epithelial cells (ECs) form highly dynamic protrusions, which are often oriented along the plane of the membrane. These dynamic MV exhibit complex and spatially correlated reorganization, which is dependent on myosin II activity. Surprisingly, myosin II is organized into an extensive network of filaments spanning the entire apical membrane in nonconfluent ECs. Dynamic MV, myosin filaments, and their associated actin filaments form an interconnected, prestressed network. Interestingly, this network regulates lateral mobility of apical membrane probes such as integrins or epidermal growth factor receptors, suggesting that coordinated actomyosin dynamics contributes to apical cell membrane organization. © 2014 Klingner et al.

Increased Cell Fusion in Cerebral Cortex May Contribute to Poststroke Regeneration

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Alexander Paltsyn

2013-01-01

Full Text Available In this study, we used a model of a hemorrhagic stroke in a motor zone of the cortex in rats at the age of 3 months The report shows that cortical neurons can fuse with oligodendrocytes. In formed binuclear cells, the nucleus of an oligodendrocyte undergoes neuron specific reprogramming. It can be confirmed by changes in chromatin structure and in size of the second nucleus, by expression of specific neuronal markers and increasing total transcription rate. The nucleus of an oligodendrocyte likely transforms into a second neuronal nucleus. The number of binuclear neurons was validated with quantitative analysis. Fusion of neurons with oligodendrocytes might be a regenerative process in general and specifically following a stroke. The appearance of additional neuronal nuclei increases the functional outcome of the population of neurons. Participation of a certain number of binuclear cells in neuronal function might compensate for a functional deficit that arises from the death of a subset of neurons. After a stroke, the number of binuclear neurons increased in cortex around the lesion zone. In this case, the rate of recovery of stroke-damaged locomotor behavior also increased, which indicates the regenerative role of fusion.

Endothelial cell density after deep anterior lamellar keratoplasty (Melles technique)

NARCIS (Netherlands)

Van Dooren, BTH; Mulder, PGH; Nieuwendaal, CP; Beekhuis, WH; Melles, GRJ

PURPOSE: To measure the recipient endothelial cell loss after the Melles technique for deep anterior lamellar keratoplasty. METHODS: In 21 eyes of 21 patients, a deep anterior lamellar keratoplasty procedure was performed. Before surgery and at 6, 12, and 24 months after surgery, specular microscopy

Severe cell reduction in the future brain cortex in human growth-restricted fetuses and infants

DEFF Research Database (Denmark)

Samuelsen, Grethe B; Pakkenberg, Bente; Bogdanović, Nenad

2007-01-01

with controls. The daily increase in brain cells in the future cortex was only half of that of the controls. In the 3 other developmental zones, no significant differences in cell numbers could be demonstrated. CONCLUSIONS: IUGR in humans is associated with a severe reduction in cortical growth...

Prenatal Co 60-irradiation effects on visual acuity, maturation of the fovea in the retina, and the striate cortex of squirrel monkey offspring

International Nuclear Information System (INIS)

Ordy, J.M.; Brizzee, K.R.; Young, R.

1982-01-01

In the present study, foveal striate cortex depth increased significantly from 1400 μm to 1650 μm by 90 days, whereas prenatal 100 rad exposure resulted in a significant reduction of foveal striate cortex thickness at 90 days of age. From birth to 90 days, cell packing density decreased, whereas overall neuropil density increased in both control and 100 rad exposed offspring. Regarding the effects of prenatal radiation on Meynert cells, there was a significant difference in the time course of early postnatal spine frequency reduction on apical dendrites of Meynert cells, particularly in laminae V and IV. It seems possible that the significant differences in the time course of perinatal increases and subsequent decreases of spines and synapses on such pyramidal neurons as Meynert cells in the deep layers of the striate cortex may play an important role in the development of binocular acuity. Future follow-up studies will be essential from 90 days to 1 and 2 years to determine the extent of recovery from, and persistence of visual acuity impairments in relation to structural alterations in the foveal projection of the retino-geniculo-striate system of diurnal primates. (orig./MG)

Deep wells integrated with microfluidic valves for stable docking and storage of cells.

Science.gov (United States)

Jang, Yun-Ho; Kwon, Cheong Hoon; Kim, Sang Bok; Selimović, Seila; Sim, Woo Young; Bae, Hojae; Khademhosseini, Ali

2011-02-01

In this paper, we describe a microfluidic mechanism that combines microfluidic valves and deep wells for cell localization and storage. Cells are first introduced into the device via externally controlled flow. Activating on-chip valves was used to interrupt the flow and to sediment the cells floating above the wells. Thus, valves could be used to localize the cells in the desired locations. We quantified the effect of valves in the cell storage process by comparing the total number of cells stored with and without valve activation. We hypothesized that in deep wells external flows generate low shear stress regions that enable stable, long-term docking of cells. To assess this hypothesis we conducted numerical calculations to understand the influence of well depth on the forces acting on cells. We verified those predictions experimentally by comparing the fraction of stored cells as a function of the well depth and input flow rate upon activation of the valves. As expected, upon reintroduction of the flow the cells in the deep wells were not moved whereas those in shallow wells were washed away. Taken together, our paper demonstrates that deep wells and valves can be combined to enable a broad range of cell studies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydroxyurea Treatment and Development of the Rat Cerebellum: Effects on the Neurogenetic Profiles and Settled Patterns of Purkinje Cells and Deep Cerebellar Nuclei Neurons.

Science.gov (United States)

Martí, Joaquín; Santa-Cruz, M C; Serra, Roger; Hervás, José P

2016-11-01

The current paper analyzes the development of the male and female rat cerebellum exposed to hydroxyurea (HU) (300 or 600 mg/kg) as embryo and collected at postnatal day 90. Our study reveals that the administration of this drug compromises neither the cytoarchitecture of the cerebellar cortex nor deep nuclei (DCN). However, in comparison with the saline group, we observed that several cerebellar parameters were lower in the HU injected groups. These parameters included area of the cerebellum, cerebellar cortex length, molecular layer area, Purkinje cell number, granule cell counts, internal granular layer, white matter and cerebellar nuclei areas, and number of deep cerebellar nuclei neurons. These features were larger in the rats injected with saline, smaller in those exposed to 300 mg/kg of HU and smallest in the group receiving 600 mg/kg of this agent. No sex differences in the effect of the HU were observed. In addition, we infer the neurogenetic timetables and the neurogenetic gradients of PCs and DCN neurons in rats exposed to either saline or HU as embryos. For this purpose, 5-bromo-2'-deoxyuridine was injected into pregnant rats previously administered with saline or HU. This thymidine analog was administered following a progressively delayed cumulative labeling method. The data presented here show that systematic differences exist in the pattern of neurogenesis and in the spatial location of cerebellar neurons between rats injected with saline or HU. No sex differences in the effect of the HU were observed. These findings have implications for the administration of this compound to women in gestation as the effects of HU on the development of the cerebellum might persist throughout their offsprings' life.

Endothelial cell density after deep anterior lamellar keratoplasty (Melles technique)

NARCIS (Netherlands)

van Dooren, Bart T. H.; Mulder, Paul G. H.; Nieuwendaal, Carla P.; Beekhuis, W. Houdijn; Melles, Gerrit R. J.

2004-01-01

To measure the recipient endothelial cell loss after the Melles technique for deep anterior lamellar keratoplasty. In 21 eyes of 21 patients, a deep anterior lamellar keratoplasty procedure was performed. Before surgery and at 6, 12, and 24 months after surgery, specular microscopy was performed to

EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.

Science.gov (United States)

Kanemitsu, Michiko; Tsupykov, Oleg; Potter, Gaël; Boitard, Michael; Salmon, Patrick; Zgraggen, Eloisa; Gascon, Eduardo; Skibo, Galina; Dayer, Alexandre G; Kiss, Jozsef Z

2017-11-01

Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transduced progenitors exhibited enhanced MMP-2 activity in vitro and showed improved motility in 3D collagen gel as well as in cortical slices. Using a rat model of neonatal ischemia, we showed that EMMPRIN overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

Does cell lineage in the developing cerebral cortex contribute to its columnar organization?

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Marcos R Costa

2010-06-01

Full Text Available Since the pioneer work of Lorente de Nó, Ramón y Cajal, Brodmann, Mountcastle, Hubel and Wiesel and others, the cerebral cortex has been seen as a jigsaw of anatomic and functional modules involved in the processing of different sets of information. In fact, a columnar distribution of neurons displaying similar functional properties throughout the cerebral cortex has been observed by many researchers. Although it has been suggested that much of the anatomical substrate for such organization would be already specified at early developmental stages, before activity-dependent mechanisms could take place, it is still unclear whether gene expression in the ventricular zone could play a role in the development of discrete functional units, such as minicolumns or columns. Cell lineage experiments using replication-incompetent retroviral vectors have shown that the progeny of a single neuroepithelial/radial glial cell in the dorsal telencephalon is organized into discrete radial clusters of sibling excitatory neurons, which have a higher propensity for developing chemical synapses with each other rather than with neighbouring non-siblings. Here, we will discuss the possibility that the cell lineage of single neuroepithelial/radial glia cells could contribute for the columnar organization of the neocortex by generating radial columns of sibling, interconnected neurons. Borrowing some concepts from the studies on cell-cell recognition and transcription factor networks, we will also touch upon the potential molecular mechanisms involved in the establishment of sibling-neuron circuits.

Fetal frontal cortex transplant (14C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

International Nuclear Information System (INIS)

Sharp, F.R.; Gonzalez, M.F.

1984-01-01

Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The ( 14 C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional

Carbon and nitrogen assimilation in deep subseafloor microbial cells

OpenAIRE

Morono, Yuki; Terada, Takeshi; Nishizawa, Manabu; Ito, Motoo; Hillion, François; Takahata, Naoto; Sano, Yuji; Inagaki, Fumio

2011-01-01

Remarkable numbers of microbial cells have been observed in global shallow to deep subseafloor sediments. Accumulating evidence indicates that deep and ancient sediments harbor living microbial life, where the flux of nutrients and energy are extremely low. However, their physiology and energy requirements remain largely unknown. We used stable isotope tracer incubation and nanometer-scale secondary ion MS to investigate the dynamics of carbon and nitrogen assimilation activities in individua...

Medial Entorhinal Cortex Lesions Only Partially Disrupt Hippocampal Place Cells and Hippocampus-Dependent Place Memory

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Jena B. Hales

2014-11-01

Full Text Available The entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of the MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired in the water maze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, the MEC is not necessary for all types of spatial coding or for all types of hippocampus-dependent memory, but it is necessary for the normal acquisition of place memory.

Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

Science.gov (United States)

de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

2014-05-01

Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Parvalbumin and calbindin immunoreactivity in the cerebral cortex of the hedgehog (Erinaceus europaeus).

Science.gov (United States)

Ferrer, I; Zujar, M J; Admella, C; Alcantara, S

1992-01-01

To investigate the morphology and distribution of nonpyramidal neurons in the brain of insectivores, parvalbumin and calbindin 28 kDa immunoreactivity was examined in the cerebral cortex of the hedgehog (Erinaceus europaeus). Parvalbumin-immunoreactive cells were found in all layers of the isocortex, but in contrast to other mammals, a laminar organisation or specific regional distribution was not seen. Characteristic parvalbumin-immunoreactive neurons were multipolar cells with large ascending and descending dendrites extending throughout several layers. Calbindin-immunoreactive neurons were similar to those found in other species, although appearing in smaller numbers than in the cerebral cortex of more advanced mammals. The morphology and distribution of parvalbumin- and calbindin-immunoreactive cells in the piriform and entorhinal cortices were similar in hedgehogs and rodents. Parvalbumin-immunoreactive cells in the hippocampal complex were pyramidal-like and bitufted neurons, which were mainly found in the stratum oriens and stratum pyramidale of the hippocampus, and in the stratum moleculare and hilus of the fascia dentata. Heavily stained cells were found in the deep part of the stratum granulare. Intense calbindin immunoreactivity occurred mainly in the granule cell and molecular layers of the dentate gyrus and in the mossy fibre layer. The most outstanding feature in the hippocampal complex of the hedgehog was the extension of calbindin immunoreactivity to CA1 field of the hippocampus, suggesting, in agreement with other reports, that mossy fibres can establish synaptic contacts throughout the pyramidal cell layer. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1452472

Initial observations of cell-mediated drug delivery to the deep lung.

Science.gov (United States)

Kumar, Arun; Glaum, Mark; El-Badri, Nagwa; Mohapatra, Shyam; Haller, Edward; Park, Seungjoo; Patrick, Leslie; Nattkemper, Leigh; Vo, Dawn; Cameron, Don F

2011-01-01

Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load (∼90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perialveloar sac area in the lower lungs. This was based on the high-density, positive quantification of both nanoparticles and curcumin in the lungs. There was a marked positive therapeutic effect achieved 24 h following curcumin treatment delivered by this Sertoli cell nanoparticle protocol (SNAP). Results identify a novel and efficient protocol for targeted delivery of drugs to the deep lung mediated by extratesticular Sertoli cells. Utilization of SNAP delivery may optimize drug therapy for conditions such as ARDS, status asthmaticus, pulmonary hypertension, lung cancer, and complications following lung transplantation where the use of high concentrations of anti-inflammatory drugs is desirable, but often limited by risks of systemic drug toxicity.

Cerebral cortex modulation of pain

Institute of Scientific and Technical Information of China (English)

Yu-feng XIE; Fu-quan HUO; Jing-shi TANG

2009-01-01

Pain is a complex experience encompassing sensory-discriminative, affective-motivational and cognitiv e-emotional com-ponents mediated by different mechanisms. Contrary to the traditional view that the cerebral cortex is not involved in pain perception, an extensive cortical network associated with pain processing has been revealed using multiple methods over the past decades. This network consistently includes, at least, the anterior cingulate cortex, the agranular insular cortex, the primary (SⅠ) and secondary somatosensory (SⅡ) cortices, the ventrolateral orbital cortex and the motor cortex. These corti-cal structures constitute the medial and lateral pain systems, the nucleus submedius-ventrolateral orbital cortex-periaque-ductal gray system and motor cortex system, respectively. Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine, are involved in the modulation of pain by these cortical structures. In addition, glial cells may also be in-volved in cortical modulation of pain and serve as one target for pain management research. This review discusses recent studies of pain modulation by these cerebral cortical structures in animals and human.

Distinction of neurons, glia and endothelial cells in the cerebral cortex: an algorithm based on cytological features

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Miguel Ángel García-Cabezas

2016-11-01

Full Text Available The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic, and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease.

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

Science.gov (United States)

García-Cabezas, Miguel Á.; John, Yohan J.; Barbas, Helen; Zikopoulos, Basilis

2016-01-01

The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following an extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease. PMID:27847469

Cell dynamic morphology classification using deep convolutional neural networks.

Science.gov (United States)

Li, Heng; Pang, Fengqian; Shi, Yonggang; Liu, Zhiwen

2018-05-15

Cell morphology is often used as a proxy measurement of cell status to understand cell physiology. Hence, interpretation of cell dynamic morphology is a meaningful task in biomedical research. Inspired by the recent success of deep learning, we here explore the application of convolutional neural networks (CNNs) to cell dynamic morphology classification. An innovative strategy for the implementation of CNNs is introduced in this study. Mouse lymphocytes were collected to observe the dynamic morphology, and two datasets were thus set up to investigate the performances of CNNs. Considering the installation of deep learning, the classification problem was simplified from video data to image data, and was then solved by CNNs in a self-taught manner with the generated image data. CNNs were separately performed in three installation scenarios and compared with existing methods. Experimental results demonstrated the potential of CNNs in cell dynamic morphology classification, and validated the effectiveness of the proposed strategy. CNNs were successfully applied to the classification problem, and outperformed the existing methods in the classification accuracy. For the installation of CNNs, transfer learning was proved to be a promising scheme. © 2018 International Society for Advancement of Cytometry. © 2018 International Society for Advancement of Cytometry.

Rhythm generation through period concatenation in rat somatosensory cortex.

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Mark A Kramer

2008-09-01

Full Text Available Rhythmic voltage oscillations resulting from the summed activity of neuronal populations occur in many nervous systems. Contemporary observations suggest that coexistent oscillations interact and, in time, may switch in dominance. We recently reported an example of these interactions recorded from in vitro preparations of rat somatosensory cortex. We found that following an initial interval of coexistent gamma ( approximately 25 ms period and beta2 ( approximately 40 ms period rhythms in the superficial and deep cortical layers, respectively, a transition to a synchronous beta1 ( approximately 65 ms period rhythm in all cortical layers occurred. We proposed that the switch to beta1 activity resulted from the novel mechanism of period concatenation of the faster rhythms: gamma period (25 ms+beta2 period (40 ms = beta1 period (65 ms. In this article, we investigate in greater detail the fundamental mechanisms of the beta1 rhythm. To do so we describe additional in vitro experiments that constrain a biologically realistic, yet simplified, computational model of the activity. We use the model to suggest that the dynamic building blocks (or motifs of the gamma and beta2 rhythms combine to produce a beta1 oscillation that exhibits cross-frequency interactions. Through the combined approach of in vitro experiments and mathematical modeling we isolate the specific components that promote or destroy each rhythm. We propose that mechanisms vital to establishing the beta1 oscillation include strengthened connections between a population of deep layer intrinsically bursting cells and a transition from antidromic to orthodromic spike generation in these cells. We conclude that neural activity in the superficial and deep cortical layers may temporally combine to generate a slower oscillation.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex.

Science.gov (United States)

Teixeira, Francisco B; de Oliveira, Ana C A; Leão, Luana K R; Fagundes, Nathália C F; Fernandes, Rafael M; Fernandes, Luanna M P; da Silva, Márcia C F; Amado, Lilian L; Sagica, Fernanda E S; de Oliveira, Edivaldo H C; Crespo-Lopez, Maria E; Maia, Cristiane S F; Lima, Rafael R

2018-01-01

Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex

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Francisco B. Teixeira

2018-05-01

Full Text Available Mercury is a toxic metal that can be found in the environment in three different forms – elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood–brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2, an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Centella asiatica increases B-cell lymphoma 2 expression in rat prefrontal cortex

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Kuswati

2015-04-01

Full Text Available Background Stress is one of the factors that cause apoptosis in neuronal cells. Centella asiatica has a neuroprotective effect that can inhibit apoptosis. This study aimed to examine the effect of Centella asiatica ethanol extract on B-cell lymphoma 2 (Bcl-2 protein expression in the prefrontal cortex of rats. Methods An experimental study was conducted on 34 brain tissue samples from male Sprague Dawley rats exposed to chronic restraint stress for 21 days. The samples were taken from following groups: non-stress group K, negative control group P1 (stress + arabic gum powder, P2 (stress + C.asiatica at 150 mg/kgBW, P3 (stress + C.asiatica at 300 mg/kg BW, P4 (stress + C.asiatica at 600 mg/kg body weight and positive control group P5 (stress + fluoxetine at 10 mg/kgBW. The samples were made into sections that were stained immunohistochemically using Bcl-2 antibody to determine the percentage of cells expressing Bcl-2. Data were analyzed using one way ANOVA test followed by a post - hoc test. Results There were significant differences in mean Bcl-2 expression between the groups receiving Centella asiatica compared with the non-stress group and stress-only group (negative control group (p<0.05. The results were comparable to those of the fluoxetine treatment group. Conclusion The Centella asiatica ethanol extract was able to increase Bcl-2 expression in the prefrontal cortex of Sprague Dawley rats exposed to restraint stress. This study suggests that Centella asiatica may be useful in the treatment of cerebral stress.

Morphology and distribution of chandelier cell axon terminals in the mouse cerebral cortex and claustroamygdaloid complex.

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Inda, M C; DeFelipe, J; Muñoz, A

2009-01-01

Chandelier cells represent a unique type of cortical gamma-aminobutityric acidergic interneuron whose axon terminals (Ch-terminals) only form synapses with the axon initial segments of some pyramidal cells. Here, we have used immunocytochemistry for the high-affinity plasma membrane transporter GAT-1 and the calcium-binding protein parvalbumin to analyze the morphology and distribution of Ch-terminals in the mouse cerebral cortex and claustroamygdaloid complex. In general, 2 types of Ch-terminals were distinguished on the basis of their size and the density of the axonal boutons that made up the terminal. Simple Ch-terminals were made up of 1 or 2 rows of labeled boutons, each row consisting of only 3-5 boutons. In contrast, complex Ch-terminals were tight cylinder-like structures made up of multiple rows of boutons. Simple Ch-terminals were detected throughout the cerebral cortex and claustroamygdaloid complex, the complex type was only occasionally found in certain regions, whereas in others they were very abundant. These results indicate that there are substantial differences in the morphology and distribution of Ch-terminals between different areas and layers of the mouse cerebral cortex. Furthermore, we suggest that the distribution of complex Ch-terminals may be related to the developmental origin of the different brain regions analyzed.

TMS-induced neural noise in sensory cortex interferes with short-term memory storage in prefrontal cortex.

Science.gov (United States)

Bancroft, Tyler D; Hogeveen, Jeremy; Hockley, William E; Servos, Philip

2014-01-01

In a previous study, Harris et al. (2002) found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation (TMS) to primary somatosensory cortex (SI) early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence from human EEG and single-cell recording in primates that instead points to prefrontal cortex as the storage substrate for vibrotactile memory. In the present study, we use computational methods to demonstrate how Harris et al.'s results can be reproduced by TMS-induced activity in sensory cortex and subsequent feedforward interference with memory traces stored in prefrontal cortex, thereby reconciling discordant findings in the tactile memory literature.

Effect of prenatal exposure to ethanol on the development of cerebral cortex: I. Neuronal generation

International Nuclear Information System (INIS)

Miller, M.W.

1988-01-01

Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair-fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with [3H]thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques. Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1-2 days later for Et-treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1-2 days longer in Et-treated rats. The numbers of neurons generated on a specific day was altered; from GD 12-19 significantly fewer neurons were generated in Et-treated rats than in Ct-treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late-generated neurons in deep cortex of Et-treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et-treated rats tended to be smaller than in Ct-treated rats, particularly early generated neurons in deep cortex. The late-generated neurons in Et-treated rats were of similar size to those in Ct-treated rats despite their abnormal position in deep cortex. Neurons in Ct-treated rats tended to be rounder than those in Et-treated rats which were more polarized in the radial orientation

Spindle neurons of the human anterior cingulate cortex

Science.gov (United States)

Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

1995-01-01

The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

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Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Vertical organization of gamma-aminobutyric acid-accumulating intrinsic neuronal systems in monkey cerebral cortex

International Nuclear Information System (INIS)

DeFelipe, J.; Jones, E.G.

1985-01-01

Light and electron microscopic methods were used to examine the neurons in the monkey cerebral cortex labeled autoradiographically following the uptake and transport of [ 3 H]-gamma-aminobutyric acid (GABA). Nonpyramidal cell somata in the sensory-motor areas and primary visual area (area 17) were labeled close to the injection site and at distances of 1 to 1.5 mm beyond the injection site, indicating labeling by retrograde axoplasmic transport. This labeling occurred preferentially in the vertical dimension of the cortex. Prior injections of colchicine, an inhibitor of axoplasmic transport, abolished all labeling of somata except those within the injection site. In each area, injections of superficial layers (I to III) produced labeling of clusters of cell somata in layer V, and injections of the deep layers (V and VI) produced labeling of clusters of cell somata in layers II and III. In area 17, injections of the superficial layers produced dense retrograde cell labeling in three bands: in layers IVC, VA, and VI. Vertically oriented chains of silver grains linked the injection sites with the resulting labeled cell clusters. In all areas, the labeling of cells in the horizontal dimension was insignificant. Electron microscopic examination of labeled neurons confirms that the neurons labeled at a distance from an injection site are nonpyramidal neurons, many with somata so small that they would be mistaken for neuroglial cells light microscopically. They receive few axosomatic synapses, most of which have symmetric membrane thickenings. The vertical chains of silver grains overlie neuronal processes identifiable as both dendrites and myelinated axons, but unmyelinated axons may also be included. The clusters of [ 3 H]GABA-labeled cells are joined to one another and to adjacent unlabeled cells by junctional complexes, including puncta adherentia and multi-lamellar cisternal complexes

Cell segmentation in histopathological images with deep learning algorithms by utilizing spatial relationships.

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Hatipoglu, Nuh; Bilgin, Gokhan

2017-10-01

In many computerized methods for cell detection, segmentation, and classification in digital histopathology that have recently emerged, the task of cell segmentation remains a chief problem for image processing in designing computer-aided diagnosis (CAD) systems. In research and diagnostic studies on cancer, pathologists can use CAD systems as second readers to analyze high-resolution histopathological images. Since cell detection and segmentation are critical for cancer grade assessments, cellular and extracellular structures should primarily be extracted from histopathological images. In response, we sought to identify a useful cell segmentation approach with histopathological images that uses not only prominent deep learning algorithms (i.e., convolutional neural networks, stacked autoencoders, and deep belief networks), but also spatial relationships, information of which is critical for achieving better cell segmentation results. To that end, we collected cellular and extracellular samples from histopathological images by windowing in small patches with various sizes. In experiments, the segmentation accuracies of the methods used improved as the window sizes increased due to the addition of local spatial and contextual information. Once we compared the effects of training sample size and influence of window size, results revealed that the deep learning algorithms, especially convolutional neural networks and partly stacked autoencoders, performed better than conventional methods in cell segmentation.

Modulation of fusiform cortex activity by cholinesterase inhibition predicts effects on subsequent memory.

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Bentley, P; Driver, J; Dolan, R J

2009-09-01

Cholinergic influences on memory are likely to be expressed at several processing stages, including via well-recognized effects of acetylcholine on stimulus processing during encoding. Since previous studies have shown that cholinesterase inhibition enhances visual extrastriate cortex activity during stimulus encoding, especially under attention-demanding tasks, we tested whether this effect correlates with improved subsequent memory. In a within-subject physostigmine versus placebo design, we measured brain activity with functional magnetic resonance imaging while healthy and mild Alzheimer's disease subjects performed superficial and deep encoding tasks on face (and building) visual stimuli. We explored regions in which physostigmine modulation of face-selective neural responses correlated with physostigmine effects on subsequent recognition performance. In healthy subjects physostigmine led to enhanced later recognition for deep- versus superficially-encoded faces, which correlated across subjects with a physostigmine-induced enhancement of face-selective responses in right fusiform cortex during deep- versus superficial-encoding tasks. In contrast, the Alzheimer's disease group showed neither a depth of processing effect nor restoration of this with physostigmine. Instead, patients showed a task-independent improvement in confident memory with physostigmine, an effect that correlated with enhancements in face-selective (but task-independent) responses in bilateral fusiform cortices. Our results indicate that one mechanism by which cholinesterase inhibitors can improve memory is by enhancing extrastriate cortex stimulus selectivity at encoding, in a manner that for healthy people but not in Alzheimer's disease is dependent upon depth of processing.

Contextual modulation of primary visual cortex by auditory signals.

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Petro, L S; Paton, A T; Muckli, L

2017-02-19

Early visual cortex receives non-feedforward input from lateral and top-down connections (Muckli & Petro 2013 Curr. Opin. Neurobiol. 23, 195-201. (doi:10.1016/j.conb.2013.01.020)), including long-range projections from auditory areas. Early visual cortex can code for high-level auditory information, with neural patterns representing natural sound stimulation (Vetter et al. 2014 Curr. Biol. 24, 1256-1262. (doi:10.1016/j.cub.2014.04.020)). We discuss a number of questions arising from these findings. What is the adaptive function of bimodal representations in visual cortex? What type of information projects from auditory to visual cortex? What are the anatomical constraints of auditory information in V1, for example, periphery versus fovea, superficial versus deep cortical layers? Is there a putative neural mechanism we can infer from human neuroimaging data and recent theoretical accounts of cortex? We also present data showing we can read out high-level auditory information from the activation patterns of early visual cortex even when visual cortex receives simple visual stimulation, suggesting independent channels for visual and auditory signals in V1. We speculate which cellular mechanisms allow V1 to be contextually modulated by auditory input to facilitate perception, cognition and behaviour. Beyond cortical feedback that facilitates perception, we argue that there is also feedback serving counterfactual processing during imagery, dreaming and mind wandering, which is not relevant for immediate perception but for behaviour and cognition over a longer time frame.This article is part of the themed issue 'Auditory and visual scene analysis'. © 2017 The Authors.

White blood cells identification system based on convolutional deep neural learning networks.

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Shahin, A I; Guo, Yanhui; Amin, K M; Sharawi, Amr A

2017-11-16

White blood cells (WBCs) differential counting yields valued information about human health and disease. The current developed automated cell morphology equipments perform differential count which is based on blood smear image analysis. Previous identification systems for WBCs consist of successive dependent stages; pre-processing, segmentation, feature extraction, feature selection, and classification. There is a real need to employ deep learning methodologies so that the performance of previous WBCs identification systems can be increased. Classifying small limited datasets through deep learning systems is a major challenge and should be investigated. In this paper, we propose a novel identification system for WBCs based on deep convolutional neural networks. Two methodologies based on transfer learning are followed: transfer learning based on deep activation features and fine-tuning of existed deep networks. Deep acrivation featues are extracted from several pre-trained networks and employed in a traditional identification system. Moreover, a novel end-to-end convolutional deep architecture called "WBCsNet" is proposed and built from scratch. Finally, a limited balanced WBCs dataset classification is performed through the WBCsNet as a pre-trained network. During our experiments, three different public WBCs datasets (2551 images) have been used which contain 5 healthy WBCs types. The overall system accuracy achieved by the proposed WBCsNet is (96.1%) which is more than different transfer learning approaches or even the previous traditional identification system. We also present features visualization for the WBCsNet activation which reflects higher response than the pre-trained activated one. a novel WBCs identification system based on deep learning theory is proposed and a high performance WBCsNet can be employed as a pre-trained network. Copyright © 2017. Published by Elsevier B.V.

Collateral Projections Innervate the Mammillary Bodies and Retrosplenial Cortex: A New Category of Hippocampal Cells

Science.gov (United States)

O’Mara, Shane M.

2018-01-01

To understand the hippocampus, it is necessary to understand the subiculum. Unlike other hippocampal subfields, the subiculum projects to almost all distal hippocampal targets, highlighting its critical importance for external networks. The present studies, in male rats and mice, reveal a new category of dorsal subiculum neurons that innervate both the mammillary bodies (MBs) and the retrosplenial cortex (RSP). These bifurcating neurons comprise almost half of the hippocampal cells that project to RSP. The termination of these numerous collateral projections was visualized within the medial mammillary nucleus and the granular RSP (area 29). These collateral projections included subiculum efferents that cross to the contralateral MBs. Within the granular RSP, the collateral projections form a particularly dense plexus in deep Layer II and Layer III. This retrosplenial termination site colocalized with markers for VGluT2 and neurotensin. While efferents from the hippocampal CA fields standardly collateralize, subiculum projections often have only one target site. Consequently, the many collateral projections involving the RSP and the MBs present a relatively unusual pattern for the subiculum, which presumably relates to how both targets have complementary roles in spatial processing. Furthermore, along with the anterior thalamic nuclei, the MBs and RSP are key members of a memory circuit, which is usually described as both starting and finishing in the hippocampus. The present findings reveal how the hippocampus simultaneously engages different parts of this circuit, so forcing an important revision of this network. PMID:29527569

Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex.

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Li, Ya-tang; Liu, Bao-hua; Chou, Xiao-lin; Zhang, Li I; Tao, Huizhong W

2015-08-05

In the primary visual cortex (V1), orientation-selective neurons can be categorized into simple and complex cells primarily based on their receptive field (RF) structures. In mouse V1, although previous studies have examined the excitatory/inhibitory interplay underlying orientation selectivity (OS) of simple cells, the synaptic bases for that of complex cells have remained obscure. Here, by combining in vivo loose-patch and whole-cell recordings, we found that complex cells, identified by their overlapping on/off subfields, had significantly weaker OS than simple cells at both spiking and subthreshold membrane potential response levels. Voltage-clamp recordings further revealed that although excitatory inputs to complex and simple cells exhibited a similar degree of OS, inhibition in complex cells was more narrowly tuned than excitation, whereas in simple cells inhibition was more broadly tuned than excitation. The differential inhibitory tuning can primarily account for the difference in OS between complex and simple cells. Interestingly, the differential synaptic tuning correlated well with the spatial organization of synaptic input: the inhibitory visual RF in complex cells was more elongated in shape than its excitatory counterpart and also was more elongated than that in simple cells. Together, our results demonstrate that OS of complex and simple cells is differentially shaped by cortical inhibition based on its orientation tuning profile relative to excitation, which is contributed at least partially by the spatial organization of RFs of presynaptic inhibitory neurons. Simple and complex cells, two classes of principal neurons in the primary visual cortex (V1), are generally thought to be equally selective for orientation. In mouse V1, we report that complex cells, identified by their overlapping on/off subfields, has significantly weaker orientation selectivity (OS) than simple cells. This can be primarily attributed to the differential tuning selectivity

Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.

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Santaniello, Sabato; Montgomery, Erwin B; Gale, John T; Sarma, Sridevi V

2012-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated. We use point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of two non-human primates during STN DBS. These features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a consistent PD-like motor impairment, while high-frequency (HF) DBS (i.e., ≥100 Hz) strongly reduces the short-term patterns (period: 3-7 ms) both before and after MPTP treatment, and elicits a short-latency post-stimulus activation. Low-frequency DBS (i.e., ≤50 Hz), instead, has negligible effects on the non-stationary features. Finally, by using tools from the information theory [i.e., receiver operating characteristic (ROC) curve and information rate (IR)], we show that the predictive power of these models is dependent on the DBS settings, i.e., the probability of spiking of the cortical neurons (which is captured by the point process models) is significantly conditioned on the timely delivery of the DBS input. This dependency increases with the DBS frequency and is significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that HF STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the BG-thalamo-cortical loop.

Rebound spiking in layer II medial entorhinal cortex stellate cells: Possible mechanism of grid cell function

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Shay, Christopher F.; Ferrante, Michele; Chapman, G. William; Hasselmo, Michael E.

2015-01-01

Rebound spiking properties of medial entorhinal cortex (mEC) stellate cells induced by inhibition may underlie their functional properties in awake behaving rats, including the temporal phase separation of distinct grid cells and differences in grid cell firing properties. We investigated rebound spiking properties using whole cell patch recording in entorhinal slices, holding cells near spiking threshold and delivering sinusoidal inputs, superimposed with realistic inhibitory synaptic inputs to test the capacity of cells to selectively respond to specific phases of inhibitory input. Stellate cells showed a specific phase range of hyperpolarizing inputs that elicited spiking, but non-stellate cells did not show phase specificity. In both cell types, the phase range of spiking output occurred between the peak and subsequent descending zero crossing of the sinusoid. The phases of inhibitory inputs that induced spikes shifted earlier as the baseline sinusoid frequency increased, while spiking output shifted to later phases. Increases in magnitude of the inhibitory inputs shifted the spiking output to earlier phases. Pharmacological blockade of h-current abolished the phase selectivity of hyperpolarizing inputs eliciting spikes. A network computational model using cells possessing similar rebound properties as found in vitro produces spatially periodic firing properties resembling grid cell firing when a simulated animal moves along a linear track. These results suggest that the ability of mEC stellate cells to fire rebound spikes in response to a specific range of phases of inhibition could support complex attractor dynamics that provide completion and separation to maintain spiking activity of specific grid cell populations. PMID:26385258

Size and Carbon Content of Sub-seafloor Microbial Cells at Landsort Deep, Baltic Sea

DEFF Research Database (Denmark)

Braun, Stefan; Morono, Yuki; Littmann, Sten

2016-01-01

determined the volume and the carbon content of microbial cells from a marine sediment drill core retrieved by the Integrated Ocean Drilling Program (IODP), Expedition 347, at Landsort Deep, Baltic Sea. To determine their shape and volume, cells were separated from the sediment matrix by multi-layer density......-specific carbon content was 19–31 fg C cell−1, which is at the lower end of previous estimates that were used for global estimates of microbial biomass. The cell-specific carbon density increased with sediment depth from about 200 to 1000 fg C μm−3, suggesting that cells decrease their water content and grow...... small cell sizes as adaptation to the long-term subsistence at very low energy availability in the deep biosphere. We present for the first time depth-related data on the cell volume and carbon content of sedimentary microbial cells buried down to 60 m below the seafloor. Our data enable estimates...

Double-bouquet cells in the monkey and human cerebral cortex with special reference to areas 17 and 18.

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DeFelipe, Javier; Ballesteros-Yáñez, Inmaculada; Inda, Maria Carmen; Muñoz, Alberto

2006-01-01

The detailed microanatomical study of the human cerebral cortex began in 1899 with the experiments of Santiago Ramón y Cajal, who applied the Golgi method to define the structure of the visual, motor, auditory and olfactory cortex. In the first article of this series, he described a special type of interneuron in the visual cortex capable of exerting its influence in the vertical dimension. These neurons are now more commonly referred to as double-bouquet cells (DBCs). The DBCs are readily distinguished owing to their characteristic axons that give rise to tightly interwoven bundles of long, vertically oriented axonal collaterals resembling a horsetail (DBC horsetail). Nevertheless, the most striking characteristic of these neurons is that they are so numerous and regularly distributed that the DBC horsetails form a microcolumnar structure. In addition, DBCs establish hundreds of inhibitory synapses within a very narrow column of cortical tissue. These features have generated considerable interest in DBCs over recent years, principally among those researchers interested in the analysis of cortical circuits. In the present chapter, we shall discuss the morphology, synaptic connections and neurochemical features of DBCs that have been defined through the study of these cells in different cortical areas and species. We will mainly consider the immunocytochemical studies of DBCs that have been carried out in the visual cortex (areas 17 and 18) of human and macaque monkey. We will see that there are important differences in the morphology, number and distribution of DBC horsetails between areas 17 and 18 in the primate. This suggests important differences in the microcolumnar organization between these areas, the functional significance of which awaits detailed correlative physiological and microanatomical studies.

Effects of noise-induced hearing loss on parvalbumin and perineuronal net expression in the mouse primary auditory cortex.

Science.gov (United States)

Nguyen, Anna; Khaleel, Haroun M; Razak, Khaleel A

2017-07-01

Noise induced hearing loss is associated with increased excitability in the central auditory system but the cellular correlates of such changes remain to be characterized. Here we tested the hypothesis that noise-induced hearing loss causes deterioration of perineuronal nets (PNNs) in the auditory cortex of mice. PNNs are specialized extracellular matrix components that commonly enwrap cortical parvalbumin (PV) containing GABAergic interneurons. Compared to somatosensory and visual cortex, relatively less is known about PV/PNN expression patterns in the primary auditory cortex (A1). Whether changes to cortical PNNs follow acoustic trauma remains unclear. The first aim of this study was to characterize PV/PNN expression in A1 of adult mice. PNNs increase excitability of PV+ inhibitory neurons and confer protection to these neurons against oxidative stress. Decreased PV/PNN expression may therefore lead to a reduction in cortical inhibition. The second aim of this study was to examine PV/PNN expression in superficial (I-IV) and deep cortical layers (V-VI) following noise trauma. Exposing mice to loud noise caused an increase in hearing threshold that lasted at least 30 days. PV and PNN expression in A1 was analyzed at 1, 10 and 30 days following the exposure. No significant changes were observed in the density of PV+, PNN+, or PV/PNN co-localized cells following hearing loss. However, a significant layer- and cell type-specific decrease in PNN intensity was seen following hearing loss. Some changes were present even at 1 day following noise exposure. Attenuation of PNN may contribute to changes in excitability in cortex following noise trauma. The regulation of PNN may open up a temporal window for altered excitability in the adult brain that is then stabilized at a new and potentially pathological level such as in tinnitus. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

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Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

2015-09-15

A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. © 2015. Published by The Company of Biologists Ltd.

Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine

DEFF Research Database (Denmark)

Rumessen, J J; Mikkelsen, H B; Thuneberg, L

1992-01-01

Evidence showing that interstitial cells of Cajal have important regulatory functions in the gut musculature is accumulating. In the current study, the ultrastructure of the deep muscular plexus and associated interstial cells of Cajal in human small intestine were studied to provide a reference...... a continuous basal lamina, caveolae, intermediate filaments, dense bodies, dense bands, and a well-developed subsurface smooth endoplasmic reticulum), but the arrangement of organelles was clearly different, and cisternae of granular endoplasmic reticulum were abundant. Interstitial cells of Cajal were......, and only few gap junctions with other interstitial cells of Cajal or with the musculature were observed. Compared with interstitial cells of Cajal from other mammals, those associated with the deep muscular plexus in the human small intestine more closely resemble smooth muscle cells...

Growth and regeneration in cultivated fragments of the boreal deep water sponge Geodia barretti Bowerbank, 1858 (Geodiidae, Tetractinellida, Demospongiae).

Science.gov (United States)

Hoffmann, Friederike; Rapp, Hans Tore; Zöller, Tobias; Reitner, Joachim

2003-01-23

A cultivation method has been developed for the boreal deep-water sponge Geodia barretti (Demospongiae, Geodiidae), a species which is common in the deep Norwegian fjords. The species is known to contain secondary metabolites which are biologically active. Choanosomal fragments of 2-4 cm(3) (approximately 3-7 g) were kept in half-open systems. Cicatrisation and regeneration processes were surveyed by histological examination during 8 months of cultivation. During the first weeks, the weight of the fragments decreased. However, after about 6 weeks the weight equalled the original weight, and after 1 year the weight had increased by about 40% compared to the original weight. The initial decrease was due to complex healing processes and the regeneration of the cortex, a sterrastral layer typical for the family of the Geodiidae. We document, for the first time, the complete cortex reconstruction in an adult G. barretti, as well as the development of egg cells during cultivation. Our study represents the first attempt at biotechnological production of boreal sponge tissue. For successful farming of G. barretti and other boreal and arctic sponges, however, further investigation is needed on factors stimulating growth and secondary metabolite production in the target species.

Three counting methods agree on cell and neuron number in chimpanzee primary visual cortex

Directory of Open Access Journals (Sweden)

Daniel James Miller

2014-05-01

Full Text Available Determining the cellular composition of specific brain regions is crucial to our understanding of the function of neurobiological systems. It is therefore useful to identify the extent to which different methods agree when estimating the same properties of brain circuitry. In this study, we estimated the number of neuronal and non-neuronal cells in the primary visual cortex (area 17 or V1 of both hemispheres from a single chimpanzee. Specifically, we processed samples distributed across V1 of the right hemisphere after cortex was flattened into a sheet using two variations of the isotropic fractionator cell and neuron counting method. We processed the left hemisphere as serial brain slices for stereological investigation. The goal of this study was to evaluate the agreement between these methods in the most direct manner possible by comparing estimates of cell density across one brain region of interest in a single individual. In our hands, these methods produced similar estimates of the total cellular population (approximately 1 billion as well as the number of neurons (approximately 675 million in chimpanzee V1, providing evidence that both techniques estimate the same parameters of interest. In addition, our results indicate the strengths of each distinct tissue preparation procedure, highlighting the importance of attention to anatomical detail. In summary, we found that the isotropic fractionator and the stereological optical fractionator produced concordant estimates of the cellular composition of V1, and that this result supports the conclusion that chimpanzees conform to the primate pattern of exceptionally high packing density in V1. Ultimately, our data suggest that investigators can optimize their experimental approach by using any of these counting methods to obtain reliable cell and neuron counts.

Targeting Aurora B to the equatorial cortex by MKlp2 is required for cytokinesis.

Directory of Open Access Journals (Sweden)

Mayumi Kitagawa

Full Text Available Although Aurora B is important in cleavage furrow ingression and completion during cytokinesis, the mechanism by which kinase activity is targeted to the cleavage furrow and the molecule(s responsible for this process have remained elusive. Here, we demonstrate that an essential mitotic kinesin MKlp2 requires myosin-II for its localization to the equatorial cortex, and this event is required to recruit Aurora B to the equatorial cortex in mammalian cells. This recruitment event is also required to promote the highly focused accumulation of active RhoA at the equatorial cortex and stable ingression of the cleavage furrow in bipolar cytokinesis. Specifically, in drug-induced monopolar cytokinesis, targeting Aurora B to the cell cortex by MKlp2 is essential for cell polarization and furrow formation. Once the furrow has formed, MKlp2 further recruits Aurora B to the growing furrow. This process together with continuous Aurora B kinase activity at the growing furrow is essential for stable furrow propagation and completion. In contrast, a MKlp2 mutant defective in binding myosin-II does not recruit Aurora B to the cell cortex and does not promote furrow formation during monopolar cytokinesis. This mutant is also defective in maintaining the ingressing furrow during bipolar cytokinesis. Together, these findings reveal that targeting Aurora B to the cell cortex (or the equatorial cortex by MKlp2 is essential for the maintenance of the ingressing furrow for successful cytokinesis.

Immunocytochemical expression of monocarboxylate transporters in the human visual cortex at midgestation.

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Fayol, Laurence; Baud, Olivier; Monier, Anne; Pellerin, Luc; Magistretti, Pierre; Evrard, Philippe; Verney, Catherine

2004-01-31

Lactate and the other monocarboxylates are a major energy source for the developing brain. We investigated the immunocytochemical expression of two monocarboxylate transporters, MCT1 and MCT2, in the human visual cortex between 13 and 26 post-ovulatory weeks. We used immunoperoxidase and immunofluorescence techniques to determine whether these transporters co-localized with markers for blood vessels (CD34), neurons (microtubule-associated protein 2 [MAP2], SMI 311), radial glia (vimentin), or astrocytes (glial fibrillary acidic protein [GFAP], S100beta protein). MCT1 immunoreactivity was visible in blood vessel walls as early as the 13th week of gestation mainly in the cortical plate and subplate. At this stage, less than 10% of vessels in the ventricular layer expressed MCT1, whereas all blood vessels walls showed this immunoreactivity at the 26th gestational week. Starting at the 19th week of gestation, sparse MCT1 positive cell bodies were detected, some of them co-localized with MAP2 immunoreactivity. MCT2 immunoreactivity was noted in astrocytic cell bodies from week 19 and spread subsequently to the astrocyte end-feet in contact with blood vessels. MCTs immunoreactivities were most marked in the subplate and deep cortical plate, where the most differentiated neurons were located. Our findings suggest that monocarboxylate trafficking between vessels (MCT1), astrocytes (MCT2) and some postmitotic neurons (MCT1) could develop gradually toward 20 gestational weeks (g.w.). These data suggest that lactate or other monocarboxylates could represent a significant energy source for the human visual cortex at this early stage.

High-efficiency, deep-junction, epitaxial InP solar cells on (100) and (111)B InP substrates

Science.gov (United States)

Venkatasubramanian, R.; Timmons, M. L.; Hutchby, J. A.; Walters, Robert J.; Summers, Geoffrey P.

1994-01-01

We report on the development and performance of deep-junction (approximately 0.25 micron), graded-emitter-doped, n(sup +)-p InP solar cells grown by metallorganic chemical vapor deposition (MOCVD). A novel, diffusion-transport process for obtaining lightly-doped p-type base regions of the solar cell is described. The I-V data and external quantum-efficiency response of these cells are presented. The best active-area AMO efficiency for these deep-junction cells on (100)-oriented InP substrates is 16.8 percent, with a J(sub SC) of 31.8 mA/sq cm, a V(sub OC) of 0.843 V, and a fill-factor of 0.85. By comparison, the best cell efficiency on the (111)B-oriented InP substrates was 15.0 percent. These efficiency values for deep-junction cells are encouraging and compare favorably with performance of thin-emitter (0.03 micron) epitaxial cells as well as that of deep-emitter diffused cells. The cell performance and breakdown voltage characteristics of a batch of 20 cells on each of the orientations are presented, indicating the superior breakdown voltage properties and other characteristics of InP cells on the (111)B orientation. Spectral response, dark I-V data, and photoluminescence (PL) measurements on the InP cells are presented with an analysis on the variation in J(sub SC) and V(sub OC) of the cells. It is observed, under open-circuit conditions, that lower-V(sub OC) cells exhibit higher band-edge PL intensity for both the (100) and (111)B orientations. This anomalous behavior suggests that radiative recombination in the heavily-doped n(sup +)-InP emitter may be detrimental to achieving higher V(sub OC) in n(sup +)-p InP solar cells.

Single cell genomics indicates horizontal gene transfer and viral infections in a deep subsurface Firmicutes population

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Jessica eLabonté

2015-04-01

Full Text Available A major fraction of Earth's prokaryotic biomass dwells in the deep subsurface, where cellular abundances per volume of sample are lower, metabolism is slower, and generation times are longer than those in surface terrestrial and marine environments. How these conditions impact biotic interactions and evolutionary processes is largely unknown. Here we employed single cell genomics to analyze cell-to-cell genome content variability and signatures of horizontal gene transfer (HGT and viral infections in five cells of Candidatus Desulforudis audaxviator, which were collected from a three km-deep fracture water in the 2.9 Ga-old Witwatersrand Basin of South Africa. Between 0 and 32 % of genes recovered from single cells were not present in the original, metagenomic assembly of Desulforudis, which was obtained from a neighboring subsurface fracture. We found a transposable prophage, a retron, multiple clustered regularly interspaced short palindromic repeats (CRISPRs and restriction-modification systems, and an unusually high frequency of transposases in the analyzed single cell genomes. This indicates that recombination, HGT and viral infections are prevalent evolutionary events in the studied population of microorganisms inhabiting a highly stable deep subsurface environment.

Stellate Cells in the Medial Entorhinal Cortex Are Required for Spatial Learning

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Sarah A. Tennant

2018-01-01

Full Text Available Spatial learning requires estimates of location that may be obtained by path integration or from positional cues. Grid and other spatial firing patterns of neurons in the superficial medial entorhinal cortex (MEC suggest roles in behavioral estimation of location. However, distinguishing the contributions of path integration and cue-based signals to spatial behaviors is challenging, and the roles of identified MEC neurons are unclear. We use virtual reality to dissociate linear path integration from other strategies for behavioral estimation of location. We find that mice learn to path integrate using motor-related self-motion signals, with accuracy that decreases steeply as a function of distance. We show that inactivation of stellate cells in superficial MEC impairs spatial learning in virtual reality and in a real world object location recognition task. Our results quantify contributions of path integration to behavior and corroborate key predictions of models in which stellate cells contribute to location estimation.

The calculation of deep levels in semiconductors by using a recursion method for super-cells

International Nuclear Information System (INIS)

Wong Yongliang.

1987-01-01

The paper presents the theory of deep levels in semiconductors, the super-cell approach to the theory of deep level impurities, the calculation of band structure by using the tight-binding method and the recursion method used to study the defects in the presence of lattice relaxation and extended defect complexes. 47 refs

Cortex proliferation in the root is a protective mechanism against abiotic stress.

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Cui, Hongchang

2015-01-01

Although as an organ the root plays a pivotal role in nutrient and water uptake as well anchorage, individual cell types function distinctly. Cortex is regarded as the least differentiated cell type in the root, but little is known about its role in plant growth and physiology. In recent studies, we found that cortex proliferation can be induced by oxidative stress. Since all types of abiotic stress lead to oxidative stress, this finding suggests a role for cortex in coping with abiotic stress. This hypothesis was tested in this study using the spy mutant, which has an extra layer of cortex in the root. Interestingly, the spy mutant was shown to be hypersensitive to salt and oxidizing reagent applied to the leaves, but it was as tolerant as the wild type to these compounds in the soil. This result lends support to the notion that cortex has a protective role against abiotic stress arising from the soil.

Publisher Correction: Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex.

Science.gov (United States)

Hrvatin, Sinisa; Hochbaum, Daniel R; Nagy, M Aurel; Cicconet, Marcelo; Robertson, Keiramarie; Cheadle, Lucas; Zilionis, Rapolas; Ratner, Alex; Borges-Monroy, Rebeca; Klein, Allon M; Sabatini, Bernardo L; Greenberg, Michael E

2018-05-11

In the version of this article initially published, the x-axis labels in Fig. 3c read Vglut, Gad1/2, Aldh1l1 and Pecam1; they should have read Vglut + , Gad1/2 + , Aldh1l1 + and Pecam1 + . In Fig. 4, the range values were missing from the color scales; they are, from left to right, 4-15, 0-15, 4-15 and 0-15 in Fig. 4a and 4-15, 4-15 and 4-8 in Fig. 4h. In the third paragraph of the main text, the phrase reading "Previous approaches have analyzed a limited number of inhibitory cell types, thus masking the full diversity of excitatory populations" should have read "Previous approaches have analyzed a limited number of inhibitory cell types and masked the full diversity of excitatory populations." In the second paragraph of Results section "Diversity of experience-regulated ERGs," the phrase reading "thus suggesting considerable divergence within the gene expression program responding to early stimuli" should have read "thus suggesting considerable divergence within the early stimulus-responsive gene expression program." In the fourth paragraph of Results section "Excitatory neuronal LRGs," the sentence reading "The anatomical organization of these cell types into sublayers, coupled with divergent transcriptional responses to a sensory stimulus, suggested previously unappreciated functional subdivisions located within the laminae of the mouse visual cortex and resembling the cytoarchitecture in higher mammals" should have read "The anatomical organization of these cell types into sublayers, coupled with divergent transcriptional responses to a sensory stimulus, suggests previously unappreciated functional subdivisions located within the laminae of the mouse visual cortex, resembling the cytoarchitecture in higher mammals." In the last sentence of the Results, "sensory-responsive genes" should have read "sensory-stimulus-responsive genes." The errors have been corrected in the HTML and PDF versions of the article.

Automated immunohistochemical method to analyze large areas of the human cortex.

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Abbass, Mohamad; Trought, Kathleen; Long, David; Semechko, Anton; Wong, Albert H C

2018-01-15

There have been inconsistencies in the histological abnormalities found in the cerebral cortex from patients with schizophrenia, bipolar disorder and major depression. Discrepancies in previously published reports may arise from small sample sizes, inconsistent methodology and biased cell counting. We applied automated quantification of neuron density, neuron size and cortical layer thickness in large regions of the cerebral cortex in psychiatric patients. This method accurately segments DAPI positive cells that are also stained with CUX2 and FEZF2. Cortical layer thickness, neuron density and neuron size were automatically computed for each cortical layer in numerous Brodmann areas. We did not find pronounced cytoarchitectural abnormalities in the anterior cingulate cortex or orbitofrontal cortex in patients with schizophrenia, bipolar disorder or major depressive disorder. There were no significant differences in layer thickness measured in immunohistochemically stained slides compared with traditional Nissl stained slides. Automated cell counts were correlated, reliable and consistent with manual counts, while being much less time-consuming. We demonstrate the validity of using a novel automated analysis approach to post-mortem brain tissue. We were able to analyze large cortical areas and quantify specific cell populations using immunohistochemical markers. Future analyses could benefit from efficient automated analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Three-dimensional visual feature representation in the primary visual cortex.

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Tanaka, Shigeru; Moon, Chan-Hong; Fukuda, Mitsuhiro; Kim, Seong-Gi

2011-12-01

In the cat primary visual cortex, it is accepted that neurons optimally responding to similar stimulus orientations are clustered in a column extending from the superficial to deep layers. The cerebral cortex is, however, folded inside a skull, which makes gyri and fundi. The primary visual area of cats, area 17, is located on the fold of the cortex called the lateral gyrus. These facts raise the question of how to reconcile the tangential arrangement of the orientation columns with the curvature of the gyrus. In the present study, we show a possible configuration of feature representation in the visual cortex using a three-dimensional (3D) self-organization model. We took into account preferred orientation, preferred direction, ocular dominance and retinotopy, assuming isotropic interaction. We performed computer simulation only in the middle layer at the beginning and expanded the range of simulation gradually to other layers, which was found to be a unique method in the present model for obtaining orientation columns spanning all the layers in the flat cortex. Vertical columns of preferred orientations were found in the flat parts of the model cortex. On the other hand, in the curved parts, preferred orientations were represented in wedge-like columns rather than straight columns, and preferred directions were frequently reversed in the deeper layers. Singularities associated with orientation representation appeared as warped lines in the 3D model cortex. Direction reversal appeared on the sheets that were delimited by orientation-singularity lines. These structures emerged from the balance between periodic arrangements of preferred orientations and vertical alignment of the same orientations. Our theoretical predictions about orientation representation were confirmed by multi-slice, high-resolution functional MRI in the cat visual cortex. We obtained a close agreement between theoretical predictions and experimental observations. The present study throws a

Deep transcranial magnetic stimulation for the treatment of auditory hallucinations: a preliminary open-label study.

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Rosenberg, Oded; Roth, Yiftach; Kotler, Moshe; Zangen, Abraham; Dannon, Pinhas

2011-02-09

Schizophrenia is a chronic and disabling disease that presents with delusions and hallucinations. Auditory hallucinations are usually expressed as voices speaking to or about the patient. Previous studies have examined the effect of repetitive transcranial magnetic stimulation (TMS) over the temporoparietal cortex on auditory hallucinations in schizophrenic patients. Our aim was to explore the potential effect of deep TMS, using the H coil over the same brain region on auditory hallucinations. Eight schizophrenic patients with refractory auditory hallucinations were recruited, mainly from Beer Ya'akov Mental Health Institution (Tel Aviv university, Israel) ambulatory clinics, as well as from other hospitals outpatient populations. Low-frequency deep TMS was applied for 10 min (600 pulses per session) to the left temporoparietal cortex for either 10 or 20 sessions. Deep TMS was applied using Brainsway's H1 coil apparatus. Patients were evaluated using the Auditory Hallucinations Rating Scale (AHRS) as well as the Scale for the Assessment of Positive Symptoms scores (SAPS), Clinical Global Impressions (CGI) scale, and the Scale for Assessment of Negative Symptoms (SANS). This preliminary study demonstrated a significant improvement in AHRS score (an average reduction of 31.7% ± 32.2%) and to a lesser extent improvement in SAPS results (an average reduction of 16.5% ± 20.3%). In this study, we have demonstrated the potential of deep TMS treatment over the temporoparietal cortex as an add-on treatment for chronic auditory hallucinations in schizophrenic patients. Larger samples in a double-blind sham-controlled design are now being preformed to evaluate the effectiveness of deep TMS treatment for auditory hallucinations. This trial is registered with clinicaltrials.gov (identifier: NCT00564096).

Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.

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Haider, Lukas; Simeonidou, Constantina; Steinberger, Günther; Hametner, Simon; Grigoriadis, Nikolaos; Deretzi, Georgia; Kovacs, Gabor G; Kutzelnigg, Alexandra; Lassmann, Hans; Frischer, Josa M

2014-12-01

In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cell-Specific Cholinergic Modulation of Excitability of Layer 5B Principal Neurons in Mouse Auditory Cortex

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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

Evidence for an early innate immune response in the motor cortex of ALS.

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Jara, Javier H; Genç, Barış; Stanford, Macdonell J; Pytel, Peter; Roos, Raymond P; Weintraub, Sandra; Mesulam, M Marsel; Bigio, Eileen H; Miller, Richard J; Özdinler, P Hande

2017-06-26

Recent evidence indicates the importance of innate immunity and neuroinflammation with microgliosis in amyotrophic lateral sclerosis (ALS) pathology. The MCP1 (monocyte chemoattractant protein-1) and CCR2 (CC chemokine receptor 2) signaling system has been strongly associated with the innate immune responses observed in ALS patients, but the motor cortex has not been studied in detail. After revealing the presence of MCP1 and CCR2 in the motor cortex of ALS patients, to elucidate, visualize, and define the timing, location and the extent of immune response in relation to upper motor neuron vulnerability and progressive degeneration in ALS, we developed MCP1-CCR2-hSOD1 G93A mice, an ALS reporter line, in which cells expressing MCP1 and CCR2 are genetically labeled by monomeric red fluorescent protein-1 and enhanced green fluorescent protein, respectively. In the motor cortex of MCP1-CCR2-hSOD1 G93A mice, unlike in the spinal cord, there was an early increase in the numbers of MCP1+ cells, which displayed microglial morphology and selectively expressed microglia markers. Even though fewer CCR2+ cells were present throughout the motor cortex, they were mainly infiltrating monocytes. Interestingly, MCP1+ cells were found in close proximity to the apical dendrites and cell bodies of corticospinal motor neurons (CSMN), further implicating the importance of their cellular interaction to neuronal pathology. Similar findings were observed in the motor cortex of ALS patients, where MCP1+ microglia were especially in close proximity to the degenerating apical dendrites of Betz cells. Our findings reveal that the intricate cellular interplay between immune cells and upper motor neurons observed in the motor cortex of ALS mice is indeed recapitulated in ALS patients. We generated and characterized a novel model system, to study the cellular and molecular basis of this close cellular interaction and how that relates to motor neuron vulnerability and progressive degeneration in

Cell Type–Specific Three-Dimensional Structure of Thalamocortical Circuits in a Column of Rat Vibrissal Cortex

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de Kock, Christiaan P. J.; Bruno, Randy M.; Ramirez, Alejandro; Meyer, Hanno S.; Dercksen, Vincent J.; Helmstaedter, Moritz; Sakmann, Bert

2012-01-01

Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify 9 cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamocortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type–specific lemniscal synaptic wiring diagram and elucidates structure–function relationships of this physiologically relevant pathway at single-cell resolution. PMID:22089425

Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells

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Ben Chung Lap Chan

2015-09-01

Full Text Available Atopic dermatitis (AD is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC culture model coupled with the high-speed counter-current chromatography (HSCCC, high pressure liquid chromatography (HPLC and Liquid Chromatography-Mass Spectrometry (LCMS analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL-12 p40 and the functional cluster of differentiation (CD surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.

Gamma-radiation produces abnormal Bergmann fibers and ectopic granule cells in mouse cerebellar cortex

International Nuclear Information System (INIS)

Inouye, Minoru; Hayasaka, Shizu; Funahashi, Atsushi; Yamamura, Hideki

1992-01-01

Morphological changes in Bergmann glial fibers in the developing cerebellar cortex produced by exposure to gamma-rays were investigated in association with ectopic granule cells. Six-day-old mice that had been exposed to 3 Gy of gamma-radiation were killed 6 hours after exposure or at 7 through 30 days of age. Their cerebella were examined histologically and immunohistochemically for glial fibrillary acidic protein in Bergmann fibers. Extensive cell death took place in the external granular layer (EGL) of the cerebellum from 6 through 24 hours after exposure. This led to the thinning of the EGL and a decrease in the number of migrating cells in the molecular layer. The number of Bergmann cells was not decreased, but the fibers in the molecular layer were distorted; whereas, in the control these fibers were straight and perpendicular to the pial surface. The EGL began to recover 2 days after exposure, and abnormally oriented migrating cells were seen. At 17 days of age, some cell clustering was observed in the molecular layer of the irradiated cerebellum. Distortion of the Bergmann fibers was marked in regions where ectopic granule cells appeared at 30 days of age. These findings suggest that the distortion of Bergmann fibers leads to the production of ectopic granule cells after exposure to gamma-radiation. (author)

Deep transcranial magnetic stimulation for the treatment of auditory hallucinations: a preliminary open-label study

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Zangen Abraham

2011-02-01

Full Text Available Abstract Background Schizophrenia is a chronic and disabling disease that presents with delusions and hallucinations. Auditory hallucinations are usually expressed as voices speaking to or about the patient. Previous studies have examined the effect of repetitive transcranial magnetic stimulation (TMS over the temporoparietal cortex on auditory hallucinations in schizophrenic patients. Our aim was to explore the potential effect of deep TMS, using the H coil over the same brain region on auditory hallucinations. Patients and methods Eight schizophrenic patients with refractory auditory hallucinations were recruited, mainly from Beer Ya'akov Mental Health Institution (Tel Aviv university, Israel ambulatory clinics, as well as from other hospitals outpatient populations. Low-frequency deep TMS was applied for 10 min (600 pulses per session to the left temporoparietal cortex for either 10 or 20 sessions. Deep TMS was applied using Brainsway's H1 coil apparatus. Patients were evaluated using the Auditory Hallucinations Rating Scale (AHRS as well as the Scale for the Assessment of Positive Symptoms scores (SAPS, Clinical Global Impressions (CGI scale, and the Scale for Assessment of Negative Symptoms (SANS. Results This preliminary study demonstrated a significant improvement in AHRS score (an average reduction of 31.7% ± 32.2% and to a lesser extent improvement in SAPS results (an average reduction of 16.5% ± 20.3%. Conclusions In this study, we have demonstrated the potential of deep TMS treatment over the temporoparietal cortex as an add-on treatment for chronic auditory hallucinations in schizophrenic patients. Larger samples in a double-blind sham-controlled design are now being preformed to evaluate the effectiveness of deep TMS treatment for auditory hallucinations. Trial registration This trial is registered with clinicaltrials.gov (identifier: NCT00564096.

Circuit Mechanisms Governing Local vs. Global Motion Processing in Mouse Visual Cortex

DEFF Research Database (Denmark)

Rasmussen, Rune; Yonehara, Keisuke

2017-01-01

components represented by component direction-selective (CDS) cells. However, how PDS and CDS cells develop their distinct response properties is still unresolved. The visual cortex of the mouse is an attractive model for experimentally solving this issue due to the large molecular and genetic toolbox...... literature on global motion processing based on works in primates and mice. Lastly, we propose what types of experiments could illuminate what circuit mechanisms are governing cortical global visual motion processing. We propose that PDS cells in mouse visual cortex appear as the perfect arena...

The Tlx gene regulates the timing of neurogenesis in the cortex.

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Roy, Kristine; Kuznicki, Kathleen; Wu, Qiang; Sun, Zhuoxin; Bock, Dagmar; Schutz, Gunther; Vranich, Nancy; Monaghan, A Paula

2004-09-22

The tailless (tlx) gene is a forebrain-restricted transcription factor. Tlx mutant animals exhibit a reduction in the size of the cerebral hemispheres and associated structures (Monaghan et al., 1997). Superficial cortical layers are specifically reduced, whereas deep layers are relatively unaltered (Land and Monaghan, 2003). To determine whether the adult laminar phenotype has a developmental etiology and whether it is associated with a change in proliferation/differentiation decisions, we examined the cell cycle and neurogenesis in the embryonic cortex. We found that there is a temporal and regional requirement for the Tlx protein in progenitor cells (PCs). Neurons prematurely differentiate at all rostrocaudal levels up to mid-neurogenesis in mutant animals. Heterozygote animals have an intermediate phenotype indicating there is a threshold requirement for Tlx in early cortical neurogenesis. Our studies indicate that PCs in the ventricular zone are sensitive to loss of Tlx in caudal regions only; however, PCs in the subventricular zone are altered at all rostrocaudal levels in tlx-deficient animals. Furthermore, we found that the cell cycle is shorter from embryonic day 9.5 in tlx-/- embryos. At mid-neurogenesis, the PC population becomes depleted, and late PCs have a longer cell cycle in tlx-deficient animals. Consequently, later generated structures, such as upper cortical layers, the dentate gyrus, and the olfactory bulbs, are severely reduced. These studies indicate that tlx is an essential intrinsic regulator in the decision to proliferate or differentiate in the developing forebrain.

Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells.

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Tait, Luke; Wedgwood, Kyle; Tsaneva-Atanasova, Krasimira; Brown, Jon T; Goodfellow, Marc

2018-07-14

The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer's disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4-12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Callosal connections of dorso-lateral premotor cortex.

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Marconi, B; Genovesio, A; Giannetti, S; Molinari, M; Caminiti, R

2003-08-01

This study investigated the organization of the callosal connections of the two subdivisions of the monkey dorsal premotor cortex (PMd), dorso-rostral (F7) and dorso-caudal (F2). In one animal, Fast blue and Diamidino yellow were injected in F7 and F2, respectively; in a second animal, the pattern of injections was reversed. F7 and F2 receive a major callosal input from their homotopic counterpart. The heterotopic connections of F7 originate mainly from F2, with smaller contingent from pre-supplementary motor area (pre-SMA, F6), area 8 (frontal eye fields), and prefrontal cortex (area 46), while those of F2 originate from F7, with smaller contributions from ventral premotor areas (F5, F4), SMA-proper (F3), and primary motor cortex (M1). Callosal cells projecting homotopically are mostly located in layers II-III, those projecting heterotopically occupy layers II-III and V-VI. A spectral analysis was used to characterize the spatial fluctuations of the distribution of callosal neurons, in both F7 and F2, as well as in adjacent cortical areas. The results revealed two main periodic components. The first, in the domain of the low spatial frequencies, corresponds to periodicities of cell density with peak-to-peak distances of approximately 10 mm, and suggests an arrangement of callosal cells in the form of 5-mm wide bands. The second corresponds to periodicities of approximately 2 mm, and probably reflects a 1-mm columnar-like arrangement. Coherency and phase analyses showed that, although similar in their spatial arrangements, callosal cells projecting to dorsal premotor areas are segregated in the tangential cortical domain.

Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

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Geissy LL Araújo

2014-03-01

Full Text Available The morphogen Sonic Hedgehog (SHH plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

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Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

2017-06-15

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Strength and fine dexterity recovery profiles after a primary motor cortex insult and effect of a neuronal cell graft.

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Vaysse, Laurence; Conchou, Fabrice; Demain, Boris; Davoust, Carole; Plas, Benjamin; Ruggieri, Cyrielle; Benkaddour, Mehdi; Simonetta-Moreau, Marion; Loubinoux, Isabelle

2015-08-01

The aim of this study was to set up (a) a large primary motor cortex (M1) lesion in rodent and (b) the conditions for evaluating a long-lasting motor deficit in order to propose a valid model to test neuronal replacement therapies aimed at improving motor deficit recovery. A mitochondrial toxin, malonate, was injected to induce extensive destruction of the forelimb M1 cortex. Three key motor functions that are usually evaluated following cerebral lesion in the clinic-strength, target reaching, and fine dexterity-were assessed in rats by 2 tests, a forelimb grip strength test and a skilled reaching task (staircase) for reaching and dexterity. The potential enhancement of postlesion recovery induced by a neuronal cell transplantation was then explored and confirmed by histological analyses. Both tests showed a severe functional impairment 2 days post lesion, however, reaching remained intact. Deficits in forelimb strength were long lasting (up to 3 months) but spontaneously recovered despite the extensive lesion size. This natural grip strength recovery could be enhanced by cell therapy. Histological analyses confirmed the presence of grafted cells 3 months postgraft and showed partial tissue reconstruction with some living neuronal cells in the graft. In contrast, fine dexterity never recovered in the staircase test even after grafting. These results suggest that cell replacement was only partially effective and that the forelimb M1 area may be a node of the sensorimotor network, where compensation from secondary pathways could account for strength recovery but recovery of forelimb fine dexterity requires extensive tissue reconstruction. (c) 2015 APA, all rights reserved).

Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study.

Science.gov (United States)

Rosenberg, Oded; Gersner, Roman; Klein, Limor Dinur; Kotler, Moshe; Zangen, Abraham; Dannon, Pinhas

2012-05-06

About 25% of schizophrenia patients with auditory hallucinations are refractory to pharmacotherapy and electroconvulsive therapy. We conducted a deep transcranial magnetic stimulation (TMS) pilot study in order to evaluate the potential clinical benefit of repeated left temporoparietal cortex stimulation in these patients. The results were encouraging, but a sham-controlled study was needed to rule out a placebo effect. A total of 18 schizophrenic patients with refractory auditory hallucinations were recruited, from Beer Yaakov MHC and other hospitals outpatient populations. Patients received 10 daily treatment sessions with low-frequency (1 Hz for 10 min) deep TMS applied over the left temporoparietal cortex, using the H1 coil at the intensity of 110% of the motor threshold. Procedure was either real or sham according to patient randomization. Patients were evaluated via the Auditory Hallucinations Rating Scale, Scale for the Assessment of Positive Symptoms-Negative Symptoms, Clinical Global Impressions, and Quality of Life Questionnaire. In all, 10 patients completed the treatment (10 TMS sessions). Auditory hallucination scores of both groups improved; however, there was no statistical difference in any of the scales between the active and the sham treated groups. Low-frequency deep TMS to the left temporoparietal cortex using the protocol mentioned above has no statistically significant effect on auditory hallucinations or the other clinical scales measured in schizophrenic patients. Clinicaltrials.gov identifier: NCT00564096.

Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration within the embryonic mouse cerebral cortex.

Science.gov (United States)

Clément, Olivier; Hemming, Isabel Anne; Gladwyn-Ng, Ivan Enghian; Qu, Zhengdong; Li, Shan Shan; Piper, Michael; Heng, Julian Ik-Tsen

2017-05-15

During the development of the mammalian cerebral cortex, newborn postmitotic projection neurons are born from local neural stem cells and must undergo radial migration so as to position themselves appropriately to form functional neural circuits. The zinc finger transcriptional repressor Rp58 (also known as Znf238 or Zbtb18) is critical for coordinating corticogenesis, but its underlying molecular mechanism remains to be better characterised. Here, we demonstrate that the co-expression of Rp58 and the cyclin dependent kinase inhibitor (CDKI) p27 kip1 is important for E14.5-born cortical neurons to coordinate cell cycle exit and initiate their radial migration. Notably, we find that the impaired radial positioning of Rp58-deficient cortical neurons within the embryonic (E17.5) mouse cortex, as well as their multipolar to bipolar transition from the intermediate zone to the cortical plate can be restored by forced expression of p27 kip1 in concert with suppression of Rnd2, a downstream target gene of Rp58. Furthermore, the restorative effects of p27 kip1 and Rnd2 abrogation are reminiscent of suppressing RhoA signalling in Rp58-deficient cells. Our findings demonstrate functional interplay between a transcriptional regulator and a CDKI to mediate neuroprogenitor cell cycle exit, as well as to promote radial migration through a molecular mechanism consistent with suppression of RhoA signalling.

Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

Institute of Scientific and Technical Information of China (English)

Jielu Tan; Xiangrong Zheng; Shanshan Zhang; Yujia Yang; Xia Wang; Xiaohe Yu; Le Zhong

2014-01-01

Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into ifve groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular en-dothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. hTe cerebral palsy model was established by ligating the letf common carotid artery followed by exposure to hypox-ia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. Atfer transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vas-cular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for ifnding water and the ifnding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. hTese ifndings indicate that the transplantation of vascu-lar endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deifcits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

Convolutional Deep Belief Networks for Single-Cell/Object Tracking in Computational Biology and Computer Vision

OpenAIRE

Zhong, Bineng; Pan, Shengnan; Zhang, Hongbo; Wang, Tian; Du, Jixiang; Chen, Duansheng; Cao, Liujuan

2016-01-01

In this paper, we propose deep architecture to dynamically learn the most discriminative features from data for both single-cell and object tracking in computational biology and computer vision. Firstly, the discriminative features are automatically learned via a convolutional deep belief network (CDBN). Secondly, we design a simple yet effective method to transfer features learned from CDBNs on the source tasks for generic purpose to the object tracking tasks using only limited amount of tra...

Membrane potential correlates of sensory perception in mouse barrel cortex.

Science.gov (United States)

Sachidhanandam, Shankar; Sreenivasan, Varun; Kyriakatos, Alexandros; Kremer, Yves; Petersen, Carl C H

2013-11-01

Neocortical activity can evoke sensory percepts, but the cellular mechanisms remain poorly understood. We trained mice to detect single brief whisker stimuli and report perceived stimuli by licking to obtain a reward. Pharmacological inactivation and optogenetic stimulation demonstrated a causal role for the primary somatosensory barrel cortex. Whole-cell recordings from barrel cortex neurons revealed membrane potential correlates of sensory perception. Sensory responses depended strongly on prestimulus cortical state, but both slow-wave and desynchronized cortical states were compatible with task performance. Whisker deflection evoked an early (sensory response that was encoded through cell-specific reversal potentials. A secondary late (50-400 ms) depolarization was enhanced on hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation. Our data reveal dynamic processing in the sensory cortex during task performance, with an early sensory response reliably encoding the stimulus and later secondary activity contributing to driving the subjective percept.

Ultrastructural changes in aster yellows phytoplasma affected Limonium sinuatum Mill. plants II. Pathology of cortex parenchyma cells

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Anna Rudzińska-Langwald

2014-01-01

Full Text Available In Limonium sinuatum Mill, plants with severe symptoms of aster yellows infection phytoplasmas were present not only in the phloem but also in some cortex parenchymas cells. These parenchyma cells were situated at some distance from the conducting bundles. The phytoplasmas were observed directly in parenchyma cells cytoplasm. The number of phytoplasmas present in each selected cell varies. The cells with a small number of phytoplasmas show little pathological changes compared with the unaffected cells of the same zone of the stem as well with the cells of healthy plants. The cells filled with a number of phytoplasmas had their protoplast very much changed. The vacuole was reduced and in the cytoplasm a reduction of the number of ribosomes was noted and regions of homogenous structure appeared. Mitochondria were moved in the direction of the tonoplast and plasma membrane. Compared to the cells unaffected by phytoplasma, the mitochondria were smaller and had an enlarged cristae internal space. The chloroplasts from affected cells had a very significant reduction in size and the tylacoids system had disappeared. The role of these changes for creating phytoplasma friendly enviroment is discused.

Peripheral nerve injury induces glial activation in primary motor cortex

OpenAIRE

Julieta Troncoso; Julieta Troncoso; Efraín Buriticá; Efraín Buriticá

2015-01-01

Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to eithe...

Robust Individual-Cell/Object Tracking via PCANet Deep Network in Biomedicine and Computer Vision

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Bineng Zhong

2016-01-01

Full Text Available Tracking individual-cell/object over time is important in understanding drug treatment effects on cancer cells and video surveillance. A fundamental problem of individual-cell/object tracking is to simultaneously address the cell/object appearance variations caused by intrinsic and extrinsic factors. In this paper, inspired by the architecture of deep learning, we propose a robust feature learning method for constructing discriminative appearance models without large-scale pretraining. Specifically, in the initial frames, an unsupervised method is firstly used to learn the abstract feature of a target by exploiting both classic principal component analysis (PCA algorithms with recent deep learning representation architectures. We use learned PCA eigenvectors as filters and develop a novel algorithm to represent a target by composing of a PCA-based filter bank layer, a nonlinear layer, and a patch-based pooling layer, respectively. Then, based on the feature representation, a neural network with one hidden layer is trained in a supervised mode to construct a discriminative appearance model. Finally, to alleviate the tracker drifting problem, a sample update scheme is carefully designed to keep track of the most representative and diverse samples during tracking. We test the proposed tracking method on two standard individual cell/object tracking benchmarks to show our tracker's state-of-the-art performance.

Effects of continuous low-dose prenatal irradiation on neuronal migration in mouse cerebral cortex

International Nuclear Information System (INIS)

Hyodo-Taguchi, Yasuko; Ishikawa, Yuji; Hirobe, Tomohisa; Fushiki, Shinji; Kinoshita, Chikako.

1997-01-01

We investigated the effects of continuous exposure to γ-rays during corticogenesis on the migration of neuronal cells in developing cerebral cortex. Pregnant mice were injected with 0.5 mg of bromodeoxyuridine (BrdU) on day 14 of gestation to label cells in the S phase. The mice were then exposed to 137 Cs γ-rays (dose rates of 0.1, 0.3, and 0.94 Gy/day) continuously for 3 days. Brains from 17-day-old embryos and from offspring at 3 and 8 weeks after birth were processed immunohistochemically to track the movements of BrdU-labeled cells. Comparative analyses of the distribution pattern of BrdU-labeled cells in the cerebral cortex revealed that the migration of neurons was delayed during the embryonic period in mice irradiated at 0.94 Gy/day, in 3-week-old mice, there was a significant difference in the distribution pattern of BrdU-labeled cells in the cerebral cortex between the mice irradiated prenatally and control, and in 8-week-old mice, there were no differences in the distribution pattern of BrdU-labeled cells between control and animals irradiated with 0.1 and 0.3 Gy/day. In contrast, in the animals irradiated with 0.94 Gy/day, the significant difference in the distribution pattern of the labeled cells relative to control was maintained. These results suggest that the migration of neuronal cells in mouse cerebral cortex is disturbed by continuous prenatal irradiation at low-dose and some modificational process occurred during the postnatal period. (author)

Neural Dynamics and Information Representation in Microcircuits of Motor Cortex

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Yasuhiro eTsubo

2013-05-01

Full Text Available The brain has to analyze and respond to external events that can change rapidly from time to time, suggesting that information processing by the brain may be essentially dynamic rather than static. The dynamical features of neural computation are of significant importance in motor cortex that governs the process of movement generation and learning. In this paper, we discuss these features based primarily on our recent findings on neural dynamics and information coding in the microcircuit of rat motor cortex. In fact, cortical neurons show a variety of dynamical behavior from rhythmic activity in various frequency bands to highly irregular spike firing. Of particular interest are the similarity and dissimilarity of the neuronal response properties in different layers of motor cortex. By conducting electrophysiological recordings in slice preparation, we report the phase response curves of neurons in different cortical layers to demonstrate their layer-dependent synchronization properties. We then study how motor cortex recruits task-related neurons in different layers for voluntary arm movements by simultaneous juxtacellular and multiunit recordings from behaving rats. The results suggest an interesting difference in the spectrum of functional activity between the superficial and deep layers. Furthermore, the task-related activities recorded from various layers exhibited power law distributions of inter-spike intervals (ISIs, in contrast to a general belief that ISIs obey Poisson or Gamma distributions in cortical neurons. We present a theoretical argument that this power law of in vivo neurons may represent the maximization of the entropy of firing rate with limited energy consumption of spike generation. Though further studies are required to fully clarify the functional implications of this coding principle, it may shed new light on information representations by neurons and circuits in motor cortex.

Deep transcranial magnetic stimulation for the treatment of pathological gambling.

Science.gov (United States)

Rosenberg, Oded; Klein, Limor Dinur; Dannon, Pinhas N

2013-03-30

Five pathological gamblers received deep transcranial magnetic stimulation (DTMS). Evaluations included rating scales and collateral anamnesis. Despite initial improvement in ratings, collateral anamnesis demonstrated failure to respond. DTMS to the pre-frontal cortex using an H1 coil was an ineffective treatment. Our study is preliminary, and additional studies are required. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex.

Science.gov (United States)

van Kerkoerle, Timo; Self, Matthew W; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Poort, Jasper; van der Togt, Chris; Roelfsema, Pieter R

2014-10-07

Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition.

Deep Hierarchies in the Primate Visual Cortex: What Can We Learn for Computer Vision?

OpenAIRE

Kruger, Norbert; Janssen, Peter; Kalkan, Sinan; Lappe, Markus; Leonardis, Ales; Piater, Justus; Rodriguez-Sanchez, Antonio J.; Wiskott, Laurenz

2013-01-01

Computational modeling of the primate visual system yields insights of potential relevance to some of the challenges that computer vision is facing, such as object recognition and categorization, motion detection and activity recognition or vision-based navigation and manipulation. This article reviews some functional principles and structures that are generally thought to underlie the primate visual cortex, and attempts to extract biological principles that could further advance computer ...

Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

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Ruixue Song

2017-01-01

Full Text Available Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC. Pregnant mice at gestational day 15.5 received 2.5% sevoflurane for 6 h. Learning function of the offspring was evaluated with the Morris water maze test at postnatal day 30. Brain tissues of fetal mice were subjected to immunofluorescence staining to assess differentiation, proliferation, and cell cycle dynamics of the fetal PFC. We found that maternal sevoflurane anesthesia impaired learning ability in offspring through inhibiting deep-layer immature neuron output and neuronal progenitor replication. With the assessment of cell cycle dynamics, we established that these effects were mediated through cell cycle arrest in neural progenitors. Our research has provided insights into the cell cycle-related mechanisms by which maternal sevoflurane exposure can induce neurodevelopmental abnormalities and learning dysfunction and appeals people to consider the neurotoxicity of anesthetics when considering the benefits and risks of nonobstetric surgical procedures.

HEp-2 cell image classification method based on very deep convolutional networks with small datasets

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Lu, Mengchi; Gao, Long; Guo, Xifeng; Liu, Qiang; Yin, Jianping

2017-07-01

Human Epithelial-2 (HEp-2) cell images staining patterns classification have been widely used to identify autoimmune diseases by the anti-Nuclear antibodies (ANA) test in the Indirect Immunofluorescence (IIF) protocol. Because manual test is time consuming, subjective and labor intensive, image-based Computer Aided Diagnosis (CAD) systems for HEp-2 cell classification are developing. However, methods proposed recently are mostly manual features extraction with low accuracy. Besides, the scale of available benchmark datasets is small, which does not exactly suitable for using deep learning methods. This issue will influence the accuracy of cell classification directly even after data augmentation. To address these issues, this paper presents a high accuracy automatic HEp-2 cell classification method with small datasets, by utilizing very deep convolutional networks (VGGNet). Specifically, the proposed method consists of three main phases, namely image preprocessing, feature extraction and classification. Moreover, an improved VGGNet is presented to address the challenges of small-scale datasets. Experimental results over two benchmark datasets demonstrate that the proposed method achieves superior performance in terms of accuracy compared with existing methods.

Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

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Maren Geissler

Full Text Available Intraperitoneal transplantation of human umbilical cord blood (hUCB cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury.

Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study

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Rosenberg Oded

2012-05-01

Full Text Available Abstract Background About 25% of schizophrenia patients with auditory hallucinations are refractory to pharmacotherapy and electroconvulsive therapy. We conducted a deep transcranial magnetic stimulation (TMS pilot study in order to evaluate the potential clinical benefit of repeated left temporoparietal cortex stimulation in these patients. The results were encouraging, but a sham-controlled study was needed to rule out a placebo effect. Methods A total of 18 schizophrenic patients with refractory auditory hallucinations were recruited, from Beer Yaakov MHC and other hospitals outpatient populations. Patients received 10 daily treatment sessions with low-frequency (1 Hz for 10 min deep TMS applied over the left temporoparietal cortex, using the H1 coil at the intensity of 110% of the motor threshold. Procedure was either real or sham according to patient randomization. Patients were evaluated via the Auditory Hallucinations Rating Scale, Scale for the Assessment of Positive Symptoms-Negative Symptoms, Clinical Global Impressions, and Quality of Life Questionnaire. Results In all, 10 patients completed the treatment (10 TMS sessions. Auditory hallucination scores of both groups improved; however, there was no statistical difference in any of the scales between the active and the sham treated groups. Conclusions Low-frequency deep TMS to the left temporoparietal cortex using the protocol mentioned above has no statistically significant effect on auditory hallucinations or the other clinical scales measured in schizophrenic patients. Trial Registration Clinicaltrials.gov identifier: NCT00564096.

The neurophysiology of figure^ground segregation in primary visual cortex

NARCIS (Netherlands)

Lamme, V.A.F.

1995-01-01

Recorded neuronal activity in the monkey primary visual cortex while Ss were viewing full screen arrays of either oriented line segments or moving random dots. Almost every cell gave a significantly larger response for texture elements perceived as a figure (FI) than for background elements. Cell

Left Posterior Orbitofrontal Cortex Is Associated With Odor-Induced Autobiographical Memory: An fMRI Study

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Keiko Watanabe

2018-05-01

Full Text Available Autobiographical odor memory (AM-odor accompanied by a sense of realism of a specific memory elicits strong emotions. AM-odor differs from memory triggered by other sensory modalities, possibly because olfaction involves a unique sensory process. Here, we examined the orbitofrontal cortex (OFC, using functional magnetic resonance imaging (fMRI to determine which OFC subregions are related to AM-odor. Both AM-odor and a control odor successively increased subjective ratings of comfortableness and pleasantness. Importantly, AM-odor also increased arousal levels and the vividness of memories, and was associated with a deep and slow breathing pattern. fMRI analysis indicated robust activation in the left posterior OFC (L-POFC. Connectivity between the POFC and whole brain regions was estimated using psychophysiological interaction analysis (PPI. We detected several trends in connectivity between L-POFC and bilateral precuneus, bilateral rostral dorsal anterior cingulate cortex (rdACC, and left parahippocampus, which will be useful for targeting our hypotheses for future investigations. The slow breathing observed in AM-odor was correlated with rdACC activation. Odor associated with emotionally significant autobiographical memories was accompanied by slow and deep breathing, possibly involving rdACC processing.

Left Posterior Orbitofrontal Cortex Is Associated With Odor-Induced Autobiographical Memory: An fMRI Study.

Science.gov (United States)

Watanabe, Keiko; Masaoka, Yuri; Kawamura, Mitsuru; Yoshida, Masaki; Koiwa, Nobuyoshi; Yoshikawa, Akira; Kubota, Satomi; Ida, Masahiro; Ono, Kenjiro; Izumizaki, Masahiko

2018-01-01

Autobiographical odor memory (AM-odor) accompanied by a sense of realism of a specific memory elicits strong emotions. AM-odor differs from memory triggered by other sensory modalities, possibly because olfaction involves a unique sensory process. Here, we examined the orbitofrontal cortex (OFC), using functional magnetic resonance imaging (fMRI) to determine which OFC subregions are related to AM-odor. Both AM-odor and a control odor successively increased subjective ratings of comfortableness and pleasantness. Importantly, AM-odor also increased arousal levels and the vividness of memories, and was associated with a deep and slow breathing pattern. fMRI analysis indicated robust activation in the left posterior OFC (L-POFC). Connectivity between the POFC and whole brain regions was estimated using psychophysiological interaction analysis (PPI). We detected several trends in connectivity between L-POFC and bilateral precuneus, bilateral rostral dorsal anterior cingulate cortex (rdACC), and left parahippocampus, which will be useful for targeting our hypotheses for future investigations. The slow breathing observed in AM-odor was correlated with rdACC activation. Odor associated with emotionally significant autobiographical memories was accompanied by slow and deep breathing, possibly involving rdACC processing.

Onset of Tlx-3 expression in the chick cerebellar cortex correlates with the morphological development of fissures and delineates a posterior transverse boundary.

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Logan, Cairine; Millar, Cassie; Bharadia, Vinay; Rouleau, Katherine

2002-06-24

Recent studies have shown that the mammalian cerebellar cortex can be subdivided into a reproducible array of zones and stripes. In particular, discontinuous patterns of gene expression together with mutational analysis suggest that there are at least four distinct transverse zones along the rostrocaudal axis in mouse: the anterior zone (lobules I-V), the central zone (lobules VI and VII), the posterior zone (lobules VIII and IX), and the nodular zone (lobule X). Here we show that the divergent homeobox-containing transcription factor, Tlx- 3 (also known as Hox11L2 or Rnx) is transiently expressed in external granule cells in a distinct transverse domain of the developing chick cerebellar cortex. Expression is first detected at Hamburger and Hamilton (HH) stage 35. Interestingly, Tlx-3 mRNA expression is initially confined to, and coincident with, the morphological development of fissures. Slightly later, at HH stage 38, expression extends throughout the developing external granular layer (EGL) of lobules I-IXab. Notably, no Tlx-3 expression was detected in lobules IXc and X at any developmental time point examined. Expression is noticeably stronger in nonproliferating cells located in the deep layer of the EGL. Tlx-3 expression is downregulated as granule cells migrate inward to form the internal granule layer and is undetectable shortly after birth. These results suggest that Tlx-3 is expressed as granule cells become postmitotic and suggest that Tlx-3 may play a role in the differentiation of distinct neuronal populations in the cerebellum. Copyright 2002 Wiley-Liss, Inc.

Induction of superficial cortical layer neurons from mouse embryonic stem cells by valproic acid.

Science.gov (United States)

Juliandi, Berry; Abematsu, Masahiko; Sanosaka, Tsukasa; Tsujimura, Keita; Smith, Austin; Nakashima, Kinichi

2012-01-01

Within the developing mammalian cortex, neural progenitors first generate deep-layer neurons and subsequently more superficial-layer neurons, in an inside-out manner. It has been reported recently that mouse embryonic stem cells (mESCs) can, to some extent, recapitulate cortical development in vitro, with the sequential appearance of neurogenesis markers resembling that in the developing cortex. However, mESCs can only recapitulate early corticogenesis; superficial-layer neurons, which are normally produced in later developmental periods in vivo, are under-represented. This failure of mESCs to reproduce later corticogenesis in vitro implies the existence of crucial factor(s) that are absent or uninduced in existing culture systems. Here we show that mESCs can give rise to superficial-layer neurons efficiently when treated with valproic acid (VPA), a histone deacetylase inhibitor. VPA treatment increased the production of Cux1-positive superficial-layer neurons, and decreased that of Ctip2-positive deep-layer neurons. These results shed new light on the mechanisms of later corticogenesis. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

[Neuroanatomy of Frontal Association Cortex].

Science.gov (United States)

Takada, Masahiko

2016-11-01

The frontal association cortex is composed of the prefrontal cortex and the motor-related areas except the primary motor cortex (i.e., the so-called higher motor areas), and is well-developed in primates, including humans. The prefrontal cortex receives and integrates large bits of diverse information from the parietal, temporal, and occipital association cortical areas (termed the posterior association cortex), and paralimbic association cortical areas. This information is then transmitted to the primary motor cortex via multiple motor-related areas. Given these facts, it is likely that the prefrontal cortex exerts executive functions for behavioral control. The functional input pathways from the posterior and paralimbic association cortical areas to the prefrontal cortex are classified primarily into six groups. Cognitive signals derived from the prefrontal cortex are conveyed to the rostral motor-related areas to transform them into motor signals, which finally enter the primary motor cortex via the caudal motor-related areas. Furthermore, it has been shown that, similar to the primary motor cortex, areas of the frontal association cortex form individual networks (known as "loop circuits") with the basal ganglia and cerebellum via the thalamus, and hence are extensively involved in the expression and control of behavioral actions.

The gene cortex controls mimicry and crypsis in butterflies and moths.

Science.gov (United States)

Nadeau, Nicola J; Pardo-Diaz, Carolina; Whibley, Annabel; Supple, Megan A; Saenko, Suzanne V; Wallbank, Richard W R; Wu, Grace C; Maroja, Luana; Ferguson, Laura; Hanly, Joseph J; Hines, Heather; Salazar, Camilo; Merrill, Richard M; Dowling, Andrea J; ffrench-Constant, Richard H; Llaurens, Violaine; Joron, Mathieu; McMillan, W Owen; Jiggins, Chris D

2016-06-02

The wing patterns of butterflies and moths (Lepidoptera) are diverse and striking examples of evolutionary diversification by natural selection. Lepidopteran wing colour patterns are a key innovation, consisting of arrays of coloured scales. We still lack a general understanding of how these patterns are controlled and whether this control shows any commonality across the 160,000 moth and 17,000 butterfly species. Here, we use fine-scale mapping with population genomics and gene expression analyses to identify a gene, cortex, that regulates pattern switches in multiple species across the mimetic radiation in Heliconius butterflies. cortex belongs to a fast-evolving subfamily of the otherwise highly conserved fizzy family of cell-cycle regulators, suggesting that it probably regulates pigmentation patterning by regulating scale cell development. In parallel with findings in the peppered moth (Biston betularia), our results suggest that this mechanism is common within Lepidoptera and that cortex has become a major target for natural selection acting on colour and pattern variation in this group of insects.

Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.

Science.gov (United States)

Mittleman, Guy; Goldowitz, Daniel; Heck, Detlef H; Blaha, Charles D

2008-07-01

Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 muA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.

Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice

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Dustin H Brewton

2016-11-01

Full Text Available Age-related changes in inhibitory neurotransmission in sensory cortex may underlie deficits in sensory function. Perineuronal nets (PNNs are extracellular matrix components that ensheath some inhibitory neurons, particularly parvalbumin positive (PV+ interneurons. PNNs may protect PV+ cells from oxidative stress and help establish their rapid spiking properties. Although PNN expression has been well characterized during development, possible changes in aging sensory cortex have not been investigated. Here we tested the hypothesis that PNN+, PV+ and PV/PNN co-localized cell densities decline with age in the primary auditory cortex (A1. This hypothesis was tested using immunohistochemistry in two strains of mice (C57BL/6 and CBA/CaJ with different susceptibility to age-related hearing loss and at three different age ranges (1-3, 6-8 and 14-24 months old. We report that PNN+ and PV/PNN co-localized cell densities decline significantly with age in A1 in both mouse strains. In the PNN+ cells that remain in the old group, the intensity of PNN staining is reduced in the C57 strain, but not the CBA strain. PV+ cell density also declines only in the C57, but not the CBA, mouse suggesting a potential exacerbation of age-effects by hearing loss in the PV/PNN system. Taken together, these data suggest that PNN deterioration may be a key component of altered inhibition in the aging sensory cortex, that may lead to altered synaptic function, susceptibility to oxidative stress and processing deficits.

A frontal cortex event-related potential driven by the basal forebrain

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Nguyen, David P; Lin, Shih-Chieh

2014-01-01

Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5–10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001 PMID:24714497

The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

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Ohi, Seigo; Roach, Allana-Nicole; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

2003-01-01

It is hypothesized that the hematopoietic stem cell therapy (HSCT) might countermeasure various space-caused disorders so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using animal models of disorders (hindlimb suspension unloading system and beta-thalassemia), the HSCT was tested for muscle loss, immunodeficiency and space anemia. The results indicate feasibility of HSCT for these disorders. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Attention modulates the responses of simple cells in monkey primary visual cortex.

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McAdams, Carrie J; Reid, R Clay

2005-11-23

Spatial attention has long been postulated to act as a spotlight that increases the salience of visual stimuli at the attended location. We examined the effects of attention on the receptive fields of simple cells in primary visual cortex (V1) by training macaque monkeys to perform a task with two modes. In the attended mode, the stimuli relevant to the animal's task overlay the receptive field of the neuron being recorded. In the unattended mode, the animal was cued to attend to stimuli outside the receptive field of that neuron. The relevant stimulus, a colored pixel, was briefly presented within a white-noise stimulus, a flickering grid of black and white pixels. The receptive fields of the neurons were mapped by correlating spikes with the white-noise stimulus in both attended and unattended modes. We found that attention could cause significant modulation of the visually evoked response despite an absence of significant effects on the overall firing rates. On further examination of the relationship between the strength of the visual stimulation and the firing rate, we found that attention appears to cause multiplicative scaling of the visually evoked responses of simple cells, demonstrating that attention reaches back to the initial stages of visual cortical processing.

Roles of molecular layer interneurons in sensory information processing in mouse cerebellar cortex Crus II in vivo.

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Chun-Ping Chu

Full Text Available Cerebellar cortical molecular layer interneurons (MLIs play essential roles in sensory information processing by the cerebellar cortex. However, recent experimental and modeling results are questioning traditional roles for molecular layer inhibition in the cerebellum.Synaptic responses of MLIs and Purkinje cells (PCs, evoked by air-puff stimulation of the ipsilateral whisker pad were recorded from cerebellar cortex Crus II in urethane-anesthetized ICR mice by in vivo whole-cell patch-clamp recording techniques. Under current-clamp (I = 0, air-puff stimuli were found to primarily produce inhibition in PCs. In MLIs, this stimulus evoked spike firing regardless of whether they made basket-type synaptic connections or not. However, MLIs not making basket-type synaptic connections had higher rates of background activity and also generated spontaneous spike-lets. Under voltage-clamp conditions, excitatory postsynaptic currents (EPSCs were recorded in MLIs, although the predominant response of recorded PCs was an inhibitory postsynaptic potential (IPSP. The latencies of EPSCs were similar for all MLIs, but the time course and amplitude of EPSCs varied with depth in the molecular layer. The highest amplitude, shortest duration EPSCs were recorded from MLIs deep in the molecular layer, which also made basket-type synaptic connections. Comparing MLI to PC responses, time to peak of PC IPSP was significantly slower than MLI recorded EPSCs. Blocking GABA(A receptors uncovered larger EPSCs in PCs whose time to peak, half-width and 10-90% rising time were also significantly slower than in MLIs. Biocytin labeling indicated that the MLIs (but not PCs are dye-coupled.These findings indicate that tactile face stimulation evokes rapid excitation in MLIs and inhibition occurring at later latencies in PCs in mouse cerebellar cortex Crus II. These results support previous suggestions that the lack of parallel fiber driven PC activity is due to the effect

Synchronous activity in cat visual cortex encodes collinear and cocircular contours.

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Samonds, Jason M; Zhou, Zhiyi; Bernard, Melanie R; Bonds, A B

2006-04-01

We explored how contour information in primary visual cortex might be embedded in the simultaneous activity of multiple cells recorded with a 100-electrode array. Synchronous activity in cat visual cortex was more selective and predictable in discriminating between drifting grating and concentric ring stimuli than changes in firing rate. Synchrony was found even between cells with wholly different orientation preferences when their receptive fields were circularly aligned, and membership in synchronous groups was orientation and curvature dependent. The existence of synchrony between cocircular cells reinforces its role as a general mechanism for contour integration and shape detection as predicted by association field concepts. Our data suggest that cortical synchrony results from common and synchronous input from earlier visual areas and that it could serve to shape extrastriate response selectivity.

GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls

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Akbarian, S.; Huntsman, M. M.; Kim, J. J.; Tafazzoli, A.; Potkin, S. G.; Bunney, W. E. Jr; Jones, E. G.; Bloom, F. E. (Principal Investigator)

1995-01-01

The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of

An excitable cortex and memory model successfully predicts new pseudopod dynamics.

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Robert M Cooper

Full Text Available Motile eukaryotic cells migrate with directional persistence by alternating left and right turns, even in the absence of external cues. For example, Dictyostelium discoideum cells crawl by extending distinct pseudopods in an alternating right-left pattern. The mechanisms underlying this zig-zag behavior, however, remain unknown. Here we propose a new Excitable Cortex and Memory (EC&M model for understanding the alternating, zig-zag extension of pseudopods. Incorporating elements of previous models, we consider the cell cortex as an excitable system and include global inhibition of new pseudopods while a pseudopod is active. With the novel hypothesis that pseudopod activity makes the local cortex temporarily more excitable--thus creating a memory of previous pseudopod locations--the model reproduces experimentally observed zig-zag behavior. Furthermore, the EC&M model makes four new predictions concerning pseudopod dynamics. To test these predictions we develop an algorithm that detects pseudopods via hierarchical clustering of individual membrane extensions. Data from cell-tracking experiments agrees with all four predictions of the model, revealing that pseudopod placement is a non-Markovian process affected by the dynamics of previous pseudopods. The model is also compatible with known limits of chemotactic sensitivity. In addition to providing a predictive approach to studying eukaryotic cell motion, the EC&M model provides a general framework for future models, and suggests directions for new research regarding the molecular mechanisms underlying directional persistence.

Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state.

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Grace E Fox

Full Text Available Ketamine is known to induce psychotic-like symptoms, including delirium and visual hallucinations. It also causes neuronal damage and cell death in the retrosplenial cortex (RSC, an area that is thought to be a part of high visual cortical pathways and at least partially responsible for ketamine's psychotomimetic activities. However, the basic physiological properties of RSC cells as well as their response to ketamine in vivo remained largely unexplored. Here, we combine a computational method, the Inter-Spike Interval Classification Analysis (ISICA, and in vivo recordings to uncover and profile excitatory cell subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious, sleep, and ketamine-induced unconscious states. We demonstrate two distinct excitatory principal cell sub-populations, namely, high-bursting excitatory principal cells and low-bursting excitatory principal cells, within layers 2&3, and show that this classification is robust over the conscious states, namely quiet awake, and natural unconscious sleep periods. Similarly, we provide evidence of high-bursting and low-bursting excitatory principal cell sub-populations within layers 5&6 that remained distinct during quiet awake and sleep states. We further examined how these subtypes are dynamically altered by ketamine. During ketamine-induced unconscious state, these distinct excitatory principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct dynamics. We also uncovered different dynamics of local field potential under various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine administration induced high gamma oscillations in layer 2&3 of the RSC, but not layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3 and 5&6 contain multiple physiologically distinct sub-populations, and they are differentially affected by ketamine.

Circuit Mechanisms Governing Local vs. Global Motion Processing in Mouse Visual Cortex

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Rune Rasmussen

2017-12-01

Full Text Available A withstanding question in neuroscience is how neural circuits encode representations and perceptions of the external world. A particularly well-defined visual computation is the representation of global object motion by pattern direction-selective (PDS cells from convergence of motion of local components represented by component direction-selective (CDS cells. However, how PDS and CDS cells develop their distinct response properties is still unresolved. The visual cortex of the mouse is an attractive model for experimentally solving this issue due to the large molecular and genetic toolbox available. Although mouse visual cortex lacks the highly ordered orientation columns of primates, it is organized in functional sub-networks and contains striate- and extrastriate areas like its primate counterparts. In this Perspective article, we provide an overview of the experimental and theoretical literature on global motion processing based on works in primates and mice. Lastly, we propose what types of experiments could illuminate what circuit mechanisms are governing cortical global visual motion processing. We propose that PDS cells in mouse visual cortex appear as the perfect arena for delineating and solving how individual sensory features extracted by neural circuits in peripheral brain areas are integrated to build our rich cohesive sensory experiences.

Pathogenesis of deep endometriosis.

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Gordts, Stephan; Koninckx, Philippe; Brosens, Ivo

2017-12-01

The pathophysiology of (deep) endometriosis is still unclear. As originally suggested by Cullen, change the definition "deeper than 5 mm" to "adenomyosis externa." With the discovery of the old European literature on uterine bleeding in 5%-10% of the neonates and histologic evidence that the bleeding represents decidual shedding, it is postulated/hypothesized that endometrial stem/progenitor cells, implanted in the pelvic cavity after birth, may be at the origin of adolescent and even the occasionally premenarcheal pelvic endometriosis. Endometriosis in the adolescent is characterized by angiogenic and hemorrhagic peritoneal and ovarian lesions. The development of deep endometriosis at a later age suggests that deep infiltrating endometriosis is a delayed stage of endometriosis. Another hypothesis is that the endometriotic cell has undergone genetic or epigenetic changes and those specific changes determine the development into deep endometriosis. This is compatible with the hereditary aspects, and with the clonality of deep and cystic ovarian endometriosis. It explains the predisposition and an eventual causal effect by dioxin or radiation. Specific genetic/epigenetic changes could explain the various expressions and thus typical, cystic, and deep endometriosis become three different diseases. Subtle lesions are not a disease until epi(genetic) changes occur. A classification should reflect that deep endometriosis is a specific disease. In conclusion the pathophysiology of deep endometriosis remains debated and the mechanisms of disease progression, as well as the role of genetics and epigenetics in the process, still needs to be unraveled. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Subplate in the developing cortex of mouse and human

DEFF Research Database (Denmark)

Wang, Wei Zhi; Hoerder-Suabedissen, Anna; Oeschger, Franziska M

2010-01-01

Abstract The subplate is a largely transient zone containing precocious neurons involved in several key steps of cortical development. The majority of subplate neurons form a compact layer in mouse, but are dispersed throughout a much larger zone in the human. In rodent, subplate neurons are among...... several genes that are specifically expressed in the subplate layer of the rodent dorsal cortex. Here we examined the human subplate for some of these markers. In the human dorsal cortex, connective tissue growth factor-positive neurons can be seen in the ventricular zone at 15-22 postconceptional weeks...... growth factor- and nuclear receptor-related 1-positive cells are two distinct cell populations of the human subplate. Furthermore, our microarray analysis in rodent suggested that subplate neurons produce plasma proteins. Here we demonstrate that the human subplate also expresses alpha2zinc...

Characterization of deep wet etching of fused silica glass for single cell and optical sensor deposition

International Nuclear Information System (INIS)

Zhu, Haixin; Holl, Mark; Ray, Tathagata; Bhushan, Shivani; Meldrum, Deirdre R

2009-01-01

The development of a high-throughput single-cell metabolic rate monitoring system relies on the use of transparent substrate material for a single cell-trapping platform. The high optical transparency, high chemical resistance, improved surface quality and compatibility with the silicon micromachining process of fused silica make it very attractive and desirable for this application. In this paper, we report the results from the development and characterization of a hydrofluoric acid (HF) based deep wet-etch process on fused silica. The pin holes and notching defects of various single-coated masking layers during the etching are characterized and the most suitable masking materials are identified for different etch depths. The dependence of the average etch rate and surface roughness on the etch depth, impurity concentration and HF composition are also examined. The resulting undercut from the deep HF etch using various masking materials is also investigated. The developed and characterized process techniques have been successfully implemented in the fabrication of micro-well arrays for single cell trapping and sensor deposition. Up to 60 µm deep micro-wells have been etched in a fused silica substrate with over 90% process yield and repeatability. To our knowledge, such etch depth has never been achieved in a fused silica substrate by using a non-diluted HF etchant and a single-coated masking layer at room temperature

Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

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Nagy, Bernadett; Szabó, István; Papp, Szilárd; Takács, Gábor; Szalay, Csaba; Karádi, Zoltán

2012-03-20

The mediodorsal prefrontal cortex (mdPFC), a key structure of the limbic neural circuitry, plays important roles in the central regulation of feeding. As an integrant part of the forebrain dopamine (DA) system, it performs complex roles via interconnections with various brain areas where glucose-monitoring (GM) neurons have been identified. The main goal of the present experiments was to examine whether similar GM neurons exist in the mediodorsal prefrontal cortex. To search for such chemosensory cells here, and to estimate their involvement in the DA circuitry, extracellular single neuron activity of the mediodorsal prefrontal cortex of anesthetized Wistar and Sprague-Dawley rats was recorded by means of tungsten wire multibarreled glass microelectrodes during microelectrophoretic administration of d-glucose and DA. One fourth of the neurons tested changed in firing rate in response to glucose, thus, proved to be elements of the forebrain GM neural network. DA responsive neurons in the mdPFC were found to represent similar proportion of all cells; the glucose-excited units were shown to display excitatory whereas the glucose-inhibited neurons were demonstrated to exert mainly inhibitory responses to dopamine. The glucose-monitoring neurons of the mdPFC and their distinct DA sensitivity are suggested to be of particular significance in adaptive processes of the central feeding control. Copyright © 2012 Elsevier B.V. All rights reserved.

Cognitive-emotional reactivation during deep transcranial magnetic stimulation over the prefrontal cortex of depressive patients affects antidepressant outcome.

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Isserles, Moshe; Rosenberg, Oded; Dannon, Pinchas; Levkovitz, Yechiel; Kotler, Moshe; Deutsch, Frederic; Lerer, Bernard; Zangen, Abraham

2011-02-01

Transcranial magnetic stimulation (TMS) enables non-surgical activation of specific brain areas. TMS over the prefrontal cortex (PFC) is emerging as a significant tool that can augment or replace non/partially effective antidepressant medications. Deep TMS (DTMS) utilizes newly developed coils that enable effective stimulation of deeper cortical layers involved in the pathophysiology of depression. We aimed to assess the H1-DTMS coil as an add-on to antidepressants in treating patients with major depression. We also intended to evaluate whether the antidepressant outcome of DTMS treatment is affected by a cognitive-emotional procedure performed during stimulation. 57 patients were enrolled in the study that included 4 weeks of daily 20 Hz stimulation sessions and additional 4 weekly sessions as a short maintenance phase. Two subgroups of patients received either positive or negative cognitive-emotional reactivation along with the stimulation sessions. 21 of 46 patients (46%) who received at least 10 stimulation sessions achieved response (improvement of ≥ 50% in the Hamilton Depression Rating Scale (HDRS)) and 13 of them (28%) achieved remission (HDRS-24 ≤ 10) by the end of the daily treatment phase. Improvements were smaller in the negatively reactivated group and Beck Depression Inventory scores were not significantly improved in this group. DTMS over the PFC proved to be safe and effective in augmenting antidepressant medications. Negative cognitive-emotional reactivation can disrupt the therapeutic effect of DTMS. A large sham controlled study is required to further establish the effectiveness of DTMS as an augmentation treatment and the role of cognitive reactivation during stimulation. © 2010 Elsevier B.V. All rights reserved.

Neuromodulation of Attentional Control in Major Depression: A Pilot DeepTMS Study

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Jodie Naim-Feil

2016-01-01

Full Text Available While Major Depressive Disorder (MDD is primarily characterized by mood disturbances, impaired attentional control is increasingly identified as a critical feature of depression. Deep transcranial magnetic stimulation (deepTMS, a noninvasive neuromodulatory technique, can modulate neural activity and induce neuroplasticity changes in brain regions recruited by attentional processes. This study examined whether acute and long-term high-frequency repetitive deepTMS to the dorsolateral prefrontal cortex (DLPFC can attenuate attentional deficits associated with MDD. Twenty-one MDD patients and 26 matched control subjects (CS were administered the Beck Depression Inventory and the Sustained Attention to Response Task (SART at baseline. MDD patients were readministered the SART and depressive assessments following a single session (n=21 and after 4 weeks (n=13 of high-frequency (20 Hz repetitive deepTMS applied to the DLPFC. To control for the practice effect, CS (n=26 were readministered the SART a further two times. The MDD group exhibited deficits in sustained attention and cognitive inhibition. Both acute and long-term high-frequency repetitive frontal deepTMS ameliorated sustained attention deficits in the MDD group. Improvement after acute deepTMS was related to attentional recovery after long-term deepTMS. Longer-term improvement in sustained attention was not related to antidepressant effects of deepTMS treatment.

Neuromodulation of Attentional Control in Major Depression: A Pilot DeepTMS Study.

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Naim-Feil, Jodie; Bradshaw, John L; Sheppard, Dianne M; Rosenberg, Oded; Levkovitz, Yechiel; Dannon, Pinhas; Fitzgerald, Paul B; Isserles, Moshe; Zangen, Abraham

2016-01-01

While Major Depressive Disorder (MDD) is primarily characterized by mood disturbances, impaired attentional control is increasingly identified as a critical feature of depression. Deep transcranial magnetic stimulation (deepTMS), a noninvasive neuromodulatory technique, can modulate neural activity and induce neuroplasticity changes in brain regions recruited by attentional processes. This study examined whether acute and long-term high-frequency repetitive deepTMS to the dorsolateral prefrontal cortex (DLPFC) can attenuate attentional deficits associated with MDD. Twenty-one MDD patients and 26 matched control subjects (CS) were administered the Beck Depression Inventory and the Sustained Attention to Response Task (SART) at baseline. MDD patients were readministered the SART and depressive assessments following a single session (n = 21) and after 4 weeks (n = 13) of high-frequency (20 Hz) repetitive deepTMS applied to the DLPFC. To control for the practice effect, CS (n = 26) were readministered the SART a further two times. The MDD group exhibited deficits in sustained attention and cognitive inhibition. Both acute and long-term high-frequency repetitive frontal deepTMS ameliorated sustained attention deficits in the MDD group. Improvement after acute deepTMS was related to attentional recovery after long-term deepTMS. Longer-term improvement in sustained attention was not related to antidepressant effects of deepTMS treatment.

Meliae cortex extract exhibits anti-allergic activity through the inhibition of Syk kinase in mast cells

International Nuclear Information System (INIS)

Lee, Jun Ho; Ko, Na Young; Kim, Nam Wook; Mun, Se Hwan; Kim, Jie Wan; Her, Erk; Kim, Bo Kyung; Seo, Dong Wan; Chang, Hyun Wook; Moon, Tae Chul; Han, Jeung Whan; Kim, Young Mi; Choi, Wahn Soo

2007-01-01

The anti-allergic action of various Oriental medicinal herbs was investigated using in vitro and in vivo experimental models. Of these extracts, the ethanol extract of Meliae cortex (MC) exhibited the most potent activity in mast cells; its IC 50 values were 29 ± 1.5 μg/ml for antigen stimulation and 57 ± 3.4 μg/ml for thapsigargin stimulation. It inhibited compound-48/80-induced systemic anaphylaxis by 52.9% at a dose of 300 mg/kg in mice; it also inhibited the expression of the proinflammatory mediator TNF-α. With regard to its mechanism of action, MC suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell signaling processes and that of Akt in a dose-dependent manner. It also inhibited the MAP kinase ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. Taken together, these results suggest that the anti-allergic activity of MC may be due to the inhibition of histamine secretion and cytokine expression through the Syk inhibition in mast cells

Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture.

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Kim, Euiseok J; Battiste, James; Nakagawa, Yasushi; Johnson, Jane E

2008-08-01

Ascl1 (previously Mash1) is a bHLH transcription factor essential for neuronal differentiation and specification in the nervous system. Although it has been studied for its role in several neural lineages, the full complement of lineages arising from Ascl1 progenitor cells remains unknown. Using an inducible Cre-flox genetic fate-mapping strategy, Ascl1 lineages were determined throughout the brain. Ascl1 is present in proliferating progenitor cells but these cells are actively differentiating as evidenced by rapid migration out of germinal zones. Ascl1 lineage cells contribute to distinct cell types in each major brain division: the forebrain including the cerebral cortex, olfactory bulb, hippocampus, striatum, hypothalamus, and thalamic nuclei, the midbrain including superior and inferior colliculi, and the hindbrain including Purkinje and deep cerebellar nuclei cells and cells in the trigeminal sensory system. Ascl1 progenitor cells at early stages in each CNS region preferentially become neurons, and at late stages they become oligodendrocytes. In conclusion, Ascl1-expressing progenitor cells in the brain give rise to multiple, but not all, neuronal subtypes and oligodendrocytes depending on the temporal and spatial context, consistent with a broad role in neural differentiation with some subtype specification.

Small proteins link coat and cortex assembly during sporulation in Bacillus subtilis

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Ebmeier, Sarah E.; Tan, Irene S.; Clapham, Katie Rose; Ramamurthi, Kumaran S.

2015-01-01

Summary Mature spores of the bacterium Bacillus subtilis are encased by two concentric shells: an inner shell (the ‘cortex’), made of peptidoglycan; and an outer proteinaceous shell (the ‘coat’), whose basement layer is anchored to the surface of the developing spore via a 26-amino-acid-long protein called SpoVM. During sporulation, initiation of cortex assembly depends on the successful initiation of coat assembly, but the mechanisms that co-ordinate the morphogenesis of both structures are largely unknown. Here, we describe a sporulation pathway involving SpoVM and a 37-amino-acid-long protein named ‘CmpA’ that is encoded by a previously un-annotated gene and is expressed under control of two sporulation-specific transcription factors (σE and SpoIIID). CmpA localized to the surface of the developing spore and deletion of cmpA resulted in cells progressing through the sporulation programme more quickly. Overproduction of CmpA did not affect normal growth or cell division, but delayed entry into sporulation and abrogated cortex assembly. In those cells that had successfully initiated coat assembly, CmpA was removed by a posttranslational mechanism, presumably in order to overcome the sporulation inhibition it imposed. We propose a model in which CmpA participates in a developmental checkpoint that ensures the proper orchestration of coat and cortex morphogenesis by repressing cortex assembly until coat assembly successfully initiates. PMID:22463703

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder.

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Enticott, Peter G; Fitzgibbon, Bernadette M; Kennedy, Hayley A; Arnold, Sara L; Elliot, David; Peachey, Amy; Zangen, Abraham; Fitzgerald, Paul B

2014-01-01

Biomedical treatment options for autism spectrum disorder (ASD) are extremely limited. Repetitive transcranial magnetic stimulation (rTMS) is a safe and efficacious technique when targeting specific areas of cortical dysfunction in major depressive disorder, and a similar approach could yield therapeutic benefits in ASD, if applied to relevant cortical regions. The aim of this study was to examine whether deep rTMS to bilateral dorsomedial prefrontal cortex improves social relating in ASD. 28 adults diagnosed with either autistic disorder (high-functioning) or Asperger's disorder completed a prospective, double-blind, randomized, placebo-controlled design with 2 weeks of daily weekday treatment. This involved deep rTMS to bilateral dorsomedial prefrontal cortex (5 Hz, 10-s train duration, 20-s inter-train interval) for 15 min (1500 pulses per session) using a HAUT-Coil. The sham rTMS coil was encased in the same helmet of the active deep rTMS coil, but no effective field was delivered into the brain. Assessments were conducted before, after, and one month following treatment. Participants in the active condition showed a near significant reduction in self-reported social relating symptoms from pre-treatment to one month follow-up, and a significant reduction in social relating symptoms (relative to sham participants) for both post-treatment assessments. Those in the active condition also showed a reduction in self-oriented anxiety during difficult and emotional social situations from pre-treatment to one month follow-up. There were no changes for those in the sham condition. Deep rTMS to bilateral dorsomedial prefrontal cortex yielded a reduction in social relating impairment and socially-related anxiety. Further research in this area should employ extended rTMS protocols that approximate those used in depression in an attempt to replicate and amplify the clinical response. Copyright © 2014 Elsevier Inc. All rights reserved.

Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

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Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine M.; Sivagnanasundaram, Sinthuja; Rothmond, Debora A.; Saunders, Richard; Noble, Pamela L.; Webster, Maree J.; Shannon Weickert, Cynthia

2011-01-01

Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia. PMID

Developmental patterns of doublecortin expression and white matter neuron density in the postnatal primate prefrontal cortex and schizophrenia.

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Samantha J Fung

Full Text Available Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC. Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX, a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque and density of white matter neurons (humans during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37 and matched controls (n = 37 and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in

Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex

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Christophe Heinrich

2014-12-01

Full Text Available The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following injury mature morphologically and some acquire NeuN while losing DCX. Patch-clamp recording of slices containing Sox2- and/or Ascl1-transduced cells revealed that a substantial fraction of these cells receive synaptic inputs from neurons neighboring the injury site. Thus, NG2 glia represent a potential target for reprogramming strategies toward cortical repair.

Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape Encoding.

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Ponce, Carlos R; Lomber, Stephen G; Livingstone, Margaret S

2017-05-10

In the macaque monkey brain, posterior inferior temporal (PIT) cortex cells contribute to visual object recognition. They receive concurrent inputs from visual areas V4, V3, and V2. We asked how these different anatomical pathways shape PIT response properties by deactivating them while monitoring PIT activity in two male macaques. We found that cooling of V4 or V2|3 did not lead to consistent changes in population excitatory drive; however, population pattern analyses showed that V4-based pathways were more important than V2|3-based pathways. We did not find any image features that predicted decoding accuracy differences between both interventions. Using the HMAX hierarchical model of visual recognition, we found that different groups of simulated "PIT" units with different input histories (lacking "V2|3" or "V4" input) allowed for comparable levels of object-decoding performance and that removing a large fraction of "PIT" activity resulted in similar drops in performance as in the cooling experiments. We conclude that distinct input pathways to PIT relay similar types of shape information, with V1-dependent V4 cells providing more quantitatively useful information for overall encoding than cells in V2 projecting directly to PIT. SIGNIFICANCE STATEMENT Convolutional neural networks are the best models of the visual system, but most emphasize input transformations across a serial hierarchy akin to the primary "ventral stream" (V1 → V2 → V4 → IT). However, the ventral stream also comprises parallel "bypass" pathways: V1 also connects to V4, and V2 to IT. To explore the advantages of mixing long and short pathways in the macaque brain, we used cortical cooling to silence inputs to posterior IT and compared the findings with an HMAX model with parallel pathways. Copyright © 2017 the authors 0270-6474/17/375019-16$15.00/0.

Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

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Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

2016-11-09

Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

Memory-guided sensory comparisons in the prefrontal cortex: contribution of putative pyramidal cells and interneurons.

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Hussar, Cory R; Pasternak, Tatiana

2012-02-22

Comparing two stimuli that occur at different times demands the coordination of bottom-up and top-down processes. It has been hypothesized that the dorsolateral prefrontal (PFC) cortex, the likely source of top-down cortical influences, plays a key role in such tasks, contributing to both maintenance and sensory comparisons. We examined this hypothesis by recording from the PFC of monkeys comparing directions of two moving stimuli, S1 and S2, separated by a memory delay. We determined the contribution of the two principal cell types to these processes by classifying neurons into broad-spiking (BS) putative pyramidal cells and narrow-spiking (NS) putative local interneurons. During the delay, BS cells were more likely to exhibit anticipatory modulation and represent the remembered direction. While this representation was transient, appearing at different times in different neurons, it weakened when direction was not task relevant, suggesting its utility. During S2, both putative cell types showed comparison-related activity modulations. These modulations were of two types, each carried by different neurons, which either preferred trials with stimuli moving in the same direction or trials with stimuli of different directions. These comparison effects were strongly correlated with choice, suggesting their role in circuitry underlying decision making. These results provide the first demonstration of distinct contributions made by principal cell types to memory-guided perceptual decisions. During sensory stimulation both cell types represent behaviorally relevant stimulus features contributing to comparison and decision-related activity. However in the absence of sensory stimulation, putative pyramidal cells dominated, carrying information about the elapsed time and the preceding direction.

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex.

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Naumann, Robert K; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L; Brecht, Michael

2016-03-01

To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin-positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin-negative and calbindin-positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin-positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin-positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10-fold over a 20,000-fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring.

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Sérgio Gomes da Silva

Full Text Available Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task. Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation and associative (spatial learning mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning and increases BDNF levels and cell numbers in the hippocampal formation of offspring.

Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

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Ohnuma, Tomokazu; Matsumoto, Takashi; Itoi, Ayano; Kawana, Ayako; Nishiyama, Takahito; Ogura, Kenichiro [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan); Hiratsuka, Akira, E-mail: hiratuka@toyaku.ac.jp [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan)

2011-10-07

Highlights: {yields} We found a novel inhibitor of Nrf2 known as a chemoresistance factor. {yields} Overexpressed Nrf2 in lung cancer cells was suppressed by Cinnamomi Cortex extract. {yields} Cytotoxic action of anticancer drugs in cells treated with the extract was enhanced. {yields} Procyanidin tetramers and pentamers were active components in suppressing Nrf2. -- Abstract: Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2.

TMS-induced neural noise in sensory cortex interferes with short-term memory storage

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Tyler D Bancroft

2014-03-01

Full Text Available In a previous study, Harris et al. (2002 found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation to primary somatosensory cortex (SI early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence from human EEG and single-cell recording in primates that instead points to prefrontal cortex as the storage substrate for vibrotactile memory. In the present study, we use computational methods to demonstrate how Harris et al.’s results can be reproduced by TMS-induced activity in sensory cortex and subsequent feedforward interference with memory traces stored in prefrontal cortex, thereby reconciling discordant findings in the tactile memory literature.

Complex neural codes in rat prelimbic cortex are stable across days on a spatial decision task

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Nathaniel J. Powell

2014-04-01

Full Text Available The rodent prelimbic cortex has been shown to play an important role in cognitive processing, and has been implicated in encoding many different parameters relevant to solving decision-making tasks. However, it is not known how the prelimbic cortex represents all these disparate variables, and if they are simultaneously represented when the task requires it. In order to investigate this question, we trained rats to run the Multiple-T Left Right Alternate (MT-LRA task and recorded multi-unit ensembles from their prelimbic regions. Significant populations of cells in the prelimbic cortex represented the strategy controlling reward receipt on a given lap, whether the animal chose to go right or left on a given lap, and whether the animal made a correct decision or an error on a given lap. These populations overlapped in the cells recorded, with several cells demonstrating differential firing to all three variables. The spatial and strategic firing patterns of individual prelimbic cells were highly conserved across several days of running this task, indicating that each cell encoded the same information across days.

Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

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L. Yang

2016-01-01

Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

Morphology and kainate-receptor immunoreactivity of identified neurons within the entorhinal cortex projecting to superior temporal sulcus in the cynomolgus monkey

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Good, P. F.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1995-01-01

Projections of the entorhinal cortex to the hippocampus are well known from the classical studies of Cajal (Ramon y Cajal, 1904) and Lorente de No (1933). Projections from the entorhinal cortex to neocortical areas are less well understood. Such connectivity is likely to underlie the consolidation of long-term declarative memory in neocortical sites. In the present study, a projection arising in layer V of the entorhinal cortex and terminating in a polymodal association area of the superior temporal gyrus has been identified with the use of retrograde tracing. The dendritic arbors of neurons giving rise to this projection were further investigated by cell filling and confocal microscopy with computer reconstruction. This analysis demonstrated that the dendritic arbor of identified projection neurons was largely confined to layer V, with the exception of a solitary, simple apical dendrite occasionally ascending to superficial laminae but often confined to the lamina dissecans (layer IV). Finally, immunoreactivity for glutamate-receptor subunit proteins GluR 5/6/7 of the dendritic arbor of identified entorhinal projection neurons was examined. The solitary apical dendrite of identified entorhinal projection neurons was prominently immunolabeled for GluR 5/6/7, as was the dendritic arbor of basilar dendrites of these neurons. The restriction of the large bulk of the dendritic arbor of identified entorhinal projection neurons to layer V implies that these neurons are likely to be heavily influenced by hippocampal output arriving in the deep layers of the entorhinal cortex. Immunoreactivity for GluR 5/6/7 throughout the dendritic arbor of such neurons indicates that this class of glutamate receptor is in a position to play a prominent role in mediating excitatory neurotransmission within hippocampal-entorhinal circuits.

Deep-Sea-Derived Butyrolactone I Suppresses Ovalbumin-Induced Anaphylaxis by Regulating Mast Cell Function in a Murine Model.

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Liu, Qing-Mei; Xie, Chun-Lan; Gao, Yuan-Yuan; Liu, Bo; Lin, Wei-Xiang; Liu, Hong; Cao, Min-Jie; Su, Wen-Jin; Yang, Xian-Wen; Liu, Guang-Ming

2018-05-22

Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.

Antarctic urchin Ctenocidaris speciosa spines: lessons from the deep

OpenAIRE

Catarino, A.I.; Guibourt, V.; Moureaux, C.; De Ridder, C.; Compère, P.; Dubois, P.

2013-01-01

Ocean acidification is leading to changes in the oceanic carbonate system. As a result, calcium carbonate saturation horizon is shallowing, especially at high latitudes. Biogenic high magnesium-calcites could be particularly vulnerable, since their solubility is either similar or greater than that of aragonite. Cidaroid urchins have magnesium-calcite spines covered by a polycrystalline cortex which becomes exposed to seawater when mature (not covered by an epidermis). However, deep species li...

[Raman spectra of monkey cerebral cortex tissue].

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Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

2010-01-01

Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex

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Naumann, Robert K.; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L.

2016-01-01

ABSTRACT To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin‐positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin‐negative and calbindin‐positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin‐positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin‐positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10‐fold over a 20,000‐fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. J. Comp. Neurol. 524:783–806, 2016. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26223342

Convolutional Deep Belief Networks for Single-Cell/Object Tracking in Computational Biology and Computer Vision.

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Zhong, Bineng; Pan, Shengnan; Zhang, Hongbo; Wang, Tian; Du, Jixiang; Chen, Duansheng; Cao, Liujuan

2016-01-01

In this paper, we propose deep architecture to dynamically learn the most discriminative features from data for both single-cell and object tracking in computational biology and computer vision. Firstly, the discriminative features are automatically learned via a convolutional deep belief network (CDBN). Secondly, we design a simple yet effective method to transfer features learned from CDBNs on the source tasks for generic purpose to the object tracking tasks using only limited amount of training data. Finally, to alleviate the tracker drifting problem caused by model updating, we jointly consider three different types of positive samples. Extensive experiments validate the robustness and effectiveness of the proposed method.

Representation of individual elements of a complex call sequence in primary auditory cortex

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Mark Nelson Wallace

2013-10-01

Full Text Available Conspecific communication calls can be rhythmic or contain extended, discontinuous series of either constant or frequency modulated harmonic tones and noise bursts separated by brief periods of silence. In the guinea pig, rhythmic calls can produce isomorphic responses within the primary auditory cortex (AI where single units respond to every call element. Other calls such as the chutter comprise a series of short irregular syllables that vary in their spectral content and are more like human speech. These calls can also evoke isomorphic responses, but may only do so in fields in the auditory belt and not in AI. Here we present evidence that cells in AI treat the individual elements within a syllable as separate auditory objects and respond selectively to one or a subset of them. We used a single chutter exemplar to compare single/multi-unit responses in the low-frequency portion of AI - AI(LF and the low-frequency part of the thalamic medial geniculate body - MGB(LF in urethane anaesthetised guinea pigs. Both thalamic and cortical cells responded with brief increases in firing rate to one, or more, of the 8 main elements present in the chutter call. Almost none of the units responded to all 8 elements. While there were many different combinations of responses to between one and five of the elements, MBG(LF and AI(LF neurons exhibited the same specific types of response combinations. Nearby units in the upper layers of the cortex tended to respond to similar combinations of elements while the deep layers were less responsive. Thus the responses from a number of AI units would need to be combined in order to represent the entire chutter call. Our results don’t rule out the possibility of constructive convergence but there was no evidence that a convergence of inputs within AI led to a complete representation of all eight elements.

Regulation of cerebral cortex development by Rho GTPases: insights from in vivo studies

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Roberta eAzzarelli

2015-01-01

Full Text Available The cerebral cortex is the site of higher human cognitive and motor functions. Histologically, it is organized into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection neurons and inhibitory interneurons. The stereotyped cellular distribution of cortical neurons is crucial for the formation of functional neural circuits and it is predominantly established during embryonic development. Cortical neuron development is a multiphasic process characterized by sequential steps of neural progenitor proliferation, cell cycle exit, neuroblast migration and neuronal differentiation. This series of events requires an extensive and dynamic remodeling of the cell cytoskeleton at each step of the process. As major regulators of the cytoskeleton, the family of small Rho GTPases has been shown to play essential functions in cerebral cortex development. Here we review in vivo findings that support the contribution of Rho GTPases to cortical projection neuron development and we address their involvement in the etiology of cerebral cortex malformations.

Data file of a deep proteome analysis of the prefrontal cortex in aged mice with progranulin deficiency or neuronal overexpression of progranulin.

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Heidler, Juliana; Hardt, Stefanie; Wittig, Ilka; Tegeder, Irmgard

2016-12-01

Progranulin deficiency is associated with neurodegeneration in humans and in mice. The mechanisms likely involve progranulin-promoted removal of protein waste via autophagy. We performed a deep proteomic screen of the pre-frontal cortex in aged (13-15 months) female progranulin-deficient mice (GRN -/- ) and mice with inducible neuron-specific overexpression of progranulin (SLICK-GRN-OE) versus the respective control mice. Proteins were extracted and analyzed per liquid chromatography/mass spectrometry (LC/MS) on a Thermo Scientific™ Q Exactive Plus equipped with an ultra-high performance liquid chromatography unit and a Nanospray Flex Ion-Source. Full Scan MS-data were acquired using Xcalibur and raw files were analyzed using the proteomics software Max Quant. The mouse reference proteome set from uniprot (June 2015) was used to identify peptides and proteins. The DiB data file is a reduced MaxQuant output and includes peptide and protein identification, accession numbers, protein and gene names, sequence coverage and label free quantification (LFQ) values of each sample. Differences in protein expression in genotypes are presented in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].

Data file of a deep proteome analysis of the prefrontal cortex in aged mice with progranulin deficiency or neuronal overexpression of progranulin

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Juliana Heidler

2016-12-01

Full Text Available Progranulin deficiency is associated with neurodegeneration in humans and in mice. The mechanisms likely involve progranulin-promoted removal of protein waste via autophagy. We performed a deep proteomic screen of the pre-frontal cortex in aged (13–15 months female progranulin-deficient mice (GRN−/− and mice with inducible neuron-specific overexpression of progranulin (SLICK-GRN-OE versus the respective control mice. Proteins were extracted and analyzed per liquid chromatography/mass spectrometry (LC/MS on a Thermo Scientific™ Q Exactive Plus equipped with an ultra-high performance liquid chromatography unit and a Nanospray Flex Ion-Source. Full Scan MS-data were acquired using Xcalibur and raw files were analyzed using the proteomics software Max Quant. The mouse reference proteome set from uniprot (June 2015 was used to identify peptides and proteins. The DiB data file is a reduced MaxQuant output and includes peptide and protein identification, accession numbers, protein and gene names, sequence coverage and label free quantification (LFQ values of each sample. Differences in protein expression in genotypes are presented in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].

Age-related changes of structures in cerebellar cortex of cat

Indian Academy of Sciences (India)

Madhu

ness of the cerebellar cortex as well as loss of neurons, and hypertrophy and ... Purkinje cells. (PCs) in old cats showed much fewer NF-IR dendrites than those in young adults. ... diminution in motor control and motor learning) underlying.

c-Fos expression is elevated in GABAergic interneurons of the gustatory cortex following novel taste learning.

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Doron, Guy; Rosenblum, Kobi

2010-07-01

Long-term sensory memories are considered to be stored in the relevant cortical region subserving the given modality. We and others have recently identified a series of molecular alterations in the gustatory cortex (GC) of the rat at different time intervals following novel taste learning. Some of these correlative modifications were also necessary for taste memory acquisition and/or consolidation. However, very little is known about the localization of these molecular modifications within the GC or about the functional activation of the GC hours after novel taste learning. Here, we hypothesize that inhibitory interneurons are activated in the GC on a scale of hours following learning and used c-Fos expression and confocal microscopy with different markers to test this hypothesis. We found that GABAergic interneurons are activated in the GC in correlation with novel taste learning. The activation was evident in the deep but not superficial layers of the dysgranular insular cortex. These results suggest that the GABAergic machinery in the deep layers of the GC participates in the processing of taste information hours after learning, and provide evidence for the involvement of a local cortical circuit not only during acquisition of new information but also during off-line processing and consolidation of taste information.

GABAergic circuits control input-spike coupling in the piriform cortex.

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Luna, Victor M; Schoppa, Nathan E

2008-08-27

Odor coding in mammals is widely believed to involve synchronized gamma frequency (30-70 Hz) oscillations in the first processing structure, the olfactory bulb. How such inputs are read in downstream cortical structures however is not known. Here we used patch-clamp recordings in rat piriform cortex slices to examine cellular mechanisms that shape how the cortex integrates inputs from bulb mitral cells. Electrical stimulation of mitral cell axons in the lateral olfactory tract (LOT) resulted in excitation of pyramidal cells (PCs), which was followed approximately 10 ms later by inhibition that was highly reproducible between trials in its onset time. This inhibition was somatic in origin and appeared to be driven through a feedforward mechanism, wherein GABAergic interneurons were directly excited by mitral cell axons. The precise inhibition affected action potential firing in PCs in two distinct ways. First, by abruptly terminating PC excitation, it limited the PC response to each EPSP to exactly one, precisely timed action potential. In addition, inhibition limited the summation of EPSPs across time, such that PCs fired action potentials in strong preference for synchronized inputs arriving in a time window of inputs arriving as a synchronized gamma frequency pattern.

Ubiquitous healthy diatoms in the deep sea confirm deep carbon injection by the biological pump

KAUST Repository

Agusti, Susana

2015-07-09

The role of the ocean as a sink for CO2 is partially dependent on the downward transport of phytoplankton cells packaged within fast-sinking particles. However, whether such fast-sinking mechanisms deliver fresh organic carbon down to the deep bathypelagic sea and whether this mechanism is prevalent across the ocean requires confirmation. Here we report the ubiquitous presence of healthy photosynthetic cells, dominated by diatoms, down to 4,000 m in the deep dark ocean. Decay experiments with surface phytoplankton suggested that the large proportion (18%) of healthy photosynthetic cells observed, on average, in the dark ocean, requires transport times from a few days to a few weeks, corresponding to sinking rates (124–732 m d−1) comparable to those of fast-sinking aggregates and faecal pellets. These results confirm the expectation that fast-sinking mechanisms inject fresh organic carbon into the deep sea and that this is a prevalent process operating across the global oligotrophic ocean.

Ubiquitous healthy diatoms in the deep sea confirm deep carbon injection by the biological pump

KAUST Repository

Agusti, Susana; Gonzá lez-Gordillo, J. I.; Vaqué , D.; Estrada, M.; Cerezo, M. I.; Salazar, G.; Gasol, J. M.; Duarte, Carlos M.

2015-01-01

The role of the ocean as a sink for CO2 is partially dependent on the downward transport of phytoplankton cells packaged within fast-sinking particles. However, whether such fast-sinking mechanisms deliver fresh organic carbon down to the deep bathypelagic sea and whether this mechanism is prevalent across the ocean requires confirmation. Here we report the ubiquitous presence of healthy photosynthetic cells, dominated by diatoms, down to 4,000 m in the deep dark ocean. Decay experiments with surface phytoplankton suggested that the large proportion (18%) of healthy photosynthetic cells observed, on average, in the dark ocean, requires transport times from a few days to a few weeks, corresponding to sinking rates (124–732 m d−1) comparable to those of fast-sinking aggregates and faecal pellets. These results confirm the expectation that fast-sinking mechanisms inject fresh organic carbon into the deep sea and that this is a prevalent process operating across the global oligotrophic ocean.

Behavior of deep level defects on voltage-induced stress of Cu(In,Ga)Se{sub 2} solar cells

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Lee, D.W.; Cho, S.E. [Department of Physics and Semiconductor Science, Dongguk University, Seoul (Korea, Republic of); Jeong, J.H. [Solar Cell Center, Korea Institute of Science and Technology, Seoul (Korea, Republic of); Cho, H.Y., E-mail: hycho@dongguk.edu [Department of Physics and Semiconductor Science, Dongguk University, Seoul (Korea, Republic of)

2015-05-01

The behavior of deep level defects by a voltage-induced stress for CuInGaSe{sub 2} (CIGS) solar cells has been investigated. CIGS solar cells were used with standard structures which are Al-doped ZnO/i-ZnO/CdS/CIGSe{sub 2}/Mo on soda lime glass, and that resulted in conversion efficiencies as high as 16%. The samples with the same structure were isothermally stressed at 100 °C under the reverse voltages. The voltage-induced stressing in CIGS samples causes a decrease in the carrier density and conversion efficiency. To investigate the behavior of deep level defects in the stressed CIGS cells, photo-induced current transient spectroscopy was utilized, and normally 3 deep level defects (including 2 hole traps and 1 electron trap) were found to be located at 0.18 eV and 0.29 eV above the valence band maximum (and 0.36 eV below the conduction band). In voltage-induced cells, especially, it was found that the decrease of the hole carrier density could be responsible for the increase of the 0.29 eV defect, which is known to be observed in less efficient CIGS solar cells. And the carrier density and the defects are reversible at least to a large extent by resting at room-temperature without the bias voltage. From optical capture kinetics in photo-induced current transient spectroscopy measurement, the types of defects could be distinguished into the isolated point defect and the extended defect. In this work, it is suggested that the increase of the 0.29 eV defect by voltage-induced stress could be due to electrical activation accompanied by a loss of positive ion species and the activated defect gives rise to reduction of the carrier density. - Highlights: • We investigated behavior of deep level defects by voltage-induced stress. • Defect generation could affect the decrease of the conversion efficiency of cells. • Defect generation could be electrically activated by a loss of positive ion species. • Type of defects could be studied with models of point defects

A radial map of multi-whisker correlation selectivity in the rat barrel cortex.

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Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E; Bourdieu, Laurent; Léger, Jean-François

2016-11-21

In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel-septal borders, forming rings of multi-whisker synchrony-preferring cells.

Shared rhythmic subcortical GABAergic input to the entorhinal cortex and presubiculum.

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Viney, Tim James; Salib, Minas; Joshi, Abhilasha; Unal, Gunes; Berry, Naomi; Somogyi, Peter

2018-04-05

Rhythmic theta frequency (~5-12 Hz) oscillations coordinate neuronal synchrony and higher frequency oscillations across the cortex. Spatial navigation and context-dependent episodic memories are represented in several interconnected regions including the hippocampal and entorhinal cortices, but the cellular mechanisms for their dynamic coupling remain to be defined. Using monosynaptically-restricted retrograde viral tracing in mice, we identified a subcortical GABAergic input from the medial septum that terminated in the entorhinal cortex, with collaterals innervating the dorsal presubiculum. Extracellularly recording and labeling GABAergic entorhinal-projecting neurons in awake behaving mice show that these subcortical neurons, named orchid cells, fire in long rhythmic bursts during immobility and locomotion. Orchid cells discharge near the peak of hippocampal and entorhinal theta oscillations, couple to entorhinal gamma oscillations, and target subpopulations of extra-hippocampal GABAergic interneurons. Thus, orchid cells are a specialized source of rhythmic subcortical GABAergic modulation of 'upstream' and 'downstream' cortico-cortical circuits involved in mnemonic functions. © 2018, Viney et al.

Separation of red blood cells in deep deterministic lateral displacement devices

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Kabacaoglu, Gokberk; Biros, George

2017-11-01

Microfluidic cell separation techniques are of great interest since they help rapid medical diagnoses and tests. Deterministic lateral displacement (DLD) is one of them. A DLD device consists of arrays of pillars. Main flow and alignment of the pillars define two different directions. Size-based separation of rigid spherical particles is possible as they follow one of these directions depending on their sizes. However, the separation of non-spherical deformable particles such as red blood cells (RBCs) is more complicated than that due to their intricate dynamics. We study the separation of RBCs in DLD using an in-house integral equation solver. We systematically investigate the effects of the interior fluid viscosity and the membrane elasticity of an RBC on its behavior. These mechanical properties of a cell determine its deformability, which can be altered by several diseases. We particularly consider deep devices in which an RBC can show rich dynamics such as tank-treading and tumbling. It turns out that strong hydrodynamic lift force moves the tank-treading cells along the pillars and downward force leads the tumbling ones to move with the flow. Thereby, deformability-based separation of RBCs is possible.

Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

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Price David J

2009-01-01

Full Text Available Abstract Background Adenomatous polyposis coli (Apc is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex. Results We used Emx1Cre to inactivate Apc specifically in proliferating cerebral cortical cells and their descendents starting from embryonic day 9.5. We observed reduction in the size of the mutant cerebral cortex, disruption to its organisation, and changes in the molecular identity of its cells. Loss of Apc leads to a decrease in the size of the proliferative pool, disrupted interkinetic nuclear migration, and increased apoptosis. β-Catenin, pericentrin, and N-cadherin proteins no longer adopt their normal high concentration at the apical surface of the cerebral cortical ventricular zone, indicating that cell polarity is disrupted. Consistent with enhanced Wnt/β-catenin signalling resulting from loss of Apc we found increased levels of TCF/LEF-dependent transcription and expression of endogenous Wnt/β-catenin target genes (Axin2 (conductin, Lef1, and c-myc in the mutant cerebral cortex. In the Apc mutant cerebral cortex the expression of transcription factors Foxg1, Pax6, Tbr1, and Tbr2 is drastically reduced compared to normal and many cells ectopically express Pax3, Wnt1, and Wt1 (but not Wnt2b, Wnt8b, Ptc, Gli1, Mash1, Olig2, or Islet1. This indicates that loss of Apc function causes cerebral cortical cells to lose their normal identity and redirect to fates normally found in more posterior-dorsal regions of the central nervous system. Conclusion Apc is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and

Peripheral nerve injury induces glial activation in primary motor cortex

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Julieta Troncoso

2015-02-01

Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

Hematopoietic Stem Cell Therapy as a Counter-Measure for Human Exploration of Deep Space

Science.gov (United States)

Ohi, S.; Roach, A.-N.; Ramsahai, S.; Kim, B. C.; Fitzgerald, W.; Riley, D. A.; Gonda, S. R.

2004-01-01

Human exploration of deep space depends, in part, on our ability to counter severe/invasive disorders that astronauts experience in space environments. The known symptoms include hematological/cardiac abnormalities,bone and muscle losses, immunodeficiency, neurological disorders, and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, we have advanced a hypothesis that ome of the space-caused disorders maybe amenable to hematopoietis stem cell therapy(HSCT) so as to maintain promote human exploration of deep space. Using mouse models of human anemia beta-thaiassemia) as well as spaceflight (hindlimb unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, in the case of HSCT for muscle loss, the beta-galactosidese marked HSCs were detected in the hindlimbs of unloaded mouse following transplantation by -X-gal wholemaunt staining procedure. Histochemicaland physical analyses indicated structural contribution of HSCs to the muscle. HSCT for immunodeficiency was investigated ising beta-galactosidese gene-tagged Escherichia coli as the infectious agent. Results of the X-gal staining procedure indicated the rapeutic role of the HSCT. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Pallidal Deep Brain Stimulation Improves Higher Control of the Oculomotor System in Parkinson's Disease.

Science.gov (United States)

Antoniades, Chrystalina A; Rebelo, Pedro; Kennard, Christopher; Aziz, Tipu Z; Green, Alexander L; FitzGerald, James J

2015-09-23

The frontal cortex and basal ganglia form a set of parallel but mostly segregated circuits called cortico-basal ganglia loops. The oculomotor loop controls eye movements and can direct relatively simple movements, such as reflexive prosaccades, without external help but needs input from "higher" loops for more complex behaviors. The antisaccade task requires the dorsolateral prefrontal cortex, which is part of the prefrontal loop. Information flows from prefrontal to oculomotor circuits in the striatum, and directional errors in this task can be considered a measure of failure of prefrontal control over the oculomotor loop. The antisaccadic error rate (AER) is increased in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no effect on the AER, but a previous case suggested that DBS of the globus pallidus interna (GPi) might. Our aim was to compare the effects of STN DBS and GPi DBS on the AER. We tested eye movements in 14 human DBS patients and 10 controls. GPi DBS substantially reduced the AER, restoring lost higher control over oculomotor function. Interloop information flow involves striatal neurons that receive cortical input and project to pallidum. They are normally silent when quiescent, but in PD they fire randomly, creating noise that may account for the degradation in interloop control. The reduced AER with GPi DBS could be explained by retrograde stimulation of striatopallidal axons with consequent activation of inhibitory collaterals and reduction in background striatal firing rates. This study may help explain aspects of PD pathophysiology and the mechanism of action of GPi DBS. Significance statement: Parkinson's disease causes symptoms including stiffness, slowness of movement, and tremor. Electrical stimulation of specific areas deep in the brain can effectively treat these symptoms, but exactly how is not fully understood. Part of the cause of such symptoms may be impairments in the way information flows

Homoacetogenesis in Deep-Sea Chloroflexi, as Inferred by Single-Cell Genomics, Provides a Link to Reductive Dehalogenation in Terrestrial Dehalococcoidetes.

Science.gov (United States)

Sewell, Holly L; Kaster, Anne-Kristin; Spormann, Alfred M

2017-12-19

The deep marine subsurface is one of the largest unexplored biospheres on Earth and is widely inhabited by members of the phylum Chloroflexi In this report, we investigated genomes of single cells obtained from deep-sea sediments of the Peruvian Margin, which are enriched in such Chloroflexi 16S rRNA gene sequence analysis placed two of these single-cell-derived genomes (DscP3 and Dsc4) in a clade of subphylum I Chloroflexi which were previously recovered from deep-sea sediment in the Okinawa Trough and a third (DscP2-2) as a member of the previously reported DscP2 population from Peruvian Margin site 1230. The presence of genes encoding enzymes of a complete Wood-Ljungdahl pathway, glycolysis/gluconeogenesis, a Rhodobacter nitrogen fixation (Rnf) complex, glyosyltransferases, and formate dehydrogenases in the single-cell genomes of DscP3 and Dsc4 and the presence of an NADH-dependent reduced ferredoxin:NADP oxidoreductase (Nfn) and Rnf in the genome of DscP2-2 imply a homoacetogenic lifestyle of these abundant marine Chloroflexi We also report here the first complete pathway for anaerobic benzoate oxidation to acetyl coenzyme A (CoA) in the phylum Chloroflexi (DscP3 and Dsc4), including a class I benzoyl-CoA reductase. Of remarkable evolutionary significance, we discovered a gene encoding a formate dehydrogenase (FdnI) with reciprocal closest identity to the formate dehydrogenase-like protein (complex iron-sulfur molybdoenzyme [CISM], DET0187) of terrestrial Dehalococcoides/Dehalogenimonas spp. This formate dehydrogenase-like protein has been shown to lack formate dehydrogenase activity in Dehalococcoides/Dehalogenimonas spp. and is instead hypothesized to couple HupL hydrogenase to a reductive dehalogenase in the catabolic reductive dehalogenation pathway. This finding of a close functional homologue provides an important missing link for understanding the origin and the metabolic core of terrestrial Dehalococcoides/Dehalogenimonas spp. and of reductive

Comparison of the nonradiative deep levels in silicon solar cells made of monocrystalline, polycrystalline and amorphous silicon using deep level transient spectroscopy (DLTS)

International Nuclear Information System (INIS)

Hammadeh, H.; Darwich, R.

2005-03-01

The aim of this work is to study the defects in solar cells fabricated from crystalline, polycrystalline and amorphous silicon. Using Deep Level Transient Spectroscopy technique, (DLTS), we have determined their activation energies, concentrations and their effect on the solar cell efficiency. Our results show a DLTS peak in crystalline silicon which we could attribute to tow peaks originating from iron contamination. In the polycrystalline based solar cells we observed a series of non conventional DLTS peaks while in amorphous silicon we observed a peak using low measurement frequencies (between 8 kHz and 20 kHz). We studied these defects and determined their activation energies as well as the capture cross section for one of them. We suggest a possible configuration of these defects. We cannot able to study the effect of these defects on the solar cell efficiency because we have not the experimental set-up which measure the solar cell efficiency. (Authors)

Deep RNA-Seq analysis reveals unexpected features of human prostate basal epithelial cells

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Dingxiao Zhang

2016-03-01

Full Text Available Prostate cancer is the second leading cause of cancer-related deaths among American men [1]. The prostate gland mainly contains basal and luminal cells, which are constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, for the first time, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing (GSE67070 [2]. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development, and RNA processing. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. We also identified genes associated with patient clinical outcome. Therefore, we provide a gene expression resource for understanding human prostate epithelial lineages, and link the cell-type specific gene signatures to subtypes of prostate cancer development. Keywords: Prostate epithelial cells, Basal cells, Luminal cells, RNA-seq

Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion.

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Kajimoto, Masaki; Ledee, Dolena R; Olson, Aaron K; Isern, Nancy G; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Portman, Michael A

2016-11-01

Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. We tested the hypothesis that selective cerebral perfusion modulates glucose utilization, and ameliorates abnormalities in glutamate flux, which occur in association with neuroapoptosis during deep hypothermic circulatory arrest. Eighteen infant male Yorkshire piglets were assigned randomly to two groups of seven (deep hypothermic circulatory arrest or deep hypothermic circulatory arrest with selective cerebral perfusion for 60 minutes at 18℃) and four control pigs without cardiopulmonary bypass support. Carbon-13-labeled glucose as a metabolic tracer was infused, and gas chromatography-mass spectrometry and nuclear magnetic resonance were used for metabolic analysis in the frontal cortex. Following 2.5 h of cerebral reperfusion, we observed similar cerebral adenosine triphosphate levels, absolute levels of lactate and citric acid cycle intermediates, and carbon-13 enrichment among three groups. However, deep hypothermic circulatory arrest induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid/glutamate along with neuroapoptosis, which were all prevented by selective cerebral perfusion. The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis. © The Author(s) 2016.

Intracellular responses to frequency modulated tones in the dorsal cortex of the mouse inferior colliculus

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Ruediger eGeis

2013-01-01

Full Text Available Frequency modulations occur in many natural sounds, including vocalizations. The neuronal response to frequency modulated (FM stimuli has been studied extensively in different brain areas, with an emphasis on the auditory cortex and the central nucleus of the inferior colliculus. Here, we measured the responses to FM sweeps in whole-cell recordings from neurons in the dorsal cortex of the mouse inferior colliculus. Both up- and downward logarithmic FM sweeps were presented at two different speeds to both the ipsi- and the contralateral ear. Based on the number of action potentials that were fired, between 10-24% of cells were selective for rate or direction of the FM sweeps. A somewhat lower percentage of cells, 6-21%, showed selectivity based on EPSP size. To study the mechanisms underlying the generation of FM selectivity, we compared FM responses with responses to simple tones in the same cells. We found that if pairs of neurons responded in a similar way to simple tones, they generally also responded in a similar way to FM sweeps. Further evidence that FM selectivity can be generated within the dorsal cortex was obtained by reconstructing FM sweeps from the response to simple tones using three different models. In about half of the direction selective neurons the selectivity was generated by spectrally asymmetric synaptic inhibition. In addition, evidence for direction selectivity based on the timing of excitatory responses was also obtained in some cells. No clear evidence for the local generation of rate selectivity was obtained. We conclude that FM direction selectivity can be generated within the dorsal cortex of the mouse inferior colliculus by multiple mechanisms.

Specific metabolomics adaptations define a differential regional vulnerability in the adult human cerebral cortex

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Rosanna Cabré

2016-12-01

Full Text Available Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

Encoding and retrieval of artificial visuoauditory memory traces in the auditory cortex requires the entorhinal cortex.

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Chen, Xi; Guo, Yiping; Feng, Jingyu; Liao, Zhengli; Li, Xinjian; Wang, Haitao; Li, Xiao; He, Jufang

2013-06-12

Damage to the medial temporal lobe impairs the encoding of new memories and the retrieval of memories acquired immediately before the damage in human. In this study, we demonstrated that artificial visuoauditory memory traces can be established in the rat auditory cortex and that their encoding and retrieval depend on the entorhinal cortex of the medial temporal lobe in the rat. We trained rats to associate a visual stimulus with electrical stimulation of the auditory cortex using a classical conditioning protocol. After conditioning, we examined the associative memory traces electrophysiologically (i.e., visual stimulus-evoked responses of auditory cortical neurons) and behaviorally (i.e., visual stimulus-induced freezing and visual stimulus-guided reward retrieval). The establishment of a visuoauditory memory trace in the auditory cortex, which was detectable by electrophysiological recordings, was achieved over 20-30 conditioning trials and was blocked by unilateral, temporary inactivation of the entorhinal cortex. Retrieval of a previously established visuoauditory memory was also affected by unilateral entorhinal cortex inactivation. These findings suggest that the entorhinal cortex is necessary for the encoding and involved in the retrieval of artificial visuoauditory memory in the auditory cortex, at least during the early stages of memory consolidation.

Effect of a low-dose x-ray irradiation on the development and differentiation of the cerebral cortex, (15)

International Nuclear Information System (INIS)

Hayashi, Yasushi; Hoshino, Kiyoshi; Hayasaka, Shizuka; Kameyama, Yoshiro

1981-01-01

Mice of 17 day's gestation received x-rays of 10 R, 25 R, or 100 R, and those of 13 or 15 day's gestation received 10 R in a single exposure. These irradiated fetuses were examined for the weight of the brain, thickness of the cerebral cortex, density of the cortical cells and branching of the pyramidal cells in the fifth layer of the cortex 12 weeks after birth. Decrease in the thickness of the cortex was observed in the mice which received 100 R at 17 day's gestation. A decrease in the branching index of the pyramidal cells was found in the mice which received 100 R. Although a decreasing tendency of the branching index was also recognized in those which received 10 R at 13 days of gestation, showing no statistically significant difference. (Ueda, J.)

Malformation of the cerebral cortex of rats caused by embryonal exposure to x-ray

Energy Technology Data Exchange (ETDEWEB)

Inoue, M [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

1978-03-01

200 R x-ray was irradiated to rat embryos, 17 days of age, and changes of the brain were observed histologically from one hour after the irradiation until they grew up. At start, there was not a great damage in the formation of bundles of major and minor hemisphere commissure passing through the terminal plate, although many cells died or fell off in the new brain mantle. After that, callosal fibers did not reach the midline because of the tissue destruction around the midline, and growth of the stem of the corpus callosum was pressed down. Defect of the stem of the corpus callosum was recognized in adult rats. Surviving mother cells gathered irregularly on the wall of the ventricle at the time of the repair of destructed tissues, and they remained as they stood around the midline of the brain mantle without rearrangement. In adult rats, there was abnormal formation of the cerebral cortex within medullary substances. Marked hypoplasia was recognized in the II-IV layer of the new cortex, bundle branches of dendritic processes of pyramidal cells in the V layer were small in number, and the directions of dendritic processes were abnormal. Pyramidal cell layer of the hippocampus fell into disorder and the directions of dendritic processes were irregular. It was demonstrated by the measurement of cubic volume of each part of the brain using reconstruction method that not only marked hypoplasia of the new cortex and the hippocampus but also hypoplasia of the old cortex, the basal ganglion, and the thalamus in which it was thought to be little disorder in the past were clear.

Malformation of the cerebral cortex of rats caused by embryonal exposure to x-ray

International Nuclear Information System (INIS)

Inoue, Minoru

1978-01-01

200 R x-ray was irradiated to rat embryos, 17 days of age, and changes of the brain were observed histologically from one hour after the irradiation until they grew up. At start, there was not a great damage in the formation of bundles of major and minor hemisphere commissure passing through the terminal plate, although many cells died or fell off in the new brain mantle. After that, callosal fibers did not reach the midline because of the tissue destruction around the midline, and growth of the stem of the corpus callosum was pressed down. Defect of the stem of the corpus callosum was recognized in adult rats. Surviving mother cells gathered irregularly on the wall of the ventricle at the time of the repair of destructed tissues, and they remained as they stood around the midline of the brain mantle without rearrangement. In adult rats, there was abnormal formation of the cerebral cortex within medullary substances. Marked hypoplasia was recognized in the II-IV layer of the new cortex, bundle branches of dendritic processes of pyramidal cells in the V layer were small in number, and the directions of dendritic processes were abnormal. Pyramidal cell layer of the hippocampus fell into disorder and the directions of dendritic processes were irregular. It was demonstrated by the measurement of cubic volume of each part of the brain using reconstruction method that not only marked hypoplasia of the new cortex and the hippocampus but also hypoplasia of the old cortex, the basal ganglion, and the thalamus in which it was thought to be little disorder in the past were clear. (Iwagami, H.)

Analytical investigation of high temperature 1 kW solid oxide fuel cell system feasibility in methane hydrate recovery and deep ocean power generation

International Nuclear Information System (INIS)

Azizi, Mohammad Ali; Brouwer, Jacob; Dunn-Rankin, Derek

2016-01-01

Highlights: • A dynamic Solid Oxide Fuel Cell (SOFC) model was developed. • Hydrate bed methane dissociation model was integrated with the SOFC model. • SOFC operated steadily for 120 days at high pressure deep ocean environment. • Burning some of the dissociated gas for SMR heat leads to more net methane produced. • Higher SOFC fuel utilization produces higher integrated system efficiency. - Abstract: Methane hydrates are potential valuable energy resources. However, finding an efficient method for methane gas recovery from hydrate sediments is still a challenge. New challenges arise from increasing environmental protection. This is due in part to the technical difficulties involved in the efficient dissociation of methane hydrates at high pressures. In this study, a new approach is proposed to produce valuable products of: 1. Net methane gas recovery from the methane hydrate sediment, and 2. Deep ocean power generation. We have taken the first steps toward utilization of a fuel cell system in methane gas recovery from deep ocean hydrate sediments. An integrated high pressure and high temperature solid oxide fuel cell (SOFC) and steam methane reformer (SMR) system is analyzed for this application and the recoverable amount of methane from deep ocean sediments is measured. System analysis is accomplished for two major cases regarding system performance: 1. Energy for SMR is provided by the burning part of the methane gas dissociated from the hydrate sediment. 2. Energy for SMR is provided through heat exchange with fuel cell effluent gases. We found that the total production of methane gas is higher in the first case compared to the second case. The net power generated by the fuel cell system is estimated for all cases. The primary goal of this study is to evaluate the feasibility of integrated electrochemical devices to accomplish energy efficient dissociation of methane hydrate gases in deep ocean sediments. Concepts for use of electrochemical devices

Comparative Single-Cell Genomics of Chloroflexi from the Okinawa Trough Deep-Subsurface Biosphere.

Science.gov (United States)

Fullerton, Heather; Moyer, Craig L

2016-05-15

Chloroflexi small-subunit (SSU) rRNA gene sequences are frequently recovered from subseafloor environments, but the metabolic potential of the phylum is poorly understood. The phylum Chloroflexi is represented by isolates with diverse metabolic strategies, including anoxic phototrophy, fermentation, and reductive dehalogenation; therefore, function cannot be attributed to these organisms based solely on phylogeny. Single-cell genomics can provide metabolic insights into uncultured organisms, like the deep-subsurface Chloroflexi Nine SSU rRNA gene sequences were identified from single-cell sorts of whole-round core material collected from the Okinawa Trough at Iheya North hydrothermal field as part of Integrated Ocean Drilling Program (IODP) expedition 331 (Deep Hot Biosphere). Previous studies of subsurface Chloroflexi single amplified genomes (SAGs) suggested heterotrophic or lithotrophic metabolisms and provided no evidence for growth by reductive dehalogenation. Our nine Chloroflexi SAGs (seven of which are from the order Anaerolineales) indicate that, in addition to genes for the Wood-Ljungdahl pathway, exogenous carbon sources can be actively transported into cells. At least one subunit for pyruvate ferredoxin oxidoreductase was found in four of the Chloroflexi SAGs. This protein can provide a link between the Wood-Ljungdahl pathway and other carbon anabolic pathways. Finally, one of the seven Anaerolineales SAGs contains a distinct reductive dehalogenase homologous (rdhA) gene. Through the use of single amplified genomes (SAGs), we have extended the metabolic potential of an understudied group of subsurface microbes, the Chloroflexi These microbes are frequently detected in the subsurface biosphere, though their metabolic capabilities have remained elusive. In contrast to previously examined Chloroflexi SAGs, our genomes (several are from the order Anaerolineales) were recovered from a hydrothermally driven system and therefore provide a unique window into

Event-related rTMS at encoding affects differently deep and shallow memory traces.

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Innocenti, Iglis; Giovannelli, Fabio; Cincotta, Massimo; Feurra, Matteo; Polizzotto, Nicola R; Bianco, Giovanni; Cappa, Stefano F; Rossi, Simone

2010-10-15

The "level of processing" effect is a classical finding of the experimental psychology of memory. Actually, the depth of information processing at encoding predicts the accuracy of the subsequent episodic memory performance. When the incoming stimuli are analyzed in terms of their meaning (semantic, or deep, encoding), the memory performance is superior with respect to the case in which the same stimuli are analyzed in terms of their perceptual features (shallow encoding). As suggested by previous neuroimaging studies and by some preliminary findings with transcranial magnetic stimulation (TMS), the left prefrontal cortex may play a role in semantic processing requiring the allocation of working memory resources. However, it still remains unclear whether deep and shallow encoding share or not the same cortical networks, as well as how these networks contribute to the "level of processing" effect. To investigate the brain areas casually involved in this phenomenon, we applied event-related repetitive TMS (rTMS) during deep (semantic) and shallow (perceptual) encoding of words. Retrieval was subsequently tested without rTMS interference. RTMS applied to the left dorsolateral prefrontal cortex (DLPFC) abolished the beneficial effect of deep encoding on memory performance, both in terms of accuracy (decrease) and reaction times (increase). Neither accuracy nor reaction times were instead affected by rTMS to the right DLPFC or to an additional control site excluded by the memory process (vertex). The fact that online measures of semantic processing at encoding were unaffected suggests that the detrimental effect on memory performance for semantically encoded items took place in the subsequent consolidation phase. These results highlight the specific causal role of the left DLPFC among the wide left-lateralized cortical network engaged by long-term memory, suggesting that it probably represents a crucial node responsible for the improved memory performance induced by

Human development VIII: a theory of "deep" quantum chemistry and cell consciousness: quantum chemistry controls genes and biochemistry to give cells and higher organisms consciousness and complex behavior.

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Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

2006-11-14

Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it "sees", and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occam's razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules' orbitals make one huge "cell-orbital", which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants) and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness.

Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta

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Tehrani, Kayvan F.; Pendleton, Emily G.; Lin, Charles P.; Mortensen, Luke J.

2016-04-01

Osteogenesis imperfecta (OI) is a currently uncurable disease where a mutation in collagen type I yields brittle bones. One potential therapy is transplantation of mesenchymal stem cells (MSCs), but controlling and enhancing transplanted cell survival has proven challenging. Therefore, we use a 2- photon imaging system to study individual transplanted cells in the living bone marrow. We ablated cells deep in the bone marrow and observed minimal collateral damage to surrounding tissue. Future work will evaluate the local impact of transplanted MSCs on bone deposition in vivo.

Chemosensory Learning in the Cortex

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Edmund eRolls

2011-09-01

Full Text Available Taste is a primary reinforcer. Olfactory-taste and visual-taste association learning takes place in the primate including human orbitofrontal cortex to build representations of flavour. Rapid reversal of this learning can occur using a rule-based learning system that can be reset when an expected taste or flavour reward is not obtained, that is by negative reward prediction error, to which a population of neurons in the orbitofrontal cortex responds. The representation in the orbitofrontal cortex but not the primary taste or olfactory cortex is of the reward value of the visual / olfactory / taste / input as shown by devaluation experiments in which food is fed to satiety, and by correlations with the activations with subjective pleasantness ratings in humans. Sensory-specific satiety for taste, olfactory, visual, and oral somatosensory inputs produced by feeding a particular food to satiety are implemented it is proposed by medium-term synaptic adaptation in the orbitofrontal cortex. Cognitive factors, including word-level descriptions, modulate the representation of the reward value of food in the orbitofrontal cortex, and this effect is learned it is proposed by associative modification of top-down synapses onto neurons activated by bottom-up taste and olfactory inputs when both are active in the orbitofrontal cortex. A similar associative synaptic learning process is proposed to be part of the mechanism for the top-down attentional control to the reward value vs the sensory properties such as intensity of taste and olfactory inputs in the orbitofrontal cortex, as part of a biased activation theory of selective attention.

Androgen receptor immunoreactivity in rat occipital cortex after callosotomy

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G Lepore

2009-08-01

Full Text Available Gonadal steroidogenesis can be influenced by direct neural links between the central nervous system and the gonads. It is known that androgen receptor (AR is expressed in many areas of the rat brain involved in neuroendocrine control of reproduction, such as the cerebral cortex. It has been recently shown that the occipital cortex exerts an inhibitory effect on testicular stereoidogenesis by a pituitary-independent neural mechanism. Moreover, the complete transection of the corpus callosum leads to an increase in testosterone (T secretion of hemigonadectomized rats. The present study was undertaken to analyze the possible corticocortical influences regulating male reproductive activities. Adult male Wistar rats were divided into 4 groups: 1 intact animals as control; 2 rats undergoing sham callosotomy; 3 posterior callosotomy; 4 gonadectomy and posterior callosotomy. Western blot analysis showed no remarkable variations in cortical AR expression in any of the groups except in group I where a significant decrease in AR levels was found. Similarly, both immunocytochemical study and cell count estimation showed a lower AR immunoreactivity in occipital cortex of callosotomized rats than in other groups. In addition, there was no difference in serum T and LH concentration between sham-callosotomized and callosotomized rats. In conclusion, our results show that posterior callosotomy led to a reduction in AR in the right occipital cortex suggesting a putative inhibiting effect of the contralateral cortical area.

Gene expression in the deep biosphere.

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Orsi, William D; Edgcomb, Virginia P; Christman, Glenn D; Biddle, Jennifer F

2013-07-11

Scientific ocean drilling has revealed a deep biosphere of widespread microbial life in sub-seafloor sediment. Microbial metabolism in the marine subsurface probably has an important role in global biogeochemical cycles, but deep biosphere activities are not well understood. Here we describe and analyse the first sub-seafloor metatranscriptomes from anaerobic Peru Margin sediment up to 159 metres below the sea floor, represented by over 1 billion complementary DNA (cDNA) sequence reads. Anaerobic metabolism of amino acids, carbohydrates and lipids seem to be the dominant metabolic processes, and profiles of dissimilatory sulfite reductase (dsr) transcripts are consistent with pore-water sulphate concentration profiles. Moreover, transcripts involved in cell division increase as a function of microbial cell concentration, indicating that increases in sub-seafloor microbial abundance are a function of cell division across all three domains of life. These data support calculations and models of sub-seafloor microbial metabolism and represent the first holistic picture of deep biosphere activities.

Secondary damage in the spinal cord after motor cortex injury in rats.

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Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

2010-08-01

When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

Morphological and cytochemical changes in the symmetric areas of the visual cortex during irradiation of one hemisphere in rabbits

International Nuclear Information System (INIS)

Gelashvili, N.A.; Kumsiashvili, L.B.; Gikoshvili, T.I.; Amashukeli, I.S.

1980-01-01

Made is an attempt of layer analysis of DNA content in the cells of brain hemisphere in connection with morphological changes of the nervous tissue after irradiation of animals. Investigations of the 17-th and 18-th fields of the brain visual cortex of rabbits have been subjected to morphologic and hystologic analysis. The left hemisphere of animals has received a single dose of irradiation while the other part of the head and body has been shielded till the formation of pronounced signs of depression of the brain bioelectric activity at the side of irradiation. It is established, that by the moment of depression of bioelectric activity of brain on the side of irradiation are characterized by similar radiosensitivity according to changes of the general amount of cells, nuclear DNA content, nucleus-cytoplasm ratio, the increase in the number of picnotic and degenerated nuclei of cells of the 17-th and 18-th fields of different layers of the visual cortex of rabbit's brain. Pyramid neurons of different layers of the visual cortex, reveal similar radiosensitivity. The difference between irradiated and shielded visual cortex to the moment of brain bioelectric activity depression in the content of nuclear DNA in nervous and macroglial cells is statistically authentic

Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes

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Leon French

2017-05-01

Full Text Available Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6 and in the vasoactive intestinal peptide (Vip neuron subtype expressing myosin binding protein C, slow type (Mybpc1. These findings provide new insights into cell specific susceptibility to normal aging

Distinct timescales of population coding across cortex.

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Runyan, Caroline A; Piasini, Eugenio; Panzeri, Stefano; Harvey, Christopher D

2017-08-03

The cortex represents information across widely varying timescales. For instance, sensory cortex encodes stimuli that fluctuate over few tens of milliseconds, whereas in association cortex behavioural choices can require the maintenance of information over seconds. However, it remains poorly understood whether diverse timescales result mostly from features intrinsic to individual neurons or from neuronal population activity. This question remains unanswered, because the timescales of coding in populations of neurons have not been studied extensively, and population codes have not been compared systematically across cortical regions. Here we show that population codes can be essential to achieve long coding timescales. Furthermore, we find that the properties of population codes differ between sensory and association cortices. We compared coding for sensory stimuli and behavioural choices in auditory cortex and posterior parietal cortex as mice performed a sound localization task. Auditory stimulus information was stronger in auditory cortex than in posterior parietal cortex, and both regions contained choice information. Although auditory cortex and posterior parietal cortex coded information by tiling in time neurons that were transiently informative for approximately 200 milliseconds, the areas had major differences in functional coupling between neurons, measured as activity correlations that could not be explained by task events. Coupling among posterior parietal cortex neurons was strong and extended over long time lags, whereas coupling among auditory cortex neurons was weak and short-lived. Stronger coupling in posterior parietal cortex led to a population code with long timescales and a representation of choice that remained consistent for approximately 1 second. In contrast, auditory cortex had a code with rapid fluctuations in stimulus and choice information over hundreds of milliseconds. Our results reveal that population codes differ across cortex

Voronoi-based spatial analysis reveals selective interneuron changes in the cortex of FALS mice.

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Minciacchi, Diego; Kassa, Roman M; Del Tongo, Claudia; Mariotti, Raffaella; Bentivoglio, Marina

2009-01-01

The neurodegenerative disease amyotrophic lateral sclerosis affects lower motoneurons and corticospinal cells. Mice expressing human mutant superoxide dismutase (SOD)1 provide widely investigated models of the familial form of disease, but information on cortical changes in these mice is still limited. We here analyzed the spatial organization of interneurons characterized by parvalbumin immunoreactivity in the motor, somatosensory, and visual cortical areas of SOD1(G93A) mice. Cell number and sociological spatial behavior were assessed by digital charts of cell location in cortical samples, cell counts, and generation of two-dimensional Voronoi diagrams. In end-stage SOD1-mutant mice, an increase of parvalbumin-containing cortical interneurons was found in the motor and somatosensory areas (about 35% and 20%, respectively) with respect to wild-type littermates. Changes in cell spatial distribution, as documented by Voronoi-derived coefficients of variation, indicated increased tendency of parvalbumin cells to aggregate into clusters in the same areas of the SOD1-mutant cortex. Counts and coefficients of variation of parvalbumin cells in the visual cortex gave instead similar results in SOD1-mutant and wild-type mice. Analyses of motor and somatosensory areas in presymptomatic SOD1-mutant mice provided findings very similar to those obtained at end-stage, indicating early changes of interneurons in these cortical areas during the pathology. Altogether the data reveal in the SOD1-mutant mouse cortex an altered architectonic pattern of interneurons, which selectively affects areas involved in motor control. The findings, which can be interpreted as pathogenic factors or early disease-related adaptations, point to changes in the cortical regulation and modulation of the motor circuit during motoneuron disease.

Astrocytes control GABAergic inhibition of neurons in the mouse barrel cortex.

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Benedetti, B; Matyash, V; Kettenmann, H

2011-03-01

Astrocytes in the barrel cortex respond with a transient Ca2+ increase to neuronal stimulation and this response is restricted to the stimulated barrel field. In the present study we suppressed the astrocyte response by dialysing these cells with the Ca2+ chelator BAPTA. Electrical stimulation triggered a depolarization in stellate or pyramidal ‘regular spiking' neurons from cortex layer 4 and 2/3 and this response was augmented in amplitude and duration after astrocytes were dialysed with BAPTA. Combined blockade of GABAA and GABAB receptors mimicked the effect of BAPTA dialysis, while glutamate receptor blockers had no effect. Moreover, the frequency of spontaneous postsynaptic currents was increased after BAPTA dialysis. Outside the range of BAPTA dialysis astrocytes responded with a Ca2+ increase, but in contrast to control, the response was no longer restricted to one barrel field. Our findings indicate that astrocytes control neuronal inhibition in the barrel cortex.

Sexually Monomorphic Maps and Dimorphic Responses in Rat Genital Cortex.

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Lenschow, Constanze; Copley, Sean; Gardiner, Jayne M; Talbot, Zoe N; Vitenzon, Ariel; Brecht, Michael

2016-01-11

Mammalian external genitals show sexual dimorphism [1, 2] and can change size and shape upon sexual arousal. Genitals feature prominently in the oldest pieces of figural art [3] and phallic depictions of penises informed psychoanalytic thought about sexuality [4, 5]. Despite this longstanding interest, the neural representations of genitals are still poorly understood [6]. In somatosensory cortex specifically, many studies did not detect any cortical representation of genitals [7-9]. Studies in humans debate whether genitals are represented displaced below the foot of the cortical body map [10-12] or whether they are represented somatotopically [13-15]. We wondered what a high-resolution mapping of genital representations might tell us about the sexual differentiation of the mammalian brain. We identified genital responses in rat somatosensory cortex in a region previously assigned as arm/leg cortex. Genital responses were more common in males than in females. Despite such response dimorphism, we observed a stunning anatomical monomorphism of cortical penis and clitoris input maps revealed by cytochrome-oxidase-staining of cortical layer 4. Genital representations were somatotopic and bilaterally symmetric, and their relative size increased markedly during puberty. Size, shape, and erect posture give the cortical penis representation a phallic appearance pointing to a role in sexually aroused states. Cortical genital neurons showed unusual multi-body-part responses and sexually dimorphic receptive fields. Specifically, genital neurons were co-activated by distant body regions, which are touched during mounting in the respective sex. Genital maps indicate a deep homology of penis and clitoris representations in line with a fundamentally bi-sexual layout [16] of the vertebrate brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deep sequencing and flow cytometric characterization of expanded effector memory CD8+CD57+ T cells frequently reveals T-cell receptor Vβ oligoclonality and CDR3 homology in acquired aplastic anemia.

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Giudice, Valentina; Feng, Xingmin; Lin, Zenghua; Hu, Wei; Zhang, Fanmao; Qiao, Wangmin; Ibanez, Maria Del Pilar Fernandez; Rios, Olga; Young, Neal S

2018-05-01

Oligoclonal expansion of CD8 + CD28 - lymphocytes has been considered indirect evidence for a pathogenic immune response in acquired aplastic anemia. A subset of CD8 + CD28 - cells with CD57 expression, termed effector memory cells, is expanded in several immune-mediated diseases and may have a role in immune surveillance. We hypothesized that effector memory CD8 + CD28 - CD57 + cells may drive aberrant oligoclonal expansion in aplastic anemia. We found CD8 + CD57 + cells frequently expanded in the blood of aplastic anemia patients, with oligoclonal characteristics by flow cytometric Vβ usage analysis: skewing in 1-5 Vβ families and frequencies of immunodominant clones ranging from 1.98% to 66.5%. Oligoclonal characteristics were also observed in total CD8 + cells from aplastic anemia patients with CD8 + CD57 + cell expansion by T-cell receptor deep sequencing, as well as the presence of 1-3 immunodominant clones. Oligoclonality was confirmed by T-cell receptor repertoire deep sequencing of enriched CD8 + CD57 + cells, which also showed decreased diversity compared to total CD4 + and CD8 + cell pools. From analysis of complementarity-determining region 3 sequences in the CD8 + cell pool, a total of 29 sequences were shared between patients and controls, but these sequences were highly expressed in aplastic anemia subjects and also present in their immunodominant clones. In summary, expansion of effector memory CD8 + T cells is frequent in aplastic anemia and mirrors Vβ oligoclonal expansion. Flow cytometric Vβ usage analysis combined with deep sequencing technologies allows high resolution characterization of the T-cell receptor repertoire, and might represent a useful tool in the diagnosis and periodic evaluation of aplastic anemia patients. (Registered at clinicaltrials.gov identifiers: 00001620, 01623167, 00001397, 00071045, 00081523, 00961064 ). Copyright © 2018 Ferrata Storti Foundation.

DeepMitosis: Mitosis detection via deep detection, verification and segmentation networks.

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Li, Chao; Wang, Xinggang; Liu, Wenyu; Latecki, Longin Jan

2018-04-01

Mitotic count is a critical predictor of tumor aggressiveness in the breast cancer diagnosis. Nowadays mitosis counting is mainly performed by pathologists manually, which is extremely arduous and time-consuming. In this paper, we propose an accurate method for detecting the mitotic cells from histopathological slides using a novel multi-stage deep learning framework. Our method consists of a deep segmentation network for generating mitosis region when only a weak label is given (i.e., only the centroid pixel of mitosis is annotated), an elaborately designed deep detection network for localizing mitosis by using contextual region information, and a deep verification network for improving detection accuracy by removing false positives. We validate the proposed deep learning method on two widely used Mitosis Detection in Breast Cancer Histological Images (MITOSIS) datasets. Experimental results show that we can achieve the highest F-score on the MITOSIS dataset from ICPR 2012 grand challenge merely using the deep detection network. For the ICPR 2014 MITOSIS dataset that only provides the centroid location of mitosis, we employ the segmentation model to estimate the bounding box annotation for training the deep detection network. We also apply the verification model to eliminate some false positives produced from the detection model. By fusing scores of the detection and verification models, we achieve the state-of-the-art results. Moreover, our method is very fast with GPU computing, which makes it feasible for clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Spiking in auditory cortex following thalamic stimulation is dominated by cortical network activity

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Krause, Bryan M.; Raz, Aeyal; Uhlrich, Daniel J.; Smith, Philip H.; Banks, Matthew I.

2014-01-01

The state of the sensory cortical network can have a profound impact on neural responses and perception. In rodent auditory cortex, sensory responses are reported to occur in the context of network events, similar to brief UP states, that produce “packets” of spikes and are associated with synchronized synaptic input (Bathellier et al., 2012; Hromadka et al., 2013; Luczak et al., 2013). However, traditional models based on data from visual and somatosensory cortex predict that ascending sensory thalamocortical (TC) pathways sequentially activate cells in layers 4 (L4), L2/3, and L5. The relationship between these two spatio-temporal activity patterns is unclear. Here, we used calcium imaging and electrophysiological recordings in murine auditory TC brain slices to investigate the laminar response pattern to stimulation of TC afferents. We show that although monosynaptically driven spiking in response to TC afferents occurs, the vast majority of spikes fired following TC stimulation occurs during brief UP states and outside the context of the L4>L2/3>L5 activation sequence. Specifically, monosynaptic subthreshold TC responses with similar latencies were observed throughout layers 2–6, presumably via synapses onto dendritic processes located in L3 and L4. However, monosynaptic spiking was rare, and occurred primarily in L4 and L5 non-pyramidal cells. By contrast, during brief, TC-induced UP states, spiking was dense and occurred primarily in pyramidal cells. These network events always involved infragranular layers, whereas involvement of supragranular layers was variable. During UP states, spike latencies were comparable between infragranular and supragranular cells. These data are consistent with a model in which activation of auditory cortex, especially supragranular layers, depends on internally generated network events that represent a non-linear amplification process, are initiated by infragranular cells and tightly regulated by feed-forward inhibitory

Developmental and visual input-dependent regulation of the CB1 cannabinoid receptor in the mouse visual cortex.

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Taisuke Yoneda

Full Text Available The mammalian visual system exhibits significant experience-induced plasticity in the early postnatal period. While physiological studies have revealed the contribution of the CB1 cannabinoid receptor (CB1 to developmental plasticity in the primary visual cortex (V1, it remains unknown whether the expression and localization of CB1 is regulated during development or by visual experience. To explore a possible role of the endocannabinoid system in visual cortical plasticity, we examined the expression of CB1 in the visual cortex of mice. We found intense CB1 immunoreactivity in layers II/III and VI. CB1 mainly localized at vesicular GABA transporter-positive inhibitory nerve terminals. The amount of CB1 protein increased throughout development, and the specific laminar pattern of CB1 appeared at P20 and remained until adulthood. Dark rearing from birth to P30 decreased the amount of CB1 protein in V1 and altered the synaptic localization of CB1 in the deep layer. Dark rearing until P50, however, did not influence the expression of CB1. Brief monocular deprivation for 2 days upregulated the localization of CB1 at inhibitory nerve terminals in the deep layer. Taken together, the expression and the localization of CB1 are developmentally regulated, and both parameters are influenced by visual experience.

Development of Rostral Prefrontal Cortex and Cognitive and Behavioural Disorders

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Dumontheil, Iroise; Burgess, Paul W.; Blakemore, Sarah-Jayne

2008-01-01

Information on the development and functions of rostral prefrontal cortex (PFC), or Brodmann area 10, has been gathered from different fields, from anatomical development to functional neuroimaging in adults, and put forward in relation to three particular cognitive and behavioural disorders. Rostral PFC is larger and has a lower cell density in…

Astrocytes control GABAergic inhibition of neurons in the mouse barrel cortex

Science.gov (United States)

Benedetti, B; Matyash, V; Kettenmann, H

2011-01-01

Astrocytes in the barrel cortex respond with a transient Ca2+ increase to neuronal stimulation and this response is restricted to the stimulated barrel field. In the present study we suppressed the astrocyte response by dialysing these cells with the Ca2+ chelator BAPTA. Electrical stimulation triggered a depolarization in stellate or pyramidal ‘regular spiking’ neurons from cortex layer 4 and 2/3 and this response was augmented in amplitude and duration after astrocytes were dialysed with BAPTA. Combined blockade of GABAA and GABAB receptors mimicked the effect of BAPTA dialysis, while glutamate receptor blockers had no effect. Moreover, the frequency of spontaneous postsynaptic currents was increased after BAPTA dialysis. Outside the range of BAPTA dialysis astrocytes responded with a Ca2+ increase, but in contrast to control, the response was no longer restricted to one barrel field. Our findings indicate that astrocytes control neuronal inhibition in the barrel cortex. PMID:21224221

Ventromedial prefrontal cortex pyramidal cells have a temporal dynamic role in recall and extinction of cocaine-associated memory.

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Van den Oever, Michel C; Rotaru, Diana C; Heinsbroek, Jasper A; Gouwenberg, Yvonne; Deisseroth, Karl; Stuber, Garret D; Mansvelder, Huibert D; Smit, August B

2013-11-13

In addicts, associative memories related to the rewarding effects of drugs of abuse can evoke powerful craving and drug seeking urges, but effective treatment to suppress these memories is not available. Detailed insight into the neural circuitry that mediates expression of drug-associated memory is therefore of crucial importance. Substantial evidence from rodent models of addictive behavior points to the involvement of the ventromedial prefrontal cortex (vmPFC) in conditioned drug seeking, but specific knowledge of the temporal role of vmPFC pyramidal cells is lacking. To this end, we used an optogenetics approach to probe the involvement of vmPFC pyramidal cells in expression of a recent and remote conditioned cocaine memory. In mice, we expressed Channelrhodopsin-2 (ChR2) or Halorhodopsin (eNpHR3.0) in pyramidal cells of the vmPFC and studied the effect of activation or inhibition of these cells during expression of a cocaine-contextual memory on days 1-2 (recent) and ∼3 weeks (remote) after conditioning. Whereas optical activation of pyramidal cells facilitated extinction of remote memory, without affecting recent memory, inhibition of pyramidal cells acutely impaired recall of recent cocaine memory, without affecting recall of remote memory. In addition, we found that silencing pyramidal cells blocked extinction learning at the remote memory time-point. We provide causal evidence of a critical time-dependent switch in the contribution of vmPFC pyramidal cells to recall and extinction of cocaine-associated memory, indicating that the circuitry that controls expression of cocaine memories reorganizes over time.

Sparse orthogonal population representation of spatial context in the retrosplenial cortex.

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Mao, Dun; Kandler, Steffen; McNaughton, Bruce L; Bonin, Vincent

2017-08-15

Sparse orthogonal coding is a key feature of hippocampal neural activity, which is believed to increase episodic memory capacity and to assist in navigation. Some retrosplenial cortex (RSC) neurons convey distributed spatial and navigational signals, but place-field representations such as observed in the hippocampus have not been reported. Combining cellular Ca 2+ imaging in RSC of mice with a head-fixed locomotion assay, we identified a population of RSC neurons, located predominantly in superficial layers, whose ensemble activity closely resembles that of hippocampal CA1 place cells during the same task. Like CA1 place cells, these RSC neurons fire in sequences during movement, and show narrowly tuned firing fields that form a sparse, orthogonal code correlated with location. RSC 'place' cell activity is robust to environmental manipulations, showing partial remapping similar to that observed in CA1. This population code for spatial context may assist the RSC in its role in memory and/or navigation.Neurons in the retrosplenial cortex (RSC) encode spatial and navigational signals. Here the authors use calcium imaging to show that, similar to the hippocampus, RSC neurons also encode place cell-like activity in a sparse orthogonal representation, partially anchored to the allocentric cues on the linear track.

The subclonal structure and genomic evolution of oral squamous cell carcinoma revealed by ultra-deep sequencing

DEFF Research Database (Denmark)

Tabatabaeifar, Siavosh; Thomassen, Mads; Larsen, Martin J

2017-01-01

Recent studies suggest that head and neck squamous cell carcinomas are very heterogeneous between patients; however the subclonal structure remains unexplored mainly due to studies using only a single biopsy per patient. To deconvolutethe clonal structure and describe the genomic cancer evolution......, we applied whole-exome sequencing combined with ultra-deep targeted sequencing on oral squamous cell carcinomas (OSCC). From each patient, a set of biopsies was sampled from distinct geographical sites in primary tumor and lymph node metastasis.We demonstrate that the included OSCCs show a high...

Opening up the blackbox: an interpretable deep neural network-based classifier for cell-type specific enhancer predictions.

Science.gov (United States)

Kim, Seong Gon; Theera-Ampornpunt, Nawanol; Fang, Chih-Hao; Harwani, Mrudul; Grama, Ananth; Chaterji, Somali

2016-08-01

Gene expression is mediated by specialized cis-regulatory modules (CRMs), the most prominent of which are called enhancers. Early experiments indicated that enhancers located far from the gene promoters are often responsible for mediating gene transcription. Knowing their properties, regulatory activity, and genomic targets is crucial to the functional understanding of cellular events, ranging from cellular homeostasis to differentiation. Recent genome-wide investigation of epigenomic marks has indicated that enhancer elements could be enriched for certain epigenomic marks, such as, combinatorial patterns of histone modifications. Our efforts in this paper are motivated by these recent advances in epigenomic profiling methods, which have uncovered enhancer-associated chromatin features in different cell types and organisms. Specifically, in this paper, we use recent state-of-the-art Deep Learning methods and develop a deep neural network (DNN)-based architecture, called EP-DNN, to predict the presence and types of enhancers in the human genome. It uses as features, the expression levels of the histone modifications at the peaks of the functional sites as well as in its adjacent regions. We apply EP-DNN to four different cell types: H1, IMR90, HepG2, and HeLa S3. We train EP-DNN using p300 binding sites as enhancers, and TSS and random non-DHS sites as non-enhancers. We perform EP-DNN predictions to quantify the validation rate for different levels of confidence in the predictions and also perform comparisons against two state-of-the-art computational models for enhancer predictions, DEEP-ENCODE and RFECS. We find that EP-DNN has superior accuracy and takes less time to make predictions. Next, we develop methods to make EP-DNN interpretable by computing the importance of each input feature in the classification task. This analysis indicates that the important histone modifications were distinct for different cell types, with some overlaps, e.g., H3K27ac was

Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen–glucose deprivation and reoxygenation

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Park SY

2017-06-01

Full Text Available Sun Young Park,1 Seon Yeong Chae,1,2 Jin Oh Park,2 Kyu Jin Lee,2 Geuntae Park1,2 1Bio-IT Fusion Technology Research Institute, 2Department of Nanofusion Technology, Graduate School, Pusan National University, Busan, Republic of Korea Abstract: Recently, environment-friendly synthesis of gold nanoparticles (GNPs has been extensively explored by biologists and chemists. However, significant research is still required to determine whether “eco-friendly” GNPs are beneficial to human health and to elucidate the molecular mechanisms of their effects on human cells. We used human neuronal SH-SY5Y cells to show that treatment with Kalopanacis Cortex extract-capped GNPs (KC-GNs, prepared via an eco-friendly, fast, one-pot synthetic route, protected neuronal cells against oxygen–glucose deprivation/reoxygenation (OGD/R-induced damage. To prepare GNPs, Kalopanacis Cortex was used without any chemical reducing and stabilizing agents. Ultraviolet–visible spectroscopy showed maximum absorbance at 526 nm owing to KC-GN surface plasmon resonance. Hydrodynamic size (54.02±2.19 nm and zeta potential (-20.3±0.04 mV were determined by dynamic light scattering. The average diameter (41.07±3.05 nm was determined by high-resolution transmission electron microscopy. Energy-dispersive X-ray diffraction spectroscopy and X-ray diffraction confirmed the presence of assembled GNPs. Fourier transform infrared analysis suggested that functional groups such as O–H, C–C, and C–N participated in KC-GN formation. Cell viability assays indicated that KC-GNs restored the viability of OGD/R-treated SH-SY5Y cells. Flow cytometry demonstrated that KC-GNs inhibited the OGD/R-induced reactive oxygen species production and mitochondrial membrane potential disruption. KC-GNs also inhibited the apoptosis of OGD/R-exposed cells. Western blot analysis indicated that the OGD/R-induced cellular apoptosis and simultaneous increases in the expression of cleaved caspase-3, p

Long-Term Potentiation in the Motor Cortex

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Iriki, Atsushi; Pavlides, Constantine; Keller, Asaf; Asanuma, Hiroshi

1989-09-01

Long-term potentiation (LTP) is a model for learning and memory processes. Tetanic stimulation of the sensory cortex produces LTP in motor cortical neurons, whereas tetanization of the ventrolateral nucleus of the thalamus, which also projects to the motor cortex, does not. However, after simultaneous high-frequency stimulation of both the sensory cortex and the ventrolateral nucleus of the thalamus, LTP of thalamic input to motor cortical neurons is induced. This associative LTP occurs only in neurons in the superficial layers of the motor cortex that receive monosynaptic input from both the sensory cortex and the ventrolateral nucleus of the thalamus. Associative LTP in the motor cortex may constitute a basis for the retention of motor skills.

Andrographolide - A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment.

Science.gov (United States)

Das, Sudeshna; Mishra, K P; Ganju, Lilly; Singh, S B

2017-12-15

Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region. Active microglial and reactive astrocytic makers were also downregulated after andrographolide treatment. Andrographolide suppressed overexpression of microglial MIP-1α, P2X7 receptor and its downstream signaling mediators including-inflammasome NLRP3, caspase1 and mature IL-1β. Furthermore, in vivo maze studies suggested that andrographolide treatment reversed LPS-induced behavioural and working memory disturbances including regulation of expression of protein markers like PKC, p-CREB, amyloid beta, APP, p-tau, synapsin and PSD-95. Andrographolide, by lowering expression of pro apoptotic genes and enhancing the expression of anti-apoptotic gene showed its anti-apoptotic nature that in turn reduces neurodegeneration. Morphology studies using Nissl and FJB staining also showed the neuroprotective effect of andrographolide in the prefrontal cortex region. The above studies indicated that andrographolide prevented neuroinflammation-associated neurodegeneration and improved synaptic plasticity markers in cortical as well as hippocampal region which suggests that andrographolide could be a novel pharmacological countermeasure for the treatment of neuroinflammation and neurological disorders related to memory impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

Prefrontal cortex and somatosensory cortex in tactile crossmodal association: an independent component analysis of ERP recordings.

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Yixuan Ku

2007-08-01

Full Text Available Our previous studies on scalp-recorded event-related potentials (ERPs showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA to the ERP data, we found independent components (ICs located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC and the primary somatosensory cortex (SI. The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex that are involved in sensation and perception of various stimuli.

Human Development VIII: A Theory of “Deep” Quantum Chemistry and Cell Consciousness: Quantum Chemistry Controls Genes and Biochemistry to Give Cells and Higher Organisms Consciousness and Complex Behavior

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Søren Ventegodt

2006-01-01

Full Text Available Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it “sees”, and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occam’s razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules’ orbitals make one huge “cell-orbital”, which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness.

The functional upregulation of piriform cortex is associated with cross-modal plasticity in loss of whisker tactile inputs.

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Bing Ye

Full Text Available Cross-modal plasticity is characterized as the hypersensitivity of remaining modalities after a sensory function is lost in rodents, which ensures their awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain unclear. We aim to study the role of different types of neurons in cross-modal plasticity.In addition to behavioral tasks in mice, whole-cell recordings at the excitatory and inhibitory neurons, and their two-photon imaging, were conducted in piriform cortex. We produced a mouse model of cross-modal sensory plasticity that olfactory function was upregulated by trimming whiskers to deprive their sensory inputs. In the meantime of olfactory hypersensitivity, pyramidal neurons and excitatory synapses were functionally upregulated, as well as GABAergic cells and inhibitory synapses were downregulated in piriform cortex from the mice of cross-modal sensory plasticity, compared with controls. A crosswire connection between barrel cortex and piriform cortex was established in cross-modal plasticity.An upregulation of pyramidal neurons and a downregulation of GABAergic neurons strengthen the activities of neuronal networks in piriform cortex, which may be responsible for olfactory hypersensitivity after a loss of whisker tactile input. This finding provides the clues for developing therapeutic strategies to promote sensory recovery and substitution.

The Effect of Salvia Rhytidea Extract on the Number of Cells of Different Layers of Cerebellar Cortex Following Ischemia Reperfusion in Rats

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M Farahmand

2016-09-01

Full Text Available Background & aim: Salvia has anti-oxidant oxygen free radicals which are generated during the interruption and reestablishment of ischemia reperfusion.  The aim of study was to investigate the effect of Salvia Rhytidea extract on the number of cells of different layers of cerebellar cortex following ischemia reperfusion in rats. Methods: In the present experimental study, 35 adult male rats were randomly divided into 7 groups of 5: Group 1 (control-: Sampling without ischemia. Group 2 (control +: Cerebellar ischemia with administration of normal saline. Group 3(sham: Manipulation without ischemia with normal saline administration. Group 4   received (3.2 mg/kg aqueous and alcoholic Salvia extract 2 hours after ischemia. Group 5 received 50 mg/kg silymarin drug, 2 hours after ischemia. Group 6 received 3.2 mg/kg aqueous and alcoholic Salvia extract 72, 48, 24 and 0 h before ischemia and group 7 received silymarin drug (50 mg/kg, 0, 24, 48, and 72, hrs. before ischemia. 24 hrs. following reperfusion, the rats were euthanized and samples of the cerebellum were obtained. By using routine histological technique, the sections were stained by H&E. The measurement of cell count in cerebellar cortex were accomplished. Data were evaluated with One-Way ANOVA and Tukey diagnostic tests. Results: A significant decrease was observed in the number of neural cells in granular layer in the non-treated ischemia group and in the groups which received Salvia extract and silymarin, two hours after the ischemia (p< 0.05. No significant decrease was observed in the number of cells of this layer in the groups which received salvia extract before ischemia. But regarding the cell number of molecular and purkinje layers in above groups, no significant difference was observed compared to the control group (P˃0.05. However, no significant differences was seen in the number of cells layers compared to the control group (P˃0.05. Conclusion: Finally, administration of

The Functions of the Orbitofrontal Cortex

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Rolls, Edmund T.

2004-01-01

The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight…

Anti-Inflammatory Activity of the Methanol Extract of Moutan Cortex in LPS-Activated Raw264.7 Cells

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Seung-Chul Chun

2007-01-01

Full Text Available Moutan Cortex (MCE has been used in traditional medicine to remove heat from the blood, promote blood circulation and alleviate blood stasis. This study was conducted to evaluate the effects of MCE on regulatory mechanisms of cytokines and nitric oxide (NO involved in immunological activity of Raw264.7 cells. Cells were pretreated with methanolic extracts of MCE, and further cultured for an appropriate time after lipopolyssacharide (LPS addition. During the entire experimental period, 0.1 and 0.3 mg ml−1 of MCE had no cytotoxicity. In these concentrations, MCE inhibited the production of NO and prostaglandin E2 (PGE2, the expression of inducible NO synthase (iNOS, cyclooxygenase-2 (COX-2 and phosphorylated inhibitor of κBα (p-IκBα, and the activation of nuclear factor κB (NF-κB. MCE also reduced the concentration of tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β and interleukin-6 (IL-6 in the Raw264.7 cells that were activated by LPS. These results demonstrate that MCE has anti-inflammatory effects through the inhibition of iNOS and COX-2 expression by suppressing the phosphorylation of I-κBα and the activation of NF-κB.

The life of the cortical column: opening the domain of functional architecture of the cortex (1955-1981).

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Haueis, Philipp

2016-09-01

The concept of the cortical column refers to vertical cell bands with similar response properties, which were initially observed by Vernon Mountcastle's mapping of single cell recordings in the cat somatic cortex. It has subsequently guided over 50 years of neuroscientific research, in which fundamental questions about the modularity of the cortex and basic principles of sensory information processing were empirically investigated. Nevertheless, the status of the column remains controversial today, as skeptical commentators proclaim that the vertical cell bands are a functionally insignificant by-product of ontogenetic development. This paper inquires how the column came to be viewed as an elementary unit of the cortex from Mountcastle's discovery in 1955 until David Hubel and Torsten Wiesel's reception of the Nobel Prize in 1981. I first argue that Mountcastle's vertical electrode recordings served as criteria for applying the column concept to electrophysiological data. In contrast to previous authors, I claim that this move from electrophysiological data to the phenomenon of columnar responses was concept-laden, but not theory-laden. In the second part of the paper, I argue that Mountcastle's criteria provided Hubel Wiesel with a conceptual outlook, i.e. it allowed them to anticipate columnar patterns in the cat and macaque visual cortex. I argue that in the late 1970s, this outlook only briefly took a form that one could call a 'theory' of the cerebral cortex, before new experimental techniques started to diversify column research. I end by showing how this account of early column research fits into a larger project that follows the conceptual development of the column into the present.

Laminar and Cellular Distribution of Monoamine Receptors in Rat Medial Prefrontal Cortex

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Noemí Santana

2017-09-01

Full Text Available The prefrontal cortex (PFC is deeply involved in higher brain functions, many of which are altered in psychiatric conditions. The PFC exerts a top-down control of most cortical and subcortical areas through descending pathways and is densely innervated by axons emerging from the brainstem monoamine cell groups, namely, the dorsal and median raphe nuclei (DR and MnR, respectively, the ventral tegmental area and the locus coeruleus (LC. In turn, the activity of these cell groups is tightly controlled by afferent pathways arising from layer V PFC pyramidal neurons. The reciprocal connectivity between PFC and monoamine cell groups is of interest to study the pathophysiology and treatment of severe psychiatric disorders, such as major depression and schizophrenia, inasmuch as antidepressant and antipsychotic drugs target monoamine receptors/transporters expressed in these areas. Here we review previous reports examining the presence of monoamine receptors in pyramidal and GABAergic neurons of the PFC using double in situ hybridization. Additionally, we present new data on the quantitative layer distribution (layers I, II–III, V, and VI of monoamine receptor-expressing cells in the cingulate (Cg, prelimbic (PrL and infralimbic (IL subfields of the medial PFC (mPFC. The receptors examined include serotonin 5-HT1A, 5-HT2A, 5-HT2C, and 5-HT3, dopamine D1 and D2 receptors, and α1A-, α1B-, and α1D-adrenoceptors. With the exception of 5-HT3 receptors, selectively expressed by layers I–III GABA interneurons, the rest of monoamine receptors are widely expressed by pyramidal and GABAergic neurons in intermediate and deep layers of mPFC (5-HT2C receptors are also expressed in layer I. This complex distribution suggests that monoamines may modulate the communications between PFC and cortical/subcortical areas through the activation of receptors expressed by neurons in intermediate (e.g., 5-HT1A, 5-HT2A, α1D-adrenoceptors, dopamine D1 receptors and deep

High-Quality Draft Single-Cell Genome Sequence Belonging to the Archaeal Candidate Division SA1, Isolated from Nereus Deep in the Red Sea

KAUST Repository

Ngugi, David; Stingl, Ulrich

2018-01-01

Candidate division SA1 encompasses a phylogenetically coherent archaeal group ubiquitous in deep hypersaline anoxic brines around the globe. Recently, the genome sequences of two cultivated representatives from hypersaline soda lake sediments were published. Here, we present a single-cell genome sequence from Nereus Deep in the Red Sea that represents a putatively novel family within SA1.

High-Quality Draft Single-Cell Genome Sequence Belonging to the Archaeal Candidate Division SA1, Isolated from Nereus Deep in the Red Sea

KAUST Repository

Ngugi, David

2018-05-09

Candidate division SA1 encompasses a phylogenetically coherent archaeal group ubiquitous in deep hypersaline anoxic brines around the globe. Recently, the genome sequences of two cultivated representatives from hypersaline soda lake sediments were published. Here, we present a single-cell genome sequence from Nereus Deep in the Red Sea that represents a putatively novel family within SA1.

The effects of low dose ionizing radiation on the development of rat cerebral cortex, (2)

International Nuclear Information System (INIS)

Matsushita, Koji

1993-01-01

In order to study the molecular mechanisms of neuronal migration on developing rat cerebral cortex, we need a tissue culture system in which neuronal migration can be observed. We prepared a tissue culture system of embryonic rat cerebral cortex starting on embryonic day 16 and cultivating it for 48 hours. The autoradiographic study in this system revealed not only the migration of 3 H-thymidine labeled neurons but also neuronal migration delays from low doses of ionizing radiation of more than 10 cGy. In addition, on immunohistochemical study, cell-cell adhesion molecule N-CAM staining was remarkably decreased in the matrix cell layer. In the tissue culture system where monoclonal anti-N-CAM antibodies were added, neuronal migration delay comparable to that of 20 cGy radiation was found. In conclusion, it was speculated that neuronal migration delay might be caused by disturbed N-CAM synthesis in matrix cells after low dose ionizing radiation. (author)

Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

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Shih-pi Ku

2017-07-01

Full Text Available The subiculum and the lateral entorhinal cortex (LEC are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1 receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum, both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors. This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex.

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Ku, Shih-Pi; Nakamura, Nozomu H; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M

2017-01-01

The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc , which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

Science.gov (United States)

Ku, Shih-pi; Nakamura, Nozomu H.; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M.

2017-01-01

The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval. PMID:28790897

Origins of the specialization for letters and numbers in ventral occipitotemporal cortex.

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Hannagan, Thomas; Amedi, Amir; Cohen, Laurent; Dehaene-Lambertz, Ghislaine; Dehaene, Stanislas

2015-07-01

Deep in the occipitotemporal cortex lie two functional regions, the visual word form area (VWFA) and the number form area (NFA), which are thought to play a special role in letter and number recognition, respectively. We review recent progress made in characterizing the origins of these symbol form areas in children or adults, sighted or blind subjects, and humans or monkeys. We propose two non-mutually-exclusive hypotheses on the origins of the VWFA and NFA: the presence of a connectivity bias, and a sensitivity to shape features. We assess the explanatory power of these hypotheses, describe their consequences, and offer several experimental tests. Copyright © 2015 Elsevier Ltd. All rights reserved.

Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

Science.gov (United States)

Wang, Rong; Wu, Lingjie; Tang, Zuohua; Sun, Xinghuai; Feng, Xiaoyuan; Tang, Weijun; Qian, Wen; Wang, Jie; Jin, Lixin; Zhong, Yufeng; Xiao, Zebin

2017-04-15

Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Strain-time cell death threshold for skeletal muscle in a tissue-engineered model system for deep tissue injury

NARCIS (Netherlands)

Gefen, A.; Nierop, van B.J.; Bader, D.L.; Oomens, C.W.J.

2008-01-01

Deep tissue injury (DTI) is a severe pressure ulcer that results from sustained deformation of muscle tissue overlying bony prominences. In order to understand the etiology of DTI, it is essential to determine the tolerance of muscle cells to large mechanical strains. In this study, a new

Illusory Motion Reproduced by Deep Neural Networks Trained for Prediction.

Science.gov (United States)

Watanabe, Eiji; Kitaoka, Akiyoshi; Sakamoto, Kiwako; Yasugi, Masaki; Tanaka, Kenta

2018-01-01

The cerebral cortex predicts visual motion to adapt human behavior to surrounding objects moving in real time. Although the underlying mechanisms are still unknown, predictive coding is one of the leading theories. Predictive coding assumes that the brain's internal models (which are acquired through learning) predict the visual world at all times and that errors between the prediction and the actual sensory input further refine the internal models. In the past year, deep neural networks based on predictive coding were reported for a video prediction machine called PredNet. If the theory substantially reproduces the visual information processing of the cerebral cortex, then PredNet can be expected to represent the human visual perception of motion. In this study, PredNet was trained with natural scene videos of the self-motion of the viewer, and the motion prediction ability of the obtained computer model was verified using unlearned videos. We found that the computer model accurately predicted the magnitude and direction of motion of a rotating propeller in unlearned videos. Surprisingly, it also represented the rotational motion for illusion images that were not moving physically, much like human visual perception. While the trained network accurately reproduced the direction of illusory rotation, it did not detect motion components in negative control pictures wherein people do not perceive illusory motion. This research supports the exciting idea that the mechanism assumed by the predictive coding theory is one of basis of motion illusion generation. Using sensory illusions as indicators of human perception, deep neural networks are expected to contribute significantly to the development of brain research.

Layer-specific modulation of the prefrontal cortex by nicotinic acetylcholine receptors

NARCIS (Netherlands)

Poorthuis, R.B.; Bloem, B.; Schak, B.; Wester, J.; de Kock, C.P.J.; Mansvelder, H.D.

2013-01-01

Acetylcholine signaling through nicotinic receptors (nAChRs) in the prefrontal cortex (PFC) is crucial for attention. Nicotinic AChRs are expressed on glutamatergic inputs to layer V (LV) cells and on LV interneurons and LVI pyramidal neurons. Whether PFC layers are activated by nAChRs to a similar

Learning invariance from natural images inspired by observations in the primary visual cortex.

Science.gov (United States)

Teichmann, Michael; Wiltschut, Jan; Hamker, Fred

2012-05-01

The human visual system has the remarkable ability to largely recognize objects invariant of their position, rotation, and scale. A good interpretation of neurobiological findings involves a computational model that simulates signal processing of the visual cortex. In part, this is likely achieved step by step from early to late areas of visual perception. While several algorithms have been proposed for learning feature detectors, only few studies at hand cover the issue of biologically plausible learning of such invariance. In this study, a set of Hebbian learning rules based on calcium dynamics and homeostatic regulations of single neurons is proposed. Their performance is verified within a simple model of the primary visual cortex to learn so-called complex cells, based on a sequence of static images. As a result, the learned complex-cell responses are largely invariant to phase and position.

In-situ detection of microbial life in the deep biosphere in igneous ocean crust

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Everett Cosio Salas

2015-11-01

Full Text Available The deep biosphere is a major frontier to science. Recent studies have shown the presence and activity of cells in deep marine sediments and in the continental deep biosphere. Volcanic lavas in the deep ocean subsurface, through which substantial fluid flow occurs, present another potentially massive deep biosphere. We present results from the deployment of a novel in-situ logging tool designed to detect microbial life harbored in a deep, native, borehole environment within igneous oceanic crust, using deep ultraviolet native fluorescence spectroscopy. Results demonstrate the predominance of microbial-like signatures within the borehole environment, with densities in the range of 105 cells/mL. Based on transport and flux models, we estimate that such a concentration of microbial cells could not be supported by transport through the crust, suggesting in situ growth of these communities.

In situ Detection of Microbial Life in the Deep Biosphere in Igneous Ocean Crust.

Science.gov (United States)

Salas, Everett C; Bhartia, Rohit; Anderson, Louise; Hug, William F; Reid, Ray D; Iturrino, Gerardo; Edwards, Katrina J

2015-01-01

The deep biosphere is a major frontier to science. Recent studies have shown the presence and activity of cells in deep marine sediments and in the continental deep biosphere. Volcanic lavas in the deep ocean subsurface, through which substantial fluid flow occurs, present another potentially massive deep biosphere. We present results from the deployment of a novel in situ logging tool designed to detect microbial life harbored in a deep, native, borehole environment within igneous oceanic crust, using deep ultraviolet native fluorescence spectroscopy. Results demonstrate the predominance of microbial-like signatures within the borehole environment, with densities in the range of 10(5) cells/mL. Based on transport and flux models, we estimate that such a concentration of microbial cells could not be supported by transport through the crust, suggesting in situ growth of these communities.

Sparse representation of sounds in the unanesthetized auditory cortex.

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Tomás Hromádka

2008-01-01

Full Text Available How do neuronal populations in the auditory cortex represent acoustic stimuli? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient, recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties. To quantify the relative contributions of these different subpopulations in the awake preparation, we have estimated the representation of sounds across the neuronal population using a representative ensemble of stimuli. We used cell-attached recording with a glass electrode, a method for which single-unit isolation does not depend on neuronal activity, to quantify the fraction of neurons engaged by acoustic stimuli (tones, frequency modulated sweeps, white-noise bursts, and natural stimuli in the primary auditory cortex of awake head-fixed rats. We find that the population response is sparse, with stimuli typically eliciting high firing rates (>20 spikes/second in less than 5% of neurons at any instant. Some neurons had very low spontaneous firing rates (<0.01 spikes/second. At the other extreme, some neurons had driven rates in excess of 50 spikes/second. Interestingly, the overall population response was well described by a lognormal distribution, rather than the exponential distribution that is often reported. Our results represent, to our knowledge, the first quantitative evidence for sparse representations of sounds in the unanesthetized auditory cortex. Our results are compatible with a model in which most neurons are silent much of the time, and in which representations are composed of small dynamic subsets of highly active neurons.

Intra- and Interhemispheric Propagation of Electrophysiological Synchronous Activity and Its Modulation by Serotonin in the Cingulate Cortex of Juvenile Mice.

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Víctor Rovira

Full Text Available Disinhibition of the cortex (e.g., by GABA -receptor blockade generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14-20 days, the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7 than in retrosplenial cortex slices (RSC: 21.99 ± 2.75 ms, n = 5; p<0.05, which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s. We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere, and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges.

High-Frequency Stimulation of the Subthalamic Nucleus Activates Motor Cortex Pyramidal Tract Neurons by a Process Involving Local Glutamate, GABA and Dopamine Receptors in Hemi-Parkinsonian Rats.

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Chuang, Chi-Fen; Wu, Chen-Wei; Weng, Ying; Hu, Pei-San; Yeh, Shin-Rung; Chang, Yen-Chung

2018-04-30

Deep brain stimulation (DBS) is widely used to treat advanced Parkinson’s disease (PD). Here, we investigated how DBS applied on the subthalamic nucleus (STN) influenced the neural activity in the motor cortex. Rats, which had the midbrain dopaminergic neurons partially depleted unilaterally, called the hemi-Parkinsonian rats, were used as a study model. c-Fos expression in the neurons was used as an indicator of neural activity. Application of high-frequency stimulation (HFS) upon the STN was used to mimic the DBS treatment. The motor cortices in the two hemispheres of hemi-Parkinsonian rats were found to contain unequal densities of c-Fos-positive (Fos+) cells, and STN-HFS rectified this bilateral imbalance. In addition, STN-HFS led to the intense c-Fos expression in a group of motor cortical neurons which exhibited biochemical and anatomical characteristics resembling those of the pyramidal tract (PT) neurons sending efferent projections to the STN. The number of PT neurons expressing high levels of c-Fos was significantly reduced by local application of the antagonists of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, gammaaminobutyric acid A (GABAA) receptors and dopamine receptors in the upper layers of the motor cortex. The results indicate that the coincident activations of synapses and dopamine receptors in the motor cortex during STN-HFS trigger the intense expression of c-Fos of the PT neurons. The implications of the results on the cellular mechanism underlying the therapeutic effects of STN-DBS on the movement disorders of PD are also discussed.

Visual Categorization and the Parietal Cortex

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Jamie K Fitzgerald

2012-05-01

Full Text Available The primate brain is adept at rapidly grouping items and events into functional classes, or categories, in order to recognize the significance of stimuli and guide behavior. Higher cognitive functions have traditionally been considered the domain of frontal areas. However, increasing evidence suggests that parietal cortex is also involved in categorical and associative processes. Previous work showed that the parietal cortex is highly involved in spatial processing, attention and saccadic eye movement planning, and more recent studies have found decision-making signals in LIP. We recently found that a subdivision of parietal cortex, the lateral intraparietal area (LIP, reflects learned categories for multiple types of visual stimuli. Additionally, a comparison of categorization signals in parietal and frontal areas found stronger and earlier categorization signals in parietal cortex, arguing that parietal abstract association or category signals are unlikely to arise via feedback from prefrontal cortex (PFC.

Occipital cortex of blind individuals is functionally coupled with executive control areas of frontal cortex.

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Deen, Ben; Saxe, Rebecca; Bedny, Marina

2015-08-01

In congenital blindness, the occipital cortex responds to a range of nonvisual inputs, including tactile, auditory, and linguistic stimuli. Are these changes in functional responses to stimuli accompanied by altered interactions with nonvisual functional networks? To answer this question, we introduce a data-driven method that searches across cortex for functional connectivity differences across groups. Replicating prior work, we find increased fronto-occipital functional connectivity in congenitally blind relative to blindfolded sighted participants. We demonstrate that this heightened connectivity extends over most of occipital cortex but is specific to a subset of regions in the inferior, dorsal, and medial frontal lobe. To assess the functional profile of these frontal areas, we used an n-back working memory task and a sentence comprehension task. We find that, among prefrontal areas with overconnectivity to occipital cortex, one left inferior frontal region responds to language over music. By contrast, the majority of these regions responded to working memory load but not language. These results suggest that in blindness occipital cortex interacts more with working memory systems and raise new questions about the function and mechanism of occipital plasticity.

Cell-Type Specific Changes in Glial Morphology and Glucocorticoid Expression During Stress and Aging in the Medial Prefrontal Cortex

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Thomas E. Chan

2018-05-01

Full Text Available Repeated exposure to stressors is known to produce large-scale remodeling of neurons within the prefrontal cortex (PFC. Recent work suggests stress-related forms of structural plasticity can interact with aging to drive distinct patterns of pyramidal cell morphological changes. However, little is known about how other cellular components within PFC might be affected by these challenges. Here, we examined the effects of stress exposure and aging on medial prefrontal cortical glial subpopulations. Interestingly, we found no changes in glial morphology with stress exposure but a profound morphological change with aging. Furthermore, we found an upregulation of non-nuclear glucocorticoid receptors (GR with aging, while nuclear levels remained largely unaffected. Both changes are selective for microglia, with no stress or aging effect found in astrocytes. Lastly, we show that the changes found within microglia inversely correlated with the density of dendritic spines on layer III pyramidal cells. These findings suggest microglia play a selective role in synaptic health within the aging brain.

Laparoscopic adrenal cortex

International Nuclear Information System (INIS)

Peyrolou, A.; Salom, A.; Harguindeguy; Taroco, L.; Ardao, G.; Broli, F. . E mail: andresssss@adinet.com.uy

2005-01-01

The paper presents the case of a female patient who carried an aldosterone-secreting tumor of adrenal cortex.In the analysis of diagnosis and para clinical examinations there is particular reference to the laparoscopic surgery mode of treatment.Diagnosis should be established on the basis of clinical and laboratory tests (hypopotassemia and hyperaldosteronism).Tumor topography was confirmed through CT scan, MRI and Scintiscan in left adrenal cortex.Resection was consequently made through laparoscopic surgery.The patients evolution was excellent from the surgical viewpoint,with I levels of blood pressure, potassium and aldosterone returned to normal

Cell-Targeted Optogenetics and Electrical Microstimulation Reveal the Primate Koniocellular Projection to Supra-granular Visual Cortex.

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Klein, Carsten; Evrard, Henry C; Shapcott, Katharine A; Haverkamp, Silke; Logothetis, Nikos K; Schmid, Michael C

2016-04-06

Electrical microstimulation and more recently optogenetics are widely used to map large-scale brain circuits. However, the neuronal specificity achieved with both methods is not well understood. Here we compare cell-targeted optogenetics and electrical microstimulation in the macaque monkey brain to functionally map the koniocellular lateral geniculate nucleus (LGN) projection to primary visual cortex (V1). Selective activation of the LGN konio neurons with CamK-specific optogenetics caused selective electrical current inflow in the supra-granular layers of V1. Electrical microstimulation targeted at LGN konio layers revealed the same supra-granular V1 activation pattern as the one elicited by optogenetics. Taken together, these findings establish a selective koniocellular LGN influence on V1 supra-granular layers, and they indicate comparable capacities of both stimulation methods to isolate thalamo-cortical circuits in the primate brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Excitatory Neuronal Hubs Configure Multisensory Integration of Slow Waves in Association Cortex

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Satoshi Kuroki

2018-03-01

Full Text Available Summary: Multisensory integration (MSI is a fundamental emergent property of the mammalian brain. During MSI, perceptual information encoded in patterned activity is processed in multimodal association cortex. The systems-level neuronal dynamics that coordinate MSI, however, are unknown. Here, we demonstrate intrinsic hub-like network activity in the association cortex that regulates MSI. We engineered calcium reporter mouse lines based on the fluorescence resonance energy transfer sensor yellow cameleon (YC2.60 expressed in excitatory or inhibitory neurons. In medial and parietal association cortex, we observed spontaneous slow waves that self-organized into hubs defined by long-range excitatory and local inhibitory circuits. Unlike directional source/sink-like flows in sensory areas, medial/parietal excitatory and inhibitory hubs had net-zero balanced inputs. Remarkably, multisensory stimulation triggered rapid phase-locking mainly of excitatory hub activity persisting for seconds after the stimulus offset. Therefore, association cortex tends to form balanced excitatory networks that configure slow-wave phase-locking for MSI. Video Abstract: : Kuroki et al. performed cell-type-specific, wide-field FRET-based calcium imaging to visualize cortical network activity induced by multisensory inputs. They observed phase-locking of cortical slow waves in excitatory neuronal hubs in association cortical areas that may underlie multisensory integration. Keywords: wide-field calcium imaging, multisensory integration, cortical slow waves, association cortex, phase locking, fluorescence resonance energy transfer, spontaneous activity, excitatory neuron, inhibitory neuron, mouse

Exposure to brominated flame retardant PBDE-99 affects cytoskeletal protein expression in the neonatal mouse cerebral cortex

DEFF Research Database (Denmark)

Alm, Henrik; Kultima, Kim; Scholz, Birger

2008-01-01

, and the cytotoxic and apoptotic effects of PBDE-99 in primary cultures of fetal rat cortical cells. We used two-dimensional difference gel electrophoresis (2D-DIGE) to analyze protein samples isolated from the cortex of NMRI mice 24h after exposure to a single oral dose of 12 mg/kg PBDE-99 on post-natal day 10....... Protein resolution was enhanced by sample pre-fractionation. In the cell model, we determined cell viability using the trypan blue exclusion assay, and apoptosis using immunocytochemical detection of cleaved caspase-3. We determined the identity of 111 differentially expressed proteins, 32 (29%) of which...... are known to be cytoskeleton-related. Similar to previous findings in the striatum, we found elevated levels of the neuron growth-associated protein Gap43 in the cortex. In cultured cortical cells, a high concentration of PBDE-99 (30 microM) induced cell death without any apparent increase in caspase-3...

Retinal Ganglion Cell Distribution and Spatial Resolving Power in Deep-Sea Lanternfishes (Myctophidae)

KAUST Repository

De Busserolles, Fanny

2014-01-01

Topographic analyses of retinal ganglion cell density are very useful in providing information about the visual ecology of a species by identifying areas of acute vision within the visual field (i.e. areas of high cell density). In this study, we investigated the neural cell distribution in the ganglion cell layer of a range of lanternfish species belonging to 10 genera. Analyses were performed on wholemounted retinas using stereology. Topographic maps were constructed of the distribution of all neurons and both ganglion and amacrine cell populations in 5 different species from Nissl-stained retinas using cytological criteria. Amacrine cell distribution was also examined immunohistochemically in 2 of the 5 species using anti-parvalbumin antibody. The distributions of both the total neuron and the amacrine cell populations were aligned in all of the species examined, showing a general increase in cell density toward the retinal periphery. However, when the ganglion cell population was topographically isolated from the amacrine cell population, which comprised up to 80% of the total neurons within the ganglion cell layer, a different distribution was revealed. Topographic maps of the true ganglion cell distribution in 18 species of lanternfishes revealed well-defined specializations in different regions of the retina. Different species possessed distinct areas of high ganglion cell density with respect to both peak density and the location and/or shape of the specialized acute zone (i.e. elongated areae ventro-temporales, areae temporales and large areae centrales). The spatial resolving power was calculated to be relatively low (varying from 1.6 to 4.4 cycles per degree), indicating that myctophids may constitute one of the less visually acute groups of deep-sea teleosts. The diversity in retinal specializations and spatial resolving power within the family is assessed in terms of possible ecological functions and evolutionary history.

Resting state cortical oscillations of patients with Parkinson disease and with and without subthalamic deep brain stimulation: a magnetoencephalography study.

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Cao, Chunyan; Li, Dianyou; Jiang, Tianxiao; Ince, Nuri Firat; Zhan, Shikun; Zhang, Jing; Sha, Zhiyi; Sun, Bomin

2015-04-01

In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.

Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex

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Kunz, Portia A; Burette, Alain C; Weinberg, Richard J; Philpot, Benjamin D

2012-01-01

Glycine receptors (GlyRs) are found in most areas of the brain, and their dysfunction can cause severe neurological disorders. While traditionally thought of as inhibitory receptors, presynaptic-acting GlyRs (preGlyRs) can also facilitate glutamate release under certain circumstances, although the underlying molecular mechanisms are unknown. In the current study, we sought to better understand the role of GlyRs in the facilitation of excitatory neurotransmitter release in mouse visual cortex. Using whole-cell recordings, we found that preGlyRs facilitate glutamate release in developing, but not adult, visual cortex. The glycinergic enhancement of neurotransmitter release in early development depends on the high intracellular to extracellular Cl− gradient maintained by the Na+–K+–2Cl− cotransporter and requires Ca2+ entry through voltage-gated Ca2+ channels. The glycine transporter 1, localized to glial cells, regulates extracellular glycine concentration and the activation of these preGlyRs. Our findings demonstrate a developmentally regulated mechanism for controlling excitatory neurotransmitter release in the neocortex. PMID:22988142

Misconceptions about mirror-induced motor cortex activation.

NARCIS (Netherlands)

Praamstra, P.; Torney, L.; Rawle, C.J.; Miall, R.C.

2011-01-01

Observation of self-produced hand movements through a mirror, creating an illusion of the opposite hand moving, was recently reported to induce ipsilateral motor cortex activation, that is, motor cortex activation for the hand in rest. The reported work goes far beyond earlier work on motor cortex

Word Recognition in Auditory Cortex

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DeWitt, Iain D. J.

2013-01-01

Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson’s disease

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Diane eWhitmer

2012-06-01

Full Text Available Parkinson’s disease (PD is marked by excessive synchronous activity in the beta (8-35 Hz band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS within the subthalamic nucleus (STN region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05. Cortical signals over the estimated origin of the hyperdirect pathway also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network.

Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

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Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

2018-01-01

Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

Maps of the Auditory Cortex.

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Brewer, Alyssa A; Barton, Brian

2016-07-08

One of the fundamental properties of the mammalian brain is that sensory regions of cortex are formed of multiple, functionally specialized cortical field maps (CFMs). Each CFM comprises two orthogonal topographical representations, reflecting two essential aspects of sensory space. In auditory cortex, auditory field maps (AFMs) are defined by the combination of tonotopic gradients, representing the spectral aspects of sound (i.e., tones), with orthogonal periodotopic gradients, representing the temporal aspects of sound (i.e., period or temporal envelope). Converging evidence from cytoarchitectural and neuroimaging measurements underlies the definition of 11 AFMs across core and belt regions of human auditory cortex, with likely homology to those of macaque. On a macrostructural level, AFMs are grouped into cloverleaf clusters, an organizational structure also seen in visual cortex. Future research can now use these AFMs to investigate specific stages of auditory processing, key for understanding behaviors such as speech perception and multimodal sensory integration.

Cellular properties of principal neurons in the rat entorhinal cortex. I. The lateral entorhinal cortex

NARCIS (Netherlands)

Canto, C.B.; Witter, M.P.

2012-01-01

The lateral entorhinal cortex (LEC) provides a major cortical input to the hippocampal formation, equaling that of the medial entorhinal cortex (MEC). To understand the functional contributions made by LEC, basic knowledge of individual neurons, in the context of the intrinsic network, is needed.

Prenatal Mercuric Chloride Exposure Causes Developmental Deficits in Rat Cortex

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Tayebeh Rastegar

2011-09-01

Full Text Available Introduction: Environmental pollution with heavy metals such as mercury is a major health problem. Growing studies on the field have shown the deleterious effects of mercury on human and nonhuman nervous system, especially in infants, however the effects of prenatal exposure to mercuricchloride on cortical development are not yet well understood. The aim of this study was to investigate the effect of prenatal exposure to mercuric chloride on morphological characteristics of brain cortex. Methods: Mercuric chloride (2 mg/kg or normal saline were injected (I.P. to 36 Sprague – dawley rats in the 8th, 9th or 10th day of gestation. The embryos were surgically removed in the 15th day of gestation, and brain cortices were studied by histological techniques. Results: Histological studies showed that embryos of mercuric chloride treated rats hadcortical neuronal disarrangement withdifferent orientations of nuclei, increased diameter of cortex, increased mitosis of cells, increased cell death, decreased cellular density and increased intracellular space. Conclusion: These findings suggest some micro structural abnormalities in cortical regions after prenatal exposure to mercuric chloride. These structural abnormalities may underliesome neurologic disturbances following mercury intoxication.

Investigating Synchronous Oscillation and Deep Brain Stimulation Treatment in A Model of Cortico-Basal Ganglia Network.

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Lu, Meili; Wei, Xile; Loparo, Kenneth A

2017-11-01

Altered firing properties and increased pathological oscillations in the basal ganglia have been proven to be hallmarks of Parkinson's disease (PD). Increasing evidence suggests that abnormal synchronous oscillations and suppression in the cortex may also play a critical role in the pathogenic process and treatment of PD. In this paper, a new closed-loop network including the cortex and basal ganglia using the Izhikevich models is proposed to investigate the synchrony and pathological oscillations in motor circuits and their modulation by deep brain stimulation (DBS). Results show that more coherent dynamics in the cortex may cause stronger effects on the synchrony and pathological oscillations of the subthalamic nucleus (STN). The pathological beta oscillations of the STN can both be efficiently suppressed with DBS applied directly to the STN or to cortical neurons, respectively, but the underlying mechanisms by which DBS suppresses the beta oscillations are different. This research helps to understand the dynamics of pathological oscillations in PD-related motor regions and supports the therapeutic potential of stimulation of cortical neurons.

A reaction-diffusion model to capture disparity selectivity in primary visual cortex.

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Mohammed Sultan Mohiuddin Siddiqui

Full Text Available Decades of experimental studies are available on disparity selective cells in visual cortex of macaque and cat. Recently, local disparity map for iso-orientation sites for near-vertical edge preference is reported in area 18 of cat visual cortex. No experiment is yet reported on complete disparity map in V1. Disparity map for layer IV in V1 can provide insight into how disparity selective complex cell receptive field is organized from simple cell subunits. Though substantial amounts of experimental data on disparity selective cells is available, no model on receptive field development of such cells or disparity map development exists in literature. We model disparity selectivity in layer IV of cat V1 using a reaction-diffusion two-eye paradigm. In this model, the wiring between LGN and cortical layer IV is determined by resource an LGN cell has for supporting connections to cortical cells and competition for target space in layer IV. While competing for target space, the same type of LGN cells, irrespective of whether it belongs to left-eye-specific or right-eye-specific LGN layer, cooperate with each other while trying to push off the other type. Our model captures realistic 2D disparity selective simple cell receptive fields, their response properties and disparity map along with orientation and ocular dominance maps. There is lack of correlation between ocular dominance and disparity selectivity at the cell population level. At the map level, disparity selectivity topography is not random but weakly clustered for similar preferred disparities. This is similar to the experimental result reported for macaque. The details of weakly clustered disparity selectivity map in V1 indicate two types of complex cell receptive field organization.

The prefrontal cortex shows context-specific changes in effective connectivity to motor or visual cortex during the selection of action or colour

DEFF Research Database (Denmark)

Rowe, James B.; Stephan, Klaas E.; Friston, Karl

2005-01-01

The role of the prefrontal cortex remains controversial. Neuroimaging studies support modality-specific and process-specific functions related to working memory and attention. Its role may also be defined by changes in its influence over other brain regions including sensory and motor cortex. We...... used functional magnetic imaging (fMRI) to study the free selection of actions and colours. Control conditions used externally specified actions and colours. The prefrontal cortex was activated during free selection, regardless of modality, in contrast to modality-specific activations outside...... included high-order interactions between modality, selection and regional activity. There was greater coupling between prefrontal cortex and motor cortex during free selection and action tasks, and between prefrontal cortex and visual cortex during free selection of colours. The results suggest...

Neural computation of visual imaging based on Kronecker product in the primary visual cortex

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Guozheng Yao

2010-03-01

Full Text Available Abstract Background What kind of neural computation is actually performed by the primary visual cortex and how is this represented mathematically at the system level? It is an important problem in the visual information processing, but has not been well answered. In this paper, according to our understanding of retinal organization and parallel multi-channel topographical mapping between retina and primary visual cortex V1, we divide an image into orthogonal and orderly array of image primitives (or patches, in which each patch will evoke activities of simple cells in V1. From viewpoint of information processing, this activated process, essentially, involves optimal detection and optimal matching of receptive fields of simple cells with features contained in image patches. For the reconstruction of the visual image in the visual cortex V1 based on the principle of minimum mean squares error, it is natural to use the inner product expression in neural computation, which then is transformed into matrix form. Results The inner product is carried out by using Kronecker product between patches and function architecture (or functional column in localized and oriented neural computing. Compared with Fourier Transform, the mathematical description of Kronecker product is simple and intuitive, so is the algorithm more suitable for neural computation of visual cortex V1. Results of computer simulation based on two-dimensional Gabor pyramid wavelets show that the theoretical analysis and the proposed model are reasonable. Conclusions Our results are: 1. The neural computation of the retinal image in cortex V1 can be expressed to Kronecker product operation and its matrix form, this algorithm is implemented by the inner operation between retinal image primitives and primary visual cortex's column. It has simple, efficient and robust features, which is, therefore, such a neural algorithm, which can be completed by biological vision. 2. It is more suitable

Automated analysis of high-content microscopy data with deep learning.

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Kraus, Oren Z; Grys, Ben T; Ba, Jimmy; Chong, Yolanda; Frey, Brendan J; Boone, Charles; Andrews, Brenda J

2017-04-18

Existing computational pipelines for quantitative analysis of high-content microscopy data rely on traditional machine learning approaches that fail to accurately classify more than a single dataset without substantial tuning and training, requiring extensive analysis. Here, we demonstrate that the application of deep learning to biological image data can overcome the pitfalls associated with conventional machine learning classifiers. Using a deep convolutional neural network (DeepLoc) to analyze yeast cell images, we show improved performance over traditional approaches in the automated classification of protein subcellular localization. We also demonstrate the ability of DeepLoc to classify highly divergent image sets, including images of pheromone-arrested cells with abnormal cellular morphology, as well as images generated in different genetic backgrounds and in different laboratories. We offer an open-source implementation that enables updating DeepLoc on new microscopy datasets. This study highlights deep learning as an important tool for the expedited analysis of high-content microscopy data. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Illusory Motion Reproduced by Deep Neural Networks Trained for Prediction

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Eiji Watanabe

2018-03-01

Full Text Available The cerebral cortex predicts visual motion to adapt human behavior to surrounding objects moving in real time. Although the underlying mechanisms are still unknown, predictive coding is one of the leading theories. Predictive coding assumes that the brain's internal models (which are acquired through learning predict the visual world at all times and that errors between the prediction and the actual sensory input further refine the internal models. In the past year, deep neural networks based on predictive coding were reported for a video prediction machine called PredNet. If the theory substantially reproduces the visual information processing of the cerebral cortex, then PredNet can be expected to represent the human visual perception of motion. In this study, PredNet was trained with natural scene videos of the self-motion of the viewer, and the motion prediction ability of the obtained computer model was verified using unlearned videos. We found that the computer model accurately predicted the magnitude and direction of motion of a rotating propeller in unlearned videos. Surprisingly, it also represented the rotational motion for illusion images that were not moving physically, much like human visual perception. While the trained network accurately reproduced the direction of illusory rotation, it did not detect motion components in negative control pictures wherein people do not perceive illusory motion. This research supports the exciting idea that the mechanism assumed by the predictive coding theory is one of basis of motion illusion generation. Using sensory illusions as indicators of human perception, deep neural networks are expected to contribute significantly to the development of brain research.

Laminar activity in the hippocampus and entorhinal cortex related to novelty and episodic encoding

Science.gov (United States)

Maass, Anne; Schütze, Hartmut; Speck, Oliver; Yonelinas, Andrew; Tempelmann, Claus; Heinze, Hans-Jochen; Berron, David; Cardenas-Blanco, Arturo; Brodersen, Kay H.; Enno Stephan, Klaas; Düzel, Emrah

2014-01-01

The ability to form long-term memories for novel events depends on information processing within the hippocampus (HC) and entorhinal cortex (EC). The HC–EC circuitry shows a quantitative segregation of anatomical directionality into different neuronal layers. Whereas superficial EC layers mainly project to dentate gyrus (DG), CA3 and apical CA1 layers, HC output is primarily sent from pyramidal CA1 layers and subiculum to deep EC layers. Here we utilize this directionality information by measuring encoding activity within HC/EC subregions with 7 T high resolution functional magnetic resonance imaging (fMRI). Multivariate Bayes decoding within HC/EC subregions shows that processing of novel information most strongly engages the input structures (superficial EC and DG/CA2–3), whereas subsequent memory is more dependent on activation of output regions (deep EC and pyramidal CA1). This suggests that while novelty processing is strongly related to HC–EC input pathways, the memory fate of a novel stimulus depends more on HC–EC output. PMID:25424131

PACAP decides neuronal laminar fate via PKA signaling in the developing cerebral cortex

International Nuclear Information System (INIS)

Ohtsuka, Masanari; Fukumitsu, Hidefumi; Furukawa, Shoei

2008-01-01

Laminar formation in the developing cerebral cortex requires the precisely regulated generation of phenotype-specified neurons. To test the possible involvement of pituitary adenylate cyclase-activating polypeptide (PACAP) in this formation, we investigated the effects of PACAP administered into the telencephalic ventricular space of 13.5-day-old mouse embryos. PACAP partially inhibited the proliferation of cortical progenitors and altered the position and gene-expression profiles of newly generated neurons otherwise expected for layer IV to those of neurons for the deeper layers, V and VI, of the cerebral cortex. The former and latter effects were seen only when the parent progenitor cells were exposed to PACAP in the later and in earlier G1 phase, respectively; and these effects were suppressed by co-treatment with a protein kinase A (PKA) inhibitor. These observations suggest that PACAP participates in the processes forming the neuronal laminas in the developing cortex via the intracellular PKA pathway

Cortical cell and neuron density estimates in one chimpanzee hemisphere.

Science.gov (United States)

Collins, Christine E; Turner, Emily C; Sawyer, Eva Kille; Reed, Jamie L; Young, Nicole A; Flaherty, David K; Kaas, Jon H

2016-01-19

The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

Intracortical Microstimulation (ICMS) Activates Motor Cortex Layer 5 Pyramidal Neurons Mainly Transsynaptically.

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Hussin, Ahmed T; Boychuk, Jeffery A; Brown, Andrew R; Pittman, Quentin J; Teskey, G Campbell

2015-01-01

Intracortical microstimulation (ICMS) is a technique used for a number of purposes including the derivation of cortical movement representations (motor maps). Its application can activate the output layer 5 of motor cortex and can result in the elicitation of body movements depending upon the stimulus parameters used. The extent to which pyramidal tract projection neurons of the motor cortex are activated transsynaptically or directly by ICMS remains an open question. Given this uncertainty in the mode of activation, we used a preparation that combined patch clamp whole-cell recordings from single layer 5 pyramidal neurons and extracellular ICMS in slices of motor cortex as well as a standard in vivo mapping technique to ask how ICMS activated motor cortex pyramidal neurons. We measured changes in synaptic spike threshold and spiking rate to ICMS in vitro and movement threshold in vivo in the presence or absence of specific pharmacological blockers of glutamatergic (AMPA, NMDA and Kainate) receptors and GABAA receptors. With major excitatory and inhibitory synaptic transmission blocked (with DNQX, APV and bicuculline methiodide), we observed a significant increase in the ICMS current intensity required to elicit a movement in vivo as well as to the first spike and an 85% reduction in spiking responses in vitro. Subsets of neurons were still responsive after the synaptic block, especially at higher current intensities, suggesting a modest direct activation. Taken together our data indicate a mainly synaptic mode of activation to ICMS in layer 5 of rat motor cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

The Effect of Cortex/Medulla Proportions on Molecular Diagnoses in Kidney Transplant Biopsies: Rejection and Injury Can Be Assessed in Medulla.

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Madill-Thomsen, K S; Wiggins, R C; Eskandary, F; Böhmig, G A; Halloran, P F

2017-08-01

Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes (e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL, and REN). Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the molecular microscope diagnostic system. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had Molecular scores for antibody-mediated rejection, T cell-mediated rejection, and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla. Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection; and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Food related processes in the insular cortex

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Sabine eFrank

2013-08-01

Full Text Available The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex.In this review, we will specifically focus on the involvement of the insula in food processing and on multimodal integration of food-related items. Influencing factors of insular activation elicited by various foods range from calorie-content to the internal physiologic state, body mass index or eating behavior. Sensory perception of food-related stimuli including seeing, smelling, and tasting elicits increased activation in the anterior and mid-dorsal part of the insular cortex. Apart from the pure sensory gustatory processing, there is also a strong association with the rewarding/hedonic aspects of food items, which is reflected in higher insular activity and stronger connections to other reward-related areas. Interestingly, the processing of food items has been found to elicit different insular activation in lean compared to obese subjects and in patients suffering from an eating disorder (anorexia nervosa, bulimia nervosa. The knowledge of functional differences in the insular cortex opens up the opportunity for possible noninvasive treatment approaches for obesity and eating disorders. To target brain functions directly, real-time functional magnetic resonance imaging neurofeedback offers a state-of-the-art tool to learn to control the anterior insular cortex activity voluntarily. First evidence indicates that obese adults have an enhanced ability to regulate the anterior insular cortex.

DeepPy: Pythonic deep learning

DEFF Research Database (Denmark)

Larsen, Anders Boesen Lindbo

This technical report introduces DeepPy – a deep learning framework built on top of NumPy with GPU acceleration. DeepPy bridges the gap between highperformance neural networks and the ease of development from Python/NumPy. Users with a background in scientific computing in Python will quickly...... be able to understand and change the DeepPy codebase as it is mainly implemented using high-level NumPy primitives. Moreover, DeepPy supports complex network architectures by letting the user compose mathematical expressions as directed graphs. The latest version is available at http...

Formation of contractile networks and fibers in the medial cell cortex through myosin-II turnover, contraction, and stress-stabilization.

Science.gov (United States)

Nie, Wei; Wei, Ming-Tzo; Ou-Yang, H Daniel; Jedlicka, Sabrina S; Vavylonis, Dimitrios

2015-01-01

The morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked fibers along the contacting surface. The motor activity and minifilament assembly of non-muscle myosin-II is an important component of cortical cytoskeletal remodeling during mechanosensing. We used experiments and computational modeling to study cortical myosin-II dynamics in adhered cells. Confocal microscopy was used to image the medial cell cortex of HeLa cells stably expressing myosin regulatory light chain tagged with GFP (MRLC-GFP). The distribution of MRLC-GFP fibers and focal adhesions was classified into three types of network morphologies. Time-lapse movies show: myosin foci appearance and disappearance; aligning and contraction; stabilization upon alignment. Addition of blebbistatin, which perturbs myosin motor activity, leads to a reorganization of the cortical networks and to a reduction of contractile motions. We quantified the kinetics of contraction, disassembly and reassembly of myosin networks using spatio-temporal image correlation spectroscopy (STICS). Coarse-grained numerical simulations include bipolar minifilaments that contract and align through specified interactions as basic elements. After assuming that minifilament turnover decreases with increasing contractile stress, the simulations reproduce stress-dependent fiber formation in between focal adhesions above a threshold myosin concentration. The STICS correlation function in simulations matches the function measured in experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness. © 2015 Wiley Periodicals, Inc.

Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.

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Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J; Jung, Hae-Yoon; Kitamura, Takashi; Suh, Junghyup; Frank, Dominic; Kajikawa, Koichiro; Mise, Nathan; Obata, Yuichi; Wickersham, Ian R; Tonegawa, Susumu

2014-02-01

The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

Intravenous injection of artificial red cells and subsequent dye laser irradiation causes deep vessel impairment in an animal model of port-wine stain.

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Rikihisa, Naoaki; Tominaga, Mai; Watanabe, Shoji; Mitsukawa, Nobuyuki; Saito, Yoshiaki; Sakai, Hiromi

2018-03-15

Our previous study proposed using artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment for port-wine stains (PWSs). Dye laser photons are absorbed by red blood cells (RBCs) and hemoglobin (Hb) mixture, which potentially produce more heat and photocoagulation and effectively destroy endothelial cells. Hb-Vs combination therapy will improve clinical outcomes of dye laser treatment for PWSs because very small vessels do not contain sufficient RBCs and they are poor absorbers/heaters of lasers. In the present study, we analyzed the relationship between vessel depth from the skin surface and vessel distraction through dye laser irradiation following intravenous Hb-Vs injection using a chicken wattle model. Hb-Vs were administered and chicken wattles underwent high-energy irradiation at energy higher than in the previous experiments. Hb-Vs location in the vessel lumen was identified to explain its photosensitizer effect using human Hb immunostaining of the irradiated wattles. Laser irradiation with Hb-Vs can effectively destroy deep vessels in animal models. Hb-Vs tend to flow in the marginal zone of both small and large vessels. Increasing laser power combined with Hb-Vs injection contributed for deep vessel impairment because of the synergetic effect of both methods. Newly added Hb tended to flow near the target endothelial cells of the laser treatment. In Hb-Vs and RBC mixture, heat transfer to endothelial cells from absorbers/heater may increase. Hb-Vs function as photosensitizers to destroy deep vessels within a restricted distance that the photon can reach.

MRI volumetry of prefrontal cortex

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Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.

1995-05-01

Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was volumetry by stereology can yield accurate and repeatable measurements. Small frontal lobe volume reductions in patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

Bacurd2 is a novel interacting partner to Rnd2 which controls radial migration within the developing mammalian cerebral cortex.

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Gladwyn-Ng, Ivan Enghian; Li, Shan Shan; Qu, Zhengdong; Davis, John Michael; Ngo, Linh; Haas, Matilda; Singer, Jeffrey; Heng, Julian Ik-Tsen

2015-03-31

During fetal brain development in mammals, newborn neurons undergo cell migration to reach their appropriate positions and form functional circuits. We previously reported that the atypical RhoA GTPase Rnd2 promotes the radial migration of mouse cerebral cortical neurons (Nature 455(7209):114-8, 2008; Neuron 69(6):1069-84, 2011), but its downstream signalling pathway is not well understood. We have identified BTB-domain containing adaptor for Cul3-mediated RhoA degradation 2 (Bacurd2) as a novel interacting partner to Rnd2, which promotes radial migration within the developing cerebral cortex. We find that Bacurd2 binds Rnd2 at its C-terminus, and this interaction is critical to its cell migration function. We show that forced expression or knockdown of Bacurd2 impairs neuronal migration within the embryonic cortex and alters the morphology of immature neurons. Our in vivo cellular analysis reveals that Bacurd2 influences the multipolar-to-bipolar transition of radially migrating neurons in a cell autonomous fashion. When we addressed the potential signalling relationship between Bacurd2 and Rnd2 using a Bacurd2-Rnd2 chimeric construct, our results suggest that Bacurd2 and Rnd2 could interact to promote radial migration within the embryonic cortex. Our studies demonstrate that Bacurd2 is a novel player in neuronal development and influences radial migration within the embryonic cerebral cortex.

Normal and abnormal neuronal migration in the developing cerebral cortex

OpenAIRE

Sun, Xue-Zhi; Takahashi, Sentaro; Cui, Chun; Zhang, Rui; Sakata-Haga, Hiromi; Sawada, Kazuhiko; Fukui, Yoshihiro

2002-01-01

Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their 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. This process is guided by radial glial fibers, requires proper receptors, ligands, other unkno...

Layer- and column-specific knockout of NMDA receptors in pyramidal neurons of the mouse barrel cortex.

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Rachel Aronoff

2007-11-01

Full Text Available Viral vectors injected into the mouse brain offer the possibility for localized genetic modifications in a highly controlled manner. Lentivector injection into mouse neocortex transduces cells within a diameter of approximately 200µm, which closely matches the lateral scale of a column in barrel cortex. The depth and volume of the injection determines which cortical layer is transduced. Furthermore, transduced gene expression from the lentivector can be limited to predominantly pyramidal neurons by using a 1.3kb fragment of the αCaMKII promoter. This technique therefore allows genetic manipulation of a specific cell type in defined columns and layers of the neocortex. By expressing Cre recombinase from such a lentivector in gene-targeted mice carrying a floxed gene, highly specific genetic lesions can be induced. Here, we demonstrate the utility of this approach by specifically knocking out NMDA receptors (NMDARs in pyramidal neurons in the somatosensory barrel cortex of gene-targeted mice carrying floxed NMDAR 1 genes. Neurons transduced with lentivector encoding GFP and Cre recombinase exhibit not only reductions in NMDAR 1 mRNA levels, but reduced NMDAR-dependent currents and pairing-induced synaptic potentiation. This technique for knockout of NMDARs in a cell type, column- and layer-specific manner in the mouse somatosensory cortex may help further our understanding of the functional roles of NMDARs in vivo during sensory perception and learning.

Homoacetogenesis in Deep-Sea Chloroflexi, as Inferred by Single-Cell Genomics, Provides a Link to Reductive Dehalogenation in Terrestrial Dehalococcoidetes

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Holly L. Sewell

2017-12-01

Full Text Available The deep marine subsurface is one of the largest unexplored biospheres on Earth and is widely inhabited by members of the phylum Chloroflexi. In this report, we investigated genomes of single cells obtained from deep-sea sediments of the Peruvian Margin, which are enriched in such Chloroflexi. 16S rRNA gene sequence analysis placed two of these single-cell-derived genomes (DscP3 and Dsc4 in a clade of subphylum I Chloroflexi which were previously recovered from deep-sea sediment in the Okinawa Trough and a third (DscP2-2 as a member of the previously reported DscP2 population from Peruvian Margin site 1230. The presence of genes encoding enzymes of a complete Wood-Ljungdahl pathway, glycolysis/gluconeogenesis, a Rhodobacter nitrogen fixation (Rnf complex, glyosyltransferases, and formate dehydrogenases in the single-cell genomes of DscP3 and Dsc4 and the presence of an NADH-dependent reduced ferredoxin:NADP oxidoreductase (Nfn and Rnf in the genome of DscP2-2 imply a homoacetogenic lifestyle of these abundant marine Chloroflexi. We also report here the first complete pathway for anaerobic benzoate oxidation to acetyl coenzyme A (CoA in the phylum Chloroflexi (DscP3 and Dsc4, including a class I benzoyl-CoA reductase. Of remarkable evolutionary significance, we discovered a gene encoding a formate dehydrogenase (FdnI with reciprocal closest identity to the formate dehydrogenase-like protein (complex iron-sulfur molybdoenzyme [CISM], DET0187 of terrestrial Dehalococcoides/Dehalogenimonas spp. This formate dehydrogenase-like protein has been shown to lack formate dehydrogenase activity in Dehalococcoides/Dehalogenimonas spp. and is instead hypothesized to couple HupL hydrogenase to a reductive dehalogenase in the catabolic reductive dehalogenation pathway. This finding of a close functional homologue provides an important missing link for understanding the origin and the metabolic core of terrestrial Dehalococcoides/Dehalogenimonas spp. and of

Auditory attention activates peripheral visual cortex.

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Anthony D Cate

Full Text Available BACKGROUND: Recent neuroimaging studies have revealed that putatively unimodal regions of visual cortex can be activated during auditory tasks in sighted as well as in blind subjects. However, the task determinants and functional significance of auditory occipital activations (AOAs remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: We examined AOAs in an intermodal selective attention task to distinguish whether they were stimulus-bound or recruited by higher-level cognitive operations associated with auditory attention. Cortical surface mapping showed that auditory occipital activations were localized to retinotopic visual cortex subserving the far peripheral visual field. AOAs depended strictly on the sustained engagement of auditory attention and were enhanced in more difficult listening conditions. In contrast, unattended sounds produced no AOAs regardless of their intensity, spatial location, or frequency. CONCLUSIONS/SIGNIFICANCE: Auditory attention, but not passive exposure to sounds, routinely activated peripheral regions of visual cortex when subjects attended to sound sources outside the visual field. Functional connections between auditory cortex and visual cortex subserving the peripheral visual field appear to underlie the generation of AOAs, which may reflect the priming of visual regions to process soon-to-appear objects associated with unseen sound sources.

AMPA Receptor Endocytosis in Rat Perirhinal Cortex Underlies Retrieval of Object Memory

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Cazakoff, Brittany N.; Howland, John G.

2011-01-01

Mechanisms consistent with long-term depression in the perirhinal cortex (PRh) play a fundamental role in object recognition memory; however, whether AMPA receptor endocytosis is involved in distinct phases of recognition memory is not known. To address this question, we used local PRh infusions of the cell membrane-permeable Tat-GluA2[subscript…

Further studies on the cortical connections of the Tegu lizard.

Science.gov (United States)

Lohman, A H; Van Woerden-Verkley, I

1976-02-13

The efferent fiber connections of the caudal half of the cerebral cortex, the lateral cortex and the pallial thickening were studied using the Nauta-Gygax and Fink-Heimer techniques. The following observations were made, (1) In the caudal half of the hemisphere corticoseptal and corticohypothalamic fibers originate from the small-celled part of the mediodorsal cortex and the thickened caudal part of the dorsal cortex in its whole mediolateral extent. (2) The dorsal cortex in the middle of the hemisphere projects by way of both the pre- and postcommissural fornices. Its rostral pole distributes its fibers solely to the postcommissural fornix, whereas its caudal part projects via the precommissural fornix. (3) The posterior pallial commissure carries fibers that arise caudally in the small-celled part of the mediodorsal cortex and terminate in the contralateral ventral cortex. (4) Projections to the dorsal striatum originate from the lateral cortex, the dorsal cortex and the superficial portion of the pallial thickening. In addition, the latter two zones project to the nucleus accumbens. (5) The deep portion of the pallial thickening projects to the ventral striatum.

Time course of cell death due to acoustic overstimulation in the mouse medial geniculate body and primary auditory cortex

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Felix Frohlich

2017-01-01

Full Text Available It has previously been shown that acoustic overstimulation induces cell death and extensive cell loss in key structures of the central auditory pathway. A correlation between noise-induced apoptosis and cell loss was hypothesized for the cochlear nucleus and colliculus inferior. To determine the role of cell death in noise-induced cell loss in thalamic and cortical structures, the present mouse study (NMRI strain describes the time course following noise exposure of cell death mechanisms for the ventral medial geniculate body (vMGB, medial MGB (mMGB, and dorsal MGB (dMGB and the six histological layers of the primary auditory cortex (AI 1–6. Therefore, a terminal deoxynucleotidyl transferase dioxyuridine triphosphate nick-end labeling assay (TUNEL was performed in these structures 24 h, 7 days, and 14 days after noise exposure (3 h, 115 dB sound pressure level, 5–20 kHz, as well as in unexposed controls. In the dMGB, TUNEL was statistically significant elevated 24 h postexposure. AI-1 showed a decrease in TUNEL after 14 days. There was no statistically significant difference between groups for the other brain areas investigated. dMGB’s widespread connection within the central auditory pathway and its nontonotopical organization might explain its prominent increase in TUNEL compared to the other MGB subdivisions and the AI. It is assumed that the onset and peak of noise-induced cell death is delayed in higher areas of the central auditory pathway and takes place between 24 h and 7 days postexposure in thalamic and cortical structures.

Retaining the 3D framework of zinc sponge anodes upon deep discharge in Zn-air cells.

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Parker, Joseph F; Nelson, Eric S; Wattendorf, Matthew D; Chervin, Christopher N; Long, Jeffrey W; Rolison, Debra R

2014-11-26

We fabricate three-dimensional zinc electrodes from emulsion-cast sponges of Zn powder that are thermally treated to produce rugged monoliths. This highly conductive, 3D-wired aperiodic scaffold achieves 740 mA h gZn(-1) when discharged in primary Zn-air cells (>90% of theoretical Zn capacity). We use scanning electron microscopy and X-ray diffraction to monitor the microstructural evolution of a series of Zn sponges when oxidized in Zn-air cells to specific depths-of-discharge (20, 40, 60, 80% DOD) at a technologically relevant rate (C/40; 4-6 mA cm(-2)). The Zn sponges maintain their 3D-monolithic form factor at all DOD. The cell resistance remains low under all test conditions, indicating that an inner core of metallic Zn persists that 3D-electrically wires the electrode, even to deep DOD.

Characterizing context-dependent differential firing activity in the hippocampus and entorhinal cortex.

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Prerau, Michael J; Lipton, Paul A; Eichenbaum, Howard B; Eden, Uri T

2014-04-01

The rat hippocampus and entorhinal cortex have been shown to possess neurons with place fields that modulate their firing properties under different behavioral contexts. Such context-dependent changes in neural activity are commonly studied through electrophysiological experiments in which a rat performs a continuous spatial alternation task on a T-maze. Previous research has analyzed context-based differential firing during this task by describing differences in the mean firing activity between left-turn and right-turn experimental trials. In this article, we develop qualitative and quantitative methods to characterize and compare changes in trial-to-trial firing rate variability for sets of experimental contexts. We apply these methods to cells in the CA1 region of hippocampus and in the dorsocaudal medial entorhinal cortex (dcMEC), characterizing the context-dependent differences in spiking activity during spatial alternation. We identify a subset of cells with context-dependent changes in firing rate variability. Additionally, we show that dcMEC populations encode turn direction uniformly throughout the T-maze stem, whereas CA1 populations encode context at major waypoints in the spatial trajectory. Our results suggest scenarios in which individual cells that sparsely provide information on turn direction might combine in the aggregate to produce a robust population encoding. Copyright © 2014 Wiley Periodicals, Inc.

EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm.

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Kim, Seong Gon; Harwani, Mrudul; Grama, Ananth; Chaterji, Somali

2016-12-08

We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types. Specifically, we use a deep neural network (DNN)-based architecture to extract enhancer signatures in a representative human embryonic stem cell type (H1) and a differentiated lung cell type (IMR90). We train EP-DNN using p300 binding sites, as enhancers, and TSS and random non-DHS sites, as non-enhancers. We perform same-cell and cross-cell predictions to quantify the validation rate and compare against two state-of-the-art methods, DEEP-ENCODE and RFECS. We find that EP-DNN has superior accuracy with a validation rate of 91.6%, relative to 85.3% for DEEP-ENCODE and 85.5% for RFECS, for a given number of enhancer predictions and also scales better for a larger number of enhancer predictions. Moreover, our H1 → IMR90 predictions turn out to be more accurate than IMR90 → IMR90, potentially because H1 exhibits a richer signature set and our EP-DNN model is expressive enough to extract these subtleties. Our work shows how to leverage the full expressivity of deep learning models, using multiple hidden layers, while avoiding overfitting on the training data. We also lay the foundation for exploration of cross-cell enhancer predictions, potentially reducing the need for expensive experimentation.

EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm

Science.gov (United States)

Kim, Seong Gon; Harwani, Mrudul; Grama, Ananth; Chaterji, Somali

2016-12-01

We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types. Specifically, we use a deep neural network (DNN)-based architecture to extract enhancer signatures in a representative human embryonic stem cell type (H1) and a differentiated lung cell type (IMR90). We train EP-DNN using p300 binding sites, as enhancers, and TSS and random non-DHS sites, as non-enhancers. We perform same-cell and cross-cell predictions to quantify the validation rate and compare against two state-of-the-art methods, DEEP-ENCODE and RFECS. We find that EP-DNN has superior accuracy with a validation rate of 91.6%, relative to 85.3% for DEEP-ENCODE and 85.5% for RFECS, for a given number of enhancer predictions and also scales better for a larger number of enhancer predictions. Moreover, our H1 → IMR90 predictions turn out to be more accurate than IMR90 → IMR90, potentially because H1 exhibits a richer signature set and our EP-DNN model is expressive enough to extract these subtleties. Our work shows how to leverage the full expressivity of deep learning models, using multiple hidden layers, while avoiding overfitting on the training data. We also lay the foundation for exploration of cross-cell enhancer predictions, potentially reducing the need for expensive experimentation.

Back to front: cerebellar connections and interactions with the prefrontal cortex

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Thomas C Watson

2014-02-01

Full Text Available Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the contralateral cerebellar fastigial nucleus (FN in awake, behaving rats evokes distinct local field potential (LFP responses (onset latency ~13 ms in the prelimbic (PrL subdivision of the medial prefrontal cortex. Trains of FN stimulation evoke heterogeneous patterns of response in putative pyramidal cells in frontal and prefrontal regions in both urethane-anaesthetized and awake, behaving rats. However, the majority of cells showed decreased firing rates during stimulation and subsequent rebound increases; more than 90% of cells showed significant changes in response. Simultaneous recording of on-going LFP activity from FN and PrL while rats were at rest or actively exploring an open field arena revealed significant network coherence restricted to the theta frequency range (5-10 Hz. Granger causality analysis indicated that this coherence was significantly directed from cerebellum to PrL during active locomotion. Our results demonstrate the presence of a cerebello-prefrontal pathway in rat and reveal behaviorally dependent coordinated network activity between the two structures, which could facilitate transfer of sensorimotor information into ongoing neocortical processing during goal directed behaviors.

The Chlamydomonas cell wall and its constituent glycoproteins analyzed by the quick-freeze, deep-etch technique

OpenAIRE

1985-01-01

Using the quick-freeze, deep-etch technique, we have analyzed the structure of the intact cell wall of Chlamydomonas reinhardi, and have visualized its component glycoproteins after mechanical shearing and after depolymerization induced by perchlorate or by the wall-disrupting agent, autolysin. The intact wall has previously been shown in a thin- section study (Roberts, K., M. Gurney-Smith, and G. J. Hills, 1972, J. Ultrastruct. Res. 40:599-613) to consist of a discrete central triplet bisect...

Histogenetic disorders of cerebral cortex induced by in utero exposure to low-doses of ionizing radiation

International Nuclear Information System (INIS)

Fushiki, Shinji; Kinoshita, Chikako; Hyodo-Taguchi, Yasuko; Ishikawa, Yuji; Hirobe, Tomohisa

1999-01-01

To elucidate the short- and long-term effects of low-level ionizing radiation on cell migration in the developing cerebral cortex of mice and rats, we irradiated them at the middle of cortical histogenesis with either γ-rays or X-rays. We have demonstrated an effect of ionizing radiation on neuronal migration at doses as low as 0.15 Gy together with a changing pattern of expression of the neural cell adhesion molecule N-CAM. Our findings suggest a possible role of N-CAM in neuronal migration and suggest the presence of a threshold in terms of the effects of small radiation doses on the developing cerebral cortex. In addition, the effects of radiation on neuronal migration during the embryonic stage remained even after birth in that aberrantly placed neurons were noted in the cerebral cortex. However, such derangement was less pronounced in mature animals compared to younger ones. These observations suggest that some modification process including apoptosis might have occurred during the postnatal period. In this review, molecular pathogenesis of neuronal migration disorders will also be discussed, based upon recent experimental as well as molecular genetic studies. (author)

Fast voltage-sensitive dye imaging of excitatory and inhibitory synaptic transmission in the rat granular retrosplenial cortex.

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Nixima, Ken'ichi; Okanoya, Kazuo; Ichinohe, Noritaka; Kurotani, Tohru

2017-09-01

Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatiotemporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2-4 to layers 5-6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer. In the presence of ionotropic glutamate receptor antagonists, inhibitory responses were observed in superficial layers, induced by direct activation of inhibitory interneurons in layer 1. In horizontal slices, excitatory signals in deep layers propagated transversely mainly from posterior to anterior via superficial layers. Cortical inhibitory responses upon layer 1a stimulation in horizontal slices were weaker than those in the coronal slices. Observed differences between coronal and horizontal planes suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are processed differently in coronal and horizontal planes of the GRS and then conveyed to other cortical areas. In both planes, GRS superficial layers play an important role in signal propagation, which suggests that superficial neuronal cascade is crucial in the integration of multiple information sources. NEW & NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS) show distinctive late-spiking (LS) firing property. However, little is known about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated LS neuron network relaying thalamic inputs to deep layers and anisotropic distribution of

Gene expression in cortex and hippocampus during acute pneumococcal meningitis

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Wittwer Matthias

2006-06-01

Full Text Available Abstract Background Pneumococcal meningitis is associated with high mortality (~30% and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI and (ii the self-organizing map (SOM, a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05, 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential

The neurophysiology of figure-ground segregation in primary visual cortex.

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Lamme, V A

1995-02-01

The activity of neurons in the primary visual cortex of the awake macaque monkey was recorded while the animals were viewing full screen arrays of either oriented line segments or moving random dots. A square patch of the screen was made to perceptually pop out as a circumscribed figure by virtue of differences between the orientation or the direction of motion of the texture elements within that patch and the surround. The animals were trained to identify the figure patches by making saccadic eye movements towards their positions. Almost every cell gave a significantly larger response to elements belonging to the figure than to similar elements belonging to the background. The figure-ground response enhancement was present along the entire extent of the patch and was absent as soon as the receptive field was outside the patch. The strength of the effect had no relation with classical receptive field properties like orientation or direction selectivity or receptive field size. The response enhancement had a latency of 30-40 msec relative to the onset of the neuronal response itself. The results show that context modulation within primary visual cortex has a highly sophisticated nature, putting the image features the cells are responding to into their fully evaluated perceptual context.

Saturation in Phosphene Size with Increasing Current Levels Delivered to Human Visual Cortex.

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Bosking, William H; Sun, Ping; Ozker, Muge; Pei, Xiaomei; Foster, Brett L; Beauchamp, Michael S; Yoshor, Daniel

2017-07-26

Electrically stimulating early visual cortex results in a visual percept known as a phosphene. Although phosphenes can be evoked by a wide range of electrode sizes and current amplitudes, they are invariably described as small. To better understand this observation, we electrically stimulated 93 electrodes implanted in the visual cortex of 13 human subjects who reported phosphene size while stimulation current was varied. Phosphene size increased as the stimulation current was initially raised above threshold, but then rapidly reached saturation. Phosphene size also depended on the location of the stimulated site, with size increasing with distance from the foveal representation. We developed a model relating phosphene size to the amount of activated cortex and its location within the retinotopic map. First, a sigmoidal curve was used to predict the amount of activated cortex at a given current. Second, the amount of active cortex was converted to degrees of visual angle by multiplying by the inverse cortical magnification factor for that retinotopic location. This simple model accurately predicted phosphene size for a broad range of stimulation currents and cortical locations. The unexpected saturation in phosphene sizes suggests that the functional architecture of cerebral cortex may impose fundamental restrictions on the spread of artificially evoked activity and this may be an important consideration in the design of cortical prosthetic devices. SIGNIFICANCE STATEMENT Understanding the neural basis for phosphenes, the visual percepts created by electrical stimulation of visual cortex, is fundamental to the development of a visual cortical prosthetic. Our experiments in human subjects implanted with electrodes over visual cortex show that it is the activity of a large population of cells spread out across several millimeters of tissue that supports the perception of a phosphene. In addition, we describe an important feature of the production of phosphenes by

Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

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Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

2016-01-01

Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

Atomic force microscopy stiffness tomography on living Arabidopsis thaliana cells reveals the mechanical properties of surface and deep cell-wall layers during growth.

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Radotić, Ksenija; Roduit, Charles; Simonović, Jasna; Hornitschek, Patricia; Fankhauser, Christian; Mutavdžić, Dragosav; Steinbach, Gabor; Dietler, Giovanni; Kasas, Sandor

2012-08-08

Cell-wall mechanical properties play a key role in the growth and the protection of plants. However, little is known about genuine wall mechanical properties and their growth-related dynamics at subcellular resolution and in living cells. Here, we used atomic force microscopy (AFM) stiffness tomography to explore stiffness distribution in the cell wall of suspension-cultured Arabidopsis thaliana as a model of primary, growing cell wall. For the first time that we know of, this new imaging technique was performed on living single cells of a higher plant, permitting monitoring of the stiffness distribution in cell-wall layers as a function of the depth and its evolution during the different growth phases. The mechanical measurements were correlated with changes in the composition of the cell wall, which were revealed by Fourier-transform infrared (FTIR) spectroscopy. In the beginning and end of cell growth, the average stiffness of the cell wall was low and the wall was mechanically homogenous, whereas in the exponential growth phase, the average wall stiffness increased, with increasing heterogeneity. In this phase, the difference between the superficial and deep wall stiffness was highest. FTIR spectra revealed a relative increase in the polysaccharide/lignin content. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

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Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

2014-01-01

Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Medial cortex activity, self-reflection and depression.

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Johnson, Marcia K; Nolen-Hoeksema, Susan; Mitchell, Karen J; Levin, Yael

2009-12-01

Using functional magnetic resonance imaging, we investigated neural activity associated with self-reflection in depressed [current major depressive episode (MDE)] and healthy control participants, focusing on medial cortex areas previously shown to be associated with self-reflection. Both the MDE and healthy control groups showed greater activity in anterior medial cortex (medial frontal gyrus, anterior cingulate gyrus) when cued to think about hopes and aspirations compared with duties and obligations, and greater activity in posterior medial cortex (precuneus, posterior cingulate) when cued to think about duties and obligations (Experiment 1). However, the MDE group showed less activity than controls in the same area of medial frontal cortex when self-referential cues were more ambiguous with respect to valence (Experiment 2), and less deactivation in a non-self-referential condition in both experiments. Furthermore, individual differences in rumination were positively correlated with activity in both anterior and posterior medial cortex during non-self-referential conditions. These results provide converging evidence for a dissociation of anterior and posterior medial cortex depending on the focus of self-relevant thought. They also provide neural evidence consistent with behavioral findings that depression is associated with disruption of positively valenced thoughts in response to ambiguous cues, and difficulty disengaging from self-reflection when it is appropriate to do so.

Advanced Solar Cell and Array Technology for NASA Deep Space Missions

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Piszczor, Michael; Benson, Scott; Scheiman, David; Finacannon, Homer; Oleson, Steve; Landis, Geoffrey

2008-01-01

A recent study by the NASA Glenn Research Center assessed the feasibility of using photovoltaics (PV) to power spacecraft for outer planetary, deep space missions. While the majority of spacecraft have relied on photovoltaics for primary power, the drastic reduction in solar intensity as the spacecraft moves farther from the sun has either limited the power available (severely curtailing scientific operations) or necessitated the use of nuclear systems. A desire by NASA and the scientific community to explore various bodies in the outer solar system and conduct "long-term" operations using using smaller, "lower-cost" spacecraft has renewed interest in exploring the feasibility of using photovoltaics for to Jupiter, Saturn and beyond. With recent advances in solar cell performance and continuing development in lightweight, high power solar array technology, the study determined that photovoltaics is indeed a viable option for many of these missions.

MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject.

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Ioannides, Andreas A; Liu, Lichan; Poghosyan, Vahe; Saridis, George A; Gjedde, Albert; Ptito, Maurice; Kupers, Ron

2013-01-01

Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45-70 Hz activity at latencies of 20-50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA) 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong, and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI) revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

Chronic Stress Reduces Nectin-1 mRNA Levels and Disrupts Dendritic Spine Plasticity in the Adult Mouse Perirhinal Cortex

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Qian Gong

2018-03-01

Full Text Available In adulthood, chronic exposure to stressful experiences disrupts synaptic plasticity and cognitive function. Previous studies have shown that perirhinal cortex-dependent object recognition memory is impaired by chronic stress. However, the stress effects on molecular expression and structural plasticity in the perirhinal cortex remain unclear. In this study, we applied the chronic social defeat stress (CSDS paradigm and measured the mRNA levels of nectin-1, nectin-3 and neurexin-1, three synaptic cell adhesion molecules (CAMs implicated in the adverse stress effects, in the perirhinal cortex of wild-type (WT and conditional forebrain corticotropin-releasing hormone receptor 1 conditional knockout (CRHR1-CKO mice. Chronic stress reduced perirhinal nectin-1 mRNA levels in WT but not CRHR1-CKO mice. In conditional forebrain corticotropin-releasing hormone conditional overexpression (CRH-COE mice, perirhinal nectin-1 mRNA levels were also reduced, indicating that chronic stress modulates nectin-1 expression through the CRH-CRHR1 system. Moreover, chronic stress altered dendritic spine morphology in the main apical dendrites and reduced spine density in the oblique apical dendrites of perirhinal layer V pyramidal neurons. Our data suggest that chronic stress disrupts cell adhesion and dendritic spine plasticity in perirhinal neurons, which may contribute to stress-induced impairments of perirhinal cortex-dependent memory.

Markers of Alzheimer’s Disease in Primary Visual Cortex in Normal Aging in Mice

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Luis Fernando Hernández-Zimbrón

2017-01-01

Full Text Available Aging is the principal risk factor for the development of Alzheimer’s disease (AD. The hallmarks of AD are accumulation of the amyloid-β peptide 1–42 (Aβ42 and abnormal hyperphosphorylation of Tau (p-Tau protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aβ42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood. Young and aged mice were used as model to analyze the presence of Aβ42, p-Tau, glial-acidic fibrillary protein (GFAP, and presenilin-2, one of the main enzymes involved in Aβ42 production. Our results show a significant increase of Aβ42 deposition in aged mice in the following cells and/or tissues: endothelial cells and blood vessels and neurons of the visual cortex; they also show an increase of the expression of GFAP and presenilin-2 in this region. These results provide a comprehensive framework for the role of Aβ42 in visual loss due to inflammation present with aging and offer some clues for fruitful avenues for the study of healthy aging.

Plasticity of orientation preference maps in the visual cortex of adult cats

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Godde, Ben; Leonhardt, Ralph; Cords, Sven M.; Dinse, Hubert R.

2002-01-01

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes. PMID:11959906

Orbitofrontal cortex contribution to working memory. N-back ERP study

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Nakao, Yoshiaki; Tamura, Toshiyo; Kodabashi, Atsushi; Fujimoto, Toshiro; Yarita, Masaru

2011-01-01

Remarkable progress in cognitive neuroscience has revealed the involvement of the prefrontal cortex and the orbitofrontal cortex in human working memory, but the orbitofrontal cortex is still one of the least understood regions in the human brain. To elucidate the contribution of the orbitofrontal cortex to human working memory, we studied electroencephalography (EEG) P300 activity in n-back task. We elicited early P3 around 300 ms and late P3 around 360 ms of P300 components in n-back event related potentials (ERP). The amplitudes of the respective peaks changed depending on the working memory load (0-back, 1-back, 2-back, 3-back). We used source analysis to evaluate the orbitofrontal cortex in P3 components. A source model was constructed with the sources seeded from fMRI meta-analysis of n-back task and additional sources in the orbitofrontal cortex and the visual cortex estimated with P100 and late P3 components in the n-back ERP. This source model had more than 99% of GOF (goodness of fit) in n-back ERP. It gave us an insight of brain activity at the positions where sources existed. Early P3 was mainly produced by the dorsolateral prefrontal cortex, the ventrolateral prefrontal cortex, the inferior parietal lobule, the medial posterior parietal and the visual cortex. Late P3 was mainly produced by the medial premotor, the lateral premotor, the frontal pole and the orbitofrontal cortex. The contribution of the frontal pole and the orbitofrontal cortex had peaks around 390 ms which were later than late P3 component. In this study, the method to evaluate the orbitofrontal cortex activity in n-back ERP was provided. Our results elicited the involvement of the orbitofrontal cortex in late P3 component of n-back ERP. (author)

Neural correlates of memory retrieval in the prefrontal cortex.

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Nácher, Verónica; Ojeda, Sabiela; Cadarso-Suárez, Carmen; Roca-Pardiñas, Javier; Acuña, Carlos

2006-08-01

Working memory includes short-term representations of information that were recently experienced or retrieved from long-term representations of sensory stimuli. Evidence is presented here that working memory activates the same dorsolateral prefrontal cortex neurons that: (a) maintained recently perceived visual stimuli; and (b) retrieved visual stimuli from long-term memory (LTM). Single neuron activity was recorded in the dorsolateral prefrontal cortex while trained monkeys discriminated between two orientated lines shown sequentially, separated by a fixed interstimulus interval. This visual task required the monkey to compare the orientation of the second line with the memory trace of the first and to decide the relative orientation of the second. When the behavioural task required the monkey to maintain in working memory a first stimulus that continually changed from trial to trial, the discharge in these cells was related to the parameters--the orientation--of the memorized item. Then, what the monkey had to recall from memory was manipulated by switching to another task in which the first stimulus was not shown, and had to be retrieved from LTM. The discharge rates of the same neurons also varied depending on the parameters of the memorized stimuli, and their response was progressively delayed as the monkey performed the task. These results suggest that working memory activates dorsolateral prefrontal cortex neurons that maintain parametrical visual information in short-term and LTM, and that the contents of working memory cannot be limited to what has recently happened in the sensory environment.

FGF-2 induces behavioral recovery after early adolescent injury to the motor cortex of rats.

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Nemati, Farshad; Kolb, Bryan

2011-11-20

Motor cortex injuries in adulthood lead to poor performance in behavioral tasks sensitive to limb movements in the rat. We have shown previously that motor cortex injury on day 10 or day 55 allow significant spontaneous recovery but not injury in early adolescence (postnatal day 35 "P35"). Previous studies have indicated that injection of basic fibroblast growth factor (FGF-2) enhances behavioral recovery after neonatal cortical injury but such effect has not been studied following motor cortex lesions in early adolescence. The present study undertook to investigate the possibility of such behavioral recovery. Rats with unilateral motor cortex lesions were assigned to two groups in which they received FGF-2 or bovine serum albumin (BSA) and were tested in a number of behavioral tests (postural asymmetry, skilled reaching, sunflower seed manipulation, forepaw inhibition in swimming). Golgi-Cox analysis was used to examine the dendritic structure of pyramidal cells in the animals' parietal (layer III) and forelimb (layer V) area of the cortex. The results indicated that rats injected with FGF-2 (but not BSA) showed significant behavioral recovery that was associated with increased dendritic length and spine density. The present study suggests a role for FGF-2 in the recovery of function following injury during early adolescence. Copyright © 2011 Elsevier B.V. All rights reserved.

Antibody-supervised deep learning for quantification of tumor-infiltrating immune cells in hematoxylin and eosin stained breast cancer samples.

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Turkki, Riku; Linder, Nina; Kovanen, Panu E; Pellinen, Teijo; Lundin, Johan

2016-01-01

Immune cell infiltration in tumor is an emerging prognostic biomarker in breast cancer. The gold standard for quantification of immune cells in tissue sections is visual assessment through a microscope, which is subjective and semi-quantitative. In this study, we propose and evaluate an approach based on antibody-guided annotation and deep learning to quantify immune cell-rich areas in hematoxylin and eosin (H&E) stained samples. Consecutive sections of formalin-fixed parafin-embedded samples obtained from the primary tumor of twenty breast cancer patients were cut and stained with H&E and the pan-leukocyte CD45 antibody. The stained slides were digitally scanned, and a training set of immune cell-rich and cell-poor tissue regions was annotated in H&E whole-slide images using the CD45-expression as a guide. In analysis, the images were divided into small homogenous regions, superpixels, from which features were extracted using a pretrained convolutional neural network (CNN) and classified with a support of vector machine. The CNN approach was compared to texture-based classification and to visual assessments performed by two pathologists. In a set of 123,442 labeled superpixels, the CNN approach achieved an F-score of 0.94 (range: 0.92-0.94) in discrimination of immune cell-rich and cell-poor regions, as compared to an F-score of 0.88 (range: 0.87-0.89) obtained with the texture-based classification. When compared to visual assessment of 200 images, an agreement of 90% (κ = 0.79) to quantify immune infiltration with the CNN approach was achieved while the inter-observer agreement between pathologists was 90% (κ = 0.78). Our findings indicate that deep learning can be applied to quantify immune cell infiltration in breast cancer samples using a basic morphology staining only. A good discrimination of immune cell-rich areas was achieved, well in concordance with both leukocyte antigen expression and pathologists' visual assessment.

Antibody-supervised deep learning for quantification of tumor-infiltrating immune cells in hematoxylin and eosin stained breast cancer samples

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Riku Turkki

2016-01-01

Full Text Available Background: Immune cell infiltration in tumor is an emerging prognostic biomarker in breast cancer. The gold standard for quantification of immune cells in tissue sections is visual assessment through a microscope, which is subjective and semi-quantitative. In this study, we propose and evaluate an approach based on antibody-guided annotation and deep learning to quantify immune cell-rich areas in hematoxylin and eosin (H&E stained samples. Methods: Consecutive sections of formalin-fixed parafin-embedded samples obtained from the primary tumor of twenty breast cancer patients were cut and stained with H&E and the pan-leukocyte CD45 antibody. The stained slides were digitally scanned, and a training set of immune cell-rich and cell-poor tissue regions was annotated in H&E whole-slide images using the CD45-expression as a guide. In analysis, the images were divided into small homogenous regions, superpixels, from which features were extracted using a pretrained convolutional neural network (CNN and classified with a support of vector machine. The CNN approach was compared to texture-based classification and to visual assessments performed by two pathologists. Results: In a set of 123,442 labeled superpixels, the CNN approach achieved an F-score of 0.94 (range: 0.92-0.94 in discrimination of immune cell-rich and cell-poor regions, as compared to an F-score of 0.88 (range: 0.87-0.89 obtained with the texture-based classification. When compared to visual assessment of 200 images, an agreement of 90% (k = 0.79 to quantify immune infiltration with the CNN approach was achieved while the inter-observer agreement between pathologists was 90% (k = 0.78. Conclusions: Our findings indicate that deep learning can be applied to quantify immune cell infiltration in breast cancer samples using a basic morphology staining only. A good discrimination of immune cell-rich areas was achieved, well in concordance with both leukocyte antigen expression and

Hydrogen effects on deep level defects in proton implanted Cu(In,Ga)Se{sub 2} based thin films

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Lee, D.W.; Seol, M.S.; Kwak, D.W.; Oh, J.S. [Department of Physics, Dongguk University, Seoul 100-715 (Korea, Republic of); Jeong, J.H. [Photo-electronic Hybrids Research Center, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Cho, H.Y., E-mail: hycho@dongguk.edu [Department of Physics, Dongguk University, Seoul 100-715 (Korea, Republic of)

2012-08-01

Hydrogen effects on deep level defects and a defect generation in proton implanted Cu(In,Ga)Se{sub 2} (CIGS) based thin films for solar cell were investigated. CIGS films with a thickness of 3 {mu}m were grown on a soda-lime glass substrate by a co-evaporation method, and then were implanted with protons. To study deep level defects in the proton implanted CIGS films, deep level transient spectroscopy measurements on the CIGS-based solar cells were carried out, these measurements found 6 traps (including 3 hole traps and 3 electron traps). In the proton implanted CIGS films, the deep level defects, which are attributed to the recombination centers of the CIGS solar cell, were significantly reduced in intensity, while a deep level defect was generated around 0.28 eV above the valence band maximum. Therefore, we suggest that most deep level defects in CIGS films can be controlled by hydrogen effects. - Highlights: Black-Right-Pointing-Pointer Proton implanted Cu(In,Ga)Se{sub 2} thin film and solar cell are prepared. Black-Right-Pointing-Pointer Deep level defects of Cu(In,Ga)Se{sub 2} thin film and solar cell are investigated. Black-Right-Pointing-Pointer Hydrogenation using proton implantation and H{sub 2} annealing reduces deep level defects. Black-Right-Pointing-Pointer Hydrogenation could enhance electrical properties and efficiency of solar cells.

Auditory cortex involvement in emotional learning and memory.

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Grosso, A; Cambiaghi, M; Concina, G; Sacco, T; Sacchetti, B

2015-07-23

Emotional memories represent the core of human and animal life and drive future choices and behaviors. Early research involving brain lesion studies in animals lead to the idea that the auditory cortex participates in emotional learning by processing the sensory features of auditory stimuli paired with emotional consequences and by transmitting this information to the amygdala. Nevertheless, electrophysiological and imaging studies revealed that, following emotional experiences, the auditory cortex undergoes learning-induced changes that are highly specific, associative and long lasting. These studies suggested that the role played by the auditory cortex goes beyond stimulus elaboration and transmission. Here, we discuss three major perspectives created by these data. In particular, we analyze the possible roles of the auditory cortex in emotional learning, we examine the recruitment of the auditory cortex during early and late memory trace encoding, and finally we consider the functional interplay between the auditory cortex and subcortical nuclei, such as the amygdala, that process affective information. We conclude that, starting from the early phase of memory encoding, the auditory cortex has a more prominent role in emotional learning, through its connections with subcortical nuclei, than is typically acknowledged. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Construction of a system using a deep learning algorithm to count cell numbers in nanoliter wells for viable single-cell experiments.

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Kamatani, Takashi; Fukunaga, Koichi; Miyata, Kaede; Shirasaki, Yoshitaka; Tanaka, Junji; Baba, Rie; Matsusaka, Masako; Kamatani, Naoyuki; Moro, Kazuyo; Betsuyaku, Tomoko; Uemura, Sotaro

2017-12-04

For single-cell experiments, it is important to accurately count the number of viable cells in a nanoliter well. We used a deep learning-based convolutional neural network (CNN) on a large amount of digital data obtained as microscopic images. The training set consisted of 103 019 samples, each representing a microscopic grayscale image. After extensive training, the CNN was able to classify the samples into four categories, i.e., 0, 1, 2, and more than 2 cells per well, with an accuracy of 98.3% when compared to determination by two trained technicians. By analyzing the samples for which judgments were discordant, we found that the judgment by technicians was relatively correct although cell counting was often difficult by the images of discordant samples. Based on the results, the system was further enhanced by introducing a new algorithm in which the highest outputs from CNN were used, increasing the accuracy to higher than 99%. Our system was able to classify the data even from wells with a different shape. No other tested machine learning algorithm showed a performance higher than that of our system. The presented CNN system is expected to be useful for various single-cell experiments, and for high-throughput and high-content screening.

Distributed Cerebellar Motor Learning; a Spike-Timing-Dependent Plasticity Model

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Niceto Rafael Luque

2016-03-01

Full Text Available Deep cerebellar nuclei neurons receive both inhibitory (GABAergic synaptic currents from Purkinje cells (within the cerebellar cortex and excitatory (glutamatergic synaptic currents from mossy fibres. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP located at different cerebellar sites (parallel fibres to Purkinje cells, mossy fibres to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibres to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP and inhibitory (i-STDP mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibres to Purkinje cells synapses and then transferred to mossy fibres to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation towards optimising its working range.

The orbitofrontal cortex and beyond: from affect to decision-making.

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Rolls, Edmund T; Grabenhorst, Fabian

2008-11-01

The orbitofrontal cortex represents the reward or affective value of primary reinforcers including taste, touch, texture, and face expression. It learns to associate other stimuli with these to produce representations of the expected reward value for visual, auditory, and abstract stimuli including monetary reward value. The orbitofrontal cortex thus plays a key role in emotion, by representing the goals for action. The learning process is stimulus-reinforcer association learning. Negative reward prediction error neurons are related to this affective learning. Activations in the orbitofrontal cortex correlate with the subjective emotional experience of affective stimuli, and damage to the orbitofrontal cortex impairs emotion-related learning, emotional behaviour, and subjective affective state. With an origin from beyond the orbitofrontal cortex, top-down attention to affect modulates orbitofrontal cortex representations, and attention to intensity modulates representations in earlier cortical areas of the physical properties of stimuli. Top-down word-level cognitive inputs can bias affective representations in the orbitofrontal cortex, providing a mechanism for cognition to influence emotion. Whereas the orbitofrontal cortex provides a representation of reward or affective value on a continuous scale, areas beyond the orbitofrontal cortex such as the medial prefrontal cortex area 10 are involved in binary decision-making when a choice must be made. For this decision-making, the orbitofrontal cortex provides a representation of each specific reward in a common currency.

The logic of single-cell projections from visual cortex.

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Han, Yunyun; Kebschull, Justus M; Campbell, Robert A A; Cowan, Devon; Imhof, Fabia; Zador, Anthony M; Mrsic-Flogel, Thomas D

2018-04-05

Neocortical areas communicate through extensive axonal projections, but the logic of information transfer remains poorly understood, because the projections of individual neurons have not been systematically characterized. It is not known whether individual neurons send projections only to single cortical areas or distribute signals across multiple targets. Here we determine the projection patterns of 591 individual neurons in the mouse primary visual cortex using whole-brain fluorescence-based axonal tracing and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq). Projections were highly diverse and divergent, collectively targeting at least 18 cortical and subcortical areas. Most neurons targeted multiple cortical areas, often in non-random combinations, suggesting that sub-classes of intracortical projection neurons exist. Our results indicate that the dominant mode of intracortical information transfer is not based on 'one neuron-one target area' mapping. Instead, signals carried by individual cortical neurons are shared across subsets of target areas, and thus concurrently contribute to multiple functional pathways.

Development of neuropeptide Y (NPY) immunoreactive neurons in the rat occipital cortex: A combined immunohistochemical-autoradiographic study

International Nuclear Information System (INIS)

Cavanagh, M.E.; Parnavelas, J.G.

1990-01-01

The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14-E21, has been studied in the rat occipital cortex. Immunohistochemistry combined with autoradiography showed evidence of a modified inside-out pattern of maturation. NPY-neurons are generated between E14 and E20 and are found in layers II-VI of the cortex and the subcortical white matter. NPY neurons from all these birthdates are overproduced at first, although cells generated at E16 produce the greatest excess, followed by E15 and E17. Some of these transient neurons are found in the wrong layer for their birthdates, and their elimination produces a more correct alignment at maturity. However, most of the NPY neurons that survive are generated at E17, and these cells are found throughout layers II-VI with a preponderance in layer VI. This evidence is strongly suggestive of cell death rather than merely cessation of production of NPY

Cochlear injury and adaptive plasticity of the auditory cortex

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ANNA R. eFETONI

2015-02-01

Full Text Available Growing evidence suggests that cochlear stressors as noise exposure and aging can induce homeostatic/maladaptive changes in the central auditory system from the brainstem to the cortex. Studies centered on such changes have revealed several mechanisms that operate in the context of sensory disruption after insult (noise trauma, drug- or age-related injury. The oxidative stress is central to current theories of induced sensory neural hearing loss and aging, and interventions to attenuate the hearing loss are based on antioxidant agent. The present review addresses the recent literature on the alterations in hair cells and spiral ganglion neurons due to noise-induced oxidative stress in the cochlea, as well on the impact of cochlear damage on the auditory cortex neurons. The emerging image emphasizes that noise-induced deafferentation and upward spread of cochlear damage is associated with the altered dendritic architecture of auditory pyramidal neurons. The cortical modifications may be reversed by treatment with antioxidants counteracting the cochlear redox imbalance. These findings open new therapeutic approaches to treat the functional consequences of the cortical reorganization following cochlear damage.

Different Influences of Lipofection and Electrotransfection on In Vitro Gene Delivery to Primary Cultured Cortex Neurons.

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Zhang, Xui-Si; Huang, Jing; Zhan, Cong-Qing; Chen, Jing; Li, Tao; Kaye, Alan D; Wu, Sheng-Xi; Xiao, Lan

2016-03-01

Many pain states are linked to central nervous system (CNS) diseases involving the dysfunction of dendritic arborization, making restoration a promising therapeutic strategy. Transfection of primary cortex neurons offers the possibility to study mechanisms which are important for the restoration of proper arborization. Its progress is, however, limited at present due to the lack of suitable gene transfer techniques. To obtain better insight into the transfection potential of currently used techniques, 2 non-viral transfection methods, lipofection and gene electrotransfer (GET), were compared. This is a comparison study performed on cultured cells. The transfection efficiency and neuronal viability, as well as the neuronal dendritic arborization after lipofection or GET, were compared. Primary cultured cortex neurons were transfected with the pEGFP-N1 plasmid, either using Lipofectamine 2000 (2, 3, or 4µL) or with electroporation, with our previously optimized protocol (200V/25 ms). Transfection efficiency and cell viability were inversely proportional for lipofection. The appropriate ratio of Lipofectamine and plasmid DNA provides optimal conditions for lipofection. Although GET offered higher transfection efficiency, it could not induce complex dendritic arborization, which made it unsuitable for in vitro gene transfer into cortex neurons. Limitations include species variability and translational applicability for CNS diseases and pain states related to potential toxicity. Based on these findings, lipofection might be advantageous for in vitro application to primary cultured cortex neurons. Pain states, stress mediated pathogenesis, and certain CNS diseases might potentially utilize this important technique in the future as a therapeutic modality.

Deep supervised, but not unsupervised, models may explain IT cortical representation.

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Seyed-Mahdi Khaligh-Razavi

2014-11-01

Full Text Available Inferior temporal (IT cortex in human and nonhuman primates serves visual object recognition. Computational object-vision models, although continually improving, do not yet reach human performance. It is unclear to what extent the internal representations of computational models can explain the IT representation. Here we investigate a wide range of computational model representations (37 in total, testing their categorization performance and their ability to account for the IT representational geometry. The models include well-known neuroscientific object-recognition models (e.g. HMAX, VisNet along with several models from computer vision (e.g. SIFT, GIST, self-similarity features, and a deep convolutional neural network. We compared the representational dissimilarity matrices (RDMs of the model representations with the RDMs obtained from human IT (measured with fMRI and monkey IT (measured with cell recording for the same set of stimuli (not used in training the models. Better performing models were more similar to IT in that they showed greater clustering of representational patterns by category. In addition, better performing models also more strongly resembled IT in terms of their within-category representational dissimilarities. Representational geometries were significantly correlated between IT and many of the models. However, the categorical clustering observed in IT was largely unexplained by the unsupervised models. The deep convolutional network, which was trained by supervision with over a million category-labeled images, reached the highest categorization performance and also best explained IT, although it did not fully explain the IT data. Combining the features of this model with appropriate weights and adding linear combinations that maximize the margin between animate and inanimate objects and between faces and other objects yielded a representation that fully explained our IT data. Overall, our results suggest that explaining

Radioimmunological and radiochemical analysis of postradiation injuries of the hypophysis-adrenal cortex system

International Nuclear Information System (INIS)

Petrova, G.A.

1979-01-01

It has been established in experiments on Wistar male rats that total irradiation with 60 Co in a dose of 600 R brings about disorders in the nature of interaction between the components of the hypophysis-adrenal cortex system. Hypersecretion of the adrenocorticotropic hormone (ACTH) does not correspond to the increased corticosterone content in the blood plasma of the irradiated animals. A slowed down elimination of ACTH- 131 I from the blood plasma of the irradiated animals evidences deficiency of endogenous corticotropine in the peripheral blood. It was recorded that increased glucocorticoid activity of adrenal cortex in irradiation-induced deficiency of ACTH is provided, on one binding capacity of the adrenocortical cells and on the other side, by slowing down the dissositation speed of binded corticotropine

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

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Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

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Bárbara Núñez

Full Text Available Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2 cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8, in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

Subthalamic Nucleus Deep Brain Stimulation Alters Prefrontal Correlates of Emotion Induction.

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Bick, Sarah K B; Folley, Bradley S; Mayer, Jutta S; Park, Sohee; Charles, P David; Camalier, Corrie R; Pallavaram, Srivatsan; Konrad, Peter E; Neimat, Joseph S

2017-04-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task. We used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states. Deep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli. These results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction. © 2016 International Neuromodulation Society.

Cell biologic studies of the subplate during the development of the mammalian cerebral cortex

International Nuclear Information System (INIS)

Chun, J.J.M.

1988-01-01

This study focuses on pre- and postnatal events that may be necessary in establishing organized connections within the cat cerebral cortex. The fetal white matter beneath the cortical plate - the subplate - is shown to contain synapses and synapsin I. The likely presynaptic elements are the waiting axons from the other parts of cortex as well as the thalamus. A postsynaptic target is here identified as a transient population of neurons born between E24 and E30, based on 3 H-thymidine labeling studies combined with immunohistochemistry for the neuron-specific molecule MAP2, as well as ultrastructural and neuroanatomical studies showing that these early-generated subplate neurons receive synapses and have distant projections. The subplate neurons define the subplate by their immunoreactivity for MAP2. An identity is also demonstrated between the adult remnant of the subplate neuron population and the previously described interstitial and transmitter-immunoreactive neurons within the adult cerebral cortical white matter. The subplate neurons are further developmentally correlated with extracellular matrix molecule fibronectin and in experiments in which the subplate neurons are intentionally killed, fibronectin immunostaining decreases

MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject

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Andreas A Ioannides

2013-08-01

Full Text Available Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1 and motor (M1 cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45 to 70 Hz activity at latencies of 20 to 50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occured in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

Field-Assisted Splitting of Pure Water Based on Deep-Sub-Debye-Length Nanogap Electrochemical Cells.

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Wang, Yifei; Narayanan, S R; Wu, Wei

2017-08-22

Owing to the low conductivity of pure water, using an electrolyte is common for achieving efficient water electrolysis. In this paper, we have fundamentally broken through this common sense by using deep-sub-Debye-length nanogap electrochemical cells to achieve efficient electrolysis of pure water (without any added electrolyte) at room temperature. A field-assisted effect resulted from overlapped electrical double layers can greatly enhance water molecules ionization and mass transport, leading to electron-transfer limited reactions. We have named this process "virtual breakdown mechanism" (which is completely different from traditional mechanisms) that couples the two half-reactions together, greatly reducing the energy losses arising from ion transport. This fundamental discovery has been theoretically discussed in this paper and experimentally demonstrated in a group of electrochemical cells with nanogaps between two electrodes down to 37 nm. On the basis of our nanogap electrochemical cells, the electrolysis current density from pure water can be significantly larger than that from 1 mol/L sodium hydroxide solution, indicating the much better performance of pure water splitting as a potential for on-demand clean hydrogen production.

Deep sea biophysics

International Nuclear Information System (INIS)

Yayanos, A.A.

1982-01-01

A collection of deep-sea bacterial cultures was completed. Procedures were instituted to shelter the culture collection from accidential warming. A substantial data base on the rates of reproduction of more than 100 strains of bacteria from that collection was obtained from experiments and the analysis of that data was begun. The data on the rates of reproduction were obtained under conditions of temperature and pressure found in the deep sea. The experiments were facilitated by inexpensively fabricated pressure vessels, by the streamlining of the methods for the study of kinetics at high pressures, and by computer-assisted methods. A polybarothermostat was used to study the growth of bacteria along temperature gradients at eight distinct pressures. This device should allow for the study of microbial processes in the temperature field simulating the environment around buried HLW. It is small enough to allow placement in a radiation field in future studies. A flow fluorocytometer was fabricated. This device will be used to determine the DNA content per cell in bacteria grown in laboratory culture and in microorganisms in samples from the ocean. The technique will be tested for its rapidity in determining the concentration of cells (standing stock of microorganisms) in samples from the ocean

Morphological and functional correlates of VIP neurons in cerebral cortex

International Nuclear Information System (INIS)

Magistretti, P.J.; Morrison, J.H.; Shoemaker, W.J.; Bloom, F.E.

1984-01-01

Vasoactive Intestinal Polypeptide (VIP) promotes the hydrolysis of 3H-glycogen newly synthesized from 3H-glucose by mouse cortical slices. This effect occurs rapidly, approximately 50% of the maximal effect being reached within one minute. The maximal effect is achieved after 5 minutes and maintained for at least 25 minutes. Furthermore the glycogenolytic effect of VIP is reversible, and pharmacologically specific. Thus several neuropeptides present in cerebral cortex such as cholecystokinin-8, somatostatin-28, somatostatin-14, met-enkephalin, leu-enkephalin, do not affect 3H-glycogen levels. VIP fragments 6-28, 16-28 and 21-28 are similarly inactive. Furthermore, among the peptides which share structural homologies with VIP, such as glucagon, secretin, PHI-27 and Gastric Inhibitory Peptide, only secretin and PHI-27 promote 3H-glycogen hydrolysis, with EC50 of 500 and 300 nM respectively, compared to an EC50 of 25 nM for VIP. Immunohistochemical observations indicate that each VIP-containing bipolar cell is identified with a unique radical cortical volume, which is generally between 15-60 micrograms in diameter and overlaps with the contiguous domains of neighbouring VIP-containing bipolar cells. Thus this set of biochemical and morphological observations support the notion that VIP neurons have the capacity to regulate the availability of energy substrates in cerebral cortex locally, within circumscribed, contiguous, radial domains

Triglycerides in the Human Kidney Cortex: Relationship with Body Size

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Bobulescu, Ion Alexandru; Lotan, Yair; Zhang, Jianning; Rosenthal, Tara R.; Rogers, John T.; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W.

2014-01-01

Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis. PMID:25170827

Auditory Connections and Functions of Prefrontal Cortex

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Bethany ePlakke

2014-07-01

Full Text Available The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC. In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition.

Auditory connections and functions of prefrontal cortex

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Plakke, Bethany; Romanski, Lizabeth M.

2014-01-01

The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

Connectivity changes underlying neurofeedback training of visual cortex activity.

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Frank Scharnowski

Full Text Available Neurofeedback based on real-time functional magnetic resonance imaging (fMRI is a new approach that allows training of voluntary control over regionally specific brain activity. However, the neural basis of successful neurofeedback learning remains poorly understood. Here, we assessed changes in effective brain connectivity associated with neurofeedback training of visual cortex activity. Using dynamic causal modeling (DCM, we found that training participants to increase visual cortex activity was associated with increased effective connectivity between the visual cortex and the superior parietal lobe. Specifically, participants who learned to control activity in their visual cortex showed increased top-down control of the superior parietal lobe over the visual cortex, and at the same time reduced bottom-up processing. These results are consistent with efficient employment of top-down visual attention and imagery, which were the cognitive strategies used by participants to increase their visual cortex activity.

Sensorimotor cortex ablation induces time-dependent response of ACTH cells in adult rats: behavioral, immunohistomorphometric and hormonal study.

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Lavrnja, Irena; Trifunovic, Svetlana; Ajdzanovic, Vladimir; Pekovic, Sanja; Bjelobaba, Ivana; Stojiljkovic, Mirjana; Milosevic, Verica

2014-02-10

Traumatic brain injury (TBI) represents a serious event with far reaching complications, including pituitary dysfunction. Pars distalis corticotropes (ACTH cells), that represent the active module of hypothalamo-pituitary-adrenocortical axis, seem to be affected as well. Since pituitary failure after TBI has been associated with neurobehavioral impairments the aim of this study was to evaluate the effects of TBI on recovery of motor functions, morphology and secretory activity of ACTH cells in the pituitary of adult rats. Wistar male rats, initially exposed to sensorimotor cortex ablation (SCA), were sacrificed at the 2nd, 7th, 14th and 30th days post-surgery (dps). A beam walking test was used to evaluate the recovery of motor functions. Pituitary glands and blood were collected for morphological and hormonal analyses. During the first two weeks post-injury increased recovery of locomotor function was detected, reaching almost the control value at day 30. SCA induces significant increase of pituitary weights compared to their time-matched controls. The volume of ACTH-immunopositive cells was reduced at the 7th dps, while at the 14th dps their volume was enlarged, in comparison to corresponding sham controls. Volume density of ACTH cells was increased only at 14th dps, while at day 30 this increase was insignificant. The plasma level of ACTH transiently increased after the injury. The most pronounced changes were observed at the 7th and 14th dps, and were followed by decrease toward control levels at the 30th dps. Thus, temporal changes in the hypothalamic-pituitary-adrenal axis after traumatic brain injury appear to correlate with the recovery process. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of microgravity on muscle and cerebral cortex: a suggested interaction

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D'Amelio, F.; Fox, R. A.; Wu, L. C.; Daunton, N. G.; Corcoran, M. L.

The ``slow'' antigravity muscle adductor longus was studied in rats after 14 days of spaceflight (SF). The techniques employed included standard methods for light microscopy, neural cell adhesion molecule (N-CAM) immunocytochemistry and electron microscopy. Light and electron microscopy revealed myofiber atrophy, segmental necrosis and regenerative myofibers. Regenerative myofibers were N-CAM immunoreactive (N-CAM-IR). The neuromuscular junctions showed axon terminals with a decrease or absence of synaptic vesicles, degenerative changes, vacant axonal spaces and changes suggestive of axonal sprouting. No alterations of muscle spindles was seen either by light or electron microscopy. These observations suggest that muscle regeneration and denervation and synaptic remodeling at the level of the neuromuscular junction may take place during spaceflight. In a separate study, GABA immunoreactivity (GABA-IR) was evaluated at the level of the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension (``simulated'' microgravity). A reduction in number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-IR terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system after spaceflight and hindlimb suspension it is suggested that after limb unloading there are alterations of afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the changes observed in GABA immunoreactivity of cells and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

Swept-source optical coherence tomography powered by a 1.3-μm vertical cavity surface emitting laser enables 2.3-mm-deep brain imaging in mice in vivo

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Choi, Woo June; Wang, Ruikang K.

2015-10-01

We report noninvasive, in vivo optical imaging deep within a mouse brain by swept-source optical coherence tomography (SS-OCT), enabled by a 1.3-μm vertical cavity surface emitting laser (VCSEL). VCSEL SS-OCT offers a constant signal sensitivity of 105 dB throughout an entire depth of 4.25 mm in air, ensuring an extended usable imaging depth range of more than 2 mm in turbid biological tissue. Using this approach, we show deep brain imaging in mice with an open-skull cranial window preparation, revealing intact mouse brain anatomy from the superficial cerebral cortex to the deep hippocampus. VCSEL SS-OCT would be applicable to small animal studies for the investigation of deep tissue compartments in living brains where diseases such as dementia and tumor can take their toll.

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes

International Nuclear Information System (INIS)

Tohgi, H.; Yonezawa, H.; Takahashi, S.; Sato, N.; Kato, E.; Kudo, M.; Hatano, K.; Sasaki, T.

1998-01-01

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO 2 ), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO 2 and rCBV were determined using C 15 O 2 , 15 O 2 and C 15 O, respectively. rCBF and CMRO 2 were significantly decreased in the frontal, parietal and temporal cortex (P 2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. (orig.)

From sensorimotor learning to memory cells in prefrontal and temporal association cortex: a neurocomputational study of disembodiment.

Science.gov (United States)

Pulvermüller, Friedemann; Garagnani, Max

2014-08-01

Memory cells, the ultimate neurobiological substrates of working memory, remain active for several seconds and are most commonly found in prefrontal cortex and higher multisensory areas. However, if correlated activity in "embodied" sensorimotor systems underlies the formation of memory traces, why should memory cells emerge in areas distant from their antecedent activations in sensorimotor areas, thus leading to "disembodiment" (movement away from sensorimotor systems) of memory mechanisms? We modelled the formation of memory circuits in six-area neurocomputational architectures, implementing motor and sensory primary, secondary and higher association areas in frontotemporal cortices along with known between-area neuroanatomical connections. Sensorimotor learning driven by Hebbian neuroplasticity led to formation of cell assemblies distributed across the different areas of the network. These action-perception circuits (APCs) ignited fully when stimulated, thus providing a neural basis for long-term memory (LTM) of sensorimotor information linked by learning. Subsequent to ignition, activity vanished rapidly from APC neurons in sensorimotor areas but persisted in those in multimodal prefrontal and temporal areas. Such persistent activity provides a mechanism for working memory for actions, perceptions and symbols, including short-term phonological and semantic storage. Cell assembly ignition and "disembodied" working memory retreat of activity to multimodal areas are documented in the neurocomputational models' activity dynamics, at the level of single cells, circuits, and cortical areas. Memory disembodiment is explained neuromechanistically by APC formation and structural neuroanatomical features of the model networks, especially the central role of multimodal prefrontal and temporal cortices in bridging between sensory and motor areas. These simulations answer the "where" question of cortical working memory in terms of distributed APCs and their inner structure

Retinal oscillations carry visual information to cortex

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Kilian Koepsell

2009-04-01

Full Text Available Thalamic relay cells fire action potentials that transmit information from retina to cortex. The amount of information that spike trains encode is usually estimated from the precision of spike timing with respect to the stimulus. Sensory input, however, is only one factor that influences neural activity. For example, intrinsic dynamics, such as oscillations of networks of neurons, also modulate firing pattern. Here, we asked if retinal oscillations might help to convey information to neurons downstream. Specifically, we made whole-cell recordings from relay cells to reveal retinal inputs (EPSPs and thalamic outputs (spikes and then analyzed these events with information theory. Our results show that thalamic spike trains operate as two multiplexed channels. One channel, which occupies a low frequency band (<30 Hz, is encoded by average firing rate with respect to the stimulus and carries information about local changes in the visual field over time. The other operates in the gamma frequency band (40-80 Hz and is encoded by spike timing relative to retinal oscillations. At times, the second channel conveyed even more information than the first. Because retinal oscillations involve extensive networks of ganglion cells, it is likely that the second channel transmits information about global features of the visual scene.

State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats.

Science.gov (United States)

Brazhnik, Elena; Cruz, Ana V; Avila, Irene; Wahba, Marian I; Novikov, Nikolay; Ilieva, Neda M; McCoy, Alex J; Gerber, Colin; Walters, Judith R

2012-06-06

Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, 7 d after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8-25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25-40 Hz band with a peak frequency at 30-35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons, and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25-40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity.

Intraoperative functional MRI as a new approach to monitor deep brain stimulation in Parkinson's disease

International Nuclear Information System (INIS)

Hesselmann, Volker; Sorger, Bettina; Girnus, Ralf; Lasek, Kathrin; Schulte, Oliver; Krug, Barbara; Lackner, Klaus; Maarouf, Mohammad; Sturm, Volker; Wedekind, Christoph; Bunke, Juergen

2004-01-01

This article deals with technical aspects of intraoperative functional magnetic resonance imaging (fMRI) for monitoring the effect of deep brain stimulation (DBS) in a patient with Parkinson's disease. Under motor activation, therapeutic high-frequency stimulation of the subthalamic nucleus was accompanied by an activation decrease in the contralateral primary sensorimotor cortex and the ipsilateral cerebellum. Furthermore, an activation increase in the contralateral basal ganglia and insula region were detected. These findings demonstrate that fMRI constitutes a promising clinical application for investigating brain activity changes induced by DBS. (orig.)

PSA-NCAM is Expressed in Immature, but not Recently Generated, Neurons in the Adult Cat Cerebral Cortex Layer II.

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Varea, Emilio; Belles, Maria; Vidueira, Sandra; Blasco-Ibáñez, José M; Crespo, Carlos; Pastor, Angel M; Nacher, Juan

2011-01-01

Neuronal production persists during adulthood in the dentate gyrus and the olfactory bulb, where substantial numbers of immature neurons can be found. These cells can also be found in the paleocortex layer II of adult rodents, but in this case most of them have been generated during embryogenesis. Recent reports have described the presence of similar cells, with a wider distribution, in the cerebral cortex of adult cats and primates and have suggested that they may develop into interneurons. The objective of this study is to verify this hypothesis and to explore the origin of these immature neurons in adult cats. We have analyzed their distribution using immunohistochemical analysis of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and their phenotype using markers of mature neurons and different interneuronal populations. Additionally, we have explored the origin of these cells administering 5'bromodeoxyuridine (5'BrdU) during adulthood. Immature neurons were widely dispersed in the cerebral cortex layers II and upper III, being specially abundant in the piriform and entorhinal cortices, in the ventral portions of the frontal and temporoparietal lobes, but relatively scarce in dorsal regions, such as the primary visual areas. Only a small fraction of PSA-NCAM expressing cells in layer II expressed the mature neuronal marker NeuN and virtually none of them expressed calcium binding proteins or neuropeptides. By contrast, most, if not all of these cells expressed the transcription factor Tbr-1, specifically expressed by pallium-derived principal neurons, but not CAMKII, a marker of mature excitatory neurons. Absence of PSA-NCAM/5'BrdU colocalization suggests that, as in rats, these cells were not generated during adulthood. Together, these results indicate that immature neurons in the adult cat cerebral cortex layer II are not recently generated and that they may differentiate into principal neurons.

PSA-NCAM is expressed in immature, but not recently generated, neurons in the adult cat cerebral cortex layer II

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Emilio eVarea

2011-02-01

Full Text Available Neuronal production persists during adulthood in the dentate gyrus and the olfactory bulb, where substantial numbers of immature neurons can be found. These cells can also be found in the paleocortex layer II of adult rodents, but in this case most of them have been generated during embryogenesis. Recent reports have described the presence of similar cells, with a wider distribution, in the cerebral cortex of adult cats and primates and have suggested that they may develop into interneurons. The objective of this study is to verify this hypothesis and to explore the origin of these immature neurons in adult cats. We have analysed their distribution using immunohistochemical analysis of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM and their phenotype using markers of mature neurons and different interneuronal populations. Additionally, we have explored the origin of these cells administering 5'bromodeoxyuridine (5’BrdU during adulthood. Immature neurons were widely dispersed in the cerebral cortex layers II and upper III, being specially abundant in the piriform and entorhinal cortices, in the ventral portions of the frontal and temporoparietal lobes, but relatively scarce in dorsal regions, such as the primary visual areas. Only a small fraction of PSA-NCAM expressing cells in layer II expressed the mature neuronal marker NeuN and virtually none of them expressed calcium binding proteins or neuropeptides. By contrast, most, if not all of these cells expressed the transcription factor Tbr-1, specifically expressed by pallium-derived principal neurons, but not CAMKII, a marker of mature excitatory neurons. Absence of PSA-NCAM/5’BrdU co-localization suggests that, as in rats, these cells were not generated during adulthood. Together, these results indicate that immature neurons in the adult cat cerebral cortex layer II are not recently generated and that they may differentiate into principal neurons.

Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

Science.gov (United States)

Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

2013-01-01

Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

Estradiol and the Development of the Cerebral Cortex: An Unexpected Role?

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Matthew C. S. Denley

2018-05-01

Full Text Available The cerebral cortex undergoes rapid folding in an “inside-outside” manner during embryonic development resulting in the establishment of six discrete cortical layers. This unique cytoarchitecture occurs via the coordinated processes of neurogenesis and cell migration. In addition, these processes are fine-tuned by a number of extracellular cues, which exert their effects by regulating intracellular signaling pathways. Interestingly, multiple brain regions have been shown to develop in a sexually dimorphic manner. In many cases, estrogens have been demonstrated to play an integral role in mediating these sexual dimorphisms in both males and females. Indeed, 17β-estradiol, the main biologically active estrogen, plays a critical organizational role during early brain development and has been shown to be pivotal in the sexually dimorphic development and regulation of the neural circuitry underlying sex-typical and socio-aggressive behaviors in males and females. However, whether and how estrogens, and 17β-estradiol in particular, regulate the development of the cerebral cortex is less well understood. In this review, we outline the evidence that estrogens are not only present but are engaged and regulate molecular machinery required for the fine-tuning of processes central to the cortex. We discuss how estrogens are thought to regulate the function of key molecular players and signaling pathways involved in corticogenesis, and where possible, highlight if these processes are sexually dimorphic. Collectively, we hope this review highlights the need to consider how estrogens may influence the development of brain regions directly involved in the sex-typical and socio-aggressive behaviors as well as development of sexually dimorphic regions such as the cerebral cortex.

Novel light trapping scheme for thin crystalline cells utilizing deep structures on both wafer sides [solar cells

DEFF Research Database (Denmark)

Jørgensen, Anders Michael; Clausen, Thomas; Leistiko, Otto

1998-01-01

62 times the average thickness. The structure consists of deep (-200 μm) inverted pyramids on the front side and deep (-200 μm) truncated pyramids with eight sides on the back. The structure is realized in crystalline silicon by wet chemical etching using potassium hydroxide (KOH) and isopropanol...

Combination of deep eutectic solvent and ionic liquid to improve biocatalytic reduction of 2-octanone with Acetobacter pasteurianus GIM1.158 cell

OpenAIRE

Pei Xu; Peng-Xuan Du; Min-Hua Zong; Ning Li; Wen-Yong Lou

2016-01-01

The efficient anti-Prelog asymmetric reduction of 2-octanone with Acetobacter pasteurianus GIM1.158 cells was successfully performed in a biphasic system consisting of deep eutectic solvent (DES) and water-immiscible ionic liquid (IL). Various DESs exerted different effects on the synthesis of (R)-2-octanol. Choline chloride/ethylene glycol (ChCl/EG) exhibited good biocompatibility and could moderately increase the cell membrane permeability thus leading to the better results. Adding ChCl/EG ...

Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

Science.gov (United States)

Volonté, M A; Garibotto, V; Spagnolo, F; Panzacchi, A; Picozzi, P; Franzin, A; Giovannini, E; Leocani, L; Cursi, M; Comi, G; Perani, D

2012-07-01

Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

Single unit activity in the medial prefrontal cortex during Pavlovian heart rate conditioning: Effects of peripheral autonomic blockade.

Science.gov (United States)

Powell, D A; Ginsberg, Jay P

2005-11-01

Electrical activity was recorded from single neurons in the medial prefrontal cortex of rabbits during differential Pavlovian heart rate (HR) conditioning. A heterogeneous population of cells were found, some of which showed CS-evoked increases and others CS-evoked decreases in discharge, while some cells were biphasic. A subset of cells also showed trial-related changes in discharge that were related to acquisition of the HR discrimination between the reinforced CS+ and non-reinforced CS-. Administration of the peripheral cholinergic antagonist, methylscopolamine, and the andrenergic antagonist, atenolol, either increased or decreased maintained baseline activity of many cells, but had little or no effect on the CS-evoked activity of these cells. Waveform changes also did not result from administration of these drugs. This finding suggests that CS-evoked mPFC activity is not being driven by cardiac afferent input to CNS cardiac control centers. Previous studies have shown that ibotenic acid lesions of this area greatly decreases the magnitude of decelerative heart rate conditioned responses; the latter finding, plus the results of the present study, suggest that processing of CS/US contingencies by the prefrontal cortex contributes to the acquisition of autonomic changes during Pavlovian conditioning.

Dual Gamma Rhythm Generators Control Interlaminar Synchrony in Auditory Cortex

Science.gov (United States)

Ainsworth, Matthew; Lee, Shane; Cunningham, Mark O.; Roopun, Anita K.; Traub, Roger D.; Kopell, Nancy J.; Whittington, Miles A.

2013-01-01

Rhythmic activity in populations of cortical neurons accompanies, and may underlie, many aspects of primary sensory processing and short-term memory. Activity in the gamma band (30 Hz up to > 100 Hz) is associated with such cognitive tasks and is thought to provide a substrate for temporal coupling of spatially separate regions of the brain. However, such coupling requires close matching of frequencies in co-active areas, and because the nominal gamma band is so spectrally broad, it may not constitute a single underlying process. Here we show that, for inhibition-based gamma rhythms in vitro in rat neocortical slices, mechanistically distinct local circuit generators exist in different laminae of rat primary auditory cortex. A persistent, 30 – 45 Hz, gap-junction-dependent gamma rhythm dominates rhythmic activity in supragranular layers 2/3, whereas a tonic depolarization-dependent, 50 – 80 Hz, pyramidal/interneuron gamma rhythm is expressed in granular layer 4 with strong glutamatergic excitation. As a consequence, altering the degree of excitation of the auditory cortex causes bifurcation in the gamma frequency spectrum and can effectively switch temporal control of layer 5 from supragranular to granular layers. Computational modeling predicts the pattern of interlaminar connections may help to stabilize this bifurcation. The data suggest that different strategies are used by primary auditory cortex to represent weak and strong inputs, with principal cell firing rate becoming increasingly important as excitation strength increases. PMID:22114273

Distribution of catecholamines and serotonin in the rat cerebral cortex:

International Nuclear Information System (INIS)

Reader, T.A.

1981-01-01

The rat cerebral cortex was dissected in five regions and analyzed for the catecholamines noradrenaline, adrenaline and dopamine, and for the indoleamine seroton in using sensitive radioenzymatic assay methods with thin-layer-chromatography. The noradrenaline concentration was highest in the ventral cortex, lateral to the hypothalamus, had intermediate values for the prefrontal, frontal and parietal cortical areas and was lowest in the occipital cortex. Dopamine levels were also highest in the cortex lateral to the hypothalamus, and moderate in the prefrontal and frontal cortical areas, with the lowest values measured for the occipital cortex. The ratios dopamine/noradrenaline further support the hypothesis that they are independent transmitters. Traces of adrenaline were measured in all regions examined. The serotonin distribution was found to be non-homogeneous, with the highest values for the prefrontal cortex and ventral cortex lateral to the hypothalamus. The functional significance of these amines and their ratios are discussed in relation to their role as putative modulators of cortical neuronal excitability. (author)

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

Science.gov (United States)

Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

2016-03-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

Directory of Open Access Journals (Sweden)

Matthew W Self

2016-03-01

Full Text Available Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

Patchwork-Type Spontaneous Activity in Neonatal Barrel Cortex Layer 4 Transmitted via Thalamocortical Projections

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Hidenobu Mizuno

2018-01-01

Full Text Available Summary: Establishment of precise neuronal connectivity in the neocortex relies on activity-dependent circuit reorganization during postnatal development; however, the nature of cortical activity during this period remains largely unknown. Using two-photon calcium imaging of the barrel cortex in vivo during the first postnatal week, we reveal that layer 4 (L4 neurons within the same barrel fire synchronously in the absence of peripheral stimulation, creating a “patchwork” pattern of spontaneous activity corresponding to the barrel map. By generating transgenic mice expressing GCaMP6s in thalamocortical axons, we show that thalamocortical axons also demonstrate the spontaneous patchwork activity pattern. Patchwork activity is diminished by peripheral anesthesia but is mostly independent of self-generated whisker movements. The patchwork activity pattern largely disappeared during postnatal week 2, as even L4 neurons within the same barrel tended to fire asynchronously. This spontaneous L4 activity pattern has features suitable for thalamocortical (TC circuit refinement in the neonatal barrel cortex. : By two-photon calcium imaging of layer 4 neurons and thalamocortical axon terminals in neonatal mouse barrel cortex, Mizuno et al. find a patchwork-like spontaneous activity pattern corresponding to the barrel map, which may be important for thalamocortical circuit maturation. Keywords: activity-dependent development, spontaneous activity, synchronized activity, barrel cortex, thalamocortical axons, neonates, in vivo calcium imaging, awake, single-cell labeling, whisker monitoring

Inflammation and neuronal death in the motor cortex of the wobbler mouse, an ALS animal model

DEFF Research Database (Denmark)

Dahlke, Carolin; Saberi, Darius; Ott, Bastian

2015-01-01

microscopy, and transmission electron microscopy techniques, we analyze the proliferation behavior of microglial cells and astrocytes. We also investigate possible motor neuron death in the mouse motor cortex at different stages of the wobbler disease, which so far has not received much attention. Results...

Charles Bonnet syndrome: evidence for a generative model in the cortex?

Directory of Open Access Journals (Sweden)

David P Reichert

Full Text Available Several theories propose that the cortex implements an internal model to explain, predict, and learn about sensory data, but the nature of this model is unclear. One condition that could be highly informative here is Charles Bonnet syndrome (CBS, where loss of vision leads to complex, vivid visual hallucinations of objects, people, and whole scenes. CBS could be taken as indication that there is a generative model in the brain, specifically one that can synthesise rich, consistent visual representations even in the absence of actual visual input. The processes that lead to CBS are poorly understood. Here, we argue that a model recently introduced in machine learning, the deep Boltzmann machine (DBM, could capture the relevant aspects of (hypothetical generative processing in the cortex. The DBM carries both the semantics of a probabilistic generative model and of a neural network. The latter allows us to model a concrete neural mechanism that could underlie CBS, namely, homeostatic regulation of neuronal activity. We show that homeostatic plasticity could serve to make the learnt internal model robust against e.g. degradation of sensory input, but overcompensate in the case of CBS, leading to hallucinations. We demonstrate how a wide range of features of CBS can be explained in the model and suggest a potential role for the neuromodulator acetylcholine. This work constitutes the first concrete computational model of CBS and the first application of the DBM as a model in computational neuroscience. Our results lend further credence to the hypothesis of a generative model in the brain.

Minimally invasive trans-portal resection of deep intracranial lesions.

Science.gov (United States)

Raza, S M; Recinos, P F; Avendano, J; Adams, H; Jallo, G I; Quinones-Hinojosa, A

2011-02-01

The surgical management of deep intra-axial lesions still requires microsurgical approaches that utilize retraction of deep white matter to obtain adequate visualization. We report our experience with a new tubular retractor system, designed specifically for intracranial applications, linked with frameless neuronavigation for a cohort of intraventricular and deep intra-axial tumors. The ViewSite Brain Access System (Vycor, Inc) was used in a series of 9 adult and pediatric patients with a variety of pathologies. Histological diagnoses either resected or biopsied with the system included: colloid cyst, DNET, papillary pineal tumor, anaplastic astrocytoma, toxoplasmosis and lymphoma. The locations of the lesions approached include: lateral ventricle, basal ganglia, pulvinar/posterior thalamus and insular cortex. Post-operative imaging was assessed to determine extent of resection and extent of white matter damage along the surgical trajectory (based on T (2)/FLAIR and diffusion restriction/ADC signal). Satisfactory resection or biopsy was obtained in all patients. Radiographic analysis demonstrated evidence of white matter damage along the surgical trajectory in one patient. None of the patients experienced neurological deficits as a result of white matter retraction/manipulation. Based on a retrospective review of our experience, we feel that this access system, when used in conjunction with frameless neuronavigational systems, provides adequate visualization for tumor resection while permitting the use of standard microsurgical techniques through minimally invasive craniotomies. Our initial data indicate that this system may minimize white matter injury, but further studies are necessary. © Georg Thieme Verlag KG Stuttgart · New York.

Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear

DEFF Research Database (Denmark)

Marek, Roger; Jin, Jingji; Goode, Travis D.

2018-01-01

The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished...... fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons...... in the IL eliminated vHPC-mediated inhibition. In behaving rats, pharmacogenetic activation of vHPC→IL projections impaired extinction recall, whereas silencing IL projectors diminished fear renewal. Intra-IL infusion of GABA receptor agonists or antagonists, respectively, reproduced these effects. Together...

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

Science.gov (United States)

Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

2018-02-01

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

Science.gov (United States)

Azmitia, E. C.; Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

2016-01-01

In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was…

SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex.

Science.gov (United States)

Saud, K; Cánovas, J; Lopez, C I; Berndt, F A; López, E; Maass, J C; Barriga, A; Kukuljan, M

2017-04-01

The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex.

Science.gov (United States)

Raz, Aeyal; Grady, Sean M; Krause, Bryan M; Uhlrich, Daniel J; Manning, Karen A; Banks, Matthew I

2014-01-01

The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up "core" thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness.

Normal and abnormal neuronal migration in the developing cerebral cortex.

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Sun, Xue-Zhi; Takahashi, Sentaro; Cui, Chun; Zhang, Rui; Sakata-Haga, Hiromi; Sawada, Kazuhiko; Fukui, Yoshihiro

2002-08-01

Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their 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. This process is guided by radial glial fibers, requires proper receptors, ligands, other unknown extracellular factors, and local signaling to stop neuronal migration. This process is also highly sensitive to various physical, chemical and biological agents as well as to genetic mutations. Any disturbance of the normal process may result in neuronal migration disorder. Such neuronal migration disorder is believed as major cause of both gross brain malformation and more special cerebral structural and functional abnormalities in experimental animals and in humans. An increasing number of instructive studies on experimental models and several genetic model systems of neuronal migration disorder have established the foundation of cortex formation and provided deeper insights into the genetic and molecular mechanisms underlying normal and abnormal neuronal migration.

Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats.

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Dejanovic, Bratislav; Stevanovic, Ivana; Ninkovic, Milica; Stojanovic, Ivana; Lavrnja, Irena; Radicevic, Tatjana; Pavlovic, Milos

2016-03-01

This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.

Different phase delays of peripheral input to primate motor cortex and spinal cord promote cancellation at physiological tremor frequencies.

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Koželj, Saša; Baker, Stuart N

2014-05-01

Neurons in the spinal cord and motor cortex (M1) are partially phase-locked to cycles of physiological tremor, but with opposite phases. Convergence of spinal and cortical activity onto motoneurons may thus produce phase cancellation and a reduction in tremor amplitude. The mechanisms underlying this phase difference are unknown. We investigated coherence between spinal and M1 activity with sensory input. In two anesthetized monkeys, we electrically stimulated the medial, ulnar, deep radial, and superficial radial nerves; stimuli were timed as independent Poisson processes (rate 10 Hz). Single units were recorded from M1 (147 cells) or cervical spinal cord (61 cells). Ninety M1 cells were antidromically identified as pyramidal tract neurons (PTNs); M1 neurons were additionally classified according to M1 subdivision (rostral/caudal, M1r/c). Spike-stimulus coherence analysis revealed significant coupling over a broad range of frequencies, with the strongest coherence at <50 Hz. Delays implied by the slope of the coherence phase-frequency relationship were greater than the response onset latency, reflecting the importance of late response components for the transmission of oscillatory inputs. The spike-stimulus coherence phase over the 6-13 Hz physiological tremor band differed significantly between M1 and spinal cells (phase differences relative to the cord of 2.72 ± 0.29 and 1.72 ± 0.37 radians for PTNs from M1c and M1r, respectively). We conclude that different phases of the response to peripheral input could partially underlie antiphase M1 and spinal cord activity during motor behavior. The coordinated action of spinal and cortical feedback will act to reduce tremulous oscillations, possibly improving the overall stability and precision of motor control. Copyright © 2014 the American Physiological Society.

Entorhinal Cortex: Antemortem Cortical Thickness and Postmortem Neurofibrillary Tangles and Amyloid Pathology.

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Thaker, A A; Weinberg, B D; Dillon, W P; Hess, C P; Cabral, H J; Fleischman, D A; Leurgans, S E; Bennett, D A; Hyman, B T; Albert, M S; Killiany, R J; Fischl, B; Dale, A M; Desikan, R S

2017-05-01

The entorhinal cortex, a critical gateway between the neocortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the entorhinal cortex, whether antemortem entorhinal cortex thickness is associated with postmortem tangle burden within the entorhinal cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of entorhinal cortex thickness and postmortem neuropathological measures. We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the entorhinal cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between entorhinal cortex thickness and tangles and amyloid-β load within the entorhinal cortex and medial temporal and neocortical regions. We found a significant relationship between antemortem entorhinal cortex thickness and entorhinal cortex ( P = .006) and medial temporal lobe tangles ( P = .002); we found no relationship between entorhinal cortex thickness and entorhinal cortex ( P = .09) and medial temporal lobe amyloid-β ( P = .09). We also found a significant association between entorhinal cortex thickness and cortical tangles ( P = .003) and amyloid-β ( P = .01). We found no relationship between parahippocampal gyrus thickness and entorhinal cortex ( P = .31) and medial temporal lobe tangles ( P = .051). Our findings indicate that entorhinal cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology. © 2017 by American Journal of Neuroradiology.

The complexity of the calretinin-expressing progenitors in the human cerebral cortex

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Nevena V Radonjic

2014-08-01

Full Text Available The complex structure and function of the cerebral cortex critically depend on the balance of excitation and inhibition provided by the pyramidal projection neurons and GABAergic interneurons, respectively. The calretinin-expressing (CalR+ cell is a subtype of GABAergic cortical interneurons that is more prevalent in humans than in rodents. In rodents, CalR+ interneurons originate in the caudal ganglionic eminence (CGE from Gsx2+ progenitors, but in humans it has been suggested that a subpopulation of CalR+ cells can also be generated in the cortical ventricular/subventricular zone (VZ/SVZ. The progenitors for cortically generated CalR+ subpopulation in primates are not yet characterized. Hence, the aim of this study was to identify patterns of expression of the transcription factors (TFs that commit cortical stem cells to the CalR fate, with a focus on Gsx2. First, we studied the expression of Gsx2 and its downstream effectors, Ascl1 and Sp8 in the cortical regions of the fetal human forebrain at midgestation. Next, we established that a subpopulation of cells expressing these TFs are proliferating in the cortical SVZ, and can be co-labeled with CalR. The presence and proliferation of Gsx2+ cells, not only in the ventral telencephalon (GE as previously reported, but also in the cerebral cortex suggests cortical origin of a subpopulation of CalR+ neurons in humans. In vitro treatment of human cortical progenitors with Sonic hedgehog (Shh, an important morphogen in the specification of interneurons, decreased levels of Ascl1 and Sp8 proteins, but did not affect Gsx2 levels. Taken together, our ex-vivo and in vitro results on human fetal brain suggest complex endogenous and exogenous regulation of TFs implied in the specification of different subtypes of CalR+ cortical interneurons.

Effects of Arousal on Mouse Sensory Cortex Depend on Modality

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Daisuke Shimaoka

2018-03-01

Full Text Available Summary: Changes in arousal modulate the activity of mouse sensory cortex, but studies in different mice and different sensory areas disagree on whether this modulation enhances or suppresses activity. We measured this modulation simultaneously in multiple cortical areas by imaging mice expressing voltage-sensitive fluorescent proteins (VSFP. VSFP imaging estimates local membrane potential across large portions of cortex. We used temporal filters to predict local potential from running speed or from pupil dilation, two measures of arousal. The filters provided good fits and revealed that the effects of arousal depend on modality. In the primary visual cortex (V1 and auditory cortex (Au, arousal caused depolarization followed by hyperpolarization. In the barrel cortex (S1b and a secondary visual area (LM, it caused only hyperpolarization. In all areas, nonetheless, arousal reduced the phasic responses to trains of sensory stimuli. These results demonstrate diverse effects of arousal across sensory cortex but similar effects on sensory responses. : Shimaoka et al. use voltage-sensitive imaging to show that the effects of arousal on the mouse cortex are markedly different across areas and over time. In all the sensory areas studied, nonetheless, arousal reduced the phasic voltage responses to trains of sensory stimuli. Keywords: cerebral cortex, cortical state, locomotion, sensory processing, widefield imaging

TMS-induced neural noise in sensory cortex interferes with short-term memory storage in prefrontal cortex

OpenAIRE

Bancroft, Tyler D.; Hogeveen, Jeremy; Hockley, William E.; Servos, Philip

2014-01-01

In a previous study, Harris et al. (2002) found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation (TMS) to primary somatosensory cortex (SI) early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence f...

Activation of Phosphatidylinositol-Linked Dopamine Receptors Induces a Facilitation of Glutamate-Mediated Synaptic Transmission in the Lateral Entorhinal Cortex.

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Iulia Glovaci

Full Text Available The lateral entorhinal cortex receives strong inputs from midbrain dopamine neurons that can modulate its sensory and mnemonic function. We have previously demonstrated that 1 µM dopamine facilitates synaptic transmission in layer II entorhinal cortex cells via activation of D1-like receptors, increased cAMP-PKA activity, and a resulting enhancement of AMPA-receptor mediated currents. The present study assessed the contribution of phosphatidylinositol (PI-linked D1 receptors to the dopaminergic facilitation of transmission in layer II of the rat entorhinal cortex, and the involvement of phospholipase C activity and release of calcium from internal stores. Whole-cell patch-clamp recordings of glutamate-mediated evoked excitatory postsynaptic currents were obtained from pyramidal and fan cells. Activation of D1-like receptors using SKF38393, SKF83959, or 1 µM dopamine induced a reversible facilitation of EPSCs which was abolished by loading cells with either the phospholipase C inhibitor U-73122 or the Ca2+ chelator BAPTA. Neither the L-type voltage-gated Ca2+ channel blocker nifedipine, nor the L/N-type channel blocker cilnidipine, blocked the facilitation of synaptic currents. However, the facilitation was blocked by blocking Ca2+ release from internal stores via inositol 1,4,5-trisphosphate (InsP3 receptors or ryanodine receptors. Follow-up studies demonstrated that inhibiting CaMKII activity with KN-93 failed to block the facilitation, but that application of the protein kinase C inhibitor PKC(19-36 completely blocked the dopamine-induced facilitation. Overall, in addition to our previous report indicating a role for the cAMP-PKA pathway in dopamine-induced facilitation of synaptic transmission, we demonstrate here that the dopaminergic facilitation of synaptic responses in layer II entorhinal neurons also relies on a signaling cascade dependent on PI-linked D1 receptors, PLC, release of Ca2+ from internal stores, and PKC activation which is

The significance of memory in sensory cortex

OpenAIRE

Muckli, Lars; Petro, Lucy S.

2017-01-01

Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing.

The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

International Nuclear Information System (INIS)

Chen Bo; Xia Jing; Li Guangxing; Zhou Yifeng

2010-01-01

Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unit responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.

Sensory modality specificity of neural activity related to memory in visual cortex.

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Gibson, J R; Maunsell, J H

1997-09-01

Previous studies have shown that when monkeys perform a delayed match-to-sample (DMS) task, some neurons in inferotemporal visual cortex are activated selectively during the delay period when the animal must remember particular visual stimuli. This selective delay activity may be involved in short-term memory. It does not depend on visual stimulation: both auditory and tactile stimuli can trigger selective delay activity in inferotemporal cortex when animals expect to respond to visual stimuli in a DMS task. We have examined the overall modality specificity of delay period activity using a variety of auditory/visual cross-modal and unimodal DMS tasks. The cross-modal DMS tasks involved making specific long-term memory associations between visual and auditory stimuli, whereas the unimodal DMS tasks were standard identity matching tasks. Delay activity existed in auditory/visual cross-modal DMS tasks whether the animal anticipated responding to visual or auditory stimuli. No evidence of selective delay period activation was seen in a purely auditory DMS task. Delay-selective cells were relatively common in one animal where they constituted up to 53% neurons tested with a given task. This was only the case for up to 9% of cells in a second animal. In the first animal, a specific long-term memory representation for learned cross-modal associations was observed in delay activity, indicating that this type of representation need not be purely visual. Furthermore, in this same animal, delay activity in one cross-modal task, an auditory-to-visual task, predicted correct and incorrect responses. These results suggest that neurons in inferotemporal cortex contribute to abstract memory representations that can be activated by input from other sensory modalities, but these representations are specific to visual behaviors.

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines

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Ruijie Li

2018-04-01

Full Text Available In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca2+ indicators, we recorded the Ca2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca2+ indicators (GECIs, we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors.

Optogenetic stimulation of lateral amygdala input to posterior piriform cortex modulates single-unit and ensemble odor processing

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Benjamin eSadrian

2015-12-01

Full Text Available Olfactory information is synthesized within the olfactory cortex to provide not only an odor percept, but also a contextual significance that supports appropriate behavioral response to specific odor cues. The piriform cortex serves as a communication hub within this circuit by sharing reciprocal connectivity with higher processing regions, such as the lateral entorhinal cortex and amygdala. The functional significance of these descending inputs on piriform cortical processing of odorants is currently not well understood. We have employed optogenetic methods to selectively stimulate lateral and basolateral amygdala (BLA afferent fibers innervating the posterior piriform cortex (pPCX to quantify BLA modulation of pPCX odor-evoked activity. Single unit odor-evoked activity of anaesthetized BLA-infected animals was significantly modulated compared with control animal recordings, with individual cells displaying either enhancement or suppression of odor-driven spiking. In addition, BLA activation induced a decorrelation of odor-evoked pPCX ensemble activity relative to odor alone. Together these results indicate a modulatory role in pPCX odor processing for the BLA complex, which could contribute to learned changes in PCX activity following associative conditioning.

Deep Echo State Network (DeepESN): A Brief Survey

OpenAIRE

Gallicchio, Claudio; Micheli, Alessio

2017-01-01

The study of deep recurrent neural networks (RNNs) and, in particular, of deep Reservoir Computing (RC) is gaining an increasing research attention in the neural networks community. The recently introduced deep Echo State Network (deepESN) model opened the way to an extremely efficient approach for designing deep neural networks for temporal data. At the same time, the study of deepESNs allowed to shed light on the intrinsic properties of state dynamics developed by hierarchical compositions ...

Hypergravity exposure decreases gamma-aminobutyric acid immunoreactivity in axon terminals contacting pyramidal cells in the rat somatosensory cortex: a quantitative immunocytochemical image analysis

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D'Amelio, F.; Wu, L. C.; Fox, R. A.; Daunton, N. G.; Corcoran, M. L.; Polyakov, I.

1998-01-01

Quantitative evaluation of gamma-aminobutyric acid immunoreactivity (GABA-IR) in the hindlimb representation of the rat somatosensory cortex after 14 days of exposure to hypergravity (hyper-G) was conducted by using computer-assisted image processing. The area of GABA-IR axosomatic terminals apposed to pyramidal cells of cortical layer V was reduced in rats exposed to hyper-G compared with control rats, which were exposed either to rotation alone or to vivarium conditions. Based on previous immunocytochemical and behavioral studies, we suggest that this reduction is due to changes in sensory feedback information from muscle receptors. Consequently, priorities for muscle recruitment are altered at the cortical level, and a new pattern of muscle activity is thus generated. It is proposed that the reduction observed in GABA-IR of the terminal area around pyramidal neurons is the immunocytochemical expression of changes in the activity of GABAergic cells that participate in reprogramming motor outputs to achieve effective movement control in response to alterations in the afferent information.

The effect of deep frying or conventional oven cooking on inactivation of Shiga toxin-producing cells of Escherichia coli (STEC) in meatballs

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We investigated the effects deep frying or oven cooking on inactivation of Shiga toxin-producing cells of Escherichia coli (STEC) in meatballs. A finely-ground veal and/or a beef-pork-veal mixture were inoculated (ca. 7.0 log CFU/g) with an eight-strain, genetically-marked cocktail of rifampicin-res...

Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma

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Kroeger, Daniel; Florea, Bogdan; Amzica, Florin

2013-01-01

The electroencephalogram (EEG) reflects brain electrical activity. A flat (isoelectric) EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human) or by application of high doses of anesthesia (isoflurane in animals) leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes). Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region) we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma. PMID:24058669

Functional organization and visual representations in human ventral lateral prefrontal cortex

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Annie Wai Yiu Chan

2013-07-01

Full Text Available Recent neuroimaging studies in both human and non-human primates have identified face selective activation in the ventral lateral prefrontal cortex even in the absence of working memory demands. Further, research has suggested that this face-selective response is largely driven by the presence of the eyes. However, the nature and origin of visual category responses in the ventral lateral prefrontal cortex remain unclear. Further, in a broader sense, how do these findings relate to our current understandings of lateral prefrontal cortex? What do these findings tell us about the underlying function and organization principles of the ventral lateral prefrontal cortex? What is the future direction for investigating visual representations in this cortex? This review focuses on the function, topography, and circuitry of the ventral lateral prefrontal cortex to enhance our understanding of the evolution and development of this cortex.

Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining

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Yuri Gonchar

2008-03-01

Full Text Available The majority of cortical interneurons use GABA (gamma amino butyric acid as inhibitory neurotransmitter. GABAergic neurons are morphologically, connectionally, electrically and chemically heterogeneous. In rat cerebral cortex three distinct groups of GABAergic interneurons have been identifi ed by the expression of parvalbumin (PV, calretinin (CR and somatostatin (SOM. Recent studies in mouse cerebral cortex have revealed a different organization in which the CR and SOM populations are partially overlapping. Because CR and SOM neurons derive from different progenitors located in different embryonic structures, the coexpression of CR + SOM suggests that the chemical differentiation of interneurons is regulated postmitotically. Here, we have taken an important fi rst step towards understanding this process by triple immunostaining mouse visual cortex with a panel of antibodies, which has been used extensively for classifying developing interneurons. We have found at least 13 distinct groups of GABAergic neurons which include PV, CR, SOM, CCK (cholecystokinin, CR + SOM, CR + NPY (neuropeptide Y, CR + VIP (vasointestinal polypeptide, SOM + NPY, SOM + VIP, VIP + ChAT (choline acetyltransferase, CCK + NPY, CR + SOM + NPY and CR + SOM + VIP expressing cells. Triple immunostaining with PV, CR and SOM antibodies during postnatal development further showed that PV is never colocalized with CR and SOM. Importantly, expression of SOM and CR + SOM developed after the percentage of CR cells that do not express SOM has reached the mature level, suggesting that the chemical differentiation of SOM and CR + SOM neurons is a postnatal event, which may be controlled by transcriptional regulation.

Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

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Takata, Kotaro; Yamauchi, Hideki; Tatsuno, Hisashi; Hashimoto, Keiji; Abo, Masahiro

2006-01-01

To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model. Copyright 2006 S. Karger AG, Basel.

Investigation of electrically active defects in InGaAs quantum wire intermediate-band solar cells using deep-level transient spectroscopy (DLTS) technique

OpenAIRE

Al Saqri, Noor alhuda; Felix, Jorlandio F.; Aziz, Mohsin; Kunets, Vasyl P.; Jameel, Dler Adil; Taylor, David; Henini, M.; Abd El-sadek, Mahmmoud S.; Furrow, Colin; Ware, Morgan E.; Benamara, Mourad; Mortazavi, Mansour; Salamo, Gregory

2016-01-01

InGaAs quantum wire (QWr) intermediate-band solar cell based nanostructures grown by molecular beam epitaxy are studied. The electrical and interface properties of these solar cell devices, as determined by current–voltage (I–V) and capacitance–voltage (C-V) techniques, were found to change with temperature over a wide range of 20–340 K. The electron and hole traps present in these devices have been investigated using deep-level transient spectroscopy (DLTS). The DLTS results showed that the ...

Monocular Visual Deprivation Suppresses Excitability in Adult Human Visual Cortex

DEFF Research Database (Denmark)

Lou, Astrid Rosenstand; Madsen, Kristoffer Hougaard; Paulson, Olaf Bjarne

2011-01-01

The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we...... of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.......The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we...... employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex...

Autoradiographic study of the efferent connections of the entorhinal cortex in the rat

International Nuclear Information System (INIS)

Wyss, J.M.

1981-01-01

The major findings can be summarized as follows. Whereas the projection of the lateral entorhinal area (LEA) to the dentate gyrus is broad in its longitudinal extent, the medial entorhinal area (MEA), and especially the ventral portion of this zone, projects in a more lamellar fashion. In the transverse plane the LEA preferentially projects to the inner (dorsal) blade of the dentate gyrus, while the MEA innervates both blades equally. Within the radial dimension, the entorhinal cortex projects to the dentate gyrus according to a medial to lateral gradient, with lateral portions of the LEA projecting along the pial surface and successively more medial portions of the entorhinal projecting closer to the granule cells. The commissural entorhinal to dentate projections are similar to the ipsilateral projections in location; however, they are considerably reduced in septotemporal extent and do not arise from cells in the ventral half of either LEA or the intermediate entorhinal area (IEA). The projection of the entorhinal cortex to Ammon's horn reflects the same longitudinal characteristics as the dentate projections. An alvear input which extends only to the pyramidal cells at the CA1-subicular junction was most noticeable at ventral hippocampal levels. The extrahippocampal projections arise predominantly from cells in the LEA and project forward along the angular bundle to the piriform and periamygdaloid cortices, as well as the endopiriform nucleus, the lateral, basolateral, and cortical amygdaloid nuclei, the nucleus of the lateral olfactory tract, the olfactory tubercle, the anterior olfactory nucleus, the taenia tecta, and the indusium griseum

DAPs: Deep Action Proposals for Action Understanding

KAUST Repository

Escorcia, Victor; Caba Heilbron, Fabian; Niebles, Juan Carlos; Ghanem, Bernard

2016-01-01

action proposals from long videos. We show how to take advantage of the vast capacity of deep learning models and memory cells to retrieve from untrimmed videos temporal segments, which are likely to contain actions. A comprehensive evaluation indicates

Levels of glutamate, aspartate, GABA, and taurine in different regions of the cerebellum after x-irradiation-induced neuronal loss

International Nuclear Information System (INIS)

Rea, M.A.; McBride, W.J.; Rohde, B.H.

1981-01-01

The levels of glutamate (Glu), aspartate (Asp), gamma-amino-n-butyric acid (GABA), and taurine (Tau) were determined in the cortex, molecular layer, and deep nuclei of cerebella of adult rats exposed to X-irradiation at 12-15 days following birth (to prevent the acquisition of late-forming granule cells; 12-15x group) and 8-15 days following birth (to prevent the acquisition of granule and stellate cells; 8-15x group). Also, the levels of the four amino acids were measured in the crude synaptosomal fraction (P2) isolated from the whole cerebella of the control, 12-15x, and 8-15x groups. The level of Glu was significantly decreased by (1) 6-20% in the cerebellar cortex; (2) 15-20% in the molecular layer; and (3) 25-50% in the P2 fraction of the X-irradiated groups relative to control values. The content of Glu in the deep nuclei was not changed by X-irradiation treatment. Regional levels of Asp were unchanged by X-irradiation, while its level in P2 decreased by 15-30% after treatment. The levels of GABA and Tau in the molecular layer, deep nuclei, or P2 were not changed in the experimental groups. However, there was a 15% increase in the levels of GABA and Tau in the cerebellar cortex of the 8-15x group relative to control values. The data support the proposed role of glutamate as the excitatory transmitter released from the cerebellar granule cells but are inconclusive regarding a transmitter role for either Tau or GABA from cerebellar stellate cells

Noradrenaline decreases spike voltage threshold and induces electrographic sharp waves in turtle medial cortex in vitro.

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Lorenzo, Daniel; Velluti, Julio C

2004-01-01

The noradrenergic modulation of neuronal properties has been described at different levels of the mammalian brain. Although the anatomical characteristics of the noradrenergic system are well known in reptiles, functional data are scarce. In our study the noradrenergic modulation of cortical electrogenesis in the turtle medial cortex was studied in vitro using a combination of field and intracellular recordings. Turtle EEG consists of a low voltage background interspersed by spontaneous large sharp waves (LSWs). Noradrenaline (NA, 5-40 microM) induced (or enhanced) the generation of LSWs in a dose-dependent manner. Pharmacological experiments suggest the participation of alpha and beta receptors in this effect. In medial cortex neurons NA induced a hyperpolarization of the resting potential and a decrease of input resistance. Both effects were observed also after TTX treatment. Noradrenaline increased the response of the cells to depolarizing pulses, resulting in an upward shift of the frequency/current relation. In most cells the excitability change was mediated by a decrease of the spike voltage threshold resulting in the reduction of the amount of depolarization needed to fire the cell (voltage threshold minus resting potential). As opposed to the mechanisms reported in mammalian neurons, no changes in the frequency adaptation or the post-train afterhyperpolarization were observed. The NA effects at the cellular level were not reproduced by noradrenergic agonists. Age- and species-dependent properties in the pharmacology of adrenergic receptors could be involved in this result. Cellular effects of NA in turtle cortex are similar to those described in mammals, although the increase in cellular excitability seems to be mediated by a different mechanism. Copyright 2004 S. Karger AG, Basel

Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

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Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

2015-01-01

Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic. PMID:25729353

Pressure induced deep tissue injury explained

NARCIS (Netherlands)

Oomens, C.W.J.; Bader, D.L.; Loerakker, S.; Baaijens, F.P.T.

The paper describes the current views on the cause of a sub-class of pressure ulcers known as pressure induced deep tissue injury (DTI). A multi-scale approach was adopted using model systems ranging from single cells in culture, tissue engineered muscle to animal studies with small animals. This

A role for the deep orange and carnation eye color genes in lysosomal delivery in Drosophila.

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Sevrioukov, E A; He, J P; Moghrabi, N; Sunio, A; Krämer, H

1999-10-01

Deep orange and carnation are two of the classic eye color genes in Drosophila. Here, we demonstrate that Deep orange is part of a protein complex that localizes to endosomal compartments. A second component of this complex is Carnation, a homolog of Sec1p-like regulators of membrane fusion. Because complete loss of deep orange function is lethal, the role of this complex in intracellular trafficking was analyzed in deep orange mutant clones. Retinal cells devoid of deep orange function completely lacked pigmentation and exhibited exaggerated multivesicular structures. Furthermore, a defect in endocytic trafficking was visualized in developing photoreceptor cells. These results provide direct evidence that eye color mutations of the granule group also disrupt vesicular trafficking to lysosomes.

The AMERE project: Enabling real-time detection of radiation effects in individual cells in deep space

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De Vos, Winnok H.; Meesen, Geert; Szpirer, Cedric; Scohy, Sophie; Cherukuri, Chaitanya; Evrard, Olivier; Hutsebaut, Xavier; Beghuin, Didier

2012-12-01

A major concern for long-term deep space missions is the detrimental impact of cosmic radiation on human health. Especially the presence of high-energy particles of high atomic mass (HZE) represents a serious threat. To contribute to a fundamental understanding of space radiation effects and to help improving risk assessment for humans on the Moon, the ESA Lunar Lander mission model payload includes a package dedicated to cell-based radiobiology experiments in the form of an Autonomous Microscope for Examination of Radiation Effects (AMERE). The purpose of this setup is to enable real-time visualization of DNA damage repair in living cells after traversal of HZE particles on the Moon. To assess the feasibility of this challenging experiment, we have analysed the biological and technological demands. In this article, we discuss the experimental concept, the biological considerations and describe the implications for system design.

Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy

Science.gov (United States)

Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Claude Boccara, A.; Bourdieu, Laurent

2011-11-01

Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.

Science.gov (United States)

Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

2011-11-01

Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

The deep cerebral stimulation of the under thalamic nucleus modifies the cerebral metabolism in {sup 18}FDG-Tep of obsessive compulsive patients; La stimulation cerebrale profonde du noyau sous thalamique modifie le metabolisme cerebral en 18FDG-TEP des patients obsessionnels compulsifs

Energy Technology Data Exchange (ETDEWEB)

Le Jeune, F.; Garin, E. [Service de medecine nucleaire, centre Eugene-Marquis, Rennes, (France); Verin, M.; Peron, J. [service de neurologie, CHU Pontchaillou, Rennes, (France); Mallet, L.; Yelnik, J. [Inserm, Avenir Team, Behavior, Emotion and Basal Ganglia, IFR 70, Pitie-Salpetriere, Paris, (France); Kreps, M.O. [Inserm U796, service de psychiatrie, hopital Sainte-Anne, Paris, (France); Drapier, D.; Millet, B. [service de psychiatrie adulte, centre hospitalier Guillaume-Regnier, Rennes, (France)

2009-05-15

The aim of this work was to find again this orbito-frontal hyper metabolism among the resistant obsessive compulsive disorder patients that are going to benefit of a deep cerebral stimulation of the under thalamus nucleus and to demonstrate that this new therapy approach leads a reduction of the metabolism in this area in correlation with the clinical improvement. It is about the first study realized in isotopic functional imaging on ten resistant compulsive disorder patients treated by bilateral deep cerebral stimulation of the under thalamus nucleus. It shows that the treatment efficiency is in relation with a reduction of the glucide metabolism in the right orbito-frontal cortex. It suggests equally that the under thalamus nucleus would be functionally linked to the orbito-frontal cortex. (N.C.)

Crosstalk between intracellular and extracellular signals regulating interneuron production, migration and integration into the cortex.

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Peyre, Elise; Silva, Carla G; Nguyen, Laurent

2015-01-01

During embryogenesis, cortical interneurons are generated by ventral progenitors located in the ganglionic eminences of the telencephalon. They travel along multiple tangential paths to populate the cortical wall. As they reach this structure they undergo intracortical dispersion to settle in their final destination. At the cellular level, migrating interneurons are highly polarized cells that extend and retract processes using dynamic remodeling of microtubule and actin cytoskeleton. Different levels of molecular regulation contribute to interneuron migration. These include: (1) Extrinsic guidance cues distributed along migratory streams that are sensed and integrated by migrating interneurons; (2) Intrinsic genetic programs driven by specific transcription factors that grant specification and set the timing of migration for different subtypes of interneurons; (3) Adhesion molecules and cytoskeletal elements/regulators that transduce molecular signalings into coherent movement. These levels of molecular regulation must be properly integrated by interneurons to allow their migration in the cortex. The aim of this review is to summarize our current knowledge of the interplay between microenvironmental signals and cell autonomous programs that drive cortical interneuron porduction, tangential migration, and intergration in the developing cerebral cortex.

Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism

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Herve eLefebvre

2015-04-01

Full Text Available It has been well established that, in the human adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes and endothelial cells. These different types of cells are present in bilateral macronodular adrenal hyperplasia, a rare etiology of primary adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events which cause the disease favor abnormal adrenal differenciation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms which are likely to play a role in the pathophysiology of bilateral macronodular adrenal hyperplasia-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept.

The medial prefrontal cortex-lateral entorhinal cortex circuit is essential for episodic-like memory and associative object-recognition.

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Chao, Owen Y; Huston, Joseph P; Li, Jay-Shake; Wang, An-Li; de Souza Silva, Maria A

2016-05-01

The prefrontal cortex directly projects to the lateral entorhinal cortex (LEC), an important substrate for engaging item-associated information and relaying the information to the hippocampus. Here we ask to what extent the communication between the prefrontal cortex and LEC is critically involved in the processing of episodic-like memory. We applied a disconnection procedure to test whether the interaction between the medial prefrontal cortex (mPFC) and LEC is essential for the expression of recognition memory. It was found that male rats that received unilateral NMDA lesions of the mPFC and LEC in the same hemisphere, exhibited intact episodic-like (what-where-when) and object-recognition memories. When these lesions were placed in the opposite hemispheres (disconnection), episodic-like and associative memories for object identity, location and context were impaired. However, the disconnection did not impair the components of episodic memory, namely memory for novel object (what), object place (where) and temporal order (when), per se. Thus, the present findings suggest that the mPFC and LEC are a critical part of a neural circuit that underlies episodic-like and associative object-recognition memory. © 2015 Wiley Periodicals, Inc.

Deep learning improves prediction of CRISPR-Cpf1 guide RNA activity.

Science.gov (United States)

Kim, Hui Kwon; Min, Seonwoo; Song, Myungjae; Jung, Soobin; Choi, Jae Woo; Kim, Younggwang; Lee, Sangeun; Yoon, Sungroh; Kim, Hyongbum Henry

2018-03-01

We present two algorithms to predict the activity of AsCpf1 guide RNAs. Indel frequencies for 15,000 target sequences were used in a deep-learning framework based on a convolutional neural network to train Seq-deepCpf1. We then incorporated chromatin accessibility information to create the better-performing DeepCpf1 algorithm for cell lines for which such information is available and show that both algorithms outperform previous machine learning algorithms on our own and published data sets.

Deep-Sea Microbes: Linking Biogeochemical Rates to -Omics Approaches

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Herndl, G. J.; Sintes, E.; Bayer, B.; Bergauer, K.; Amano, C.; Hansman, R.; Garcia, J.; Reinthaler, T.

2016-02-01

Over the past decade substantial progress has been made in determining deep ocean microbial activity and resolving some of the enigmas in understanding the deep ocean carbon flux. Also, metagenomics approaches have shed light onto the dark ocean's microbes but linking -omics approaches to biogeochemical rate measurements are generally rare in microbial oceanography and even more so for the deep ocean. In this presentation, we will show by combining metagenomics, -proteomics and biogeochemical rate measurements on the bulk and single-cell level that deep-sea microbes exhibit characteristics of generalists with a large genome repertoire, versatile in utilizing substrate as revealed by metaproteomics. This is in striking contrast with the apparently rather uniform dissolved organic matter pool in the deep ocean. Combining the different -omics approaches with metabolic rate measurements, we will highlight some major inconsistencies and enigmas in our understanding of the carbon cycling and microbial food web structure in the dark ocean.

The effects of early hypo- and hyperthyroidism on the development of rat cerebellar cortex. III. Kinetics of cell proliferation in the external granular layer.

Science.gov (United States)

Lauder, J M

1977-04-22

The effects of early hypo- and hyperthyroidism on the rates of cell acquisition and proliferation have been studied in the external granular layer (EGL) of the developing rat cerebellar cortex at 10 days of age using quantitative autoradiographic methods. Both altered thyroid states reduce the rate of cell acquisition in the EGL, but appear to do so for different reasons. Hyperthyroidism shortens the average length of the cell cycle by decreasing the duration of the pre-DNA synthetic phase (G1), indicating that excess thyroxine may exert a direct effect on the EGL. This action involves the early onset of neuronal differentiation (cessation of proliferation)46 which presumably leads to the observed decrease in the rate of cell acquisition (increased doubling time). Such differentiating cells do not, however, leave the proliferative zone or the EGL prematurely, resulting in a reduced labeling index, mitotic index, and growth fraction as non-dividing cells dilute the proliferating cell population. Hypothyroidism, on the other hand, leads to no significant change in the length of the cell cycle or in the mitotic index, but causes a decreased labeling index and growth fraction, as well as a reduced rate of cell acquisition (increased doubling time). No significant change in the amount of cell death in the EGL could be found to explain this apparent discrepancy between the rate of cell proliferation (cell cycle length) and cell acqusiition. The answer to this puzzle appears to lie in the mitotic index, which is not affected to the same extent as the labeling index, although it is also slightly reduced. If cells were to remain longer in mitosis, this could result in a decreased labeling index and growth fraction but nearly normal mitotic index and cell cycle length (as measured using the % labeled mitoses method), since those cells dropping out of the cycling population would be counted as mitoses...

Potential Osteoporosis Recovery by Deep Sea Water through Bone Regeneration in SAMP8 Mice

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Hen-Yu Liu

2013-01-01

Full Text Available The aim of this study is to examine the therapeutic potential of deep sea water (DSW on osteoporosis. Previously, we have established the ovariectomized senescence-accelerated mice (OVX-SAMP8 and demonstrated strong recovery of osteoporosis by stem cell and platelet-rich plasma (PRP. Deep sea water at hardness (HD 1000 showed significant increase in proliferation of osteoblastic cell (MC3T3 by MTT assay. For in vivo animal study, bone mineral density (BMD was strongly enhanced followed by the significantly increased trabecular numbers through micro-CT examination after a 4-month deep sea water treatment, and biochemistry analysis showed that serum alkaline phosphatase (ALP activity was decreased. For stage-specific osteogenesis, bone marrow-derived stromal cells (BMSCs were harvested and examined. Deep sea water-treated BMSCs showed stronger osteogenic differentiation such as BMP2, RUNX2, OPN, and OCN, and enhanced colony forming abilities, compared to the control group. Interestingly, most untreated OVX-SAMP8 mice died around 10 months; however, approximately 57% of DSW-treated groups lived up to 16.6 months, a life expectancy similar to the previously reported life expectancy for SAMR1 24 months. The results demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy as a complementary and alternative medicine (CAM.

Exploring frontiers of the deep biosphere through scientific ocean drilling

Science.gov (United States)

Inagaki, F.; D'Hondt, S.; Hinrichs, K. U.

2015-12-01

Since the first deep biosphere-dedicated Ocean Drilling Program (ODP) Leg 201 using the US drill ship JOIDES Resolution in 2002, scientific ocean drilling has offered unique opportunities to expand our knowledge of the nature and extent of the deep biosphere. The latest estimate of the global subseafloor microbial biomass is ~1029cells, accounting for 4 Gt of carbon and ~1% of the Earth's total living biomass. The subseafloor microbial communities are evolutionarily diverse and their metabolic rates are extraordinarily slow. Nevertheless, accumulating activity most likely plays a significant role in elemental cycles over geological time. In 2010, during Integrated Ocean Drilling Program (IODP) Expedition 329, the JOIDES Resolutionexplored the deep biosphere in the open-ocean South Pacific Gyre—the largest oligotrophic province on our planet. During Expedition 329, relatively high concentrations of dissolved oxygen and significantly low biomass of microbial populations were observed in the entire sediment column, indicating that (i) there is no limit to life in open-ocean sediment and (ii) a significant amount of oxygen reaches through the sediment to the upper oceanic crust. This "deep aerobic biosphere" inhabits the sediment throughout up to ~37 percent of the world's oceans. The remaining ~63 percent of the oceans is comprised of higher productivity areas that contain the "deep anaerobic biosphere". In 2012, during IODP Expedition 337, the Japanese drill ship Chikyu explored coal-bearing sediments down to 2,466 meters below the seafloor off the Shimokita Peninsula, Japan. Geochemical and microbiological analyses consistently showed the occurrence of methane-producing communities associated with the coal beds. Cell concentrations in deep sediments were notably lower than those expected from the global regression line, implying that the bottom of the deep biosphere is approached in these beds. Taxonomic composition of the deep coal-bearing communities profoundly

Two whisker motor areas in the rat cortex: evidence from thalamocortical connections.

Science.gov (United States)

Mohammed, Hisham; Jain, Neeraj

2014-02-15

In primates, the motor cortex consists of at least seven different areas, which are involved in movement planning, coordination, initiation, and execution. However, for rats, only the primary motor cortex has been well described. A rostrally located second motor area has been proposed, but its extent, organization, and even definitive existence remain uncertain. Only a rostral forelimb area (RFA) has been definitively described, besides few reports of a rostral hindlimb area. We have previously proposed existence of a second whisker area, which we termed the rostral whisker area (RWA), based on its differential response to intracortical microstimulation compared with the caudal whisker area (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci 27:228). To establish that RWA is distinct from the caudally contiguous CWA, we determined sources of thalamic inputs to the two proposed whisker areas. Sources of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were determined for comparison. The results show that RWA and CWA can be distinguished based on differences in their thalamic inputs. RWA receives major projections from mediodorsal and ventromedial nuclei, whereas the major projections to CWA are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the nuclei projecting to CWA are same as for CFA. The results suggest that rats have a second rostrally located motor area with RWA and RFA as its constituents. Copyright © 2013 Wiley Periodicals, Inc.

Classification of C2C12 cells at differentiation by convolutional neural network of deep learning using phase contrast images.

Science.gov (United States)

Niioka, Hirohiko; Asatani, Satoshi; Yoshimura, Aina; Ohigashi, Hironori; Tagawa, Seiichi; Miyake, Jun

2018-01-01

In the field of regenerative medicine, tremendous numbers of cells are necessary for tissue/organ regeneration. Today automatic cell-culturing system has been developed. The next step is constructing a non-invasive method to monitor the conditions of cells automatically. As an image analysis method, convolutional neural network (CNN), one of the deep learning method, is approaching human recognition level. We constructed and applied the CNN algorithm for automatic cellular differentiation recognition of myogenic C2C12 cell line. Phase-contrast images of cultured C2C12 are prepared as input dataset. In differentiation process from myoblasts to myotubes, cellular morphology changes from round shape to elongated tubular shape due to fusion of the cells. CNN abstract the features of the shape of the cells and classify the cells depending on the culturing days from when differentiation is induced. Changes in cellular shape depending on the number of days of culture (Day 0, Day 3, Day 6) are classified with 91.3% accuracy. Image analysis with CNN has a potential to realize regenerative medicine industry.

Why & When Deep Learning Works: Looking Inside Deep Learnings

OpenAIRE

Ronen, Ronny

2017-01-01

The Intel Collaborative Research Institute for Computational Intelligence (ICRI-CI) has been heavily supporting Machine Learning and Deep Learning research from its foundation in 2012. We have asked six leading ICRI-CI Deep Learning researchers to address the challenge of "Why & When Deep Learning works", with the goal of looking inside Deep Learning, providing insights on how deep networks function, and uncovering key observations on their expressiveness, limitations, and potential. The outp...

Anisotropy of ongoing neural activity in the primate visual cortex

Directory of Open Access Journals (Sweden)

Maier A

2014-09-01

Full Text Available Alexander Maier,1 Michele A Cox,1 Kacie Dougherty,1 Brandon Moore,1 David A Leopold2 1Department of Psychology, College of Arts and Science, Vanderbilt University, Nashville, TN, USA; 2Section on Cognitive Neurophysiology and Imaging, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA Abstract: The mammalian neocortex features distinct anatomical variation in its tangential and radial extents. This review consolidates previously published findings from our group in order to compare and contrast the spatial profile of neural activity coherence across these distinct cortical dimensions. We focus on studies of ongoing local field potential (LFP data obtained simultaneously from multiple sites in the primary visual cortex in two types of experiments in which electrode contacts were spaced either along the cortical surface or at different laminar positions. These studies demonstrate that across both dimensions the coherence of ongoing LFP fluctuations diminishes as a function of interelectrode distance, although the nature and spatial scale of this falloff is very different. Along the cortical surface, the overall LFP coherence declines gradually and continuously away from a given position. In contrast, across the cortical layers, LFP coherence is discontinuous and compartmentalized as a function of depth. Specifically, regions of high LFP coherence fall into discrete superficial and deep laminar zones, with an abrupt discontinuity between the granular and infragranular layers. This spatial pattern of ongoing LFP coherence is similar when animals are at rest and when they are engaged in a behavioral task. These results point to the existence of partially segregated laminar zones of cortical processing that extend tangentially within the laminar compartments and are thus oriented orthogonal to the cortical columns. We interpret these electrophysiological observations in light of the known anatomical organization of

Cortical plasticity induced by spike-triggered microstimulation in primate somatosensory cortex.

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Weiguo Song

Full Text Available Electrical stimulation of the nervous system for therapeutic purposes, such as deep brain stimulation in the treatment of Parkinson's disease, has been used for decades. Recently, increased attention has focused on using microstimulation to restore functions as diverse as somatosensation and memory. However, how microstimulation changes the neural substrate is still not fully understood. Microstimulation may cause cortical changes that could either compete with or complement natural neural processes, and could result in neuroplastic changes rendering the region dysfunctional or even epileptic. As part of our efforts to produce neuroprosthetic devices and to further study the effects of microstimulation on the cortex, we stimulated and recorded from microelectrode arrays in the hand area of the primary somatosensory cortex (area 1 in two awake macaque monkeys. We applied a simple neuroprosthetic microstimulation protocol to a pair of electrodes in the area 1 array, using either random pulses or pulses time-locked to the recorded spiking activity of a reference neuron. This setup was replicated using a computer model of the thalamocortical system, which consisted of 1980 spiking neurons distributed among six cortical layers and two thalamic nuclei. Experimentally, we found that spike-triggered microstimulation induced cortical plasticity, as shown by increased unit-pair mutual information, while random microstimulation did not. In addition, there was an increased response to touch following spike-triggered microstimulation, along with decreased neural variability. The computer model successfully reproduced both qualitative and quantitative aspects of the experimental findings. The physiological findings of this study suggest that even simple microstimulation protocols can be used to increase somatosensory information flow.

A defined network of fast-spiking interneurons in orbitofrontal cortex: responses to behavioral contingencies and ketamine administration

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Michael C Quirk

2009-11-01

Full Text Available Orbitofrontal cortex (OFC is a region of prefrontal cortex implicated in the motivational control of behavior and in related abnormalities seen in psychosis and depression. It has been hypothesized that a critical mechanism in these disorders is the dysfunction of GABAergic interneurons that normally regulate prefrontal information processing. Here, we studied a subclass of interneurons isolated in rat OFC using extracellular waveform and spike train analysis. During performance of a goal-directed behavioral task, the firing of this class of putative fast-spiking (FS interneurons showed robust temporal correlations indicative of a functionally coherent network. FS cell activity also co-varied with behavioral response latency, a key indicator of motivational state. Systemic administration of ketamine, a drug that can mimic psychosis, preferentially inhibited this cell class. Together, these results support the idea that OFC-FS interneurons form a critical link in the regulation of motivation by prefrontal circuits during normal and abnormal brain and behavioral states.

[Glucose-monitoring neurons of the medial ventrolateral prefrontal (orbitofrontal) cortex are involved in the maintenance of homeostasis].

Science.gov (United States)

Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Karádi, Zoltán

2017-05-01

The medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells. The functional significance of these chemosensory neurons was to be elucidated. Electrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed. Fifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group. Glucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis. Orv Hetil. 2017; 158(18): 692-700.

The Significance of Memory in Sensory Cortex.

Science.gov (United States)

Muckli, Lars; Petro, Lucy S

2017-05-01

Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Olfactocentric paralimbic cortex morphology in adolescents with bipolar disorder

OpenAIRE

Wang, Fei; Kalmar, Jessica H.; Womer, Fay Y.; Edmiston, Erin E.; Chepenik, Lara G.; Chen, Rachel; Spencer, Linda; Blumberg, Hilary P.

2011-01-01

The olfactocentric paralimbic cortex plays a critical role in the regulation of emotional and neurovegetative functions that are disrupted in core features of bipolar disorder. Adolescence is thought to be a critical period in both the maturation of the olfactocentric paralimbic cortex and in the emergence of bipolar disorder pathology. Together, these factors implicate a central role for the olfactocentric paralimbic cortex in the development of bipolar disorder and suggest that abnormalitie...

The non-lemniscal auditory cortex in ferrets: convergence of corticotectal inputs in the superior colliculus

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Victoria M Bajo