The Impact of Development and Sensory Deprivation on Dendritic Protrusions in the Mouse Barrel Cortex

PubMed Central

Chen, Chia-Chien; Bajnath, Adesh; Brumberg, Joshua C.

2015-01-01

Dendritic protrusions (spines and filopodia) are structural indicators of synapses that have been linked to neuronal learning and memory through their morphological alterations induced by development and experienced-dependent activities. Although previous studies have demonstrated that depriving sensory experience leads to structural changes in neocortical organization, the more subtle effects on dendritic protrusions remain unclear, mostly due to focus on only one specific cell type and/or age of manipulation. Here, we show that sensory deprivation induced by whisker trimming influences the dendritic protrusions of basilar dendrites located in thalamocortical recipient lamina (IV and VI) of the mouse barrel cortex in a layer-specific manner. Following 1 month of whisker trimming after birth, the density of dendritic protrusions increased in layer IV, but decreased in layer VI. Whisker regrowth for 1 month returned protrusion densities to comparable level of age-matched controls in layer VI, but not in layer IV. In adults, chronic sensory deprivation led to an increase in protrusion densities in layer IV, but not in layer VI. In addition, chronic pharmacological blockade of N-methyl-d-aspartate receptors (NMDARs) increased protrusion density in both layers IV and VI, which returned to the control level after 1 month of drug withdrawal. Our data reveal that different cortical layers respond to chronic sensory deprivation in different ways, with more pronounced effects during developmental critical periods than adulthood. We also show that chronically blocking NMDARs activity during developmental critical period also influences the protrusion density and morphology in the cerebral cortex. PMID:24408954

Somatosensory map expansion and altered processing of tactile inputs in a mouse model of fragile X syndrome.

PubMed

Juczewski, Konrad; von Richthofen, Helen; Bagni, Claudia; Celikel, Tansu; Fisone, Gilberto; Krieger, Patrik

2016-12-01

Fragile X syndrome (FXS) is a common inherited form of intellectual disability caused by the absence or reduction of the fragile X mental retardation protein (FMRP) encoded by the FMR1 gene. In humans, one symptom of FXS is hypersensitivity to sensory stimuli, including touch. We used a mouse model of FXS (Fmr1 KO) to study sensory processing of tactile information conveyed via the whisker system. In vivo electrophysiological recordings in somatosensory barrel cortex showed layer-specific broadening of the receptive fields at the level of layer 2/3 but not layer 4, in response to whisker stimulation. Furthermore, the encoding of tactile stimuli at different frequencies was severely affected in layer 2/3. The behavioral effect of this broadening of the receptive fields was tested in the gap-crossing task, a whisker-dependent behavioral paradigm. In this task the Fmr1 KO mice showed differences in the number of whisker contacts with platforms, decrease in the whisker sampling duration and reduction in the whisker touch-time while performing the task. We propose that the increased excitability in the somatosensory barrel cortex upon whisker stimulation may contribute to changes in the whisking strategy as well as to other observed behavioral phenotypes related to tactile processing in Fmr1 KO mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Lhx2 Expression in Postmitotic Cortical Neurons Initiates Assembly of the Thalamocortical Somatosensory Circuit.

PubMed

Wang, Chia-Fang; Hsing, Hsiang-Wei; Zhuang, Zi-Hui; Wen, Meng-Hsuan; Chang, Wei-Jen; Briz, Carlos G; Nieto, Marta; Shyu, Bai Chuang; Chou, Shen-Ju

2017-01-24

Cortical neurons must be specified and make the correct connections during development. Here, we examine a mechanism initiating neuronal circuit formation in the barrel cortex, a circuit comprising thalamocortical axons (TCAs) and layer 4 (L4) neurons. When Lhx2 is selectively deleted in postmitotic cortical neurons using conditional knockout (cKO) mice, L4 neurons in the barrel cortex are initially specified but fail to form cellular barrels or develop polarized dendrites. In Lhx2 cKO mice, TCAs from the thalamic ventral posterior nucleus reach the barrel cortex but fail to further arborize to form barrels. Several activity-regulated genes and genes involved in regulating barrel formation are downregulated in the Lhx2 cKO somatosensory cortex. Among them, Btbd3, an activity-regulated gene controlling dendritic development, is a direct downstream target of Lhx2. We find that Lhx2 confers neuronal competency for activity-dependent dendritic development in L4 neurons by inducing the expression of Btbd3. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Late emergence of the vibrissa direction selectivity map in the rat barrel cortex.

PubMed

Kremer, Yves; Léger, Jean-François; Goodman, Dan; Brette, Romain; Bourdieu, Laurent

2011-07-20

In the neocortex, neuronal selectivities for multiple sensorimotor modalities are often distributed in topographical maps thought to emerge during a restricted period in early postnatal development. Rodent barrel cortex contains a somatotopic map for vibrissa identity, but the existence of maps representing other tactile features has not been clearly demonstrated. We addressed the issue of the existence in the rat cortex of an intrabarrel map for vibrissa movement direction using in vivo two-photon imaging. We discovered that the emergence of a direction map in rat barrel cortex occurs long after all known critical periods in the somatosensory system. This map is remarkably specific, taking a pinwheel-like form centered near the barrel center and aligned to the barrel cortex somatotopy. We suggest that this map may arise from intracortical mechanisms and demonstrate by simulation that the combination of spike-timing-dependent plasticity at synapses between layer 4 and layer 2/3 and realistic pad stimulation is sufficient to produce such a map. Its late emergence long after other classical maps suggests that experience-dependent map formation and refinement continue throughout adult life.

Texture coarseness responsive neurons and their mapping in layer 2–3 of the rat barrel cortex in vivo

PubMed Central

Garion, Liora; Dubin, Uri; Rubin, Yoav; Khateb, Mohamed; Schiller, Yitzhak; Azouz, Rony; Schiller, Jackie

2014-01-01

Texture discrimination is a fundamental function of somatosensory systems, yet the manner by which texture is coded and spatially represented in the barrel cortex are largely unknown. Using in vivo two-photon calcium imaging in the rat barrel cortex during artificial whisking against different surface coarseness or controlled passive whisker vibrations simulating different coarseness, we show that layer 2–3 neurons within barrel boundaries differentially respond to specific texture coarsenesses, while only a minority of neurons responded monotonically with increased or decreased surface coarseness. Neurons with similar preferred texture coarseness were spatially clustered. Multi-contact single unit recordings showed a vertical columnar organization of texture coarseness preference in layer 2–3. These findings indicate that layer 2–3 neurons perform high hierarchical processing of tactile information, with surface coarseness embodied by distinct neuronal subpopulations that are spatially mapped onto the barrel cortex. DOI: http://dx.doi.org/10.7554/eLife.03405.001 PMID:25233151

Development of a method to evaluate glutamate receptor function in rat barrel cortex slices.

PubMed

Lehohla, M; Russell, V; Kellaway, L; Govender, A

2000-12-01

The rat is a nocturnal animal and uses its vibrissae extensively to navigate its environment. The vibrissae are linked to a highly organized part of the sensory cortex, called the barrel cortex which contains spiny neurons that receive whisker specific thalamic input and distribute their output mainly within the cortical column. The aim of the present study was to develop a method to evaluate glutamate receptor function in the rat barrel cortex. Long Evans rats (90-160 g) were killed by cervical dislocation and decapitated. The brain was rapidly removed, cooled in a continuously oxygenated, ice-cold Hepes buffer (pH 7.4) and sliced using a vibratome to produce 0.35 mm slices. The barrel cortex was dissected from slices corresponding to 8.6 to 4.8 mm anterior to the interaural line and divided into rostral, middle and caudal regions. Depolarization-induced uptake of 45Ca2+ was achieved by incubating test slices in a high K+ (62.5 mM) buffer for 2 minutes at 35 degrees C. Potassium-stimulated uptake of 45Ca2+ into the rostral region was significantly lower than into middle and caudal regions of the barrel cortex. Glutamate had no effect. NMDA significantly increased uptake of 45Ca2+ into all regions of the barrel cortex. The technique is useful in determining NMDA receptor function and will be applied to study differences between spontaneously hypertensive rats (SHR) that are used as a model for attention deficit disorder and their normotensive control rats.

Learning-Dependent Plasticity of the Barrel Cortex Is Impaired by Restricting GABA-Ergic Transmission.

PubMed

Posluszny, Anna; Liguz-Lecznar, Monika; Turzynska, Danuta; Zakrzewska, Renata; Bielecki, Maksymilian; Kossut, Malgorzata

2015-01-01

Experience-induced plastic changes in the cerebral cortex are accompanied by alterations in excitatory and inhibitory transmission. Increased excitatory drive, necessary for plasticity, precedes the occurrence of plastic change, while decreased inhibitory signaling often facilitates plasticity. However, an increase of inhibitory interactions was noted in some instances of experience-dependent changes. We previously reported an increase in the number of inhibitory markers in the barrel cortex of mice after fear conditioning engaging vibrissae, observed concurrently with enlargement of the cortical representational area of the row of vibrissae receiving conditioned stimulus (CS). We also observed that an increase of GABA level accompanied the conditioning. Here, to find whether unaltered GABAergic signaling is necessary for learning-dependent rewiring in the murine barrel cortex, we locally decreased GABA production in the barrel cortex or reduced transmission through GABAA receptors (GABAARs) at the time of the conditioning. Injections of 3-mercaptopropionic acid (3-MPA), an inhibitor of glutamic acid decarboxylase (GAD), into the barrel cortex prevented learning-induced enlargement of the conditioned vibrissae representation. A similar effect was observed after injection of gabazine, an antagonist of GABAARs. At the behavioral level, consistent conditioned response (cessation of head movements in response to CS) was impaired. These results show that appropriate functioning of the GABAergic system is required for both manifestation of functional cortical representation plasticity and for the development of a conditioned response.

Structured networks support sparse traveling waves in rodent somatosensory cortex.

PubMed

Moldakarimov, Samat; Bazhenov, Maxim; Feldman, Daniel E; Sejnowski, Terrence J

2018-05-15

Neurons responding to different whiskers are spatially intermixed in the superficial layer 2/3 (L2/3) of the rodent barrel cortex, where a single whisker deflection activates a sparse, distributed neuronal population that spans multiple cortical columns. How the superficial layer of the rodent barrel cortex is organized to support such distributed sensory representations is not clear. In a computer model, we tested the hypothesis that sensory representations in L2/3 of the rodent barrel cortex are formed by activity propagation horizontally within L2/3 from a site of initial activation. The model explained the observed properties of L2/3 neurons, including the low average response probability in the majority of responding L2/3 neurons, and the existence of a small subset of reliably responding L2/3 neurons. Sparsely propagating traveling waves similar to those observed in L2/3 of the rodent barrel cortex occurred in the model only when a subnetwork of strongly connected neurons was immersed in a much larger network of weakly connected neurons.

Neural coding in barrel cortex during whisker-guided locomotion

PubMed Central

Sofroniew, Nicholas James; Vlasov, Yurii A; Hires, Samuel Andrew; Freeman, Jeremy; Svoboda, Karel

2015-01-01

Animals seek out relevant information by moving through a dynamic world, but sensory systems are usually studied under highly constrained and passive conditions that may not probe important dimensions of the neural code. Here, we explored neural coding in the barrel cortex of head-fixed mice that tracked walls with their whiskers in tactile virtual reality. Optogenetic manipulations revealed that barrel cortex plays a role in wall-tracking. Closed-loop optogenetic control of layer 4 neurons can substitute for whisker-object contact to guide behavior resembling wall tracking. We measured neural activity using two-photon calcium imaging and extracellular recordings. Neurons were tuned to the distance between the animal snout and the contralateral wall, with monotonic, unimodal, and multimodal tuning curves. This rich representation of object location in the barrel cortex could not be predicted based on simple stimulus-response relationships involving individual whiskers and likely emerges within cortical circuits. DOI: http://dx.doi.org/10.7554/eLife.12559.001 PMID:26701910

Functional recovery of neuronal activity in rat whisker-barrel cortex sensory pathway from freezing injury after transplantation of adult bone marrow stromal cells.

PubMed

Mori, Kentaro; Iwata, Junko; Miyazaki, Masahiro; Nakao, Yasuaki; Maeda, Minoru

2005-07-01

The effect of transplantation of adult bone marrow stromal cells (MSCs) into the freeze-lesioned left barrel field cortex in the rat was investigated by measurement of local cerebral glucose utilization (lCMR(glc)) in the anatomic structures of the whisker-to-barrel cortex sensory pathway. Bone marrow stromal cells or phosphate-buffered saline (PBS) were injected intracerebrally into the boundary zone 1 h after induction of the freezing cortical lesion. Three weeks after surgery, the 2-[(14)C]deoxyglucose method was used to measure lCMR(glc) during right whisker stimulation. The volume of the primary necrotic freezing lesion was significantly reduced (P<0.05), and secondary retrograde degeneration in the left ventral posteromedial (VPM) thalamic nucleus was diminished in the MSC-treated group. Local cerebral glucose utilization measurements showed that the freezing cortical lesion did not alter the metabolic responses to stimulation in the brain stem trigeminal nuclei, but eliminated the responses in the left VPM nucleus and periphery of the barrel cortex in the PBS-treated group. The left/right (stimulated/unstimulated) lCMR(glc) ratios were significantly improved in both the VPM nucleus and periphery of the barrel cortex in the MSC-treated group compared with the PBS-treated group (P<0.05). These results indicate that MSC transplantation in adults may stimulate metabolic and functional recovery in injured neuronal pathways.

Molecular Correlates of Cortical Network Modulation by Long-Term Sensory Experience in the Adult Rat Barrel Cortex

ERIC Educational Resources Information Center

Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J. M.

2014-01-01

Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

An evaluation of the conductivity profile in the somatosensory barrel cortex of Wistar rats.

PubMed

Goto, Takakuni; Hatanaka, Rieko; Ogawa, Takeshi; Sumiyoshi, Akira; Riera, Jorge; Kawashima, Ryuta

2010-12-01

Microelectrode arrays used to record local field potentials from the brain are being built with increasingly more spatial resolution, ranging from the initially developed laminar arrays to those with planar and three-dimensional (3D) formats. In parallel with such development in recording techniques, current source density (CSD) analyses have recently been expanded up to the continuous-3D form. Unfortunately, the effect of the conductivity profile on the CSD analysis performed with contemporary microelectrode arrays has not yet been evaluated and most of the studies assumed it was homogeneous and isotropic. In this study, we measured the conductivity profile in the somatosensory barrel cortex of Wistar rats. To that end, we combined multisite electrophysiological data recorded with a homemade assembly of silicon-based probes and a nonlinear least-squares algorithm that implicitly assumed that the cerebral cortex of rodents could be locally approximated as a layered anisotropic spherical volume conductor. The eccentricity of the six cortical layers in the somatosensory barrel cortex was evaluated from postmortem histological images. We provided evidence for the local spherical character of the entire barrels field, with concentric cortical layers. We found significant laminar dependencies in the conductivity values with radial/tangential anisotropies. These results were in agreement with the layer-dependent orientations of myelinated axons, but hardly related to densities of cells. Finally, we demonstrated through simulations that ignoring the real conductivity profile in the somatosensory barrel cortex of rats caused considerable errors in the CSD reconstruction, with pronounced effects on the continuous-3D form and charge-unbalanced CSD. We concluded that the conductivity profile must be included in future developments of CSD analysis, especially for rodents.

Forebrain-specific expression of monoamine oxidase A reduces neurotransmitter levels, restores the brain structure, and rescues aggressive behavior in monoamine oxidase A-deficient mice.

PubMed

Chen, Kevin; Cases, Olivier; Rebrin, Igor; Wu, Weihua; Gallaher, Timothy K; Seif, Isabelle; Shih, Jean Chen

2007-01-05

Previous studies have established that abrogation of monoamine oxidase (MAO) A expression leads to a neurochemical, morphological, and behavioral specific phenotype with increased levels of serotonin (5-HT), norepinephrine, and dopamine, loss of barrel field structure in mouse somatosensory cortex, and an association with increased aggression in adults. Forebrain-specific MAO A transgenic mice were generated from MAO A knock-out (KO) mice by using the promoter of calcium-dependent kinase IIalpha (CaMKIIalpha). The presence of human MAO A transgene and its expression were verified by PCR of genomic DNA and reverse transcription-PCR of mRNA and Western blot, respectively. Significant MAO A catalytic activity, autoradiographic labeling of 5-HT, and immunocytochemistry of MAO A were found in the frontal cortex, striatum, and hippocampus but not in the cerebellum of the forebrain transgenic mice. Also, compared with MAO A KO mice, lower levels of 5-HT, norepinephrine, and DA and higher levels of MAO A metabolite 5-hydroxyindoleacetic acid were found in the forebrain regions but not in the cerebellum of the transgenic mice. These results suggest that MAO A is specifically expressed in the forebrain regions of transgenic mice. This forebrain-specific differential expression resulted in abrogation of the aggressive phenotype. Furthermore, the disorganization of the somatosensory cortex barrel field structure associated with MAO A KO mice was restored and became morphologically similar to wild type. Thus, the lack of MAO A in the forebrain of MAO A KO mice may underlie their phenotypes.

Postnatal Development of CB1 Receptor Expression in Rodent Somatosensory Cortex

PubMed Central

Deshmukh, Suvarna; Onozuka, Kaori; Bender, Kevin J.; Bender, Vanessa A.; Lutz, Beat; Mackie, Ken; Feldman, Daniel E.

2007-01-01

Endocannabinoids are powerful modulators of synaptic transmission that act on presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the dominant receptor in the CNS, and is present in many brain regions, including sensory cortex. To investigate the potential role of CB1 receptors in cortical development, we examined the developmental expression of CB1 in rodent primary somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific antibody. We found that before postnatal day (P) 6, CB1 receptor staining was present exclusively in the cortical white matter, and that CB1 staining appeared in the grey matter between P6 and P20 in a specific laminar pattern. CB1 staining was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6. CB1 null (−/−) mice showed altered anatomical barrel maps in layer 4, with enlarged inter-barrel septa, but normal barrel size. These results indicate that CB1 receptors are present in early postnatal development and influence development of sensory maps. PMID:17210229

Experimental Traumatic Brain Injury Results in Long-Term Recovery of Functional Responsiveness in Sensory Cortex but Persisting Structural Changes and Sensorimotor, Cognitive, and Emotional Deficits.

PubMed

Johnstone, Victoria P A; Wright, David K; Wong, Kendrew; O'Brien, Terence J; Rajan, Ramesh; Shultz, Sandy R

2015-09-01

Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits.

Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex

PubMed Central

Wagener, Robin J.; Witte, Mirko; Guy, Julien; Mingo-Moreno, Nieves; Kügler, Sebastian; Staiger, Jochen F.

2016-01-01

Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory “barrel” cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position. PMID:26564256

Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons.

PubMed

Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

2017-01-06

The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals.

Optogenetic stimulation of cortex to map evoked whisker movements in awake head-restrained mice.

PubMed

Auffret, Matthieu; Ravano, Veronica L; Rossi, Giulia M C; Hankov, Nicolas; Petersen, Merissa F A; Petersen, Carl C H

2018-01-01

Whisker movements are used by rodents to touch objects in order to extract spatial and textural tactile information about their immediate surroundings. To understand the mechanisms of such active sensorimotor processing it is important to investigate whisker motor control. The activity of neurons in the neocortex affects whisker movements, but many aspects of the organization of cortical whisker motor control remain unknown. Here, we filmed whisker movements evoked by sequential optogenetic stimulation of different locations across the left dorsal sensorimotor cortex of awake head-restrained mice. Whisker movements were evoked by optogenetic stimulation of many regions in the dorsal sensorimotor cortex. Optogenetic stimulation of whisker sensory barrel cortex evoked retraction of the contralateral whisker after a short latency, and a delayed rhythmic protraction of the ipsilateral whisker. Optogenetic stimulation of frontal cortex evoked rhythmic bilateral whisker protraction with a longer latency compared to stimulation of sensory cortex. Compared to frontal cortex stimulation, larger amplitude bilateral rhythmic whisking in a less protracted position was evoked at a similar latency by stimulating a cortical region posterior to Bregma and close to the midline. These data suggest that whisker motor control might be broadly distributed across the dorsal mouse sensorimotor cortex. Future experiments must investigate the complex neuronal circuits connecting specific cell-types in various cortical regions with the whisker motor neurons located in the facial nucleus. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Intracortical pathways mediate nonlinear fast oscillation (>200 Hz) interactions within rat barrel cortex.

PubMed

Staba, Richard J; Ard, Tyler D; Benison, Alexander M; Barth, Daniel S

2005-05-01

Whisker evoked fast oscillations (FOs; >200 Hz) within the rodent posteromedial barrel subfield are thought to reflect very rapid integration of multiwhisker stimuli, yet the pathways mediating FO interactions remain unclear and may involve interactions within thalamus and/or cortex. In the present study using anesthetized rats, a cortical incision was made between sites representing the stimulated whiskers to determine how intracortical networks contributed to patterns of FOs. With cortex intact, simultaneous stimulation of a pair of whiskers aligned in a row evoked supralinear responses between sites separated by several millimeters. In contrast, stimulation of a nonadjacent pair of whiskers within an arc evoked FOs with no evidence for nonlinear interactions. However, stimulation of an adjacent pair of whiskers in an arc did evoke supralinear responses. After a cortical cut, supralinear interactions associated with FOs within a row were lost. These data indicate a distinct bias for stronger long-range connectivity that extends along barrel rows and that horizontal intracortical pathways exclusively mediate FO-related integration of tactile information.

Quantitative 3D Ultrastructure of Thalamocortical Synapses from the "Lemniscal" Ventral Posteromedial Nucleus in Mouse Barrel Cortex.

PubMed

Rodriguez-Moreno, Javier; Rollenhagen, Astrid; Arlandis, Jaime; Santuy, Andrea; Merchan-Pérez, Angel; DeFelipe, Javier; Lübke, Joachim H R; Clasca, Francisco

2017-07-28

Thalamocortical synapses from "lemniscal" neurons of the dorsomedial portion of the rodent ventral posteromedial nucleus (VPMdm) are able to induce with remarkable efficacy, despite their relative low numbers, the firing of primary somatosensory cortex (S1) layer 4 (L4) neurons. To which extent this high efficacy depends on structural synaptic features remains unclear. Using both serial transmission (TEM) and focused ion beam milling scanning electron microscopy (FIB/SEM), we 3D-reconstructed and quantitatively analyzed anterogradely labeled VPMdm axons in L4 of adult mouse S1. All VPMdm synapses are asymmetric. Virtually all are established by axonal boutons, 53% of which contact multiple (2-4) elements (overall synapse/bouton ratio = 1.6). Most boutons are large (mean 0.47 μm3), and contain 1-3 mitochondria. Vesicle pools and postsynaptic density (PSD) surface areas are large compared to others in rodent cortex. Most PSDs are complex. Most synapses (83%) are established on dendritic spine heads. Furthermore, 15% of the postsynaptic spines receive a second, symmetric synapse. In addition, 13% of the spine heads have a large protrusion inserted into a membrane pouch of the VPMdm bouton. The unusual combination of structural features in VPMdm synapses is likely to contribute significantly to the high efficacy, strength, and plasticity of these thalamocortical synapses. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Critical period inhibition of NKCC1 rectifies synapse plasticity in the somatosensory cortex and restores adult tactile response maps in fragile X mice.

PubMed

He, Qionger; Arroyo, Erica D; Smukowski, Samuel N; Xu, Jian; Piochon, Claire; Savas, Jeffrey N; Portera-Cailliau, Carlos; Contractor, Anis

2018-04-27

Sensory perturbations in visual, auditory and tactile perception are core problems in fragile X syndrome (FXS). In the Fmr1 knockout mouse model of FXS, the maturation of synapses and circuits during critical period (CP) development in the somatosensory cortex is delayed, but it is unclear how this contributes to altered tactile sensory processing in the mature CNS. Here we demonstrate that inhibiting the juvenile chloride co-transporter NKCC1, which contributes to altered chloride homeostasis in developing cortical neurons of FXS mice, rectifies the chloride imbalance in layer IV somatosensory cortex neurons and corrects the development of thalamocortical excitatory synapses during the CP. Comparison of protein abundances demonstrated that NKCC1 inhibition during early development caused a broad remodeling of the proteome in the barrel cortex. In addition, the abnormally large size of whisker-evoked cortical maps in adult Fmr1 knockout mice was corrected by rectifying the chloride imbalance during the early CP. These data demonstrate that correcting the disrupted driving force through GABA A receptors during the CP in cortical neurons restores their synaptic development, has an unexpectedly large effect on differentially expressed proteins, and produces a long-lasting correction of somatosensory circuit function in FXS mice.

Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex.

PubMed

Stehberg, Jimmy; Dang, Phat T; Frostig, Ron D

2014-01-01

Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI) of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI) and primary visual (VI). It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA) and retrograde (CTb) tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging, and cortical parcellation are discussed.

Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

PubMed Central

Stehberg, Jimmy; Dang, Phat T.; Frostig, Ron D.

2014-01-01

Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI) of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI) and primary visual (VI). It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA) and retrograde (CTb) tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging, and cortical parcellation are discussed. PMID:25309339

Plasticity of Astrocytic Coverage and Glutamate Transporter Expression in Adult Mouse Cortex

PubMed Central

Steiner, Pascal; Hirling, Harald; Welker, Egbert; Knott, Graham W

2006-01-01

Astrocytes play a major role in the removal of glutamate from the extracellular compartment. This clearance limits the glutamate receptor activation and affects the synaptic response. This function of the astrocyte is dependent on its positioning around the synapse, as well as on the level of expression of its high-affinity glutamate transporters, GLT1 and GLAST. Using Western blot analysis and serial section electron microscopy, we studied how a change in sensory activity affected these parameters in the adult cortex. Using mice, we found that 24 h of whisker stimulation elicited a 2-fold increase in the expression of GLT1 and GLAST in the corresponding cortical column of the barrel cortex. This returns to basal levels 4 d after the stimulation was stopped, whereas the expression of the neuronal glutamate transporter EAAC1 remained unaltered throughout. Ultrastructural analysis from the same region showed that sensory stimulation also causes a significant increase in the astrocytic envelopment of excitatory synapses on dendritic spines. We conclude that a period of modified neuronal activity and synaptic release of glutamate leads to an increased astrocytic coverage of the bouton–spine interface and an increase in glutamate transporter expression in astrocytic processes. PMID:17048987

Cellular organization of cortical barrel columns is whisker-specific

PubMed Central

Meyer, Hanno S.; Egger, Robert; Guest, Jason M.; Foerster, Rita; Reissl, Stefan; Oberlaender, Marcel

2013-01-01

The cellular organization of the cortex is of fundamental importance for elucidating the structural principles that underlie its functions. It has been suggested that reconstructing the structure and synaptic wiring of the elementary functional building block of mammalian cortices, the cortical column, might suffice to reverse engineer and simulate the functions of entire cortices. In the vibrissal area of rodent somatosensory cortex, whisker-related “barrel” columns have been referred to as potential cytoarchitectonic equivalents of functional cortical columns. Here, we investigated the structural stereotypy of cortical barrel columns by measuring the 3D neuronal composition of the entire vibrissal area in rat somatosensory cortex and thalamus. We found that the number of neurons per cortical barrel column and thalamic “barreloid” varied substantially within individual animals, increasing by ∼2.5-fold from dorsal to ventral whiskers. As a result, the ratio between whisker-specific thalamic and cortical neurons was remarkably constant. Thus, we hypothesize that the cellular architecture of sensory cortices reflects the degree of similarity in sensory input and not columnar and/or cortical uniformity principles. PMID:24101458

An electrode to record the mouse cornea electroretinogram.

PubMed

Goto, Y

The mouse has become a popular model for the study of retinal degeneration, but an electrode suitable for recording electroretinograms from the mouse cornea is not available commercially. I developed a simple electrode suitable for the relatively small mouse eye by attaching a thin stainless-steel wire through the barrel of a 1-cc syringe. The end of the wire is formed into a coil by wrapping it around a 0.5- or 1.0-mm pin. The syringe barrel serves as a convenient way to hold the electrode in a goose-neck holder. This electrode has been used successfully to obtain electroretinograms from hundreds of mice as young as 14 days.

Training-Dependent Associative Learning Induced Neocortical Structural Plasticity: A Trace Eyeblink Conditioning Analysis

PubMed Central

Chau, Lily S.; Prakapenka, Alesia V.; Zendeli, Liridon; Davis, Ashley S.; Galvez, Roberto

2014-01-01

Studies utilizing general learning and memory tasks have suggested the importance of neocortical structural plasticity for memory consolidation. However, these learning tasks typically result in learning of multiple different tasks over several days of training, making it difficult to determine the synaptic time course mediating each learning event. The current study used trace-eyeblink conditioning to determine the time course for neocortical spine modification during learning. With eyeblink conditioning, subjects are presented with a neutral, conditioned stimulus (CS) paired with a salient, unconditioned stimulus (US) to elicit an unconditioned response (UR). With multiple CS-US pairings, subjects learn to associate the CS with the US and exhibit a conditioned response (CR) when presented with the CS. Trace conditioning is when there is a stimulus free interval between the CS and the US. Utilizing trace-eyeblink conditioning with whisker stimulation as the CS (whisker-trace-eyeblink: WTEB), previous findings have shown that primary somatosensory (barrel) cortex is required for both acquisition and retention of the trace-association. Additionally, prior findings demonstrated that WTEB acquisition results in an expansion of the cytochrome oxidase whisker representation and synaptic modification in layer IV of barrel cortex. To further explore these findings and determine the time course for neocortical learning-induced spine modification, the present study utilized WTEB conditioning to examine Golgi-Cox stained neurons in layer IV of barrel cortex. Findings from this study demonstrated a training-dependent spine proliferation in layer IV of barrel cortex during trace associative learning. Furthermore, findings from this study showing that filopodia-like spines exhibited a similar pattern to the overall spine density further suggests that reorganization of synaptic contacts set the foundation for learning-induced neocortical modifications through the different neocortical layers. PMID:24760074

Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins.

PubMed

Tarusawa, Etsuko; Sanbo, Makoto; Okayama, Atsushi; Miyashita, Toshio; Kitsukawa, Takashi; Hirayama, Teruyoshi; Hirabayashi, Takahiro; Hasegawa, Sonoko; Kaneko, Ryosuke; Toyoda, Shunsuke; Kobayashi, Toshihiro; Kato-Itoh, Megumi; Nakauchi, Hiromitsu; Hirabayashi, Masumi; Yagi, Takeshi; Yoshimura, Yumiko

2016-12-02

The specificity of synaptic connections is fundamental for proper neural circuit function. Specific neuronal connections that underlie information processing in the sensory cortex are initially established without sensory experiences to a considerable extent, and then the connections are individually refined through sensory experiences. Excitatory neurons arising from the same single progenitor cell are preferentially connected in the postnatal cortex, suggesting that cell lineage contributes to the initial wiring of neurons. However, the postnatal developmental process of lineage-dependent connection specificity is not known, nor how clonal neurons, which are derived from the same neural stem cell, are stamped with the identity of their common neural stem cell and guided to form synaptic connections. We show that cortical excitatory neurons that arise from the same neural stem cell and reside within the same layer preferentially establish reciprocal synaptic connections in the mouse barrel cortex. We observed a transient increase in synaptic connections between clonal but not nonclonal neuron pairs during postnatal development, followed by selective stabilization of the reciprocal connections between clonal neuron pairs. Furthermore, we demonstrate that selective stabilization of the reciprocal connections between clonal neuron pairs is impaired by the deficiency of DNA methyltransferase 3b (Dnmt3b), which determines DNA-methylation patterns of genes in stem cells during early corticogenesis. Dnmt3b regulates the postnatal expression of clustered protocadherin (cPcdh) isoforms, a family of adhesion molecules. We found that cPcdh deficiency in clonal neuron pairs impairs the whole process of the formation and stabilization of connections to establish lineage-specific connection reciprocity. Our results demonstrate that local, reciprocal neural connections are selectively formed and retained between clonal neurons in layer 4 of the barrel cortex during postnatal development, and that Dnmt3b and cPcdhs are required for the establishment of lineage-specific reciprocal connections. These findings indicate that lineage-specific connection reciprocity is predetermined by Dnmt3b during embryonic development, and that the cPcdhs contribute to postnatal cortical neuron identification to guide lineage-dependent synaptic connections in the neocortex.

Neurons immunoreactive for vasoactive intestinal polypeptide in the rat primary somatosensory cortex: morphology and spatial relationship to barrel-related columns.

PubMed

Bayraktar, T; Welker, E; Freund, T F; Zilles, K; Staiger, J F

2000-05-08

Vasoactive intestinal polypeptide (VIP) in neocortex affects neuronal excitability as well as cortical blood flow and metabolism. Interneurons immunoreactive for VIP (VIP-IR neurons) are characterized by their predominantly bipolar appearance and the radial orientation of their main dendrites. In order to determine whether the morphology of VIP-IR neurons is related to the functional organization of the cortex into vertical columns, we combined both immunostaining of neurons containing VIP and cytochrome oxidase histochemistry for visualizing barrels, morphological layer IV correlates of functional columns, in the primary somatosensory (barrel) cortex of rats. VIP-IR neurons were localized in supragranular (48%), granular (16%), and infragranular layers (36%) as well as in the white matter. In the granular layer, a clear trend that more neurons were located in interbarrel septa rather than in barrels could be observed, resulting in a neuronal density which was about one-third higher in the septal area. VIP-IR neurons from the different cortical layers were three-dimensionally reconstructed from serial sections by using a computer microscope system. The neurons were mostly bipolar. Striking morphological differences in both axonal and dendritic trees were found between neurons whose cell bodies were located in supragranular, granular, and the upper part of infragranular layers, and those whose cell bodies were located in the area below. The former had dendrites which often reached layer I, where they bifurcated several times, and axonal trees which were particularly oriented vertically, with a tangential extent smaller than the width of barrels. Therefore, these neurons were mostly confined to either a barrel- or septum-related column. By contrast, the dendrites of neurons of the latter group did not reach the granular layer. Furthermore, these neurons had axons with sometimes very long horizontal collaterals, which often spanned two, in one case three, barrel columns. It is proposed that the differential morphology of neurons with different locations as stated above parallels to some extent the divergence of input streaming into the corresponding layer-defined areas. As a possible consequence of this, VIP-IR neurons may be capable of adapting the excitability and metabolism of cortical compartments either in a spatially limited or more extensive way. Copyright 2000 Wiley-Liss, Inc.

Experience-dependent increase in spine calcium evoked by backpropagating action potentials in layer 2/3 pyramidal neurons in rat somatosensory cortex.

PubMed

Krieger, Patrik

2009-11-01

In spines on basal dendrites of layer 2/3 pyramidal neurons in somatosensory barrel cortex, calcium transients evoked by back-propagating action potentials (bAPs) were investigated (i) along the length of the basal dendrite, (ii) with postnatal development and (iii) with sensory deprivation during postnatal development. Layer 2/3 pyramidal neurons were investigated at three different ages. At all ages [postnatal day (P)8, P14, P21] the bAP-evoked calcium transient amplitude increased with distance from the soma with a peak at around 50 microm, followed by a gradual decline in amplitude. The effect of sensory deprivation on the bAP-evoked calcium was investigated using two different protocols. When all whiskers on one side of the rat snout were trimmed daily from P8 to P20-24 there was no difference in the bAP-evoked calcium transient between cells in the contralateral hemisphere, lacking sensory input from the whisker, and cells in the ipsilateral barrel cortex, with intact whisker activation. When, however, only the D-row whiskers on one side were trimmed the distribution of bAP-evoked calcium transients in spines was shifted towards larger amplitudes in cells located in the deprived D-column. In conclusion, (i) the bAP-evoked calcium transient gradient along the dendrite length is established at P8, (ii) the calcium transient increases in amplitude with age and (iii) this increase is enhanced in layer 2/3 pyramidal neurons located in a sensory-deprived barrel column that is bordered by non-deprived barrel columns.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex.

PubMed

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex

PubMed Central

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants. PMID:29311827

Sub- and suprathreshold receptive field properties of pyramidal neurones in layers 5A and 5B of rat somatosensory barrel cortex

PubMed Central

Manns, Ian D; Sakmann, Bert; Brecht, Michael

2004-01-01

Layer 5 (L5) pyramidal neurones constitute a major sub- and intracortical output of the somatosensory cortex. This layer 5 is segregated into layers 5A and 5B which receive and distribute relatively independent afferent and efferent pathways. We performed in vivo whole-cell recordings from L5 neurones of the somatosensory (barrel) cortex of urethane-anaesthetized rats (aged 27–31 days). By delivering 6 deg single whisker deflections, whisker pad receptive fields were mapped for 16 L5A and 11 L5B neurones located below the layer 4 whisker-barrels. Average resting membrane potentials were −75.6±1.1 mV, and spontaneous action potential (AP) rates were 0.54± 0.14 APs s−1. Principal whisker (PW) evoked responses were similar in L5A and L5B neurones, with an average 5.0 ± 0.6 mV postsynaptic potential (PSP) and 0.12 ± 0.03 APs per stimulus. The layer 5A sub- and suprathreshold receptive fields (RFs) were more confined to the principle whisker than those of layer 5B. The basal dendritic arbors of layer 5A and 5B cells were located below both layer 4 barrels and septa, and the cell bodies were biased towards the barrel walls. Responses in both L5A and L5B developed slowly, with onset latencies of 10.1 ± 0.5 ms and peak latencies of 33.9 ± 3.3 ms. Contralateral multi-whisker stimulation evoked PSPs similar in amplitude to those of PW deflections; whereas, ipsilateral stimulation evoked smaller and longer latency PSPs. We conclude that in L5 a whisker deflection is represented in two ways: focally by L5A pyramids and more diffusely by L5B pyramids as a result of combining different inputs from lemniscal and paralemniscal pathways. The relevant output evoked by a whisker deflection could be the ensemble activity in the anatomically defined cortical modules associated with a single or a few barrel-columns. PMID:14724202

Correlated physiological and perceptual effects of noise in a tactile stimulus.

PubMed

Lak, Armin; Arabzadeh, Ehsan; Harris, Justin A; Diamond, Mathew E

2010-04-27

We investigated connections between the physiology of rat barrel cortex neurons and the sensation of vibration in humans. One set of experiments measured neuronal responses in anesthetized rats to trains of whisker deflections, each train characterized either by constant amplitude across all deflections or by variable amplitude ("amplitude noise"). Firing rate and firing synchrony were, on average, boosted by the presence of noise. However, neurons were not uniform in their responses to noise. Barrel cortex neurons have been categorized as regular-spiking units (putative excitatory neurons) and fast-spiking units (putative inhibitory neurons). Among regular-spiking units, amplitude noise caused a higher firing rate and increased cross-neuron synchrony. Among fast-spiking units, noise had the opposite effect: It led to a lower firing rate and decreased cross-neuron synchrony. This finding suggests that amplitude noise affects the interaction between inhibitory and excitatory neurons. From these physiological effects, we expected that noise would lead to an increase in the perceived intensity of a vibration. We tested this notion using psychophysical measurements in humans. As predicted, subjects overestimated the intensity of noisy vibrations. Thus the physiological mechanisms present in barrel cortex also appear to be at work in the human tactile system, where they affect vibration perception.

Genetically expressed voltage sensor ArcLight for imaging large scale cortical activity in the anesthetized and awake mouse

PubMed Central

Borden, Peter Y.; Ortiz, Alex D.; Waiblinger, Christian; Sederberg, Audrey J.; Morrissette, Arthur E.; Forest, Craig R.; Jaeger, Dieter; Stanley, Garrett B.

2017-01-01

Abstract. With the recent breakthrough in genetically expressed voltage indicators (GEVIs), there has been a tremendous demand to determine the capabilities of these sensors in vivo. Novel voltage sensitive fluorescent proteins allow for direct measurement of neuron membrane potential changes through changes in fluorescence. Here, we utilized ArcLight, a recently developed GEVI, and examined the functional characteristics in the widely used mouse somatosensory whisker pathway. We measured the resulting evoked fluorescence using a wide-field microscope and a CCD camera at 200 Hz, which enabled voltage recordings over the entire cortical region with high temporal resolution. We found that ArcLight produced a fluorescent response in the S1 barrel cortex during sensory stimulation at single whisker resolution. During wide-field cortical imaging, we encountered substantial hemodynamic noise that required additional post hoc processing through noise subtraction techniques. Over a period of 28 days, we found clear and consistent ArcLight fluorescence responses to a simple sensory input. Finally, we demonstrated the use of ArcLight to resolve cortical S1 sensory responses in the awake mouse. Taken together, our results demonstrate the feasibility of ArcLight as a measurement tool for mesoscopic, chronic imaging. PMID:28491905

Susceptibility of Primary Sensory Cortex to Spreading Depolarizations.

PubMed

Bogdanov, Volodymyr B; Middleton, Natalie A; Theriot, Jeremy J; Parker, Patrick D; Abdullah, Osama M; Ju, Y Sungtaek; Hartings, Jed A; Brennan, K C

2016-04-27

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury. Spreading depolarizations (SDs) are involved in neurologic disorders as diverse as migraine and traumatic brain injury. In migraine, the nature of aura symptoms suggests that sensory cortex may be preferentially susceptible. In brain injury, SDs occur at a vulnerable time, during which the issue of sensory stimulation is much debated. We show, in mouse and human, that sensory cortex is more susceptible to SDs. We find that sensory stimulation biases the timing but not the location of the depolarizations. Finally, we show a relative impairment of potassium clearance in sensory cortex, providing a potential mechanism for the susceptibility. Our data help to explain the sensory nature of the migraine aura and reveal that sensory cortices are vulnerable in brain injury. Copyright © 2016 the authors 0270-6474/16/364733-11$15.00/0.

Susceptibility of Primary Sensory Cortex to Spreading Depolarizations

PubMed Central

Bogdanov, Volodymyr B.; Middleton, Natalie A.; Theriot, Jeremy J.; Parker, Patrick D.; Abdullah, Osama M.; Ju, Y. Sungtaek; Hartings, Jed A.

2016-01-01

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury. SIGNIFICANCE STATEMENT Spreading depolarizations (SDs) are involved in neurologic disorders as diverse as migraine and traumatic brain injury. In migraine, the nature of aura symptoms suggests that sensory cortex may be preferentially susceptible. In brain injury, SDs occur at a vulnerable time, during which the issue of sensory stimulation is much debated. We show, in mouse and human, that sensory cortex is more susceptible to SDs. We find that sensory stimulation biases the timing but not the location of the depolarizations. Finally, we show a relative impairment of potassium clearance in sensory cortex, providing a potential mechanism for the susceptibility. Our data help to explain the sensory nature of the migraine aura and reveal that sensory cortices are vulnerable in brain injury. PMID:27122032

Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex.

PubMed

Maglio, Laura Eva; Noriega-Prieto, José Antonio; Maraver, Maria Jesús; Fernández de Sevilla, David

2018-05-01

Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca2+ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-N,N,N,N'-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex.

Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences.

PubMed

Just, Nathalie; Xin, Lijing; Frenkel, Hanne; Gruetter, Rolf

2013-07-01

To date, only a couple of functional MR spectroscopy (fMRS) studies were conducted in rats. Due to the low temporal resolution of (1)H MRS techniques, prolonged stimulation paradigms are necessary for investigating the metabolic outcome in the rat brain during functional challenge. However, sustained activation of cortical areas is usually difficult to obtain due to neural adaptation. Anesthesia, habituation, high variability of the basal state metabolite concentrations as well as low concentrations of the metabolites of interest such as lactate (Lac), glucose (Glc) or γ-aminobutyric acid (GABA) and small expected changes of metabolite concentrations need to be addressed. In the present study, the rat barrel cortex was reliably and reproducibly activated through sustained trigeminal nerve (TGN) stimulation. In addition, TGN stimulation induced significant positive changes in lactate (+1.01 μmol/g, p<0.008) and glutamate (+0.92 μmol/g, p<0.02) and significant negative aspartate changes (-0.63 μmol/g, p<0.004) using functional (1)H MRS at 9.4 T in agreement with previous changes observed in human fMRS studies. Finally, for the first time, the dynamics of lactate, glucose, aspartate and glutamate concentrations during sustained somatosensory activation in rats using fMRS were assessed. These results allow demonstrating the feasibility of fMRS measurements during prolonged barrel cortex activation in rats. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of Columnar Topography in the Excitatory Layer 4 to Layer 2/3 Projection in Rat Barrel Cortex

PubMed Central

Bender, Kevin J.; Rangel, Juliana; Feldman, Daniel E.

2011-01-01

The excitatory feedforward projection from layer (L) 4 to L2/3 in rat primary somatosensory (S1) cortex exhibits precise, columnar topography that is critical for columnar processing of whisker inputs. Here, we characterize the development of axonal topography in this projection using single-cell reconstructions in S1 slices. In the mature projection [postnatal day (P) 14 –26], axons of L4 cells extending into L2/3 were confined almost entirely to the home barrel column, consistent with previous results. At younger ages (P8 –11), however, axonal topography was significantly less columnar, with a large proportion of branches innervating neighboring barrel columns representing adjacent whisker rows. Mature topography developed from this initial state by targeted axonal growth within the home column and by growth of barrel columns themselves. Raising rats with all or a subset of whiskers plucked from P8 –9, manipulations that induce reorganization of functional whisker maps and synaptic depression at L4 to L2/3 synapses, did not alter normal anatomical development of L4 to L2/3 axons. Thus, development of this projection does not require normal sensory experience after P8, and deprivation-induced reorganization of whisker maps at this age is unlikely to involve physical remodeling of L4 to L2/3 axons. PMID:14507976

Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue.

PubMed

Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena; Tang, Qinggong; Chen, Yu; Erzurumlu, Reha S; Papkovsky, Dmitri B

2017-04-01

Brain imaging methods are continually improving. Imaging of the cerebral cortex is widely used in both animal experiments and charting human brain function in health and disease. Among the animal models, the rodent cerebral cortex has been widely used because of patterned neural representation of the whiskers on the snout and relative ease of activating cortical tissue with whisker stimulation. We tested a new planar solid-state oxygen sensor comprising a polymeric film with a phosphorescent oxygen-sensitive coating on the working side, to monitor dynamics of oxygen metabolism in the cerebral cortex following sensory stimulation. Sensory stimulation led to changes in oxygenation and deoxygenation processes of activated areas in the barrel cortex. We demonstrate the possibility of dynamic mapping of relative changes in oxygenation in live mouse brain tissue with such a sensor. Oxygenation-based functional magnetic resonance imaging (fMRI) is very effective method for functional brain mapping but have high costs and limited spatial resolution. Optical imaging of intrinsic signal (IOS) does not provide the required sensitivity, and voltage-sensitive dye optical imaging (VSDi) has limited applicability due to significant toxicity of the voltage-sensitive dye. Our planar solid-state oxygen sensor imaging approach circumvents these limitations, providing a simple optical contrast agent with low toxicity and rapid application. The planar solid-state oxygen sensor described here can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo. Further, this approach allows visualization of local neural activity with high temporal and spatial resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Response sensitivity of barrel neuron subpopulations to simulated thalamic input.

PubMed

Pesavento, Michael J; Rittenhouse, Cynthia D; Pinto, David J

2010-06-01

Our goal is to examine the relationship between neuron- and network-level processing in the context of a well-studied cortical function, the processing of thalamic input by whisker-barrel circuits in rodent neocortex. Here we focus on neuron-level processing and investigate the responses of excitatory and inhibitory barrel neurons to simulated thalamic inputs applied using the dynamic clamp method in brain slices. Simulated inputs are modeled after real thalamic inputs recorded in vivo in response to brief whisker deflections. Our results suggest that inhibitory neurons require more input to reach firing threshold, but then fire earlier, with less variability, and respond to a broader range of inputs than do excitatory neurons. Differences in the responses of barrel neuron subtypes depend on their intrinsic membrane properties. Neurons with a low input resistance require more input to reach threshold but then fire earlier than neurons with a higher input resistance, regardless of the neuron's classification. Our results also suggest that the response properties of excitatory versus inhibitory barrel neurons are consistent with the response sensitivities of the ensemble barrel network. The short response latency of inhibitory neurons may serve to suppress ensemble barrel responses to asynchronous thalamic input. Correspondingly, whereas neurons acting as part of the barrel circuit in vivo are highly selective for temporally correlated thalamic input, excitatory barrel neurons acting alone in vitro are less so. These data suggest that network-level processing of thalamic input in barrel cortex depends on neuron-level processing of the same input by excitatory and inhibitory barrel neurons.

Cell Type-Specific Structural Organization of the Six Layers in Rat Barrel Cortex

PubMed Central

Narayanan, Rajeevan T.; Udvary, Daniel; Oberlaender, Marcel

2017-01-01

The cytoarchitectonic subdivision of the neocortex into six layers is often used to describe the organization of the cortical circuitry, sensory-evoked signal flow or cortical functions. However, each layer comprises neuronal cell types that have different genetic, functional and/or structural properties. Here, we reanalyze structural data from some of our recent work in the posterior-medial barrel-subfield of the vibrissal part of rat primary somatosensory cortex (vS1). We quantify the degree to which somata, dendrites and axons of the 10 major excitatory cell types of the cortex are distributed with respect to the cytoarchitectonic organization of vS1. We show that within each layer, somata of multiple cell types intermingle, but that each cell type displays dendrite and axon distributions that are aligned to specific cytoarchitectonic landmarks. The resultant quantification of the structural composition of each layer in terms of the cell type-specific number of somata, dendritic and axonal path lengths will aid future studies to bridge between layer- and cell type-specific analyses. PMID:29081739

Experience-Dependent Rewiring of Specific Inhibitory Connections in Adult Neocortex

PubMed Central

Kätzel, Dennis; Miesenböck, Gero

2014-01-01

Although neocortical connectivity is remarkably stereotyped, the abundance of some wiring motifs varies greatly between cortical areas. To examine if regional wiring differences represent functional adaptations, we have used optogenetic raster stimulation to map the laminar distribution of GABAergic interneurons providing inhibition to pyramidal cells in layer 2/3 (L2/3) of adult mouse barrel cortex during sensory deprivation and recovery. Whisker trimming caused large, motif-specific changes in inhibitory synaptic connectivity: ascending inhibition from deep layers 4 and 5 was attenuated to 20%–45% of baseline, whereas inhibition from superficial layers remained stable (L2/3) or increased moderately (L1). The principal mechanism of deprivation-induced plasticity was motif-specific changes in inhibitory-to-excitatory connection probabilities; the strengths of extant connections were left unaltered. Whisker regrowth restored the original balance of inhibition from deep and superficial layers. Targeted, reversible modifications of specific inhibitory wiring motifs thus contribute to the adaptive remodeling of cortical circuits. PMID:24586113

Effects of GABAA receptor inhibition on response properties of barrel cortical neurons in C-fiber-depleted rats.

PubMed

Farazifard, Rasoul; Kiani, Roozbeh; Esteky, Hossein

2005-07-19

C-fiber depletion results in expansion of low threshold somatosensory mechanoreceptive fields. In this study, we investigated the role of intact C-fibers in GABAA-mediated inhibition in barrel cortical neurons. We used electronically controlled mechanical stimulation of whiskers to quantitatively examine the responses of barrel cells to whisker displacements. After systemic injection of picrotoxin neuronal responses were recorded at 5 min intervals for 20 min and then at 10 min intervals for 100 min. Picrotoxin injection caused a 3-fold increase in response magnitude of adjacent whisker stimulation and 1.4-fold increase in response magnitude of principal whisker stimulation with a maximum enhancement 50 min after the injection. There was no significant change in spontaneous activity following picrotoxin injection. The response enhancement and receptive field expansion observed in normal rats were completely absent in the C-fiber-depleted rats. These results suggest that the GABAA-mediated inhibition that modulates the receptive field functional organization of the barrel cortex depends on intact C-fibers.

Structure, function, and cortical representation of the rat submandibular whisker trident.

PubMed

Thé, Lydia; Wallace, Michael L; Chen, Christopher H; Chorev, Edith; Brecht, Michael

2013-03-13

Although the neurobiology of rodent facial whiskers has been studied intensively, little is known about sensing in other vibrissae. Here we describe the under-investigated submandibular "whisker trident" on the rat's chin. In this three-whisker array, a unique unpaired midline whisker is laterally flanked by two slightly shorter whiskers. All three whiskers point to the ground and are curved backwards. Unlike other whiskers, the trident is not located on an exposed body part. Trident vibrissae are not whisked and do not touch anything over long stretches of time. However, trident whiskers engage in sustained ground contact during head-down running while the animal is exploring or foraging. In biomechanical experiments, trident whiskers follow caudal ground movement more smoothly than facial whiskers. Remarkably, deflection angles decrease with increasing ground velocity. We identified one putative trident barrel in the left somatosensory cortex and two barrels in the right somatosensory cortex. The elongated putative trident-midline barrel is the longest and largest whisker barrel, suggesting that the midline trident whisker is of great functional significance. Cortical postsynaptic air-puff responses in the trident representation show much less temporal precision than facial whisker responses. Trident whiskers do not provide as much high-resolution information about object contacts as facial whiskers. Instead, our observations suggest an idiothetic function: their biomechanics allow trident whiskers to derive continuous measurements about ego motion from ground contacts. The midline position offers unique advantages in sensing heading direction in a laterally symmetric manner. The changes in trident deflection angle with velocity suggest that trident whiskers might function as a tactile speedometer.

Coherence between Rat Sensorimotor System and Hippocampus Is Enhanced during Tactile Discrimination

PubMed Central

Zuo, Yangfang; Stella, Federico; Diamond, Mathew E.

2016-01-01

Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5–12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats—whisker motion, hippocampal local field potential (LFP), and barrel cortex unit firing—during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task). Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers. PMID:26890254

Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex.

PubMed

Lübke, Joachim; Feldmeyer, Dirk

2007-07-01

A basic feature of the neocortex is its organization in functional, vertically oriented columns, recurring modules of signal processing and a system of transcolumnar long-range horizontal connections. These columns, together with their network of neurons, present in all sensory cortices, are the cellular substrate for sensory perception in the brain. Cortical columns contain thousands of neurons and span all cortical layers. They receive input from other cortical areas and subcortical brain regions and in turn their neurons provide output to various areas of the brain. The modular concept presumes that the neuronal network in a cortical column performs basic signal transformations, which are then integrated with the activity in other networks and more extended brain areas. To understand how sensory signals from the periphery are transformed into electrical activity in the neocortex it is essential to elucidate the spatial-temporal dynamics of cortical signal processing and the underlying neuronal 'microcircuits'. In the last decade the 'barrel' field in the rodent somatosensory cortex, which processes sensory information arriving from the mysticial vibrissae, has become a quite attractive model system because here the columnar structure is clearly visible. In the neocortex and in particular the barrel cortex, numerous neuronal connections within or between cortical layers have been studied both at the functional and structural level. Besides similarities, clear differences with respect to both physiology and morphology of synaptic transmission and connectivity were found. It is therefore necessary to investigate each neuronal connection individually, in order to develop a realistic model of neuronal connectivity and organization of a cortical column. This review attempts to summarize recent advances in the study of individual microcircuits and their functional relevance within the framework of a cortical column, with emphasis on excitatory signal flow.

The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in Cortical Networks.

PubMed

Landau, Itamar D; Egger, Robert; Dercksen, Vincent J; Oberlaender, Marcel; Sompolinsky, Haim

2016-12-07

Models of cortical dynamics often assume a homogeneous connectivity structure. However, we show that heterogeneous input connectivity can prevent the dynamic balance between excitation and inhibition, a hallmark of cortical dynamics, and yield unrealistically sparse and temporally regular firing. Anatomically based estimates of the connectivity of layer 4 (L4) rat barrel cortex and numerical simulations of this circuit indicate that the local network possesses substantial heterogeneity in input connectivity, sufficient to disrupt excitation-inhibition balance. We show that homeostatic plasticity in inhibitory synapses can align the functional connectivity to compensate for structural heterogeneity. Alternatively, spike-frequency adaptation can give rise to a novel state in which local firing rates adjust dynamically so that adaptation currents and synaptic inputs are balanced. This theory is supported by simulations of L4 barrel cortex during spontaneous and stimulus-evoked conditions. Our study shows how synaptic and cellular mechanisms yield fluctuation-driven dynamics despite structural heterogeneity in cortical circuits. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The binding cavity of mouse major urinary protein is optimised for a variety of ligand binding modes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pertinhez, Thelma A.; Ferrari, Elena; Casali, Emanuela

2009-12-25

{sup 15}N and {sup 1}HN chemical shift data and {sup 15}N relaxation studies have been used to characterise the binding of N-phenyl-naphthylamine (NPN) to mouse major urinary protein (MUP). NPN binds in the {beta}-barrel cavity of MUP, hydrogen bonding to Tyr120 and making extensive non-bonded contacts with hydrophobic side chains. In contrast to the natural pheromone 2-sec-butyl-4,5-dihydrothiazole, NPN binding gives no change to the overall mobility of the protein backbone of MUP. Comparison with 11 different ligands that bind to MUP shows a range of binding modes involving 16 different residues in the {beta}-barrel cavity. These finding justify why MUPmore » is able to adapt to allow for many successful binding partners.« less

CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

PubMed Central

Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

2016-01-01

Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV. DOI: http://dx.doi.org/10.7554/eLife.20985.001 PMID:27996938

In vivo alterations in calcium buffering capacity in transgenic mouse model of synucleinopathy.

PubMed

Reznichenko, Lidia; Cheng, Qun; Nizar, Krystal; Gratiy, Sergey L; Saisan, Payam A; Rockenstein, Edward M; González, Tanya; Patrick, Christina; Spencer, Brian; Desplats, Paula; Dale, Anders M; Devor, Anna; Masliah, Eliezer

2012-07-18

Abnormal accumulation of α-synuclein is centrally involved in the pathogenesis of many disorders with Parkinsonism and dementia. Previous in vitro studies suggest that α-synuclein dysregulates intracellular calcium. However, it is unclear whether these alterations occur in vivo. For this reason, we investigated calcium dynamics in transgenic mice expressing human WT α-synuclein using two-photon microscopy. We imaged spontaneous and stimulus-induced neuronal activity in the barrel cortex. Transgenic mice exhibited augmented, long-lasting calcium transients characterized by considerable deviation from the exponential decay. The most evident pathology was observed in response to a repetitive stimulation in which subsequent stimuli were presented before relaxation of calcium signal to the baseline. These alterations were detected in the absence of significant increase in neuronal spiking response compared with age-matched controls, supporting the possibility that α-synuclein promoted alterations in calcium dynamics via interference with intracellular buffering mechanisms. The characteristic shape of calcium decay and augmented response during repetitive stimulation can serve as in vivo imaging biomarkers in this model of neurodegeneration, to monitor progression of the disease and screen candidate treatment strategies.

Informational basis of sensory adaptation: entropy and single-spike efficiency in rat barrel cortex.

PubMed

Adibi, Mehdi; Clifford, Colin W G; Arabzadeh, Ehsan

2013-09-11

We showed recently that exposure to whisker vibrations enhances coding efficiency in rat barrel cortex despite increasing correlations in variability (Adibi et al., 2013). Here, to understand how adaptation achieves this improvement in sensory representation, we decomposed the stimulus information carried in neuronal population activity into its fundamental components in the framework of information theory. In the context of sensory coding, these components are the entropy of the responses across the entire stimulus set (response entropy) and the entropy of the responses conditional on the stimulus (conditional response entropy). We found that adaptation decreased response entropy and conditional response entropy at both the level of single neurons and the pooled activity of neuronal populations. However, the net effect of adaptation was to increase the mutual information because the drop in the conditional entropy outweighed the drop in the response entropy. The information transmitted by a single spike also increased under adaptation. As population size increased, the information content of individual spikes declined but the relative improvement attributable to adaptation was maintained.

Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity

PubMed Central

Lo, Fu-Sun; Erzurumlu, Reha S.

2016-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated gene MET tyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAA receptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAA receptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. SIGNIFICANCE STATEMENT A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAA receptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. PMID:27030755

Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome.

PubMed

Pan, Feng; Aldridge, Georgina M; Greenough, William T; Gan, Wen-Biao

2010-10-12

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and is caused by transcriptional inactivation of the X-linked fragile X mental retardation 1 (FMR1) gene. FXS is associated with increased density and abnormal morphology of dendritic spines, the postsynaptic sites of the majority of excitatory synapses. To better understand how lack of the FMR1 gene function affects spine development and plasticity, we examined spine formation and elimination of layer 5 pyramidal neurons in the whisker barrel cortex of Fmr1 KO mice with a transcranial two-photon imaging technique. We found that the rates of spine formation and elimination over days to weeks were significantly higher in both young and adult KO mice compared with littermate controls. The heightened spine turnover in KO mice was due to the existence of a larger pool of "short-lived" new spines in KO mice than in controls. Furthermore, we found that the formation of new spines and the elimination of existing ones were less sensitive to modulation by sensory experience in KO mice. These results indicate that the loss of Fmr1 gene function leads to ongoing overproduction of transient spines in the primary somatosensory cortex. The insensitivity of spine formation and elimination to sensory alterations in Fmr1 KO mice suggest that the developing synaptic circuits may not be properly tuned by sensory stimuli in FXS.

Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

PubMed

Lo, Fu-Sun; Erzurumlu, Reha S; Powell, Elizabeth M

2016-03-30

Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated geneMETtyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAAreceptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAAreceptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. Copyright © 2016 the authors 0270-6474/16/363691-07$15.00/0.

Active sensing of target location encoded by cortical microstimulation.

PubMed

Venkatraman, Subramaniam; Carmena, Jose M

2011-06-01

Cortical microstimulation has been proposed as a method to deliver sensory percepts to circumvent damaged sensory receptors or pathways. However, much of perception involves the active movement of sensory organs and the integration of information across sensory and motor modalities. The efficacy of cortical microstimulation in such an active sensing paradigm has not been demonstrated. We report a novel behavioral paradigm which delivers microstimulation in real-time based on a rat's movements and show that rats can perform sensorimotor integration with electrically delivered stimuli. Using a real-time whisker tracking system, we delivered microstimulation in barrel cortex of actively whisking rats when their whisker crossed a particular spatial location which defined the target. Rats learned to integrate microstimulation cues with their knowledge of whisker position to infer target location along the rostro-caudal axis in less than 200 ms. In a separate experiment, we found that rats trained to respond to cortical microstimulation responded similarly to whisker deflections while ignoring auditory distracters, suggesting that barrel cortex stimulation may be perceptually similar to somatosensory stimuli. This ability to deliver sensory percepts using cortical microstimulation in an active sensing system might have significant implications for the development of sensorimotor neuroprostheses.

Astrocyte and Neuronal Plasticity in the Somatosensory System

PubMed Central

Sims, Robert E.; Butcher, John B.; Parri, H. Rheinallt; Glazewski, Stanislaw

2015-01-01

Changing the whisker complement on a rodent's snout can lead to two forms of experience-dependent plasticity (EDP) in the neurons of the barrel cortex, where whiskers are somatotopically represented. One form, termed coding plasticity, concerns changes in synaptic transmission and connectivity between neurons. This is thought to underlie learning and memory processes and so adaptation to a changing environment. The second, called homeostatic plasticity, serves to maintain a restricted dynamic range of neuronal activity thus preventing its saturation or total downregulation. Current explanatory models of cortical EDP are almost exclusively neurocentric. However, in recent years, increasing evidence has emerged on the role of astrocytes in brain function, including plasticity. Indeed, astrocytes appear as necessary partners of neurons at the core of the mechanisms of coding and homeostatic plasticity recorded in neurons. In addition to neuronal plasticity, several different forms of astrocytic plasticity have recently been discovered. They extend from changes in receptor expression and dynamic changes in morphology to alteration in gliotransmitter release. It is however unclear how astrocytic plasticity contributes to the neuronal EDP. Here, we review the known and possible roles for astrocytes in the barrel cortex, including its plasticity. PMID:26345481

Connectional Modularity of Top-Down and Bottom-Up Multimodal Inputs to the Lateral Cortex of the Mouse Inferior Colliculus

PubMed Central

Lesicko, Alexandria M.H.; Hristova, Teodora S.; Maigler, Kathleen C.

2016-01-01

The lateral cortex of the inferior colliculus receives information from both auditory and somatosensory structures and is thought to play a role in multisensory integration. Previous studies in the rat have shown that this nucleus contains a series of distinct anatomical modules that stain for GAD-67 as well as other neurochemical markers. In the present study, we sought to better characterize these modules in the mouse inferior colliculus and determine whether the connectivity of other neural structures with the lateral cortex is spatially related to the distribution of these neurochemical modules. Staining for GAD-67 and other markers revealed a single modular network throughout the rostrocaudal extent of the mouse lateral cortex. Somatosensory inputs from the somatosensory cortex and dorsal column nuclei were found to terminate almost exclusively within these modular zones. However, projections from the auditory cortex and central nucleus of the inferior colliculus formed patches that interdigitate with the GAD-67-positive modules. These results suggest that the lateral cortex of the mouse inferior colliculus exhibits connectional as well as neurochemical modularity and may contain multiple segregated processing streams. This finding is discussed in the context of other brain structures in which neuroanatomical and connectional modularity have functional consequences. SIGNIFICANCE STATEMENT Many brain regions contain subnuclear microarchitectures, such as the matrix-striosome organization of the basal ganglia or the patch-interpatch organization of the visual cortex, that shed light on circuit complexities. In the present study, we demonstrate the presence of one such micro-organization in the rodent inferior colliculus. While this structure is typically viewed as an auditory integration center, its lateral cortex appears to be involved in multisensory operations and receives input from somatosensory brain regions. We show here that the lateral cortex can be further subdivided into multiple processing streams: modular regions, which are targeted by somatosensory inputs, and extramodular zones that receive auditory information. PMID:27798184

A Map of Anticipatory Activity in Mouse Motor Cortex.

PubMed

Chen, Tsai-Wen; Li, Nuo; Daie, Kayvon; Svoboda, Karel

2017-05-17

Activity in the mouse anterior lateral motor cortex (ALM) instructs directional movements, often seconds before movement initiation. It is unknown whether this preparatory activity is localized to ALM or widely distributed within motor cortex. Here we imaged activity across motor cortex while mice performed a whisker-based object localization task with a delayed, directional licking response. During tactile sensation and the delay epoch, object location was represented in motor cortex areas that are medial and posterior relative to ALM, including vibrissal motor cortex. Preparatory activity appeared first in deep layers of ALM, seconds before the behavioral response, and remained localized to ALM until the behavioral response. Later, widely distributed neurons represented the outcome of the trial. Cortical area was more predictive of neuronal selectivity than laminar location or axonal projection target. Motor cortex therefore represents sensory, motor, and outcome information in a spatially organized manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Reelin is essential for neuronal migration but not for radial glial elongation in neonatal ferret cortex.

PubMed

Schaefer, Alisa; Poluch, Sylvie; Juliano, Sharon

2008-04-01

Numerous functions related to neuronal migration are linked to the glycoprotein reelin. Reelin also elongates radial glia, which are disrupted in mutant reeler mice. Our lab developed a model of cortical dysplasia in ferrets that shares features with the reeler mouse, including impaired migration of neurons into the cerebral cortex and disrupted radial glia. Explants of normal ferret cortex in coculture with dysplastic ferret cortex restore the deficits in this model. To determine if reelin is integral to the repair, we used explants of P0 mouse cortex either of the wild type (WT) or heterozygous (het) for the reelin gene, as well as P0 reeler cortex (not containing reelin), in coculture with organotypic cultures of dysplastic ferret cortex. This arrangement revealed that all types of mouse cortical explants (WT, het, reeler) elongated radial glia in ferret cortical dysplasia, indicating that reelin is not required for proper radial glial morphology. Migration of cells into ferret neocortex, however, did not improve with explants of reeler cortex, but was almost normal after pairing with WT or het explants. We also placed an exogenous source of reelin in ferret cultures at the pial surface to reveal that migrating cells move toward the reelin source in dysplastic cortex; radial glia in these cultures were also improved toward normal. Our results demonstrate that the normotopic position of reelin is important for proper neuronal positioning, and that reelin is capable of elongating radial glial cells but is not the only radialization factor.

Manipulating neuronal activity with low frequency transcranial ultrasound

NASA Astrophysics Data System (ADS)

Moore, Michele Elizabeth

Stimulation of the rodent cerebral cortex is used to investigate the underlying biological basis for the restorative effects of slow wave sleep. Neuronal activation by optogenetic and ultrasound stimulation elicits changes in action potentials across the cerebral cortex that are recorded as electroencephalograms. Optogenetic stimulation requires an invasive implantation procedure limiting its application in human studies. We sought to determine whether ultrasound stimulation could be as effective as optogenetic techniques currently used, in an effort to further understand the physiological and metabolic requirements of sleep. We successfully recorded electroencephalograms in response to transcranial ultrasound stimulation of the barrel cortex at 1 and 7 Hz frequencies, comparing them to those recorded in response to optogenetic stimuli applied at the same frequencies. Our results showed application of a 473 nm blue LED positioned 6 cm above the skull and ultrasound stimulation at an output voltage of 1000 mVpp produced electroencephalograms with physiological responses of similar amplitude. We concluded that there exists an intensity-proportionate response in the optogenetic stimulation, but not with ultrasound stimulation at the frequencies we surveyed. Activation of neuronal cells in response to optogenetic stimulation in a Thy1-ChR2 transgenic mouse line is specifically targeted to pyramidal cells in the cerebral cortex. ChR2 responses to optogenetic stimulation are mediated by a focal activation of neuronal ion channels. We measured electrophysiological responses to ultrasound stimulation, comparing them to those recorded from optogenetic stimuli. Our results show striking similarities between ultrasound-induced responses and optogenetically-induced responses, which may indicate that transcranial ultrasound stimulation is also mediated by ion channel dependent processes in cerebral cortical neurons. The biophysical substrates for electrical excitability of neurons impose temporal constraints on their response to stimulation. If ultrasound-mediated responses are, in fact, ion channel mediated responses, ultrasound-induced responses should exhibit time-dependence characteristics similar to those of optogenetically-triggered responses. Minimal stimulus duration thresholds and the temporal limits of paired pulse facilitation for ultrasound stimulation were identical to those of optogenetic stimulation. Collectively, these experiments demonstrate an electrophysiological basis for low-frequency transcranial ultrasound stimulation of cerebral cortical neuronal activity.

Neuronal Representation of Ultraviolet Visual Stimuli in Mouse Primary Visual Cortex

PubMed Central

Tan, Zhongchao; Sun, Wenzhi; Chen, Tsai-Wen; Kim, Douglas; Ji, Na

2015-01-01

The mouse has become an important model for understanding the neural basis of visual perception. Although it has long been known that mouse lens transmits ultraviolet (UV) light and mouse opsins have absorption in the UV band, little is known about how UV visual information is processed in the mouse brain. Using a custom UV stimulation system and in vivo calcium imaging, we characterized the feature selectivity of layer 2/3 neurons in mouse primary visual cortex (V1). In adult mice, a comparable percentage of the neuronal population responds to UV and visible stimuli, with similar pattern selectivity and receptive field properties. In young mice, the orientation selectivity for UV stimuli increased steadily during development, but not direction selectivity. Our results suggest that, by expanding the spectral window through which the mouse can acquire visual information, UV sensitivity provides an important component for mouse vision. PMID:26219604

Prenatal alcohol exposure reduces the size of the forelimb representation in motor cortex in rat: an intracortical microstimulation (ICMS) mapping study.

PubMed

Xie, Ni; Yang, Qiuhong; Chappell, Tyson D; Li, Cheng-Xiang; Waters, Robert S

2010-03-01

Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems. Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on the development and organization of somatosensory barrel field cortex. To this end, PAE delayed the development of somatosensory cortex, reduced the size of whisker and forelimb representations in somatosensory barrel field cortex, and delayed acquisition time to learn a skilled reaching task. However, whether PAE also affects the motor cortex (MI) remains to be determined. In the present study, we investigated the effect of PAE on the size of the forelimb representation in rat MI, thresholds for activation, and the overlap between motor and sensory cortical forelimb maps in sensorimotor cortex. Pregnant Sprague-Dawley rats were assigned to alcohol (Alc), pair-fed (PF), and chow-fed (CF) groups on gestation day 1 (GD1). Rats in the Alc group (n=4) were chronically intubated daily with binge doses of alcohol (6g/kg body weight) from GD1 to GD20 that resulted in averaged blood alcohol levels measured on GD10 (mean=191.5+/-41.9mg/dL) and on GD17 (mean=247.0+/-72.4mg/dL). PF (n=2) and CF (n=3) groups of pregnant rats served as controls. The effect of PAE on the various dependent measures was obtained from multiple male offspring from each dam within treatment groups, and litter means were compared between the groups from alcohol-treated and control (Ct: CF and PF) dams. At approximately 8 weeks of age, rats were anesthetized with ketamine/xylazine and the skull opened over sensorimotor cortex. A tungsten microelectrode was then inserted into the depths of layer V and intracortical microstimulation was used to deliver trains of pulses to evoke muscle contractions and/or movements; maximum stimulating < or =100microA. When a motor response was observed, the threshold for movement was measured and the motor receptive field projected to the cortical surface to serve as representative point for that location. A motor map for the forelimb representation was generated by systematically stimulating at adjacent sites until current thresholds reached the maximum and/or motor responses were no longer evoked. The major findings in this study were as follows: (1) PAE significantly reduced the area of the forelimb representation in the Alc offspring (6.01mm(2), standard error of the mean=+/-0.278) compared with the Ct offspring (8.03mm(2)+/-0.586), (2) PAE did not significantly reduce the averaged threshold for activation of movements between groups, (3) PAE significantly reduced the percent overlap (Alc=31.1%, Ct=55.4%) between the forelimb representation in sensory and motor cortices, and (4) no significant differences were observed in averaged body weight, hemisphere weight, or age of animal between treatment groups. These findings suggest that the effects of PAE are not restricted to somatosensory barrel field cortex but also involve the MI and may underlie deficits in motor control and sensorimotor integration observed among children with FASD. 2010. Published by Elsevier Inc.

Use of a simplified method of optical recording to identify foci of maximal neuron activity in the somatosensory cortex of white rats.

PubMed

Inyushin, M Y; Volnova, A B; Lenkov, D N

2001-01-01

Eight mongrel white male rats were studied under urethane anesthesia, and neuron activity evoked by mechanical and/or electrical stimulation of the contralateral whiskers was recorded in the primary somatosensory cortex. Recordings were made using a digital USB chamber attached to the printer port of a Pentium 200MMX computer running standard programs. Optical images were obtained in the barrel-field zone using a differential signal, i.e., the difference signal for cortex images in control and experimental animals. The results obtained here showed that subtraction of averaged sequences of frames yielded images consisting of spots reflecting the probable position of activated groups of neurons. The most effective stimulation consisted of natural low-frequency stimulation of the whiskers. The method can be used for preliminary mapping of cortical zones, as it provides for rapid and reproducible testing of the activity of neuron ensembles over large areas of the cortex.

Scaling of Topologically Similar Functional Modules Defines Mouse Primary Auditory and Somatosensory Microcircuitry

PubMed Central

Sadovsky, Alexander J.

2013-01-01

Mapping the flow of activity through neocortical microcircuits provides key insights into the underlying circuit architecture. Using a comparative analysis we determined the extent to which the dynamics of microcircuits in mouse primary somatosensory barrel field (S1BF) and auditory (A1) neocortex generalize. We imaged the simultaneous dynamics of up to 1126 neurons spanning multiple columns and layers using high-speed multiphoton imaging. The temporal progression and reliability of reactivation of circuit events in both regions suggested common underlying cortical design features. We used circuit activity flow to generate functional connectivity maps, or graphs, to test the microcircuit hypothesis within a functional framework. S1BF and A1 present a useful test of the postulate as both regions map sensory input anatomically, but each area appears organized according to different design principles. We projected the functional topologies into anatomical space and found benchmarks of organization that had been previously described using physiology and anatomical methods, consistent with a close mapping between anatomy and functional dynamics. By comparing graphs representing activity flow we found that each region is similarly organized as highlighted by hallmarks of small world, scale free, and hierarchical modular topologies. Models of prototypical functional circuits from each area of cortex were sufficient to recapitulate experimentally observed circuit activity. Convergence to common behavior by these models was accomplished using preferential attachment to scale from an auditory up to a somatosensory circuit. These functional data imply that the microcircuit hypothesis be framed as scalable principles of neocortical circuit design. PMID:23986241

Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex

PubMed Central

Sreenivasan, Varun; Kyriakatos, Alexandros; Mateo, Celine; Jaeger, Dieter; Petersen, Carl C.H.

2016-01-01

Abstract. The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs. PMID:27921067

Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo

PubMed Central

Liston, Conor; Gan, Wen-Biao

2011-01-01

Glucocorticoids are a family of hormones that coordinate diverse physiological processes in responding to stress. Prolonged glucocorticoid exposure over weeks has been linked to dendritic atrophy and spine loss in fixed tissue studies of adult brains, but it is unclear how glucocorticoids may affect the dynamic processes of dendritic spine formation and elimination in vivo. Furthermore, relatively few studies have examined the effects of stress and glucocorticoids on spines during the postnatal and adolescent period, which is characterized by rapid synaptogenesis followed by protracted synaptic pruning. To determine whether and to what extent glucocorticoids regulate dendritic spine development and plasticity, we used transcranial two-photon microscopy to track the formation and elimination of dendritic spines in vivo after treatment with glucocorticoids in developing and adult mice. Corticosterone, the principal murine glucocorticoid, had potent dose-dependent effects on dendritic spine dynamics, increasing spine turnover within several hours in the developing barrel cortex. The adult barrel cortex exhibited diminished baseline spine turnover rates, but these rates were also enhanced by corticosterone. Similar changes occurred in multiple cortical areas, suggesting a generalized effect. However, reducing endogenous glucocorticoid activity by dexamethasone suppression or corticosteroid receptor antagonists caused a substantial reduction in spine turnover rates, and the former was reversed by corticosterone replacement. Notably, we found that chronic glucocorticoid excess led to an abnormal loss of stable spines that were established early in life. Together, these findings establish a critical role for glucocorticoids in the development and maintenance of dendritic spines in the living cortex. PMID:21911374

Reduced inhibitory gate in the barrel cortex of Neuroligin3R451C knock‐in mice, an animal model of autism spectrum disorders

PubMed Central

Cellot, Giada; Cherubini, Enrico

2014-01-01

Abstract Neuroligins are postsynaptic adhesion molecules that interacting with presynaptic neurexins ensure the cross‐talk between pre‐ and postsynaptic specializations. Rare mutations in neurexin–neuroligin genes have been linked to autism spectrum disorders (ASDs). One of these, the R451C mutation of the gene encoding for Neuroligin3 (Nlgn3), has been found in patients with familial forms of ASDs. Animals carrying this mutation (NL3R451C knock‐in mice) exhibit impaired social behaviors, reminiscent of those observed in ASD patients, associated with major alterations in both GABAergic and glutamatergic transmission, which vary among different brain regions and at different developmental stages. Here, pair recordings from parvalbumin‐ (PV) expressing basket cells and spiny neurons were used to study GABAergic synaptic signaling in layer IV barrel cortex of NL3R451C mutant mice. We found that the R451C mutation severely affects the probability of GABA release from PV‐expressing basket cells, responsible for controlling via thalamo‐cortical inputs the feed‐forward inhibition. No changes in excitatory inputs to parvalbumin‐positive basket cells or spiny neurons were detected. These data clearly show that primary targets of the NL3 mutation are PV‐expressing basket cells, independently of the brain region where they are localized. Changes in the inhibitory gate of layer IV somatosensory cortex may alter sensory processing in ASD patients leading to misleading sensory representations with difficulties to combine pieces of information into a unified perceptual whole. PMID:25347860

High Stimulus-Related Information in Barrel Cortex Inhibitory Interneurons

PubMed Central

Reyes-Puerta, Vicente; Kim, Suam; Sun, Jyh-Jang; Imbrosci, Barbara; Kilb, Werner; Luhmann, Heiko J.

2015-01-01

The manner in which populations of inhibitory (INH) and excitatory (EXC) neocortical neurons collectively encode stimulus-related information is a fundamental, yet still unresolved question. Here we address this question by simultaneously recording with large-scale multi-electrode arrays (of up to 128 channels) the activity of cell ensembles (of up to 74 neurons) distributed along all layers of 3–4 neighboring cortical columns in the anesthetized adult rat somatosensory barrel cortex in vivo. Using two different whisker stimulus modalities (location and frequency) we show that individual INH neurons – classified as such according to their distinct extracellular spike waveforms – discriminate better between restricted sets of stimuli (≤6 stimulus classes) than EXC neurons in granular and infra-granular layers. We also demonstrate that ensembles of INH cells jointly provide as much information about such stimuli as comparable ensembles containing the ~20% most informative EXC neurons, however presenting less information redundancy – a result which was consistent when applying both theoretical information measurements and linear discriminant analysis classifiers. These results suggest that a consortium of INH neurons dominates the information conveyed to the neocortical network, thereby efficiently processing incoming sensory activity. This conclusion extends our view on the role of the inhibitory system to orchestrate cortical activity. PMID:26098109

Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons.

PubMed

Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

2017-01-01

According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca 2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca 2+ spike and Ca 2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information.

Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons

PubMed Central

Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

2017-01-01

According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca2+ spike and Ca2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information. PMID:28203145

Borders and Comparative Cytoarchitecture of the Perirhinal and Postrhinal Cortices in an F1 Hybrid Mouse

PubMed Central

Beaudin, Stephane A.; Singh, Teghpal; Agster, Kara L.

2013-01-01

We examined the cytoarchitectonic and chemoarchitectonic organization of the cortical regions associated with the posterior rhinal fissure in the mouse brain, within the framework of what is known about these regions in the rat. Primary observations were in a first-generation hybrid mouse line, B6129PF/J1. The F1 hybrid was chosen because of the many advantages afforded in the study of the molecular and cellular bases of learning and memory. Comparisons with the parent strains, the C57BL6/J and 129P3/J are also reported. Mouse brain tissue was processed for visualization of Nissl material, myelin, acetyl cholinesterase, parvalbumin, and heavy metals. Tissue stained for heavy metals by the Timm’s method was particularly useful in the assignment of borders and in the comparative analyses because the patterns of staining were similar across species and strains. As in the rat, the areas examined were parcellated into 2 regions, the perirhinal and the postrhinal cortices. The perirhinal cortex was divided into areas 35 and 36, and the postrhinal cortex was divided into dorsal (PORd) and ventral (PORv) subregions. In addition to identifying the borders of the perirhinal cortex, we were able to identify a region in the mouse brain that shares signature features with the rat postrhinal cortex. PMID:22368084

Critical period plasticity is disrupted in the barrel cortex of Fmr1 knockout mice

PubMed Central

Harlow, Emily G.; Till, Sally M.; Russell, Theron A.; Wijetunge, Lasani S.; Kind, Peter; Contractor, Anis

2010-01-01

Summary Alterations in sensory processing constitute prominent symptoms of Fragile X syndrome; however, little is known about how disrupted synaptic and circuit development in sensory cortex contributes to these deficits. To investigate how the loss of fragile X mental retardation protein (FMRP) impacts the development of cortical synapses, we examined excitatory thalamocortical synapses in somatosensory cortex during the perinatal critical period in Fmr1 knockout mice. FMRP ablation resulted in dysregulation of glutamatergic signaling maturation. The fraction of silent synapses persisting to later developmental times was increased, there was a temporal delay in the window for synaptic plasticity, while other forms of developmental plasticity were not altered in Fmr1 knockout mice. Our results indicate that FMRP is required for the normal developmental progression of synaptic maturation, and loss of this important RNA binding protein impacts the timing of the critical period for layer IV synaptic plasticity. PMID:20159451

A mouse model of ocular blast injury that induces closed globe anterior and posterior pole damage

PubMed Central

Hines-Beard, Jessica; Marchetta, Jeffrey; Gordon, Sarah; Chaum, Edward; Geisert, Eldon E.; Rex, Tonia S.

2012-01-01

We developed and characterized a mouse model of primary ocular blast injury. The device consists of: a pressurized air tank attached to a regulated paintball gun with a machined barrel; a chamber that protects the mouse from direct injury and recoil, while exposing the eye; and a secure platform that enables fine, controlled movement of the chamber in relation to the barrel. Expected pressures were calculated and the optimal pressure transducer, based on the predicted pressures, was positioned to measure output pressures at the location where the mouse eye would be placed. Mice were exposed to one of three blast pressures (23.6, 26.4, or 30.4psi). Gross pathology, intraocular pressure, optical coherence tomography, and visual acuity were assessed 0, 3, 7, 14, and 28 days after exposure. Contralateral eyes and non-blast exposed mice were used as controls. We detected increased damage with increased pressures and a shift in the damage profile over time. Gross pathology included corneal edema, corneal abrasions, and optic nerve avulsion. Retinal damage was detected by optical coherence tomography and a deficit in visual acuity was detected by optokinetics. Our findings are comparable to those identified in Veterans of the recent wars with closed eye injuries as a result of blast exposure. In summary, this is a relatively simple system that creates injuries with features similar to those seen in patients with ocular blast trauma. This is an important new model for testing the short-term and long-term spectrum of closed globe blast injuries and potential therapeutic interventions. PMID:22504073

Traumatic Brain Injury and Neuronal Functionality Changes in Sensory Cortex

PubMed Central

Carron, Simone F.; Alwis, Dasuni S.; Rajan, Ramesh

2016-01-01

Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relative head-brain movement, can result in long-lasting cognitive and motor deficits which can be particularly consequential when they occur in young people with a long life ahead. Much is known of the molecular and anatomical changes produced in TBI but much less is known of the consequences of these changes to neuronal functionality, especially in the cortex. Given that much of our interior and exterior lives are dependent on responsiveness to information from and about the world around us, we have hypothesized that a significant contributor to the cognitive and motor deficits seen after TBI could be changes in sensory processing. To explore this hypothesis, and to develop a model test system of the changes in neuronal functionality caused by TBI, we have examined neuronal encoding of simple and complex sensory input in the rat’s exploratory and discriminative tactile system, the large face macrovibrissae, which feeds to the so-called “barrel cortex” of somatosensory cortex. In this review we describe the short-term and long-term changes in the barrel cortex encoding of whisker motion modeling naturalistic whisker movement undertaken by rats engaged in a variety of tasks. We demonstrate that the most common form of TBI results in persistent neuronal hyperexcitation specifically in the upper cortical layers, likely due to changes in inhibition. We describe the types of cortical inhibitory neurons and their roles and how selective effects on some of these could produce the particular forms of neuronal encoding changes described in TBI, and then generalize to compare the effects on inhibition seen in other forms of brain injury. From these findings we make specific predictions as to how non-invasive extra-cranial electrophysiology can be used to provide the high-precision information needed to monitor and understand the temporal evolution of changes in neuronal functionality in humans suffering TBI. Such detailed understanding of the specific changes in an individual patient’s cortex can allow for treatment to be tailored to the neuronal changes in that particular patient’s brain in TBI, a precision that is currently unavailable with any technique. PMID:27313514

Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function

PubMed Central

Castejon, Carlos; Barros-Zulaica, Natali; Nuñez, Angel

2016-01-01

Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane-anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas. PMID:26820514

Reduced inhibitory gate in the barrel cortex of Neuroligin3R451C knock-in mice, an animal model of autism spectrum disorders.

PubMed

Cellot, Giada; Cherubini, Enrico

2014-07-16

Neuroligins are postsynaptic adhesion molecules that interacting with presynaptic neurexins ensure the cross-talk between pre- and postsynaptic specializations. Rare mutations in neurexin-neuroligin genes have been linked to autism spectrum disorders (ASDs). One of these, the R451C mutation of the gene encoding for Neuroligin3 (Nlgn3), has been found in patients with familial forms of ASDs. Animals carrying this mutation (NL3(R451C) knock-in mice) exhibit impaired social behaviors, reminiscent of those observed in ASD patients, associated with major alterations in both GABAergic and glutamatergic transmission, which vary among different brain regions and at different developmental stages. Here, pair recordings from parvalbumin- (PV) expressing basket cells and spiny neurons were used to study GABAergic synaptic signaling in layer IV barrel cortex of NL3(R451C) mutant mice. We found that the R451C mutation severely affects the probability of GABA release from PV-expressing basket cells, responsible for controlling via thalamo-cortical inputs the feed-forward inhibition. No changes in excitatory inputs to parvalbumin-positive basket cells or spiny neurons were detected. These data clearly show that primary targets of the NL3 mutation are PV-expressing basket cells, independently of the brain region where they are localized. Changes in the inhibitory gate of layer IV somatosensory cortex may alter sensory processing in ASD patients leading to misleading sensory representations with difficulties to combine pieces of information into a unified perceptual whole. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Double-barreled and Concentric Microelectrodes for Measurement of Extracellular Ion Signals in Brain Tissue

PubMed Central

Haack, Nicole; Durry, Simone; Kafitz, Karl W.; Chesler, Mitchell; Rose, Christine R.

2015-01-01

Electrical activity in the brain is accompanied by significant ion fluxes across membranes, resulting in complex changes in the extracellular concentration of all major ions. As these ion shifts bear significant functional consequences, their quantitative determination is often required to understand the function and dysfunction of neural networks under physiological and pathophysiological conditions. In the present study, we demonstrate the fabrication and calibration of double-barreled ion-selective microelectrodes, which have proven to be excellent tools for such measurements in brain tissue. Moreover, so-called “concentric” ion-selective microelectrodes are also described, which, based on their different design, offer a far better temporal resolution of fast ion changes. We then show how these electrodes can be employed in acute brain slice preparations of the mouse hippocampus. Using double-barreled, potassium-selective microelectrodes, changes in the extracellular potassium concentration ([K+]o) in response to exogenous application of glutamate receptor agonists or during epileptiform activity are demonstrated. Furthermore, we illustrate the response characteristics of sodium-sensitive, double-barreled and concentric electrodes and compare their detection of changes in the extracellular sodium concentration ([Na+]o) evoked by bath or pressure application of drugs. These measurements show that while response amplitudes are similar, the concentric sodium microelectrodes display a superior signal-to-noise ratio and response time as compared to the double-barreled design. Generally, the demonstrated procedures will be easily transferable to measurement of other ions species, including pH or calcium, and will also be applicable to other preparations. PMID:26381747

Mouse auditory cortex differs from visual and somatosensory cortices in the laminar distribution of cytochrome oxidase and acetylcholinesterase.

PubMed

Anderson, L A; Christianson, G B; Linden, J F

2009-02-03

Cytochrome oxidase (CYO) and acetylcholinesterase (AChE) staining density varies across the cortical layers in many sensory areas. The laminar variations likely reflect differences between the layers in levels of metabolic activity and cholinergic modulation. The question of whether these laminar variations differ between primary sensory cortices has never been systematically addressed in the same set of animals, since most studies of sensory cortex focus on a single sensory modality. Here, we compared the laminar distribution of CYO and AChE activity in the primary auditory, visual, and somatosensory cortices of the mouse, using Nissl-stained sections to define laminar boundaries. Interestingly, for both CYO and AChE, laminar patterns of enzyme activity were similar in the visual and somatosensory cortices, but differed in the auditory cortex. In the visual and somatosensory areas, staining densities for both enzymes were highest in layers III/IV or IV and in lower layer V. In the auditory cortex, CYO activity showed a reliable peak only at the layer III/IV border, while AChE distribution was relatively homogeneous across layers. These results suggest that laminar patterns of metabolic activity and cholinergic influence are similar in the mouse visual and somatosensory cortices, but differ in the auditory cortex.

Multiscale Imaging of the Mouse Cortex Using Two-Photon Microscopy and Wide-Field Illumination

NASA Astrophysics Data System (ADS)

Bumstead, Jonathan R.

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing the difference in spatial scales imaged with two-photon microscopy (TPM) and optical intrinsic signal imaging (OISI). Central to this work has been the formulation of a principled design strategy for extending the FOV of the two-photon microscope. Using this design approach, we constructed a TPM system with subcellular resolution and a FOV area 100 times greater than a conventional two-photon microscope. To image the ellipsoidal shape of the mouse cortex, we also developed the microscope to image arbitrary surfaces within a single frame using an electrically tunable lens. Finally, to address the speed limitations of the TPM systems developed during my dissertation, I also conducted research in large-scale neural phenomena occurring in the mouse brain imaged with high-speed OISI. The work conducted during my dissertation addresses some of the fundamental principles in designing and applying optical systems for multiscale imaging of the mouse brain.

Lactate and glutamate dynamics during prolonged stimulation of the rat barrel cortex suggest adaptation of cerebral glucose and oxygen metabolism.

PubMed

Sonnay, Sarah; Duarte, João M N; Just, Nathalie

2017-03-27

A better understanding of BOLD responses stems from a better characterization of the brain's ability to metabolize glucose and oxygen. Non-invasive techniques such as functional magnetic resonance spectroscopy (fMRS) have thus been developed allowing for the reproducible assessment of metabolic changes during barrel cortex (S1BF) activations in rats. The present study aimed at further exploring the role of neurotransmitters on local and temporal changes in vascular and metabolic function in S1BF. fMRS and fMRI data were acquired sequentially in α-chloralose anesthetized rats during 32-min rest and trigeminal nerve stimulation periods. During stimulation, concentrations of lactate (Lac) and glutamate (Glu) increased in S1BF by 0.23±0.05 and 0.34±0.05μmol/g respectively in S1BF. Dynamic analysis of metabolite concentrations allowed estimating changes in cerebral metabolic rates of glucose (ΔCMR Glc ) and oxygen (ΔCMR O2 ). Findings confirmed a prevalence of oxidative metabolism during prolonged S1BF activation. Habituation led to a significant BOLD magnitude decline as a function of time while both total ΔCMR Glc and ΔCMR O2 remained constant revealing adaptation of glucose and oxygen metabolisms to support ongoing trigeminal nerve stimulation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Dynamic Re-wiring of Neural Circuits in the Motor Cortex in Mouse Models of Parkinson's Disease

PubMed Central

Lalchandani, Rupa R.; Cui, Yuting; Shu, Yu; Xu, Tonghui; Ding, Jun B.

2015-01-01

SUMMARY Dynamic adaptations in synaptic plasticity are critical for learning new motor skills and maintaining memory throughout life, which rapidly decline with Parkinson's disease (PD). Plasticity in the motor cortex is important for acquisition and maintenance of novel motor skills, but how the loss of dopamine in PD leads to disrupted structural and functional plasticity in the motor cortex is not well understood. Here, we utilized mouse models of PD and 2-photon imaging to show that dopamine depletion resulted in structural changes in the motor cortex. We further discovered that dopamine D1 and D2 receptor signaling were linked to selectively and distinctly regulating these aberrant changes in structural and functional plasticity. Our findings suggest that both D1 and D2 receptor signaling regulate motor cortex plasticity, and loss of dopamine results in atypical synaptic adaptations that may contribute to the impairment of motor performance and motor memory observed in PD. PMID:26237365

Cultured embryonic non-innervated mouse muzzle is capable of generating a whisker pattern.

PubMed

Andrés, F L; Van Der Loos, H

1983-01-01

The whisker pattern on the muzzle of the mouse is mapped in the contralateral parietal neocortex, each whisker follicle projecting to its own multineuronal unit ('barrel'). To determine the role, if any, of the peripheral innervation in the establishment of the vibrissal array, we cultured non-innervated prospective whiskerpads from 9- and 10-day-old embryos, mostly on chorioallantoic membrane. The results show that skin, alone, is capable of generating the whisker pattern, thus adducing a strong argument for the hypothesis that the central brain maps have their origin in the periphery. Copyright © 1983. Published by Elsevier Ltd.

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

PubMed Central

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

The Circadian Oscillator of the Cerebral Cortex: Molecular, Biochemical and Behavioral Effects of Deleting the Arntl Clock Gene in Cortical Neurons.

PubMed

Bering, Tenna; Carstensen, Mikkel Bloss; Wörtwein, Gitta; Weikop, Pia; Rath, Martin Fredensborg

2018-02-01

A molecular circadian oscillator resides in neurons of the cerebral cortex, but its role is unknown. Using the Cre-LoxP method, we have here abolished the core clock gene Arntl in those neurons. This mouse represents the first model carrying a deletion of a circadian clock component specifically in an extrahypothalamic cell type of the brain. Molecular analyses of clock gene expression in the cerebral cortex of the Arntl conditional knockout mouse revealed disrupted circadian expression profiles, whereas clock gene expression in the suprachiasmatic nucleus was still rhythmic, thus showing that Arntl is required for normal function of the cortical circadian oscillator. Daily rhythms in running activity and temperature were not influenced, whereas the resynchronization response to experimental jet-lag exhibited minor though significant differences between genotypes. The tail-suspension test revealed significantly prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of Prenatal Testosterone Exposure on Sexually Dimorphic Gene Expression in the Neonatal Mouse Cortex and Hippocampus

PubMed Central

Armoskus, Chris; Mota, Thomas; Moreira, Debbie; Tsai, Houng-Wei

2014-01-01

Objective Using gene expression microarrays and reverse transcription with quantitative polymerase chain reaction (RT-qPCR), we have recently identified several novel genes that are differentially expressed in the neonatal male versus female mouse cortex/hippocampus (Armoskus et al.). Since perinatal testosterone (T) secreted by the developing testes masculinizes cortical and hippocampal structures and the behaviors regulated by these brain regions, we hypothesized that sexually dimorphic expression of specific selected genes in these areas might be regulated by T during early development. Methods To test our hypothesis, we treated timed pregnant female mice daily with vehicle or testosterone propionate (TP) starting on embryonic day 16 until the day of birth. The cortex/hippocampus was collected from vehicle- and TP-treated, male and female neonatal pups. Total RNA was extracted from these brain tissues, followed by RT-qPCR to measure relative mRNA levels of seven sex chromosome genes and three autosomal genes that have previously showed sex differences. Results The effect of prenatal TP was confirmed as it stimulated Dhcr24 expression in the neonatal mouse cortex/hippocampus and increased the anogenital distance in females. We found a significant effect of sex, but not TP, on expression of three Y-linked (Ddx3y, Eif2s3y, and Kdm5d), four X-linked (Eif2s3x, Kdm6a, Mid1, and Xist), and one autosomal (Klk8) genes in the neonatal mouse cortex/hippocampus. Conclusion Although most of the selected genes are not directly regulated by prenatal T, their sexually dimorphic expression might play an important role in the control of sexually differentiated cognitive and social behaviors as well as in the etiology of sex-biased neurological disorders and mental illnesses. PMID:25411648

Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

PubMed

Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

2016-11-01

Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

3D Reconstruction and Standardization of the Rat Vibrissal Cortex for Precise Registration of Single Neuron Morphology

PubMed Central

Egger, Robert; Narayanan, Rajeevan T.; Helmstaedter, Moritz; de Kock, Christiaan P. J.; Oberlaender, Marcel

2012-01-01

The three-dimensional (3D) structure of neural circuits is commonly studied by reconstructing individual or small groups of neurons in separate preparations. Investigation of structural organization principles or quantification of dendritic and axonal innervation thus requires integration of many reconstructed morphologies into a common reference frame. Here we present a standardized 3D model of the rat vibrissal cortex and introduce an automated registration tool that allows for precise placement of single neuron reconstructions. We (1) developed an automated image processing pipeline to reconstruct 3D anatomical landmarks, i.e., the barrels in Layer 4, the pia and white matter surfaces and the blood vessel pattern from high-resolution images, (2) quantified these landmarks in 12 different rats, (3) generated an average 3D model of the vibrissal cortex and (4) used rigid transformations and stepwise linear scaling to register 94 neuron morphologies, reconstructed from in vivo stainings, to the standardized cortex model. We find that anatomical landmarks vary substantially across the vibrissal cortex within an individual rat. In contrast, the 3D layout of the entire vibrissal cortex remains remarkably preserved across animals. This allows for precise registration of individual neuron reconstructions with approximately 30 µm accuracy. Our approach could be used to reconstruct and standardize other anatomically defined brain areas and may ultimately lead to a precise digital reference atlas of the rat brain. PMID:23284282

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

NASA Astrophysics Data System (ADS)

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.

Combinatorial expression of Lef1, Lhx2, Lhx5, Lhx9, Lmo3, Lmo4, and Prox1 helps to identify comparable subdivisions in the developing hippocampal formation of mouse and chicken

PubMed Central

Abellán, Antonio; Desfilis, Ester; Medina, Loreta

2014-01-01

We carried out a study of the expression patterns of seven developmental regulatory genes (Lef1, Lhx2, Lhx9, Lhx5, Lmo3, Lmo4, and Prox1), in combination with topological position, to identify the medial pallial derivatives, define its major subdivisions, and compare them between mouse and chicken. In both species, the medial pallium is defined as a pallial sector adjacent to the cortical hem and roof plate/choroid tela, showing moderate to strong ventricular zone expression of Lef1, Lhx2, and Lhx9, but not Lhx5. Based on this, the hippocampal formation (indusium griseum, dentate gyrus, Ammon's horn fields, and subiculum), the medial entorhinal cortex, and part of the amygdalo-hippocampal transition area of mouse appeared to derive from the medial pallium. In the chicken, based on the same position and gene expression profile, we propose that the hippocampus (including the V-shaped area), the parahippocampal area (including its caudolateral part), the entorhinal cortex, and the amygdalo-hippocampal transition area are medial pallial derivatives. Moreover, the combinatorial expression of Lef1, Prox1, Lmo4, and Lmo3 allowed the identification of dentate gyrus/CA3-like, CA1/subicular-like, and medial entorhinal-like comparable sectors in mouse and chicken, and point to the existence of mostly conserved molecular networks involved in hippocampal complex development. Notably, while the mouse medial entorhinal cortex derives from the medial pallium (similarly to the hippocampal formation, both being involved in spatial navigation and spatial memory), the lateral entorhinal cortex (involved in processing non-spatial, contextual information) appears to derive from a distinct dorsolateral caudal pallial sector. PMID:25071464

Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

PubMed Central

Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

2013-01-01

How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later. PMID:24155697

Real-time million-synapse simulation of rat barrel cortex.

PubMed

Sharp, Thomas; Petersen, Rasmus; Furber, Steve

2014-01-01

Simulations of neural circuits are bounded in scale and speed by available computing resources, and particularly by the differences in parallelism and communication patterns between the brain and high-performance computers. SpiNNaker is a computer architecture designed to address this problem by emulating the structure and function of neural tissue, using very many low-power processors and an interprocessor communication mechanism inspired by axonal arbors. Here we demonstrate that thousand-processor SpiNNaker prototypes can simulate models of the rodent barrel system comprising 50,000 neurons and 50 million synapses. We use the PyNN library to specify models, and the intrinsic features of Python to control experimental procedures and analysis. The models reproduce known thalamocortical response transformations, exhibit known, balanced dynamics of excitation and inhibition, and show a spatiotemporal spread of activity though the superficial cortical layers. These demonstrations are a significant step toward tractable simulations of entire cortical areas on the million-processor SpiNNaker machines in development.

Real-time million-synapse simulation of rat barrel cortex

PubMed Central

Sharp, Thomas; Petersen, Rasmus; Furber, Steve

2014-01-01

Simulations of neural circuits are bounded in scale and speed by available computing resources, and particularly by the differences in parallelism and communication patterns between the brain and high-performance computers. SpiNNaker is a computer architecture designed to address this problem by emulating the structure and function of neural tissue, using very many low-power processors and an interprocessor communication mechanism inspired by axonal arbors. Here we demonstrate that thousand-processor SpiNNaker prototypes can simulate models of the rodent barrel system comprising 50,000 neurons and 50 million synapses. We use the PyNN library to specify models, and the intrinsic features of Python to control experimental procedures and analysis. The models reproduce known thalamocortical response transformations, exhibit known, balanced dynamics of excitation and inhibition, and show a spatiotemporal spread of activity though the superficial cortical layers. These demonstrations are a significant step toward tractable simulations of entire cortical areas on the million-processor SpiNNaker machines in development. PMID:24910593

Chronic cranial window with access port for repeated cellular manipulations, drug application, and electrophysiology

PubMed Central

Roome, Christopher J.; Kuhn, Bernd

2014-01-01

Chronic cranial windows have been instrumental in advancing optical studies in vivo, permitting long-term, high-resolution imaging in various brain regions. However, once a window is attached it is difficult to regain access to the brain under the window for cellular manipulations. Here we describe a simple device that combines long term in vivo optical imaging with direct brain access via glass or quartz pipettes and metal, glass, or quartz electrodes for cellular manipulations like dye or drug injections and electrophysiological stimulations or recordings while keeping the craniotomy sterile. Our device comprises a regular cranial window glass coverslip with a drilled access hole later sealed with biocompatible silicone. This chronic cranial window with access port is cheap, easy to manufacture, can be mounted just as the regular chronic cranial window, and is self-sealing after retraction of the pipette or electrode. We demonstrate that multiple injections can be performed through the silicone port by repetitively bolus loading calcium sensitive dye into mouse barrel cortex and recording spontaneous cellular activity over a period of weeks. As an example to the extent of its utility for electrophysiological recording, we describe how simple removal of the silicone seal can permit patch pipette access for whole-cell patch clamp recordings in vivo. During these chronic experiments we do not observe any infections under the window or impairment of animal health. PMID:25426027

Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex.

PubMed

Chao, Dongman; Bazzy-Asaad, Alia; Balboni, Gianfranco; Salvadori, Severo; Xia, Ying

2008-09-01

We have recently found that in the mouse cortex, activation of delta-opioid receptor (DOR) attenuates the disruption of K(+) homeostasis induced by hypoxia or oxygen-glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K(+) homeostasis because the disruption of K(+) homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na(+) influx and thus stimulates K(+) leakage, we investigated whether DOR protects the cortex from anoxic K(+) derangement by targeting the Na(+)-based K(+) leakage. By using K(+)-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na(+) concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K(+) derangement; 2) lowering Na(+) concentration by substituting with permeable Li(+) tended to potentiate the anoxic K(+) derangement; and 3) the DOR-induced protection against the anoxic K(+) responses was largely abolished by low-Na(+) perfusion irrespective of the substituted cation. We conclude that external Na(+) concentration greatly influences anoxic K(+) derangement and that DOR activation likely attenuates anoxic K(+) derangement induced by the Na(+)-activated mechanisms in the cortex.

Absence of bundle structure in the neocortex of the reeler mouse at the embryonic stage. Studies by scanning electron microscopic fractography.

PubMed

Mikoshiba, K; Nishimura, Y; Tsukada, Y

The reeler mutant mouse is characterized by a derangement of the cerebral cortical structure due to abnormalities during the migration step at the embryonic stage. We have analyzed both the control and reeler cerebral cortex by means of scanning electron microscopic fractography. In the control cerebral cortex, the bundle formation was composed of fine fibers on which the migrating neuroblasts were attached perpendicular to the pial surface, whereas no bundle formation was observed in the reeler; instead, there was a fine meshwork of fibers surrounding the neuroblasts. The possible role of bundle formation in the normal cerebral cortex and the correlation between the inability of cells to migrate and the absence of bundle formation in the reeler is discussed.

Efficacy and connectivity of intracolumnar pairs of layer 2/3 pyramidal cells in the barrel cortex of juvenile rats

PubMed Central

Feldmeyer, Dirk; Lübke, Joachim; Sakmann, Bert

2006-01-01

Synaptically coupled layer 2/3 (L2/3) pyramidal neurones located above the same layer 4 barrel (‘barrel-related’) were investigated using dual whole-cell voltage recordings in acute slices of rat somatosensory cortex. Recordings were followed by reconstructions of biocytin-filled neurones. The onset latency of unitary EPSPs was 1.1 ± 0.4 ms, the 20–80% rise time was 0.7 ± 0.2 ms, the average amplitude was 1.0 ± 0.7 mV and the decay time constant was 15.7 ± 4.5 ms. The coefficient of variation (c.v.) of unitary EPSP amplitudes decreased with increasing EPSP peak and was 0.33 ± 0.18. Bursts of APs in the presynaptic pyramidal cell resulted in EPSPs that, over a wide range of frequencies (5–100 Hz), displayed amplitude depression. Anatomically the barrel-related pyramidal cells in the lower half of layer 2/3 have a long apical dendrite with a small terminal tuft, while pyramidal cells in the upper half of layer 2/3 have shorter and often more ‘irregularly’ shaped apical dendrites that branch profusely in layer 1. The number of putative excitatory synaptic contacts established by the axonal collaterals of a L2/3 pyramidal cell with a postsynaptic pyramidal cell in the same column varied between 2 and 4, with an average of 2.8 ± 0.7 (n = 8 pairs). Synaptic contacts were established predominantly on the basal dendrites at a mean geometric distance of 91 ± 47 μm from the pyramidal cell soma. L2/3-to-L2/3 connections formed a blob-like innervation domain containing 2.8 mm of the presynaptic axon collaterals with a bouton density of 0.3 boutons per μm axon. Within the supragranular layers of its home column a single L2/3 pyramidal cell established about 900 boutons suggesting that 270 pyramidal cells in layer 2/3 are innervated by an individual pyramidal cell. In turn, a single pyramidal cell received synaptic inputs from 270 other L2/3 pyramidal cells. The innervation domain of L2/3-to-L2/3 connections superimposes almost exactly with that of L4-to-L2/3 connections. This suggests that synchronous feed-forward excitation of L2/3 pyramidal cells arriving from layer 4 could be potentially amplified in layer 2/3 by feedback excitation within a column and then relayed to the neighbouring columns. PMID:16793907

Local classifiers for evoked potentials recorded from behaving rats.

PubMed

Jakuczun, Wit; Kublik, Ewa; Wójcik, Daniel K; Wróbel, Andrzej

2005-01-01

Dynamic states of the brain determine the way information is processed in local neural networks. We have applied classical conditioning paradigm in order to study whether habituated and aroused states can be differentiated in single barrel column of rat's somatosensory cortex by means of analysis of field potentials evoked by stimulation of a single vibrissa. A new method using local classifiers is presented which allows for reliable and meaningful classification of single evoked potentials which might be consequently attributed to different functional states of the cortical column.

Transformation of Cortex-wide Emergent Properties during Motor Learning.

PubMed

Makino, Hiroshi; Ren, Chi; Liu, Haixin; Kim, An Na; Kondapaneni, Neehar; Liu, Xin; Kuzum, Duygu; Komiyama, Takaki

2017-05-17

Learning involves a transformation of brain-wide operation dynamics. However, our understanding of learning-related changes in macroscopic dynamics is limited. Here, we monitored cortex-wide activity of the mouse brain using wide-field calcium imaging while the mouse learned a motor task over weeks. Over learning, the sequential activity across cortical modules became temporally more compressed, and its trial-by-trial variability decreased. Moreover, a new flow of activity emerged during learning, originating from premotor cortex (M2), and M2 became predictive of the activity of many other modules. Inactivation experiments showed that M2 is critical for the post-learning dynamics in the cortex-wide activity. Furthermore, two-photon calcium imaging revealed that M2 ensemble activity also showed earlier activity onset and reduced variability with learning, which was accompanied by changes in the activity-movement relationship. These results reveal newly emergent properties of macroscopic cortical dynamics during motor learning and highlight the importance of M2 in controlling learned movements. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurogranin binds α-synuclein in the human superior temporal cortex and interaction is decreased in Parkinson's disease.

PubMed

Koob, Andrew O; Shaked, Gideon M; Bender, Andreas; Bisquertt, Alejandro; Rockenstein, Edward; Masliah, Eliezer

2014-12-03

Neurogranin is a calmodulin binding protein that has been implicated in learning and memory, long-term potentiation and synaptic plasticity. Neurons expressing neurogranin in the cortex degenerate in late stages of Parkinson's disease with widespread α-synuclein pathology. While analyzing neurogranin gene expression levels through rtPCR in brains of mouse models overexpressing human α-synuclein, we found levels were elevated 2.5 times when compared to nontransgenic animals. Immunohistochemistry in the cortex revealed colocalization between α-synuclein and neurogranin in mouse transgenics when compared to control mice. Coimmunoprecipitation studies in the superior temporal cortex in humans confirmed interaction between α-synuclein and neurogranin, and decreased interaction between α-synuclein and neurogranin was noticed in patients diagnosed with Parkinson's disease when compared to normal control brains. Additionally, phosphorylated neurogranin levels were also decreased in the human superior temporal cortex in patients diagnosed with Parkinson's disease and patients diagnosed with dementia with Lewy bodies. Here, we show for the first time that neurogranin binds to α-synuclein in the human cortex, and this interaction decreases in Parkinson's disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurogranin binds α-synuclein in the human superior temporal cortex and interaction is decreased in Parkinson’s disease

PubMed Central

Koob, Andrew O.; Shaked, Gideon M.; Bender, Andreas; Bisquertt, Alejandro; Rockenstein, Edward; Masliah, Eliezer

2016-01-01

Neurogranin is a calmodulin binding protein that has been implicated in learning and memory, long-term potentiation and synaptic plasticity. Neurons expressing neurogranin in the cortex degenerate in late stages of Parkinson’s disease with widespread α-synuclein pathology. While analyzing neurogranin gene expression levels through rtPCR in brains of mouse models overexpressing human α-synuclein, we found levels were elevated 2.5 times when compared to nontransgenic animals. Immunohistochemistry in the cortex revealed colocalization between α-synuclein and neurogranin in mouse transgenics when compared to control mice. Coimmunoprecipitation studies in the superior temporal cortex in humans confirmed interaction between α-synuclein and neurogranin, and decreased interaction between α-synuclein and neurogranin was noticed in patients diagnosed with Parkinson’s disease when compared to normal control brains. Additionally, phosphorylated neurogranin levels were also decreased in the human superior temporal cortex in patients diagnosed with Parkinson’s disease and patients diagnosed with dementia with Lewy bodies. Here, we show for the first time that neurogranin binds to α-synuclein in the human cortex, and this interaction decreases in Parkinson’s disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory. PMID:25446004

Arc restores juvenile plasticity in adult mouse visual cortex

PubMed Central

Jenks, Kyle R.; Kim, Taekeun; Pastuzyn, Elissa D.; Okuno, Hiroyuki; Taibi, Andrew V.; Bear, Mark F.

2017-01-01

The molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here, we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild-type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation. PMID:28790183

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

PubMed

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

2017-07-01

Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na + and K + channel function could reliably reproduce the observed increase in action potential firing and altered action potential waveform. These results, in conjunction with our prior findings on L5 neurons, suggest that principal neurons in the circuitry of the medial prefrontal cortex are altered in distinct ways in the fmr1 -/y mouse and may contribute to dysfunctional prefrontal cortex processing in fragile X syndrome. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Low-noise encoding of active touch by layer 4 in the somatosensory cortex.

PubMed

Hires, Samuel Andrew; Gutnisky, Diego A; Yu, Jianing; O'Connor, Daniel H; Svoboda, Karel

2015-08-06

Cortical spike trains often appear noisy, with the timing and number of spikes varying across repetitions of stimuli. Spiking variability can arise from internal (behavioral state, unreliable neurons, or chaotic dynamics in neural circuits) and external (uncontrolled behavior or sensory stimuli) sources. The amount of irreducible internal noise in spike trains, an important constraint on models of cortical networks, has been difficult to estimate, since behavior and brain state must be precisely controlled or tracked. We recorded from excitatory barrel cortex neurons in layer 4 during active behavior, where mice control tactile input through learned whisker movements. Touch was the dominant sensorimotor feature, with >70% spikes occurring in millisecond timescale epochs after touch onset. The variance of touch responses was smaller than expected from Poisson processes, often reaching the theoretical minimum. Layer 4 spike trains thus reflect the millisecond-timescale structure of tactile input with little noise.

Prenatal thalamic waves regulate cortical area size prior to sensory processing.

PubMed

Moreno-Juan, Verónica; Filipchuk, Anton; Antón-Bolaños, Noelia; Mezzera, Cecilia; Gezelius, Henrik; Andrés, Belen; Rodríguez-Malmierca, Luis; Susín, Rafael; Schaad, Olivier; Iwasato, Takuji; Schüle, Roland; Rutlin, Michael; Nelson, Sacha; Ducret, Sebastien; Valdeolmillos, Miguel; Rijli, Filippo M; López-Bendito, Guillermina

2017-02-03

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing.

Prenatal thalamic waves regulate cortical area size prior to sensory processing

PubMed Central

Moreno-Juan, Verónica; Filipchuk, Anton; Antón-Bolaños, Noelia; Mezzera, Cecilia; Gezelius, Henrik; Andrés, Belen; Rodríguez-Malmierca, Luis; Susín, Rafael; Schaad, Olivier; Iwasato, Takuji; Schüle, Roland; Rutlin, Michael; Nelson, Sacha; Ducret, Sebastien; Valdeolmillos, Miguel; Rijli, Filippo M.; López-Bendito, Guillermina

2017-01-01

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing. PMID:28155854

Orientation-selective Responses in the Mouse Lateral Geniculate Nucleus

PubMed Central

Zhao, Xinyu; Chen, Hui; Liu, Xiaorong

2013-01-01

The dorsal lateral geniculate nucleus (dLGN) receives visual information from the retina and transmits it to the cortex. In this study, we made extracellular recordings in the dLGN of both anesthetized and awake mice, and found that a surprisingly high proportion of cells were selective for stimulus orientation. The orientation selectivity of dLGN cells was unchanged after silencing the visual cortex pharmacologically, indicating that it is not due to cortical feedback. The orientation tuning of some dLGN cells correlated with their elongated receptive fields, while in others orientation selectivity was observed despite the fact that their receptive fields were circular, suggesting that their retinal input might already be orientation selective. Consistently, we revealed orientation/axis-selective ganglion cells in the mouse retina using multielectrode arrays in an in vitro preparation. Furthermore, the orientation tuning of dLGN cells was largely maintained at different stimulus contrasts, which could be sufficiently explained by a simple linear feedforward model. We also compared the degree of orientation selectivity in different visual structures under the same recording condition. Compared with the dLGN, orientation selectivity is greatly improved in the visual cortex, but is similar in the superior colliculus, another major retinal target. Together, our results demonstrate prominent orientation selectivity in the mouse dLGN, which may potentially contribute to visual processing in the cortex. PMID:23904611

Surface-based atlases of cerebellar cortex in the human, macaque, and mouse.

PubMed

Van Essen, David C

2002-12-01

This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles.

PubMed

Gămănuţ, Răzvan; Kennedy, Henry; Toroczkai, Zoltán; Ercsey-Ravasz, Mária; Van Essen, David C; Knoblauch, Kenneth; Burkhalter, Andreas

2018-02-07

The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse. Copyright © 2017 Elsevier Inc. All rights reserved.

Modularity in the Organization of Mouse Primary Visual Cortex

PubMed Central

Ji, Weiqing; Gămănuţ, Răzvan; Bista, Pawan; D’Souza, Rinaldo D.; Wang, Quanxin; Burkhalter, Andreas

2015-01-01

SUMMARY Layer 1 (L1) of primary visual cortex (V1) is the target of projections from many brain regions outside of V1. We found that inputs to the non-columnar mouse V1 from the dorsal lateral geniculate nucleus and feedback projections from multiple higher cortical areas to L1 are patchy. The patches are matched to a pattern of M2 muscarinic acetylcholine receptor expression at fixed locations of mouse, rat and monkey V1. Neurons in L2/3 aligned with M2-rich patches have high spatial acuity whereas cells in M2-poor zones exhibited high temporal acuity. Together M2+ and M2− zones form constant-size domains that are repeated across V1. Domains map subregions of the receptive field, such that multiple copies are contained within the point image. The results suggest that the modular network in mouse V1 selects spatiotemporally distinct clusters of neurons within the point image for top-down control and differential routing of inputs to cortical streams. PMID:26247867

Surface-based atlases of cerebellar cortex in the human, macaque, and mouse

NASA Technical Reports Server (NTRS)

Van Essen, David C.

2002-01-01

This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

Effects of high fat diet, ovariectomy, and physical activity on leptin receptor expression in rat brain and white fat tissue

PubMed Central

Blažetić, Senka; Labak, Irena; Viljetić, Barbara; Balog, Marta; Vari, Sandor G.; Krivošíková, Zora; Gajdoš, Martin; Kramárová, Patrícia; Kebis, Anton; Vuković, Rosemary; Puljak, Livia; Has-Schön, Elizabeta; Heffer, Marija

2014-01-01

Aim To evaluate in a rat animal model whether ovariectomy, high fat diet (HFD), and physical activity in the form of running affect leptin receptor (Ob-R) distribution in the brain and white fat tissue compared to sham (Sh) surgery, standard diet (StD), and sedentary conditions. Methods The study included 48 female laboratory Wistar rats (4 weeks old). Following eight weeks of feeding with standard or HFD, rats were subjected to either OVX or Sh surgery. After surgery, all animals continued StD or HFD for the next 10 weeks. During these 10 weeks, ovariectomy and Sh groups were subjected to physical activity or sedentary conditions. Free-floating immunohistochemistry and Western blot methods were carried out to detect Ob-R in the brain and adipose tissue. Results StD-ovariectomy-sedentary group had a greater number of Ob-R positive neurons in lateral hypothalamic nuclei than StD-Sh-sedentary group. There was no difference in Ob-R positive neurons in arcuatus nuclei between all groups. Ob-R distribution in the barrel cortex was higher in HFD group than in StD group. Ob-R presence in perirenal and subcutaneous fat was decreased in StD-ovariectomy group. Conclusion HFD and ovariectomy increased Ob-R distribution in lateral hypothalamic nuclei, but there was no effect on arcuatus nuclei. Our results are first to suggest that HFD, ovariectomy, and physical activity affect Ob-R distribution in the barrel cortex, which might be correlated with the role of Ob-R in election of food in rats. PMID:24891281

Effects of high fat diet, ovariectomy, and physical activity on leptin receptor expression in rat brain and white fat tissue.

PubMed

Blažetić, Senka; Labak, Irena; Viljetić, Barbara; Balog, Marta; Vari, Sandor G; Krivošíková, Zora; Gajdoš, Martin; Kramárová, Patrícia; Kebis, Anton; Vuković, Rosemary; Puljak, Livia; Has-Schön, Elizabeta; Heffer, Marija

2014-06-01

To evaluate in a rat animal model whether ovariectomy, high fat diet (HFD), and physical activity in the form of running affect leptin receptor (Ob-R) distribution in the brain and white fat tissue compared to sham (Sh) surgery, standard diet (StD), and sedentary conditions. The study included 48 female laboratory Wistar rats (4 weeks old). Following eight weeks of feeding with standard or HFD, rats were subjected to either OVX or Sh surgery. After surgery, all animals continued StD or HFD for the next 10 weeks. During these 10 weeks, ovariectomy and Sh groups were subjected to physical activity or sedentary conditions. Free-floating immunohistochemistry and Western blot methods were carried out to detect Ob-R in the brain and adipose tissue. StD-ovariectomy-sedentary group had a greater number of Ob-R positive neurons in lateral hypothalamic nuclei than StD-Sh-sedentary group. There was no difference in Ob-R positive neurons in arcuatus nuclei between all groups. Ob-R distribution in the barrel cortex was higher in HFD group than in StD group. Ob-R presence in perirenal and subcutaneous fat was decreased in StD-ovariectomy group. HFD and ovariectomy increased Ob-R distribution in lateral hypothalamic nuclei, but there was no effect on arcuatus nuclei. Our results are first to suggest that HFD, ovariectomy, and physical activity affect Ob-R distribution in the barrel cortex, which might be correlated with the role of Ob-R in election of food in rats.

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid-β from the mouse brain.

PubMed

Hawkes, Cheryl A; Gatherer, Maureen; Sharp, Matthew M; Dorr, Adrienne; Yuen, Ho Ming; Kalaria, Rajesh; Weller, Roy O; Carare, Roxana O

2013-04-01

Development of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) is associated with failure of elimination of amyloid-β (Aβ) from the brain along perivascular basement membranes that form the pathways for drainage of interstitial fluid and solutes from the brain. In transgenic APP mouse models of AD, the severity of cerebral amyloid angiopathy is greater in the cerebral cortex and hippocampus, intermediate in the thalamus, and least in the striatum. In this study we test the hypothesis that age-related regional variation in (1) vascular basement membranes and (2) perivascular drainage of Aβ contribute to the different regional patterns of CAA in the mouse brain. Quantitative electron microscopy of the brains of 2-, 7-, and 23-month-old mice revealed significant age-related thickening of capillary basement membranes in cerebral cortex, hippocampus, and thalamus, but not in the striatum. Results from Western blotting and immunocytochemistry experiments showed a significant reduction in collagen IV in the cortex and hippocampus with age and a reduction in laminin and nidogen 2 in the cortex and striatum. Injection of soluble Aβ into the hippocampus or thalamus showed an age-related reduction in perivascular drainage from the hippocampus but not from the thalamus. The results of the study suggest that changes in vascular basement membranes and perivascular drainage with age differ between brain regions, in the mouse, in a manner that may help to explain the differential deposition of Aβ in the brain in AD and may facilitate development of improved therapeutic strategies to remove Aβ from the brain in AD. © 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Functional magnetic resonance imaging examination of two modular architectures for switching multiple internal models.

PubMed

Imamizu, Hiroshi; Kuroda, Tomoe; Yoshioka, Toshinori; Kawato, Mitsuo

2004-02-04

An internal model is a neural mechanism that can mimic the input-output properties of a controlled object such as a tool. Recent research interests have moved on to how multiple internal models are learned and switched under a given context of behavior. Two representative computational models for task switching propose distinct neural mechanisms, thus predicting different brain activity patterns in the switching of internal models. In one model, called the mixture-of-experts architecture, switching is commanded by a single executive called a "gating network," which is different from the internal models. In the other model, called the MOSAIC (MOdular Selection And Identification for Control), the internal models themselves play crucial roles in switching. Consequently, the mixture-of-experts model predicts that neural activities related to switching and internal models can be temporally and spatially segregated, whereas the MOSAIC model predicts that they are closely intermingled. Here, we directly examined the two predictions by analyzing functional magnetic resonance imaging activities during the switching of one common tool (an ordinary computer mouse) and two novel tools: a rotated mouse, the cursor of which appears in a rotated position, and a velocity mouse, the cursor velocity of which is proportional to the mouse position. The switching and internal model activities temporally and spatially overlapped each other in the cerebellum and in the parietal cortex, whereas the overlap was very small in the frontal cortex. These results suggest that switching mechanisms in the frontal cortex can be explained by the mixture-of-experts architecture, whereas those in the cerebellum and the parietal cortex are explained by the MOSAIC model.

Visual Information Present in Infragranular Layers of Mouse Auditory Cortex.

PubMed

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.

Two-photon laser scanning microscopy imaging of intact spinal cord and cerebral cortex reveals requirement for CXCR6 and neuroinflammation in immune cell infiltration of cortical injury sites.

PubMed

Kim, Jiyun V; Jiang, Ning; Tadokoro, Carlos E; Liu, Liping; Ransohoff, Richard M; Lafaille, Juan J; Dustin, Michael L

2010-01-31

The mouse spinal cord is an important site for autoimmune and injury models. Skull thinning surgery provides a minimally invasive window for microscopy of the mouse cerebral cortex, but there are no parallel methods for the spinal cord. We introduce a novel, facile and inexpensive method for two-photon laser scanning microscopy of the intact spinal cord in the mouse by taking advantage of the naturally accessible intervertebral space. These are powerful methods when combined with gene-targeted mice in which endogenous immune cells are labeled with green fluorescent protein (GFP). We first demonstrate that generation of the intervertebral window does not elicit a reaction of GFP(+) microglial cells in CX3CR1(gfp/+) mice. We next demonstrate a distinct rostrocaudal migration of GFP(+) immune cells in the spinal cord of CXCR6(gfp/+) mice during active experimental autoimmune encephalomyelitis (EAE). Interestingly, infiltration of the cerebral cortex by GFP(+) cells in these mice required three conditions: EAE induction, cortical injury and expression of CXCR6 on immune cells. Copyright 2009 Elsevier B.V. All rights reserved.

Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way.

PubMed

Espuny-Camacho, Ira; Michelsen, Kimmo A; Linaro, Daniele; Bilheu, Angéline; Acosta-Verdugo, Sandra; Herpoel, Adèle; Giugliano, Michele; Gaillard, Afsaneh; Vanderhaeghen, Pierre

2018-05-29

The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The Functioning of a Cortex without Layers.

PubMed

Guy, Julien; Staiger, Jochen F

2017-01-01

A major hallmark of cortical organization is the existence of a variable number of layers, i.e., sheets of neurons stacked on top of each other, in which neurons have certain commonalities. However, even for the neocortex, variable numbers of layers have been described and it is just a convention to distinguish six layers from each other. Whether cortical layers are a structural epiphenomenon caused by developmental dynamics or represent a functionally important modularization of cortical computation is still unknown. Here we present our insights from the reeler mutant mouse, a model for a developmental, "molecular lesion"-induced loss of cortical layering that could serve as ground truth of what an intact layering adds to the cortex in terms of functionality. We could demonstrate that the reeler neocortex shows no inversion of cortical layers but rather a severe disorganization that in the primary somatosensory cortex leads to the complete loss of layers. Nevertheless, the somatosensory system is well organized. When exploring an enriched environment with specific sets of whiskers, activity-dependent gene expression takes place in the corresponding modules. Precise whisker stimuli lead to the functional activation of somatotopically organized barrel columns as visualized by intrinsic signal optical imaging. Similar results were obtained in the reeler visual system. When analyzing pathways that could be responsible for preservation of tactile perception, lemniscal thalamic projections were found to be largely intact, despite the smearing of target neurons across the cortical mantle. However, with optogenetic experiments we found evidence for a mild dispersion of thalamic synapse targeting on layer IV-spiny stellate cells, together with a general weakening in thalamocortical input strength. This weakening of thalamic inputs was compensated by intracortical mechanisms involving increased recurrent excitation and/or reduced feedforward inhibition. In conclusion, a layer loss so far only led to the detection of subtle defects in sensory processing by reeler mice. This argues in favor of a view in which cortical layers are not an essential component for basic perception and cognition. A view also supported by recent studies in birds, which can have remarkable cognitive capacities despite the lack of a neocortex with multiple cortical layers. In conclusion, we suggest that future studies directed toward understanding cortical functions should rather focus on circuits specified by functional cell type composition than mere laminar location.

Mouse vocal communication system: are ultrasounds learned or innate?

PubMed Central

Arriaga, Gustavo; Jarvis, Erich D.

2013-01-01

Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production. Here we discuss the available data to assess whether male mouse song behavior and the supporting brain circuits resemble those of known vocal non-learning or vocal learning species. Recent neurobiology studies have demonstrated that the mouse USV brain system includes motor cortex and striatal regions, and that the vocal motor cortex sends a direct sparse projection to the brainstem vocal motor nucleus ambiguous, a projection thought be unique to humans among mammals. Recent behavioral studies have reported opposing conclusions on mouse vocal plasticity, including vocal ontogeny changes in USVs over early development that might not be explained by innate maturation processes, evidence for and against a role for auditory feedback in developing and maintaining normal mouse USVs, and evidence for and against limited vocal imitation of song pitch. To reconcile these findings, we suggest that the trait of vocal learning may not be dichotomous but encompass a broad set of behavioral and neural traits we call the continuum hypothesis, and that mice possess some of the traits associated with a capacity for limited vocal learning. PMID:23295209

The effects of aging, housing and ibuprofen treatment on brain neurochemistry in a triple transgene Alzheimer's disease mouse model using magnetic resonance spectroscopy and imaging.

PubMed

Choi, Ji-Kyung; Carreras, Isabel; Aytan, Nur; Jenkins-Sahlin, Eric; Dedeoglu, Alpaslan; Jenkins, Bruce G

2014-11-24

We investigated a triple transgene Alzheimer's disease (AD) mouse model that recapitulates many of the neurochemical, anatomic, pathologic and behavioral defects seen in human AD. We studied the mice as a function of age and brain region and investigated potential therapy with the non-steroidal anti-inflammatory drug ibuprofen. Magnetic resonance spectroscopy (MRS) showed alterations characteristic of AD (i.e. increased myo-inositol and decreased N-acetylaspartate (NAA)). Mice at 6 months of age showed an increase in myo-inositol in the hippocampus at a time when the Aβ is intracellular, but not in amygdala or cortex. Myo-inositol increased as a function of age in the amygdala, cortex and striatum while NAA decreased only in the hippocampus and cortex at 17-23 months of age. Ibuprofen protected the increase of myo-inositol at six months of age in the hippocampus, but had no effect at 17-23 months of age (a time when Aβ is extracellular). In vivo MRI and MRS showed that at 17-23 months of age there was a significant protective effect of ibuprofen on hippocampal volume and NAA loss. Together, these data show the following: the increase in myo-inositol occurs before the decrease in NAA in hippocampus but not cortex; the hippocampus shows earlier changes than does the amygdale or cortex consistent with earlier deposition of Aβ40-42 in the hippocampus and ibuprofen protects against multiple components of the AD pathology. These data also show a profound effect of housing on this particular mouse model. Published by Elsevier B.V.

Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex.

PubMed

Thimm, Andreas; Funke, Klaus

2015-02-15

Theta-burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability. Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex. We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8-18 ms). The effect increased with each of the five iTBS blocks applied. cTBS somewhat reduced the early response component after the first block but had a similar effect as iTBS after four to five blocks. We conclude that iTBS primarly modulates the activity of (inhibitory) cortical interneurons while cTBS may first reduce general neuronal excitability with a single block but reverse to iTBS-like effects with application of several blocks. Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW-PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4-5 stimulation blocks. Enhanced cortical c-Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent-type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Higher transport and metabolism of glucose in astrocytes compared with neurons: a multiphoton study of hippocampal and cerebellar tissue slices.

PubMed

Jakoby, Patrick; Schmidt, Elke; Ruminot, Iván; Gutiérrez, Robin; Barros, L Felipe; Deitmer, Joachim W

2014-01-01

Glucose is the most important energy substrate for the brain, and its cellular distribution is a subject of great current interest. We have employed fluorescent glucose probes, the 2-deoxy-D-glucose derivates 6- and 2-([N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose) (2-NBDG), to measure transport and metabolism of glucose in acute slices of mouse hippocampus and cerebellum. In the hippocampus, 6-NBDG, which is not metabolized and hence indicates glucose transport, was taken up faster in astrocyte-rich layers (Stratum radiatum [S.r.], Stratum oriens [S.o.]) than in pyramidal cells. Metabolizable 2-NBDG showed larger signals in S.r. and S.o. than in Stratum pyramidale, suggesting faster glucose utilization rate in the astrocyte versus the neuronal compartment. Similarly, we found higher uptake and temperature-sensitive metabolism of 2-NBDG in Bergmann glia when compared with adjacent Purkinje neurons of cerebellar slices. A comparison between 6-NBDG transport and glucose transport in cultured cells using a fluorescence resonance energy transfer nanosensor showed that relative to glucose, 6-NBDG is transported better by neurons than by astrocytes. These results indicate that the preferential transport and metabolism of glucose by glial cells versus neurons proposed for the hippocampus and cerebellum by ourselves (in vitro) and for the barrel cortex by Chuquet et al. (in vivo) is more pronounced than anticipated.

A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

PubMed Central

Mitre, Mariela; Marlin, Bianca J.; Schiavo, Jennifer K.; Morina, Egzona; Norden, Samantha E.; Hackett, Troy A.; Aoki, Chiye J.

2016-01-01

Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent–infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition. SIGNIFICANCE STATEMENT Oxytocin is an important peptide hormone involved in maternal behavior and social cognition, but it has been unclear what elements of neural circuits express oxytocin receptors due to the paucity of suitable antibodies. Here, we developed new antibodies to the mouse oxytocin receptor. Oxytocin receptors were found in discrete brain regions and at cortical synapses for modulating excitatory-inhibitory balance and plasticity. These antibodies should be useful for future studies of oxytocin and social behavior. PMID:26911697

F-actin mechanics control spindle centring in the mouse zygote

NASA Astrophysics Data System (ADS)

Chaigne, Agathe; Campillo, Clément; Voituriez, Raphaël; Gov, Nir S.; Sykes, Cécile; Verlhac, Marie-Hélène; Terret, Marie-Emilie

2016-01-01

Mitotic spindle position relies on interactions between astral microtubules nucleated by centrosomes and a rigid cortex. Some cells, such as mouse oocytes, do not possess centrosomes and astral microtubules. These cells rely only on actin and on a soft cortex to position their spindle off-centre and undergo asymmetric divisions. While the first mouse embryonic division also occurs in the absence of centrosomes, it is symmetric and not much is known on how the spindle is positioned at the exact cell centre. Using interdisciplinary approaches, we demonstrate that zygotic spindle positioning follows a three-step process: (1) coarse centring of pronuclei relying on the dynamics of an F-actin/Myosin-Vb meshwork; (2) fine centring of the metaphase plate depending on a high cortical tension; (3) passive maintenance at the cell centre. Altogether, we show that F-actin-dependent mechanics operate the switch between asymmetric to symmetric division required at the oocyte to embryo transition.

Fetal Alcohol Spectrum Disorder-associated depression: evidence for reductions in the levels of brain-derived neurotrophic factor in a mouse model

PubMed Central

Caldwell, Kevin K.; Sheema, S.; Paz, Rodrigo D; Samudio-Ruiz, Sabrina L.; Laughlin, Mary H.; Spence, Nathan E.; Roehlk, Michael J; Alcon, Sara N.; Allan, Andrea M.

2009-01-01

Prenatal ethanol exposure is associated with an increased incidence of depressive disorders in patient populations. However, the mechanisms that link prenatal ethanol exposure and depression are unknown. Several recent studies have implicated reduced brain-derived neurotrophic factor (BDNF) levels in the hippocampal formation and frontal cortex as important contributors to the etiology of depression. In the present studies, we sought to determine whether prenatal ethanol exposure is associated with behaviors that model depression, as well as with reduced BDNF levels in the hippocampal formation and/or medial frontal cortex, in a mouse model of fetal alcohol spectrum disorder (FASD). Compared to control adult mice, prenatal ethanol-exposed adult mice displayed increased learned helplessness behavior and increased immobility in the Porsolt forced swim test. Prenatal ethanol exposure was associated with decreased BDNF protein levels in the medial frontal cortex, but not the hippocampal formation, while total BDNF mRNA and BDNF transcripts containing exon III, IV or VI were reduced in both the medial frontal cortex and the hippocampal formation of prenatal ethanol-exposed mice. These results identify reduced BDNF levels in the medial frontal cortex and hippocampal formation as potential mediators of depressive disorders associated with FASD. PMID:18558427

Contralateral Bias of High Spatial Frequency Tuning and Cardinal Direction Selectivity in Mouse Visual Cortex

PubMed Central

Zeitoun, Jack H.; Kim, Hyungtae

2017-01-01

Binocular mechanisms for visual processing are thought to enhance spatial acuity by combining matched input from the two eyes. Studies in the primary visual cortex of carnivores and primates have confirmed that eye-specific neuronal response properties are largely matched. In recent years, the mouse has emerged as a prominent model for binocular visual processing, yet little is known about the spatial frequency tuning of binocular responses in mouse visual cortex. Using calcium imaging in awake mice of both sexes, we show that the spatial frequency preference of cortical responses to the contralateral eye is ∼35% higher than responses to the ipsilateral eye. Furthermore, we find that neurons in binocular visual cortex that respond only to the contralateral eye are tuned to higher spatial frequencies. Binocular neurons that are well matched in spatial frequency preference are also matched in orientation preference. In contrast, we observe that binocularly mismatched cells are more mismatched in orientation tuning. Furthermore, we find that contralateral responses are more direction-selective than ipsilateral responses and are strongly biased to the cardinal directions. The contralateral bias of high spatial frequency tuning was found in both awake and anesthetized recordings. The distinct properties of contralateral cortical responses may reflect the functional segregation of direction-selective, high spatial frequency-preferring neurons in earlier stages of the central visual pathway. Moreover, these results suggest that the development of binocularity and visual acuity may engage distinct circuits in the mouse visual system. SIGNIFICANCE STATEMENT Seeing through two eyes is thought to improve visual acuity by enhancing sensitivity to fine edges. Using calcium imaging of cellular responses in awake mice, we find surprising asymmetries in the spatial processing of eye-specific visual input in binocular primary visual cortex. The contralateral visual pathway is tuned to higher spatial frequencies than the ipsilateral pathway. At the highest spatial frequencies, the contralateral pathway strongly prefers to respond to visual stimuli along the cardinal (horizontal and vertical) axes. These results suggest that monocular, and not binocular, mechanisms set the limit of spatial acuity in mice. Furthermore, they suggest that the development of visual acuity and binocularity in mice involves different circuits. PMID:28924011

Laminar circuit organization and response modulation in mouse visual cortex

PubMed Central

Olivas, Nicholas D.; Quintanar-Zilinskas, Victor; Nenadic, Zoran; Xu, Xiangmin

2012-01-01

The mouse has become an increasingly important animal model for visual system studies, but few studies have investigated local functional circuit organization of mouse visual cortex. Here we used our newly developed mapping technique combining laser scanning photostimulation (LSPS) with fast voltage-sensitive dye (VSD) imaging to examine the spatial organization and temporal dynamics of laminar circuit responses in living slice preparations of mouse primary visual cortex (V1). During experiments, LSPS using caged glutamate provided spatially restricted neuronal activation in a specific cortical layer, and evoked responses from the stimulated layer to its functionally connected regions were detected by VSD imaging. In this study, we first provided a detailed analysis of spatiotemporal activation patterns at specific V1 laminar locations and measured local circuit connectivity. Then we examined the role of cortical inhibition in the propagation of evoked cortical responses by comparing circuit activity patterns in control and in the presence of GABAa receptor antagonists. We found that GABAergic inhibition was critical in restricting layer-specific excitatory activity spread and maintaining topographical projections. In addition, we investigated how AMPA and NMDA receptors influenced cortical responses and found that blocking AMPA receptors abolished interlaminar functional projections, and the NMDA receptor activity was important in controlling visual cortical circuit excitability and modulating activity propagation. The NMDA receptor antagonist reduced neuronal population activity in time-dependent and laminar-specific manners. Finally, we used the quantitative information derived from the mapping experiments and presented computational modeling analysis of V1 circuit organization. Taken together, the present study has provided important new information about mouse V1 circuit organization and response modulation. PMID:23060751

Sensory-driven and spontaneous gamma oscillations engage distinct cortical circuitry

PubMed Central

2015-01-01

Gamma oscillations are a robust component of sensory responses but are also part of the background spontaneous activity of the brain. To determine whether the properties of gamma oscillations in cortex are specific to their mechanism of generation, we compared in mouse visual cortex in vivo the laminar geometry and single-neuron rhythmicity of oscillations produced during sensory representation with those occurring spontaneously in the absence of stimulation. In mouse visual cortex under anesthesia (isoflurane and xylazine), visual stimulation triggered oscillations mainly between 20 and 50 Hz, which, because of their similar functional significance to gamma oscillations in higher mammals, we define here as gamma range. Sensory representation in visual cortex specifically increased gamma oscillation amplitude in the supragranular (L2/3) and granular (L4) layers and strongly entrained putative excitatory and inhibitory neurons in infragranular layers, while spontaneous gamma oscillations were distributed evenly through the cortical depth and primarily entrained putative inhibitory neurons in the infragranular (L5/6) cortical layers. The difference in laminar distribution of gamma oscillations during the two different conditions may result from differences in the source of excitatory input to the cortex. In addition, modulation of superficial gamma oscillation amplitude did not result in a corresponding change in deep-layer oscillations, suggesting that superficial and deep layers of cortex may utilize independent but related networks for gamma generation. These results demonstrate that stimulus-driven gamma oscillations engage cortical circuitry in a manner distinct from spontaneous oscillations and suggest multiple networks for the generation of gamma oscillations in cortex. PMID:26719085

Induction, immunochemical identity and immunofluorescence localization of an 80 000-molecular-weight peroxisome-proliferation-associated polypeptide (polypeptide PPA-80) and peroxisomal enoyl-CoA hydratase of mouse liver and renal cortex.

PubMed

Lalwani, N D; Reddy, M K; Mangkornkanok-Mark, M; Reddy, J K

1981-07-15

The hypolipidaemic drugs methyl clofenapate, BR-931, Wy-14643 and procetofen induced a marked proliferation of peroxisomes in the parenchymal cells of liver and the proximal-convoluted-tubular epithelium of mouse kidney. The proliferation of peroxisomes was associated with 6-12-fold increase in the peroxisomal palmitoyl-CoA oxidizing capacity of the mouse liver. Enhanced activity of the peroxisomal palmitoyl-CoA oxidation system was also found in the renal-cortical homogenates of hypolipidaemic-drug-treated mice. The activity of enoyl-CoA hydratase in the mouse liver increased 30-50-fold and in the kidney cortex 3-5-fold with hypolipidaemic-drug-induced peroxisome proliferation in these tissues, and over 95% of this induced activity was found to be heat-labile peroxisomal enzyme in both organs. Sodium dodecyl sulphate/polyacrylamide-gel-electrophoretic analysis of large-particle and microsomal fractions obtained from the liver and kidney cortex of mice treated with hypolipidaemic peroxisome proliferators demonstrated a substantial increase in the quantity of an 80000-mol.wt. peroxisome-proliferation-associated polypeptide (polypeptide PPA-80). The heat-labile peroxisomal enoyl-CoA hydratase was purified from the livers of mice treated with the hypolipidaemic drug methyl clofenapate; the antibodies raised against this electrophoretically homogeneous protein yielded a single immunoprecipitin band with purified mouse liver enoyl-CoA hydratase and with liver and kidney cortical extracts of normal and hypolipidaemic-drug-treated mice. These anti-(mouse liver enoyl-CoA hydratase) antibodies also cross-reacted with purified rat liver enoyl-CoA hydratase and with the polypeptide PPA-80 obtained from rat and mouse liver. Immunofluorescence studies with anti-(polypeptide PPA-80) and anti-(peroxisomal enoyl-CoA hydratase) provided visual evidence for the localization and induction of polypeptide PPA-80 and peroxisomal enoyl-CoA hydratase in the liver and kidney respectively of normal and hypolipidaemic-drug-treated mice. In the kidney, the distribution of these two proteins is identical and limited exclusively to the cytoplasm of proximal-convoluted-tubular epithelium. The immunofluorescence studies clearly complement the biochemical and ultrastructural observations of peroxisome induction in the liver and kidney cortex of mice fed on hypolipidaemic drugs. In addition, preliminary ultrastructural studies with the protein-A-gold-complex technique demonstrate that the heat-labile hepatic enoyl-CoA hydratase is localized in the peroxisome matrix.

Comparison of intravital thinned skull and cranial window approaches to study CNS immunobiology in the mouse cortex

PubMed Central

Dorand, R Dixon; Barkauskas, Deborah S; Evans, Teresa A; Petrosiute, Agne; Huang, Alex Y

2014-01-01

Fluorescent imaging coupled with high-resolution femtosecond pulsed infrared lasers allows for interrogation of cellular interactions deeper in living tissues than ever imagined. Intravital imaging of the central nervous system (CNS) has provided insights into neuronal development, synaptic transmission, and even immune interactions. In this review we will discuss the two most common intravital approaches for studying the cerebral cortex in the live mouse brain for pre-clinical studies, the thinned skull and cranial window techniques, and focus on the advantages and drawbacks of each approach. In addition, we will discuss the use of neuronal physiologic parameters as determinants of successful surgical and imaging preparation. PMID:25568834

Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex

PubMed Central

Prakash, Neal; Biag, Jonathan D.; Sheth, Sameer A.; Mitsuyama, Satoshi; Theriot, Jeremy; Ramachandra, Chaithanya; Toga, Arthur W.

2007-01-01

Background Mechanisms of neurovascular coupling—the relationship between neuronal chemoelectrical activity and compensatory metabolic and hemodynamic changes—appear to be preserved across species from rats to humans despite differences in scale. However, previous work suggests that the highly cellular dense mouse somatosensory cortex has different functional hemodynamic changes compared to other species. Methods We developed novel hardware and software for 2-dimensional optical spectroscopy (2DOS). Optical changes at four simultaneously recorded wavelengths were measured in both rat and mouse primary somatosensory cortex (S1) evoked by forepaw stimulation to create four spectral maps. The spectral maps were converted to maps of deoxy-, oxy-, and total-hemoglobin (HbR, HbO, and HbT) concentration changes using the modified Beer-Lambert law and phantom HbR and HbO absorption spectra. Results Functional hemodynamics were different in mouse versus rat neocortex. On average, hemodynamics were as expected in rat primary somatosensory cortex (S1): the fractional change in the log of HbT concentration increased monophasically 2 s after stimulus, whereas HbO changes mirrored HbR changes, with HbO showing a small initial dip at 0.5 s followed by a large increase 3.0 s post stimulus. In contrast, mouse S1 showed a novel type of stimulus-evoked hemodynamic response, with prolonged, concurrent, monophasic increases in HbR and HbT and a parallel decrease in HbO that all peaked 3.5–4.5 s post stimulus onset. For rats, at any given time point the average size and shape of HbO and HbR forepaw maps were the same, whereas surface veins distorted the shape of the HbT map. For mice, HbO, HbR, and HbT forepaw maps were generally the same size and shape at any post-stimulus time point. Conclusions 2DOS using image splitting optics is feasible across species for brain mapping and quantifying the map topography of cortical hemodynamics. These results suggest that during physiologic stimulation, different species and/or cortical architecture may give rise to different hemodynamic changes during neurovascular coupling. PMID:17574868

Dynamic changes of rodent somatosensory barrel cortex are correlated with learning a novel conditioned stimulus.

PubMed

Long, John D; Carmena, Jose M

2013-05-01

The rodent somatosensory barrel cortex (S1bf) has proved a valuable model for studying neural plasticity in vivo. It has been observed that sensory deprivation or conditioning reorganizes sensory-driven activity within S1bf. These observations suggest a role for S1bf in somatosensory learning. This study evaluated the hypothesis that the response properties of extracellularly recorded neurons in S1bf would change as subjects learned to respond to stimulation of S1bf. Intracortical microstimulation (ICMS) of S1bf was used as a means for bypassing feedforward drive from the sensory periphery, midbrain, and thalamus while exciting local cortical networks. To separate the learning of this conditioned stimulus-conditioned response (CS-CR) from other elements of the task, we employed a cross-modal transfer schedule. Long-Evans rats were initially trained to respond to an auditory stimulus. All subjects were then implanted in both S1bfs with chronic microwire arrays for recording neural activity and delivering ICMS. Next, this association was transferred to ICMS of one hemisphere's S1bf. S1bf responded to ICMS with a brief increase in firing rate followed by a longer reduction in activity. We observed that the duration of reduced activity elicited by ICMS increased as the subjects began to respond correctly more often than expected by chance, and the magnitude of the initial positive response increased as they consolidated this CS-CR. Subsequent ICMS of the opposite S1bf revealed that this CS-CR did not generalize across hemispheres. These results suggest that a mechanism involving a single hemisphere's S1bf tunes cortical responses in concert with changes in rodent behavior during somatosensory learning.

Simultaneous stability and sensitivity in model cortical networks is achieved through anti-correlations between the in- and out-degree of connectivity

PubMed Central

Vasquez, Juan C.; Houweling, Arthur R.; Tiesinga, Paul

2013-01-01

Neuronal networks in rodent barrel cortex are characterized by stable low baseline firing rates. However, they are sensitive to the action potentials of single neurons as suggested by recent single-cell stimulation experiments that reported quantifiable behavioral responses in response to short spike trains elicited in single neurons. Hence, these networks are stable against internally generated fluctuations in firing rate but at the same time remain sensitive to similarly-sized externally induced perturbations. We investigated stability and sensitivity in a simple recurrent network of stochastic binary neurons and determined numerically the effects of correlation between the number of afferent (“in-degree”) and efferent (“out-degree”) connections in neurons. The key advance reported in this work is that anti-correlation between in-/out-degree distributions increased the stability of the network in comparison to networks with no correlation or positive correlations, while being able to achieve the same level of sensitivity. The experimental characterization of degree distributions is difficult because all pre-synaptic and post-synaptic neurons have to be identified and counted. We explored whether the statistics of network motifs, which requires the characterization of connections between small subsets of neurons, could be used to detect evidence for degree anti-correlations. We find that the sample frequency of the 3-neuron “ring” motif (1→2→3→1), can be used to detect degree anti-correlation for sub-networks of size 30 using about 50 samples, which is of significance because the necessary measurements are achievable experimentally in the near future. Taken together, we hypothesize that barrel cortex networks exhibit degree anti-correlations and specific network motif statistics. PMID:24223550

Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex

PubMed Central

Thimm, Andreas; Funke, Klaus

2015-01-01

Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW–PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4–5 stimulation blocks. Enhanced cortical c-Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent-type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events. PMID:25504571

Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex

PubMed Central

Allen, William E.; Kauvar, Isaac V.; Chen, Michael Z.; Richman, Ethan B.; Yang, Samuel J.; Chan, Ken; Gradinaru, Viviana; Deverman, Benjamin E.; Luo, Liqun; Deisseroth, Karl

2017-01-01

SUMMARY The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information. PMID:28521139

Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex.

PubMed

Rigas, Pavlos; Adamos, Dimitrios A; Sigalas, Charalambos; Tsakanikas, Panagiotis; Laskaris, Nikolaos A; Skaliora, Irini

2015-01-01

Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models.

Association between sociability and diffusion tensor imaging in BALB/cJ mice.

PubMed

Kim, Sungheon; Pickup, Stephen; Fairless, Andrew H; Ittyerah, Ranjit; Dow, Holly C; Abel, Ted; Brodkin, Edward S; Poptani, Harish

2012-01-01

The purpose of this study was to use high-resolution diffusion tensor imaging (DTI) to investigate the association between DTI metrics and sociability in BALB/c inbred mice. The sociability of prepubescent (30-day-old) BALB/cJ mice was operationally defined as the time that the mice spent sniffing a stimulus mouse in a social choice test. High-resolution ex vivo DTI data on 12 BALB/cJ mouse brains were acquired using a 9.4-T vertical-bore magnet. Regression analysis was conducted to investigate the association between DTI metrics and sociability. Significant positive regression (p < 0.001) between social sniffing time and fractional anisotropy was found in 10 regions located in the thalamic nuclei, zona incerta/substantia nigra, visual/orbital/somatosensory cortices and entorhinal cortex. In addition, significant negative regression (p < 0.001) between social sniffing time and mean diffusivity was found in five areas located in the sensory cortex, motor cortex, external capsule and amygdaloid region. In all regions showing significant regression with either the mean diffusivity or fractional anisotropy, the tertiary eigenvalue correlated negatively with the social sniffing time. This study demonstrates the feasibility of using DTI to detect brain regions associated with sociability in a mouse model system. Copyright © 2011 John Wiley & Sons, Ltd.

Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex

PubMed Central

Rigas, Pavlos; Adamos, Dimitrios A.; Sigalas, Charalambos; Tsakanikas, Panagiotis; Laskaris, Nikolaos A.; Skaliora, Irini

2015-01-01

Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models. PMID:26528142

Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex

PubMed Central

Ruiz-Perera, L.; Muniz, M.; Vierci, G.; Bornia, N.; Baroncelli, L.; Sale, A.; Rossi, F.M.

2015-01-01

The scarce functional recovery of the adult CNS following injuries or diseases is largely due to its reduced potential for plasticity, the ability to reorganize neural connections as a function of experience. Recently, some new strategies restoring high levels of plasticity in the adult brain have been identified, especially in the paradigmatic model of the visual system. A chronic treatment with the anti-depressant fluoxetine reinstates plasticity in the adult rat primary visual cortex, inducing recovery of vision in amblyopic animals. The molecular mechanisms underlying this effect remain largely unknown. Here, we explored fluoxetine effects on mouse visual cortical plasticity, and exploited a proteomic approach to identify possible candidates mediating the outcome of the antidepressant treatment on adult cortical plasticity. We showed that fluoxetine restores ocular dominance plasticity in the adult mouse visual cortex, and identified 31 differentially expressed protein spots in fluoxetine-treated animals vs. controls. MALDITOF/TOF mass spectrometry identification followed by bioinformatics analysis revealed that these proteins are involved in the control of cytoskeleton organization, endocytosis, molecular transport, intracellular signaling, redox cellular state, metabolism and protein degradation. Altogether, these results indicate a complex effect of fluoxetine on neuronal signaling mechanisms potentially involved in restoring plasticity in the adult brain. PMID:26205348

Principles of ipsilateral and contralateral cortico-cortical connectivity in the mouse.

PubMed

Goulas, Alexandros; Uylings, Harry B M; Hilgetag, Claus C

2017-04-01

Structural connectivity among cortical areas provides the substrate for information exchange in the cerebral cortex and is characterized by systematic patterns of presence or absence of connections. What principles govern this cortical wiring diagram? Here, we investigate the relation of physical distance and cytoarchitecture with the connectional architecture of the mouse cortex. Moreover, we examine the relation between patterns of ipsilateral and contralateral connections. Our analysis reveals a mirrored and attenuated organization of contralateral connections when compared with ipsilateral connections. Both physical distance and cytoarchitectonic similarity of cortical areas are related to the presence or absence of connections. Notably, our analysis demonstrates that the combination of these factors relates better to cortico-cortical connectivity than each factor in isolation and that the two factors relate differently to ipsilateral and contralateral connectivity. Physical distance is more tightly related to the presence or absence of ipsilateral connections, but its relevance greatly diminishes for contralateral connections, while the contribution of cytoarchitectonic similarity remains relatively stable. Our results, together with similar findings in the cat and macaque cortex, suggest that a common set of principles underlies the macroscale wiring of the mammalian cerebral cortex.

An analysis of current source density profiles activated by local stimulation in the mouse auditory cortex in vitro.

PubMed

Yamamura, Daiki; Sano, Ayaka; Tateno, Takashi

2017-03-15

To examine local network properties of the mouse auditory cortex in vitro, we recorded extracellular spatiotemporal laminar profiles driven by short electric local stimulation on a planar multielectrode array substrate. The recorded local field potentials were subsequently evaluated using current source density (CSD) analysis to identify sources and sinks. Current sinks are thought to be an indicator of net synaptic current in the small volume of cortex surrounding the recording site. Thus, CSD analysis combined with multielectrode arrays enabled us to compare mean synaptic activity in response to small current stimuli on a layer-by-layer basis. We also used senescence-accelerated mice (SAM), some strains of which show earlier onset of age-related hearing loss, to examine the characteristic spatiotemporal CSD profiles stimulated by electrodes in specific cortical layers. Thus, the CSD patterns were classified into several clusters based on stimulation sites in the cortical layers. We also found some differences in CSD patterns between the two SAM strains in terms of aging according to principle component analysis with dimension reduction. For simultaneous two-site stimulation, we modeled the obtained CSD profiles as a linear superposition of the CSD profiles to individual single-site stimulation. The model analysis indicated the nonlinearity of spatiotemporal integration over stimulus-driven activity in a layer-specific manner. Finally, on the basis of these results, we discuss the auditory cortex local network properties and the effects of aging on these mouse strains. Copyright © 2017 Elsevier B.V. All rights reserved.

Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex

PubMed Central

Gray, Lucas T; Yao, Zizhen; Nguyen, Thuc Nghi; Kim, Tae Kyung; Zeng, Hongkui; Tasic, Bosiljka

2017-01-01

Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers. Integration of these data with layer-specific transcriptomic profiles and transcription factor binding motifs enabled us to construct a regulatory network revealing potential key layer-specific regulators, including Cux1/2, Foxp2, Nfia, Pou3f2, and Rorb. This dataset is a valuable resource for identifying candidate layer-specific cis-regulatory elements in adult mouse cortex. DOI: http://dx.doi.org/10.7554/eLife.21883.001 PMID:28112643

Single-Cell Analysis of Experience-Dependent Transcriptomic States in Mouse Visual Cortex

PubMed Central

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.

2017-01-01

Activity-dependent transcriptional responses shape cortical function. However, we lack a comprehensive understanding of the diversity of these responses across the full range of cortical cell types, and how these changes contribute to neuronal plasticity and disease. Here we applied high-throughput single-cell RNA-sequencing to investigate the breadth of transcriptional changes that occur across cell types in mouse visual cortex following exposure to light. We identified significant and divergent transcriptional responses to stimulation in each of the 30 cell types characterized, revealing 611 stimulus-responsive genes. Excitatory pyramidal neurons exhibit inter- and intra-laminar heterogeneity in the induction of stimulus responsive genes. Non-neuronal cells demonstrated clear transcriptional responses that may regulate experience-dependent changes in neurovascular coupling and myelination. Together, these results reveal the dynamic landscape of stimulus-dependent transcriptional changes that occur across cell types in visual cortex, which are likely critical for cortical function and may be sites of de-regulation in developmental brain disorders. PMID:29230054

Hunger-Dependent Enhancement of Food Cue Responses in Mouse Postrhinal Cortex and Lateral Amygdala.

PubMed

Burgess, Christian R; Ramesh, Rohan N; Sugden, Arthur U; Levandowski, Kirsten M; Minnig, Margaret A; Fenselau, Henning; Lowell, Bradford B; Andermann, Mark L

2016-09-07

The needs of the body can direct behavioral and neural processing toward motivationally relevant sensory cues. For example, human imaging studies have consistently found specific cortical areas with biased responses to food-associated visual cues in hungry subjects, but not in sated subjects. To obtain a cellular-level understanding of these hunger-dependent cortical response biases, we performed chronic two-photon calcium imaging in postrhinal association cortex (POR) and primary visual cortex (V1) of behaving mice. As in humans, neurons in mouse POR, but not V1, exhibited biases toward food-associated cues that were abolished by satiety. This emergent bias was mirrored by the innervation pattern of amygdalo-cortical feedback axons. Strikingly, these axons exhibited even stronger food cue biases and sensitivity to hunger state and trial history. These findings highlight a direct pathway by which the lateral amygdala may contribute to state-dependent cortical processing of motivationally relevant sensory cues. Published by Elsevier Inc.

Functional emergence of a column-like architecture in layer 5 of mouse somatosensory cortex in vivo.

PubMed

Koizumi, Kyo; Inoue, Masatoshi; Chowdhury, Srikanta; Bito, Haruhiko; Yamanaka, Akihiro; Ishizuka, Toru; Yawo, Hiromu

2018-05-14

To investigate how the functional architecture is organized in layer 5 (L5) of the somatosensory cortex of a mouse in vivo, the input-output relationship was investigated using an all-optical approach. The neural activity in L5 was optically recorded using a Ca 2+ sensor, R-CaMP2, through a microprism inserted in the cortex under two-photon microscopy, while the L5 was regionally excited using optogenetics. The excitability was spread around the blue-light irradiated region, but the horizontal propagation was limited to within a certain distance (λ < 130 μm from the center of the illumination spot). When two regions were photostimulated with a short interval, the excitability of each cluster was reduced. Therefore, a column-like architecture had functionally emerged with reciprocal inhibition through a minimal number of synaptic relays. This could generate a synchronous output from a region of L5 with simultaneous enhancement of the signal-to-noise ratio by silencing of the neighboring regions.

PTEN regulation of local and long-range connections in mouse auditory cortex

PubMed Central

Xiong, Qiaojie; Oviedo, Hysell V; Trotman, Lloyd C; Zador, Anthony M

2012-01-01

Autism Spectrum Disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN. Through Cre-mediated recombination we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long range connectivity using channelrhodopsin-2 (ChR2) revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser scanning photostimulation (LSPS) showed that local inputs onto PTEN-cko neurons in the auditory cortex were similarly enhanced. The hyperconnectivity caused by PTEN-cko could be blocked by rapamycin, a specific inhibitor of the PTEN downstream molecule mTORC1. Together our results suggest that local and long-range hyperconnectivity may constitute a physiological basis for the effects of mutations in PTEN and possibly other ASD candidate genes. PMID:22302806

A neural circuit for gamma-band coherence across the retinotopic map in mouse visual cortex

PubMed Central

Hakim, Richard; Shamardani, Kiarash

2018-01-01

Cortical gamma oscillations have been implicated in a variety of cognitive, behavioral, and circuit-level phenomena. However, the circuit mechanisms of gamma-band generation and synchronization across cortical space remain uncertain. Using optogenetic patterned illumination in acute brain slices of mouse visual cortex, we define a circuit composed of layer 2/3 (L2/3) pyramidal cells and somatostatin (SOM) interneurons that phase-locks ensembles across the retinotopic map. The network oscillations generated here emerge from non-periodic stimuli, and are stimulus size-dependent, coherent across cortical space, narrow band (30 Hz), and depend on SOM neuron but not parvalbumin (PV) neuron activity; similar to visually induced gamma oscillations observed in vivo. Gamma oscillations generated in separate cortical locations exhibited high coherence as far apart as 850 μm, and lateral gamma entrainment depended on SOM neuron activity. These data identify a circuit that is sufficient to mediate long-range gamma-band coherence in the primary visual cortex. PMID:29480803

Impairment of Hepcidin Upregulation by Lipopolysaccharide in the Interleukin-6 Knockout Mouse Brain.

PubMed

Zhang, Fa-Li; Hou, Hui-Min; Yin, Zhi-Nan; Chang, Lan; Li, Fe-Mi; Chen, Y-J; Ke, Ya; Qian, Zhong-Ming

2017-01-01

To find out whether the Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in the expression of hepcidin in the mouse brain in vivo , we investigated the phosphorylation of STAT3, as well as the expression of hepcidin mRNA, ferroportin 1 (Fpn1) and ferritin light chain (Ft-L) proteins in the cortex and hippocampus of LPS-treated wild type (IL-6+/+) and IL-6 knockout (IL-6-/-) mice. We demonstrated that IL-6 knockout could significantly reduce the response of hepcidin mRNA, phospho-STAT3, Fpn1 and Ft-L protein expression to LPS treatment, in both the cortex and hippocampus of mice. Also, Stattic, an inhibitor of STAT3, significantly reduced the expression of phospho-STAT3 and hepcidin mRNA in the cortex and hippocampus of the LPS-treated wild type mice. These findings provide in vivo evidence for the involvement of the IL-6/STAT3 signaling pathway in the expression of hepcidin.

Anatomical Pathways Involved in Generating and Sensing Rhythmic Whisker Movements

PubMed Central

Bosman, Laurens W. J.; Houweling, Arthur R.; Owens, Cullen B.; Tanke, Nouk; Shevchouk, Olesya T.; Rahmati, Negah; Teunissen, Wouter H. T.; Ju, Chiheng; Gong, Wei; Koekkoek, Sebastiaan K. E.; De Zeeuw, Chris I.

2011-01-01

The rodent whisker system is widely used as a model system for investigating sensorimotor integration, neural mechanisms of complex cognitive tasks, neural development, and robotics. The whisker pathways to the barrel cortex have received considerable attention. However, many subcortical structures are paramount to the whisker system. They contribute to important processes, like filtering out salient features, integration with other senses, and adaptation of the whisker system to the general behavioral state of the animal. We present here an overview of the brain regions and their connections involved in the whisker system. We do not only describe the anatomy and functional roles of the cerebral cortex, but also those of subcortical structures like the striatum, superior colliculus, cerebellum, pontomedullary reticular formation, zona incerta, and anterior pretectal nucleus as well as those of level setting systems like the cholinergic, histaminergic, serotonergic, and noradrenergic pathways. We conclude by discussing how these brain regions may affect each other and how they together may control the precise timing of whisker movements and coordinate whisker perception. PMID:22065951

Disrupted cortical function underlies behavior dysfunction due to social isolation

PubMed Central

Miyazaki, Tomoyuki; Takase, Kenkichi; Nakajima, Waki; Tada, Hirobumi; Ohya, Daisuke; Sano, Akane; Goto, Takahisa; Hirase, Hajime; Malinow, Roberto; Takahashi, Takuya

2012-01-01

Stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. However, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. Here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. Neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors normally occurring during circuit formation in the rodent barrel cortex. This inhibition of AMPA receptor trafficking was mediated by an increase of the stress glucocorticoid hormone and was associated with reduced calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling, resulting in attenuated whisker sensitivity at the cortex. These effects led to defects in whisker-dependent behavior in juvenile animals. These results indicate that neonatal social isolation alters neuronal plasticity mechanisms and perturbs the initial establishment of a normal cortical circuit, which potentially explains the long-lasting behavioral effects of neonatal stress. PMID:22706303

Barrels, stripes, and fingerprints in the brain - implications for theories of cortical organization.

PubMed

Catania, Kenneth C

2002-01-01

In the last decade improvements in the histological processing of cortical tissue in conjunction with the investigation of additional mammalian species in comparative brain studies has expanded the information available to guide theories of cortical organization. Here I review some of these recent findings in the somatosensory system with an emphasis on modules related to specializations of the peripheral sensory surface. The diversity of modular representations, or cortical "isomorphs" suggest that information from the sensory sheet guides many of the features of cortical maps and suggest that cortex is not constrained to form circular units in the form of a traditional cortical column.

Layer-specific excitation/inhibition balances during neuronal synchronization in the visual cortex.

PubMed

Adesnik, Hillel

2018-05-01

Understanding the balance between synaptic excitation and inhibition in cortical circuits in the brain, and how this contributes to cortical rhythms, is fundamental to explaining information processing in the cortex. This study used cortical layer-specific optogenetic activation in mouse cortex to show that excitatory neurons in any cortical layer can drive powerful gamma rhythms, while inhibition balances excitation. The net impact of this is to keep activity within each layer in check, but simultaneously to promote the propagation of activity to downstream layers. The data show that rhythm-generating circuits exist in all principle layers of the cortex, and provide layer-specific balances of excitation and inhibition that affect the flow of information across the layers. Rhythmic activity can synchronize neural ensembles within and across cortical layers. While gamma band rhythmicity has been observed in all layers, the laminar sources and functional impacts of neuronal synchronization in the cortex remain incompletely understood. Here, layer-specific optogenetic stimulation demonstrates that populations of excitatory neurons in any cortical layer of the mouse's primary visual cortex are sufficient to powerfully entrain neuronal oscillations in the gamma band. Within each layer, inhibition balances excitation and keeps activity in check. Across layers, translaminar output overcomes inhibition and drives downstream firing. These data establish that rhythm-generating circuits exist in all principle layers of the cortex, but provide layer-specific balances of excitation and inhibition that may dynamically shape the flow of information through cortical circuits. These data might help explain how excitation/inhibition (E/I) balances across cortical layers shape information processing, and shed light on the diverse nature and functional impacts of cortical gamma rhythms. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Relationship between individual neuron and network spontaneous activity in developing mouse cortex.

PubMed

Barnett, Heather M; Gjorgjieva, Julijana; Weir, Keiko; Comfort, Cara; Fairhall, Adrienne L; Moody, William J

2014-12-15

Spontaneous synchronous activity (SSA) that propagates as electrical waves is found in numerous central nervous system structures and is critical for normal development, but the mechanisms of generation of such activity are not clear. In previous work, we showed that the ventrolateral piriform cortex is uniquely able to initiate SSA in contrast to the dorsal neocortex, which participates in, but does not initiate, SSA (Lischalk JW, Easton CR, Moody WJ. Dev Neurobiol 69: 407-414, 2009). In this study, we used Ca(2+) imaging of cultured embryonic day 18 to postnatal day 2 coronal slices (embryonic day 17 + 1-4 days in culture) of the mouse cortex to investigate the different activity patterns of individual neurons in these regions. In the piriform cortex where SSA is initiated, a higher proportion of neurons was active asynchronously between waves, and a larger number of groups of coactive cells was present compared with the dorsal cortex. When we applied GABA and glutamate synaptic antagonists, asynchronous activity and cellular clusters remained, while synchronous activity was eliminated, indicating that asynchronous activity is a result of cell-intrinsic properties that differ between these regions. To test the hypothesis that higher levels of cell-autonomous activity in the piriform cortex underlie its ability to initiate waves, we constructed a conductance-based network model in which three layers differed only in the proportion of neurons able to intrinsically generate bursting behavior. Simulations using this model demonstrated that a gradient of intrinsic excitability was sufficient to produce directionally propagating waves that replicated key experimental features, indicating that the higher level of cell-intrinsic activity in the piriform cortex may provide a substrate for SSA generation. Copyright © 2014 the American Physiological Society.

Contribution of trimeric autotransporter C-terminal domains of oligomeric coiled-coil adhesin (Oca) family members YadA, UspA1, EibA, and Hia to translocation of the YadA passenger domain and virulence of Yersinia enterocolitica.

PubMed

Ackermann, Nikolaus; Tiller, Maximilian; Anding, Gisela; Roggenkamp, Andreas; Heesemann, Jürgen

2008-07-01

The Oca family is a novel class of autotransporter-adhesins with highest structural similarity in their C-terminal transmembrane region, which supposedly builds a beta-barrel pore in the outer membrane (OM). The prototype of the Oca family is YadA, an adhesin of Yersinia enterocolitica and Yersinia pseudotuberculosis. YadA forms a homotrimeric lollipop-like structure on the bacterial surface. The C-terminal regions of three YadA monomers form a barrel in the OM and translocate the trimeric N-terminal passenger domain, consisting of stalk, neck, and head region to the exterior. To elucidate the structural and functional role of the C-terminal translocator domain (TLD) and to assess its promiscuous capability with respect to transport of related passenger domains, we constructed chimeric YadA proteins, which consist of the N-terminal YadA passenger domain and C-terminal TLDs of Oca family members UspA1 (Moraxella catarrhalis), EibA (Escherichia coli), and Hia (Haemophilus influenzae). These constructs were expressed in Y. enterocolitica and compared for OM localization, surface exposure, oligomerization, adhesion properties, serum resistance, and mouse virulence. We demonstrate that all chimeric YadA proteins translocated the YadA passenger domain across the OM. Y. enterocolitica strains producing YadA chimeras or wild-type YadA showed comparable binding to collagen and epithelial cells. However, strains producing YadA chimeras were attenuated in serum resistance and mouse virulence. These results demonstrate for the first time that TLDs of Oca proteins of different origin are efficient translocators of the YadA passenger domain and that the cognate TLD of YadA is essential for bacterial survival in human serum and mouse virulence.

Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.

PubMed

Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki

2002-12-30

Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity.

Development of a novel mouse glioma model using lentiviral vectors

PubMed Central

Marumoto, Tomotoshi; Tashiro, Ayumu; Friedmann-Morvinski, Dinorah; Scadeng, Miriam; Soda, Yasushi; Gage, Fred H; Verma, Inder M

2009-01-01

We report the development of a new method to induce glioblastoma multiforme in adult immunocompetent mice by injecting Cre-loxP–controlled lentiviral vectors expressing oncogenes. Cell type- or region-specific expression of activated forms of the oncoproteins Harvey-Ras and AKT in fewer than 60 glial fibrillary acidic protein–positive cells in the hippocampus, subventricular zone or cortex of mice heterozygous for the gene encoding the tumor suppressor Tp53 were tested. Mice developed glioblastoma multiforme when transduced either in the subventricular zone or the hippocampus. However, tumors were rarely detected when the mice were transduced in the cortex. Transplantation of brain tumor cells into naive recipient mouse brain resulted in the formation of glioblastoma multiforme–like tumors, which contained CD133+ cells, formed tumorspheres and could differentiate into neurons and astrocytes. We suggest that the use of Cre-loxP–controlled lentiviral vectors is a novel way to generate a mouse glioblastoma multiforme model in a region- and cell type-specific manner in adult mice. PMID:19122659

Voltage-sensitive dye imaging of mouse neocortex during a whisker detection task

PubMed Central

Kyriakatos, Alexandros; Sadashivaiah, Vijay; Zhang, Yifei; Motta, Alessandro; Auffret, Matthieu; Petersen, Carl C. H.

2016-01-01

Abstract. Sensorimotor processing occurs in a highly distributed manner in the mammalian neocortex. The spatiotemporal dynamics of electrical activity in the dorsal mouse neocortex can be imaged using voltage-sensitive dyes (VSDs) with near-millisecond temporal resolution and ∼100-μm spatial resolution. Here, we trained mice to lick a water reward spout after a 1-ms deflection of the C2 whisker, and we imaged cortical dynamics during task execution with VSD RH1691. Responses to whisker deflection were highly dynamic and spatially highly distributed, exhibiting high variability from trial to trial in amplitude and spatiotemporal dynamics. We differentiated trials based on licking and whisking behavior. Hit trials, in which the mouse licked after the whisker stimulus, were accompanied by overall greater depolarization compared to miss trials, with the strongest hit versus miss differences being found in frontal cortex. Prestimulus whisking decreased behavioral performance by increasing the fraction of miss trials, and these miss trials had attenuated cortical sensorimotor responses. Our data suggest that the spatiotemporal dynamics of depolarization in mouse sensorimotor cortex evoked by a single brief whisker deflection are subject to important behavioral modulation during the execution of a simple, learned, goal-directed sensorimotor transformation. PMID:27921068

Structural studies of viperin, an antiviral radical SAM enzyme.

PubMed

Fenwick, Michael K; Li, Yue; Cresswell, Peter; Modis, Yorgo; Ealick, Steven E

2017-06-27

Viperin is an IFN-inducible radical S -adenosylmethionine (SAM) enzyme that inhibits viral replication. We determined crystal structures of an anaerobically prepared fragment of mouse viperin (residues 45-362) complexed with S -adenosylhomocysteine (SAH) or 5'-deoxyadenosine (5'-dAdo) and l-methionine (l-Met). Viperin contains a partial (βα) 6 -barrel fold with a disordered N-terminal extension (residues 45-74) and a partially ordered C-terminal extension (residues 285-362) that bridges the partial barrel to form an overall closed barrel structure. Cys84, Cys88, and Cys91 located after the first β-strand bind a [4Fe-4S] cluster. The active site architecture of viperin with bound SAH (a SAM analog) or 5'-dAdo and l-Met (SAM cleavage products) is consistent with the canonical mechanism of 5'-deoxyadenosyl radical generation. The viperin structure, together with sequence alignments, suggests that vertebrate viperins are highly conserved and that fungi contain a viperin-like ortholog. Many bacteria and archaebacteria also express viperin-like enzymes with conserved active site residues. Structural alignments show that viperin is similar to several other radical SAM enzymes, including the molybdenum cofactor biosynthetic enzyme MoaA and the RNA methyltransferase RlmN, which methylates specific nucleotides in rRNA and tRNA. The viperin putative active site contains several conserved positively charged residues, and a portion of the active site shows structural similarity to the GTP-binding site of MoaA, suggesting that the viperin substrate may be a nucleoside triphosphate of some type.

Orientation selectivity of synaptic input to neurons in mouse and cat primary visual cortex.

PubMed

Tan, Andrew Y Y; Brown, Brandon D; Scholl, Benjamin; Mohanty, Deepankar; Priebe, Nicholas J

2011-08-24

Primary visual cortex (V1) is the site at which orientation selectivity emerges in mammals: visual thalamus afferents to V1 respond equally to all stimulus orientations, whereas their target V1 neurons respond selectively to stimulus orientation. The emergence of orientation selectivity in V1 has long served as a model for investigating cortical computation. Recent evidence for orientation selectivity in mouse V1 opens cortical computation to dissection by genetic and imaging tools, but also raises two essential questions: (1) How does orientation selectivity in mouse V1 neurons compare with that in previously described species? (2) What is the synaptic basis for orientation selectivity in mouse V1? A comparison of orientation selectivity in mouse and in cat, where such measures have traditionally been made, reveals that orientation selectivity in mouse V1 is weaker than in cat V1, but that spike threshold plays a similar role in narrowing selectivity between membrane potential and spike rate. To uncover the synaptic basis for orientation selectivity, we made whole-cell recordings in vivo from mouse V1 neurons, comparing neuronal input selectivity-based on membrane potential, synaptic excitation, and synaptic inhibition-to output selectivity based on spiking. We found that a neuron's excitatory and inhibitory inputs are selective for the same stimulus orientations as is its membrane potential response, and that inhibitory selectivity is not broader than excitatory selectivity. Inhibition has different dynamics than excitation, adapting more rapidly. In neurons with temporally modulated responses, the timing of excitation and inhibition was different in mice and cats.

Orientation Selectivity of Synaptic Input to Neurons in Mouse and Cat Primary Visual Cortex

PubMed Central

Tan (陈勇毅), Andrew Y. Y.; Brown, Brandon D.; Scholl, Benjamin; Mohanty, Deepankar; Priebe, Nicholas J.

2011-01-01

Primary visual cortex (V1) is the site at which orientation selectivity emerges in mammals: visual thalamus afferents to V1 respond equally to all stimulus orientations whereas their target V1 neurons respond selectively to stimulus orientation. The emergence of orientation selectivity in V1 has long served as a model for investigating cortical computation. Recent evidence for orientation selectivity in mouse V1 opens cortical computation to dissection by genetic and imaging tools, but also raises two essential questions: 1) how does orientation selectivity in mouse V1 neurons compare with that in previously described species? 2) what is the synaptic basis for orientation selectivity in mouse V1? A comparison of orientation selectivity in mouse and in cat, where such measures have traditionally been made, reveals that orientation selectivity in mouse V1 is weaker than in cat V1, but that spike threshold plays a similar role in narrowing selectivity between membrane potential and spike rate. To uncover the synaptic basis for orientation selectivity, we made whole-cell recordings in vivo from mouse V1 neurons, comparing neuronal input selectivity - based on membrane potential, synaptic excitation, and synaptic inhibition - to output selectivity based on spiking. We found that a neuron's excitatory and inhibitory inputs are selective for the same stimulus orientations as is its membrane potential response, and that inhibitory selectivity is not broader than excitatory selectivity. Inhibition has different dynamics than excitation, adapting more rapidly. In neurons with temporally modulated responses, the timing of excitation and inhibition was different in mice and cats. PMID:21865476

Mapping arealisation of the visual cortex of non-primate species: lessons for development and evolution

PubMed Central

Homman-Ludiye, Jihane; Bourne, James A.

2014-01-01

The integration of the visual stimulus takes place at the level of the neocortex, organized in anatomically distinct and functionally unique areas. Primates, including humans, are heavily dependent on vision, with approximately 50% of their neocortical surface dedicated to visual processing and possess many more visual areas than any other mammal, making them the model of choice to study visual cortical arealisation. However, in order to identify the mechanisms responsible for patterning the developing neocortex, specifying area identity as well as elucidate events that have enabled the evolution of the complex primate visual cortex, it is essential to gain access to the cortical maps of alternative species. To this end, species including the mouse have driven the identification of cellular markers, which possess an area-specific expression profile, the development of new tools to label connections and technological advance in imaging techniques enabling monitoring of cortical activity in a behaving animal. In this review we present non-primate species that have contributed to elucidating the evolution and development of the visual cortex. We describe the current understanding of the mechanisms supporting the establishment of areal borders during development, mainly gained in the mouse thanks to the availability of genetically modified lines but also the limitations of the mouse model and the need for alternate species. PMID:25071460

[Effects of postnatal lambda-cyhalothrin exposure on synaptic proteins in ICR mouse brain].

PubMed

Bao, Xun-Di; Wang, Qu-Nan; Li, Fang-Fang; Chai, Xiao-Yu; Gao, Ye

2011-04-01

To evaluate the influence on the synaptic protein expression in different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure during postnatal period. Two male and 4 female healthy ICR mice were put in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from postnatal days (PND) 5 to PND13, control animals were treated with normal saline or DMSO by the same route. The brains were removed from pups on PND 14, the synaptic protein expression levels in cortex, hippocampus and striatum were measured by western blot. GFAP levels of cortex and hippocampus in the LCT exposure group increased with doses, as compared with control group (P < 0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed mouse hippocampus and in female ICR mouse cortex increased with doses, as compared with control group (P < 0.05). Presynaptic protein (Synapsin I) expression levels did not change obviously in various brain regions. However, postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT groups, and of female offspring in all exposure groups, of striatum, in 1.0 or 10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05). Early postnatal exposure to LCT affects synaptic protein expression. These effects may ultimately affect the construction of synaptic connections.

5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice.

PubMed

Amodeo, D A; Rivera, E; Cook, E H; Sweeney, J A; Ragozzino, M E

2017-03-01

Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT 2A receptor activity is altered in autism, while recent work indicates that systemic 5HT 2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT 2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT 2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT 2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT 2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT 2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

TrpM8-mediated somatosensation in mouse neocortex.

PubMed

Beukema, Patrick; Cecil, Katherine L; Peterson, Elena; Mann, Victor R; Matsushita, Megumi; Takashima, Yoshio; Navlakha, Saket; Barth, Alison L

2018-06-15

Somatosensation is a complex sense mediated by more than a dozen distinct neural subtypes in the periphery. Although pressure and touch sensation have been mapped to primary somatosensory cortex in rodents, it has been controversial whether pain and temperature inputs are also directed to this area. Here we use a well-defined somatosensory modality, cool sensation mediated by peripheral TrpM8-receptors, to investigate the neural substrate for cool perception in the mouse neocortex. Using activation of cutaneous TrpM8 receptor-expressing neurons, we identify candidate neocortical areas responsive for cool sensation. Initially, we optimized TrpM8 stimulation and determined that menthol, a selective TrpM8 agonist, was more effective than cool stimulation at inducing expression of the immediate-early gene c-fos in the spinal cord. We developed a broad-scale brain survey method for identification of activated brain areas, using automated methods to quantify c-fos immunoreactivity (fos-IR) across animals. Brain areas corresponding to the posterior insular cortex and secondary somatosensory (S2) show elevated fos-IR after menthol stimulation, in contrast to weaker activation in primary somatosensory cortex (S1). In addition, menthol exposure triggered fos-IR in piriform cortex, the amygdala, and the hypothalamus. Menthol-mediated activation was absent in TrpM8-knock-out animals. Our results indicate that cool somatosensory input broadly drives neural activity across the mouse brain, with neocortical signal most elevated in the posterior insula, as well as S2 and S1. These findings are consistent with data from humans indicating that the posterior insula is specialized for somatosensory information encoding temperature, pain, and gentle touch. © 2018 Wiley Periodicals, Inc.

Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain.

PubMed

Chang, Mengqi; Lv, Hongyi; Zhang, Weilong; Ma, Chunhui; He, Xue; Zhao, Shunli; Zhang, Zhi-Wei; Zeng, Yi-Xin; Song, Shuhui; Niu, Yamei; Tong, Wei-Min

2017-09-01

N 6 -methyladenosine (m 6 A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m 6 A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m 6 A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m 6 A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m 6 A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain. © 2017 The Authors.

15 CFR 241.2 - Legal standard barrels.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., VEGETABLES AND OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.2 Legal standard barrels. (a) Any barrel..., other than cranberries, in section 1 of the standard-barrel law, or any barrel or a subdivision thereof... than cranberries, or a legal subdivision thereof. No other barrel or subdivision in barrel form is a...

15 CFR 241.2 - Legal standard barrels.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., VEGETABLES AND OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.2 Legal standard barrels. (a) Any barrel..., other than cranberries, in section 1 of the standard-barrel law, or any barrel or a subdivision thereof... than cranberries, or a legal subdivision thereof. No other barrel or subdivision in barrel form is a...

15 CFR 241.2 - Legal standard barrels.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., VEGETABLES AND OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.2 Legal standard barrels. (a) Any barrel..., other than cranberries, in section 1 of the standard-barrel law, or any barrel or a subdivision thereof... than cranberries, or a legal subdivision thereof. No other barrel or subdivision in barrel form is a...

Preservation of primordial follicles from lions by slow freezing and xenotransplantation of ovarian cortex into an immunodeficient mouse.

PubMed

Wiedemann, C; Hribal, R; Ringleb, J; Bertelsen, M F; Rasmusen, K; Andersen, C Y; Kristensen, S G; Jewgenow, K

2012-12-01

Assisted reproductive technology (ART) is considered an important tool in the conservation of endangered species, but often the most limiting factor of ART is the availability of mature oocytes. The aim of the present study was to investigate the feasibility of preserving female germ cells from ovaries of female lions (Panthera leo). Good quality cumulus-oocyte complexes (COCs) were isolated and subjected to in vitro maturation (IVM). In addition, ovarian cortex was obtained and cut into pieces for culture and cryopreservation by slow freezing. The survival of ovarian follicles was assessed by histology. Frozen-thawed samples of ovarian cortex samples were xenotransplanted under the skin of ovariectomized immunodeficient mouse for 28 days. Overall, 178 intact COCs were obtained from 13 lions, but only 28.1% were matured in vitro indicating insufficient IVM conditions. In contrast, almost all follicles within the ovarian cortex survived culture when the original sample was from a young healthy lion collected immediately after euthanasia. Within the xenotransplants, the number of primordial follicles decreased after 28 days by 20%, but the relation between primordial and growing follicles changed in favour of follicular growth. Female gamete rescue from valuable felids may be performed by slow freeze cryopreservation of ovarian cortex. Although the IVM protocol for lions is not yet optimized, mature oocytes may be obtained after long-term xenotransplantation and IVM and could potentially represent one way of salvage of endangered felid species in the future. © 2012 Blackwell Verlag GmbH.

Cholinergic neurodegeneration in an Alzheimer mouse model overexpressing amyloid-precursor protein with the Swedish-Dutch-Iowa mutations.

PubMed

Foidl, Bettina Maria; Do-Dinh, Patricia; Hutter-Schmid, Bianca; Bliem, Harald R; Humpel, Christian

2016-12-01

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is mainly characterized by beta-amyloid (Aβ) plaque deposition, Tau pathology and dysfunction of the cholinergic system causing memory impairment. The aim of the present study was to examine (1) anxiety and cognition, (2) Aβ plaque deposition and (3) degeneration of cholinergic neurons in the nucleus basalis of Meynert (nbM) and cortical cholinergic innervation in an Alzheimer mouse model (APP_SweDI; overexpressing amyloid precursor protein (APP) with the Swedish K670N/M671L, Dutch E693Q, and Iowa D694N mutations). Our results show that 12-month-old APP_SweDI mice were more anxious and had more memory impairment. A large number of Aβ plaques were already visible at the age of 6 months and increased with age. A significant decrease in cholinergic neurons was seen in the transgenic mouse model in comparison to the wild-type mice, identified by immunohistochemistry against choline acetyltransferase (ChAT) and p75 neurotrophin receptor as well as by in situ hybridization. Moreover, a significant decrease in cortical cholinergic fiber density was found in the transgenic mice as compared to the wild-type. In the cerebral cortex of APP_SweDI mice, swollen cholinergic varicosities were seen in the vicinity of Aβ plaques. In conclusion, the present study shows that in an AD mouse model (APP_SweDI mice) a high Aβ plaque load in the cortex causes damage to cholinergic axons in the cortex, followed by subsequent retrograde-induced cell death of cholinergic neurons and some forms of compensatory processes. This degeneration was accompanied by enhanced anxiety and impaired cognition. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed Central

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

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

PubMed

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.

Preservation of Cognitive Function by Lepidium meyenii (Maca) Is Associated with Improvement of Mitochondrial Activity and Upregulation of Autophagy-Related Proteins in Middle-Aged Mouse Cortex

PubMed Central

Guo, Shan-Shan; Gao, Xiao-Fang; Gu, Yan-Rong

2016-01-01

Maca has been used as a foodstuff and a traditional medicine in the Andean region for over 2,000 years. Recently the neuroprotective effects of maca also arouse interest of researchers. Decrease in mitochondrial function and decline in autophagy signaling may participate in the process of age-related cognitive decline. This study aimed to investigate if maca could improve cognitive function of middle-aged mice and if this effect was associated with improvement of mitochondrial activity and modulation of autophagy signaling in mouse cortex. Fourteen-month-old male ICR mice received maca powder administered by gavage for five weeks. Maca improved cognitive function, motor coordination, and endurance capacity in middle-aged mice, accompanied by increased mitochondrial respiratory function and upregulation of autophagy-related proteins in cortex. Our findings suggest that maca is a newly defined nutritional plant which can improve mitochondrial function and upregulate autophagy-related proteins and may be an effective functional food for slowing down age-related cognitive decline. PMID:27648102

Preservation of Cognitive Function by Lepidium meyenii (Maca) Is Associated with Improvement of Mitochondrial Activity and Upregulation of Autophagy-Related Proteins in Middle-Aged Mouse Cortex.

PubMed

Guo, Shan-Shan; Gao, Xiao-Fang; Gu, Yan-Rong; Wan, Zhong-Xiao; Lu, A-Ming; Qin, Zheng-Hong; Luo, Li

2016-01-01

Maca has been used as a foodstuff and a traditional medicine in the Andean region for over 2,000 years. Recently the neuroprotective effects of maca also arouse interest of researchers. Decrease in mitochondrial function and decline in autophagy signaling may participate in the process of age-related cognitive decline. This study aimed to investigate if maca could improve cognitive function of middle-aged mice and if this effect was associated with improvement of mitochondrial activity and modulation of autophagy signaling in mouse cortex. Fourteen-month-old male ICR mice received maca powder administered by gavage for five weeks. Maca improved cognitive function, motor coordination, and endurance capacity in middle-aged mice, accompanied by increased mitochondrial respiratory function and upregulation of autophagy-related proteins in cortex. Our findings suggest that maca is a newly defined nutritional plant which can improve mitochondrial function and upregulate autophagy-related proteins and may be an effective functional food for slowing down age-related cognitive decline.

PTEN regulation of local and long-range connections in mouse auditory cortex.

PubMed

Xiong, Qiaojie; Oviedo, Hysell V; Trotman, Lloyd C; Zador, Anthony M

2012-02-01

Autism spectrum disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN (phosphatase and tensin homolog deleted on chromosome 10). Through Cre-mediated recombination, we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long-range connectivity using channelrhodopsin-2 revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser-scanning photostimulation showed that local inputs onto PTEN-cko neurons in the auditory cortex were similarly enhanced. The hyperconnectivity caused by PTEN-cko could be blocked by rapamycin, a specific inhibitor of the PTEN downstream molecule mammalian target of rapamycin complex 1. Together, our results suggest that local and long-range hyperconnectivity may constitute a physiological basis for the effects of mutations in PTEN and possibly other ASD candidate genes.

Two-photon voltage imaging using a genetically encoded voltage indicator

PubMed Central

Akemann, Walther; Sasaki, Mari; Mutoh, Hiroki; Imamura, Takeshi; Honkura, Naoki; Knöpfel, Thomas

2013-01-01

Voltage-sensitive fluorescent proteins (VSFPs) are a family of genetically-encoded voltage indicators (GEVIs) reporting membrane voltage fluctuation from genetically-targeted cells in cell cultures to whole brains in awake mice as demonstrated earlier using 1-photon (1P) fluorescence excitation imaging. However, in-vivo 1P imaging captures optical signals only from superficial layers and does not optically resolve single neurons. Two-photon excitation (2P) imaging, on the other hand, has not yet been convincingly applied to GEVI experiments. Here we show that 2P imaging of VSFP Butterfly 1.2 expresssing pyramidal neurons in layer 2/3 reports optical membrane voltage in brain slices consistent with 1P imaging but with a 2–3 larger ΔR/R value. 2P imaging of mouse cortex in-vivo achieved cellular resolution throughout layer 2/3. In somatosensory cortex we recorded sensory responses to single whisker deflections in anesthetized mice at full frame video rate. Our results demonstrate the feasibility of GEVI-based functional 2P imaging in mouse cortex. PMID:23868559

Glycogen synthase kinase-3 levels and phosphorylation undergo large fluctuations in mouse brain during development

PubMed Central

Beurel, Eléonore; Mines, Marjelo A; Song, Ling; Jope, Richard S

2012-01-01

Objectives Dysregulated glycogen synthase kinase-3 (GSK3) may contribute to the pathophysiology of mood disorders and other diseases, and appears to be a target of certain therapeutic drugs. The growing recognition of heightened vulnerability during development to many psychiatric diseases, including mood disorders, led us to test if there are developmental changes in mouse brain GSK3 and its regulation by phosphorylation and by therapeutic drugs. Methods GSK3 levels and phosphorylation were measured at seven ages of development in mouse cerebral cortex and hippocampus. Results Two periods of rapid transitions in GSK3 levels were identified, a large rise between postnatal day 1 and two to three weeks of age, where GSK3 levels were as high as four-fold adult mouse brain levels, and a rapid decline between two to four and eight weeks of age, when adult levels were reached. Inhibitory serine-phosphorylation of GSK3, particularly GSK3β, was extremely high in one-day postnatal mouse brain, and rapidly declined thereafter. These developmental changes in GSK3 were equivalent in male and female cerebral cortex, and differed from other signaling kinases, including Akt, ERK1/2, JNK, and p38 levels and phosphorylation. In contrast to adult mouse brain, where administration of lithium or fluoxetine rapidly and robustly increased serine-phosphorylation of GSK3, in young mice these responses were blunted or absent. Conclusions High brain levels of GSK3 and large fluctuations in its levels and phosphorylation in juvenile and adolescent mouse brain raise the possibility that they may contribute to destabilized mood regulation induced by environmental and genetic factors. PMID:23167932

Oligodendrocyte- and Neuron-Specific Nogo-A Restrict Dendritic Branching and Spine Density in the Adult Mouse Motor Cortex.

PubMed

Zemmar, Ajmal; Chen, Chia-Chien; Weinmann, Oliver; Kast, Brigitt; Vajda, Flora; Bozeman, James; Isaad, Noel; Zuo, Yi; Schwab, Martin E

2018-06-01

Nogo-A has been well described as a myelin-associated inhibitor of neurite outgrowth and functional neuroregeneration after central nervous system (CNS) injury. Recently, a new role of Nogo-A has been identified as a negative regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in neurons and oligodendrocytes. However, it is yet unclear which of these two pools regulate synaptic plasticity. To address this question we used newly generated mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes (oligoNogo-A KO) or (2) neurons (neuroNogo-A KO). We show that both oligodendrocyte- and neuron-specific Nogo-A KO mice have enhanced dendritic branching and spine densities in layer 2/3 cortical pyramidal neurons. These effects are compartmentalized: neuronal Nogo-A affects proximal dendrites whereas oligodendrocytic Nogo-A affects distal regions. Finally, we used two-photon laser scanning microscopy to measure the spine turnover rate of adult mouse motor cortex layer 5 cells and find that both Nogo-A KO mouse lines show enhanced spine remodeling after 4 days. Our results suggest relevant control functions of glial as well as neuronal Nogo-A for synaptic plasticity and open new possibilities for more selective and targeted plasticity enhancing strategies.

fMRI mapping of the visual system in the mouse brain with interleaved snapshot GE-EPI.

PubMed

Niranjan, Arun; Christie, Isabel N; Solomon, Samuel G; Wells, Jack A; Lythgoe, Mark F

2016-10-01

The use of functional magnetic resonance imaging (fMRI) in mice is increasingly prevalent, providing a means to non-invasively characterise functional abnormalities associated with genetic models of human diseases. The predominant stimulus used in task-based fMRI in the mouse is electrical stimulation of the paw. Task-based fMRI in mice using visual stimuli remains underexplored, despite visual stimuli being common in human fMRI studies. In this study, we map the mouse brain visual system with BOLD measurements at 9.4T using flashing light stimuli with medetomidine anaesthesia. BOLD responses were observed in the lateral geniculate nucleus, the superior colliculus and the primary visual area of the cortex, and were modulated by the flashing frequency, diffuse vs focussed light and stimulus context. Negative BOLD responses were measured in the visual cortex at 10Hz flashing frequency; but turned positive below 5Hz. In addition, the use of interleaved snapshot GE-EPI improved fMRI image quality without diminishing the temporal contrast-noise-ratio. Taken together, this work demonstrates a novel methodological protocol in which the mouse brain visual system can be non-invasively investigated using BOLD fMRI. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Laterodorsal Nucleus of the Thalamus: A Processor of Somatosensory Inputs

PubMed Central

BEZDUDNAYA, TATIANA; KELLER, ASAF

2009-01-01

The laterodorsal (LD) nucleus of the thalamus has been considered a “higher order” nucleus that provides inputs to limbic cortical areas. Although its functions are largely unknown, it is often considered to be involved in spatial learning and memory. Here we provide evidence that LD is part of a hitherto unknown pathway for processing somatosensory information. Juxtacellular and extracellular recordings from LD neurons reveal that they respond to vibrissa stimulation with short latency (median = 7 ms) and large magnitude responses (median = 1.2 spikes/stimulus). Most neurons (62%) had large receptive fields, responding to six and more individual vibrissae. Electrical stimulation of the trigeminal nucleus interpolaris (SpVi) evoked short latency responses (median = 3.8 ms) in vibrissa-responsive LD neurons. Labeling produced by anterograde and retrograde neuroanatomical tracers confirmed that LD neurons receive direct inputs from SpVi. Electrophysiological and neuroanatomical analyses revealed also that LD projects upon the cingulate and retrosplenial cortex, but has only sparse projections to the barrel cortex. These findings suggest that LD is part of a novel processing stream involved in spatial orientation and learning related to somatosensory cues. PMID:18273888

Neural Correlation Is Stimulus Modulated by Feedforward Inhibitory Circuitry

PubMed Central

Middleton, Jason W.; Omar, Cyrus; Doiron, Brent; Simons, Daniel J.

2012-01-01

Correlated variability of neural spiking activity has important consequences for signal processing. How incoming sensory signals shape correlations of population responses remains unclear. Cross-correlations between spiking of different neurons may be particularly consequential in sparsely firing neural populations such as those found in layer 2/3 of sensory cortex. In rat whisker barrel cortex, we found that pairs of excitatory layer 2/3 neurons exhibit similarly low levels of spike count correlation during both spontaneous and sensory-evoked states. The spontaneous activity of excitatory–inhibitory neuron pairs is positively correlated, while sensory stimuli actively decorrelate joint responses. Computational modeling shows how threshold nonlinearities and local inhibition form the basis of a general decorrelating mechanism. We show that inhibitory population activity maintains low correlations in excitatory populations, especially during periods of sensory-evoked coactivation. The role of feedforward inhibition has been previously described in the context of trial-averaged phenomena. Our findings reveal a novel role for inhibition to shape correlations of neural variability and thereby prevent excessive correlations in the face of feedforward sensory-evoked activation. PMID:22238086

Cortical organization in insectivora: the parallel evolution of the sensory periphery and the brain.

PubMed

Catania, K C

2000-06-01

Insectivores are traditionally described as a primitive group that has not changed much in the course of mammalian evolution. In contrast, recent studies reveal a great diversity of sensorimotor specializations among insectivores adapted to a number of different ecological niches, indicating that there has been significant diversification and change in the course of their evolution. Here the organization of sensory cortex is compared in the African hedgehog (Atelerix albiventris), the masked shrew (Sorex cinereus), the eastern mole (Scalopus aquaticus), and the star-nosed mole (Condylura cristata). Each of these four closely related species lives in a unique ecological niche, exhibits a different repertoire of behaviors, and has a different configuration of peripheral sensory receptors. Corresponding specializations of cortical sensory areas reveal a number of ways in which the cortex has evolved in parallel with changes to the sensory periphery. These specializations include expansion of cortical representations (cortical magnification), the addition or loss of cortical areas in the processing network, and the subdivision of areas into modules (barrels and stripes). Copyright 2000 S. Karger AG, Basel

15 CFR 240.6 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE STANDARDS FOR BARRELS BARRELS AND OTHER CONTAINERS FOR LIME § 240.6 Tolerances. (a) When lime is packed in barrels the tolerance to be allowed on the large barrel or the small barrel of lime shall be 5 pounds in excess or in deficiency on any individual barrel...

In Vivo Visualization of Active Polysynaptic Circuits With Longitudinal Manganese-Enhanced MRI (MEMRI).

PubMed

Almeida-Corrêa, Suellen; Czisch, Michael; Wotjak, Carsten T

2018-01-01

Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo non-invasive whole-brain mapping of neuronal activity. Mn 2+ enters active neurons via voltage-gated calcium channels and increases local contrast in T 1 -weighted images. Given the property of Mn 2+ of axonal transport, this technique can also be used for tract tracing after local administration of the contrast agent. However, MEMRI is still not widely employed in basic research due to the lack of a complete description of the Mn 2+ dynamics in the brain. Here, we sought to investigate how the activity state of neurons modulates interneuronal Mn 2+ transport. To this end, we injected mice with low dose MnCl 2 2. (i.p., 20 mg/kg; repeatedly for 8 days) followed by two MEMRI scans at an interval of 1 week without further MnCl 2 injections. We assessed changes in T 1 contrast intensity before (scan 1) and after (scan 2) partial sensory deprivation (unilateral whisker trimming), while keeping the animals in a sensory enriched environment. After correcting for the general decay in Mn 2+ content, whole brain analysis revealed a single cluster with higher signal in scan 1 compared to scan 2: the left barrel cortex corresponding to the right untrimmed whiskers. In the inverse contrast (scan 2 > scan 1), a number of brain structures, including many efferents of the left barrel cortex were observed. These results suggest that continuous neuronal activity elicited by ongoing sensory stimulation accelerates Mn 2+ transport from the uptake site to its projection terminals, while the blockage of sensory-input and the resulting decrease in neuronal activity attenuates Mn 2+ transport. The description of this critical property of Mn 2+ dynamics in the brain allows a better understanding of MEMRI functional mechanisms, which will lead to more carefully designed experiments and clearer interpretation of the results.

Optogenetic conditioning of paradigm and pattern discrimination in the rat somatosensory system

PubMed Central

Abe, Kenta

2017-01-01

The rodent whisker-barrel cortical system is a model for studying somatosensory discrimination at high spatiotemporal precision. Here, we applied optogenetics to produce somatosensory inputs in the whisker area using one of transgenic rat lines, W-TChR2V4, which expresses channelrhodopsin-2 (ChR2) in the mechanoreceptive nerve endings around whisker follicles. An awake W-TChR2V4 rat was head-fixed and irradiated by blue LED light on the whisker area with a paradigm conditioned with a reward. The Go task was designed so the rat is allowed to receive a reward, when it licked the nozzle within 5 s after photostimulation. The No-go task was designed so as the rat has to withhold licking for at least 5 s to obtain a reward after photostimulation. The Go-task conditioning was established within 1 hr of training with a reduction in the reaction time and increase of the success rate. To investigate the relationship between the spatiotemporal pattern of sensory inputs and the behavioral output, we designed a multi-optical fiber system that irradiates the whisker area at 9 spots in a 3×3 matrix. Although the Go-task conditioning was established using synchronous irradiation of 9 spots, the success rate was decreased with an increase of the reaction time for the asynchronous irradiation. After conditioning to the Go task, the rat responded to the blue LED flash irradiated on the barrel cortex, where many neurons also express ChR2, or photostimulation of the contralateral whisker area with a similar reaction time and success rate. Synchronous activation of the peripheral mechanoreceptive nerves is suggested to drive a neural circuit in the somatosensory cortex that efficiently couples with the decision. Our optogenetic system would enable the precise evaluation of the psychophysical values, such as the reaction time and success rate, to gain some insight into the brain mechanisms underlying conditioned behaviors. PMID:29267341

Enduring critical period plasticity visualized by transcranial flavoprotein imaging in mouse primary visual cortex.

PubMed

Tohmi, Manavu; Kitaura, Hiroki; Komagata, Seiji; Kudoh, Masaharu; Shibuki, Katsuei

2006-11-08

Experience-dependent plasticity in the visual cortex was investigated using transcranial flavoprotein fluorescence imaging in mice anesthetized with urethane. On- and off-responses in the primary visual cortex were elicited by visual stimuli. Fluorescence responses and field potentials elicited by grating patterns decreased similarly as contrasts of visual stimuli were reduced. Fluorescence responses also decreased as spatial frequency of grating stimuli increased. Compared with intrinsic signal imaging in the same mice, fluorescence imaging showed faster responses with approximately 10 times larger signal changes. Retinotopic maps in the primary visual cortex and area LM were constructed using fluorescence imaging. After monocular deprivation (MD) of 4 d starting from postnatal day 28 (P28), deprived eye responses were suppressed compared with nondeprived eye responses in the binocular zone but not in the monocular zone. Imaging faithfully recapitulated a critical period for plasticity with maximal effects of MD observed around P28 and not in adulthood even under urethane anesthesia. Visual responses were compared before and after MD in the same mice, in which the skull was covered with clear acrylic dental resin. Deprived eye responses decreased after MD, whereas nondeprived eye responses increased. Effects of MD during a critical period were tested 2 weeks after reopening of the deprived eye. Significant ocular dominance plasticity was observed in responses elicited by moving grating patterns, but no long-lasting effect was found in visual responses elicited by light-emitting diode light stimuli. The present results indicate that transcranial flavoprotein fluorescence imaging is a powerful tool for investigating experience-dependent plasticity in the mouse visual cortex.

Encoding of contextual fear memory requires de novo proteins in the prelimbic cortex

PubMed Central

Rizzo, Valerio; Touzani, Khalid; Raveendra, Bindu L.; Swarnkar, Supriya; Lora, Joan; Kadakkuzha, Beena M.; Liu, Xin-An; Zhang, Chao; Betel, Doron; Stackman, Robert W.; Puthanveettil, Sathyanarayanan V.

2016-01-01

Background Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories (LTM), its role in the encoding of LTM remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory. Methods Because a change in the association of mRNAs to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential gene expression in mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in mPFC was determined by focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex manipulation (n = 56) of Homer 3, a candidate identified from polyribosome profiling. Results We identified several mRNAs that are differentially and temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex (ACC) region of the mPFC immediately after CFC disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA enriched in polyribosomes following CFC, in the PL constrained encoding of contextual fear memory. Conclusions Our studies identify several molecular substrates of new protein synthesis in the mPFC and establish that encoding of contextual fear memories require new protein synthesis in PL subregion of mPFC. PMID:28503670

Small arms mini-fire control system: fiber-optic barrel deflection sensor

NASA Astrophysics Data System (ADS)

Rajic, S.; Datskos, P.; Lawrence, W.; Marlar, T.; Quinton, B.

2012-06-01

Traditionally the methods to increase firearms accuracy, particularly at distance, have concentrated on barrel isolation (free floating) and substantial barrel wall thickening to gain rigidity. This barrel stiffening technique did not completely eliminate barrel movement but the problem was significantly reduced to allow a noticeable accuracy enhancement. This process, although highly successful, came at a very high weight penalty. Obviously the goal would be to lighten the barrel (firearm), yet achieve even greater accuracy. Thus, if lightweight barrels could ultimately be compensated for both their static and dynamic mechanical perturbations, the result would be very accurate, yet significantly lighter weight, weapons. We discuss our development of a barrel reference sensor system that is designed to accomplish this ambitious goal. Our optical fiber-based sensor monitors the barrel muzzle position and autonomously compensates for any induced perturbations. The reticle is electronically adjusted in position to compensate for the induced barrel deviation in real time.

Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus.

PubMed

Mahmoudian, Alireza; Rajaei, Ziba; Haghir, Hossein; Banihashemian, Shahaboldin; Hami, Javad

2012-04-01

The aim of the present study was to determine the effects of valerian (Valeriana officinalis) consumption in pregnancy on cortical volume and the levels of zinc and copper, two essential elements that affect brain development and function, in the brain tissues of mouse fetuses. Pregnant female mice were treated with either saline or 1.2 g/kg body weight valerian extract intraperitoneally daily on gestation days (GD) 7 to 17. On GD 20, mice were sacrificed and their fetuses were collected. Fetal brains were dissected, weighed and processed for histological analysis. The volume of cerebral cortex was estimated by the Cavalieri principle. The levels of zinc and copper in the brain tissues were measured by atomic absorption spectroscopy. The results indicated that valerian consumption in pregnancy had no significant effect on brain weight, cerebral cortex volume and copper level in fetal brain. However,it significantly decreased the level of zinc in the brain (P<0.05). Using valerian during midgestation do not have an adverse effect on cerebral cortex; however,it caused a significant decrease in zinc level in the fetal brain. This suggests that valerian use should be limited during pregnancy.

Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain.

PubMed

Kosi, Nina; Alić, Ivan; Kolačević, Matea; Vrsaljko, Nina; Jovanov Milošević, Nataša; Sobol, Margarita; Philimonenko, Anatoly; Hozák, Pavel; Gajović, Srećko; Pochet, Roland; Mitrečić, Dinko

2015-02-09

The nucleolar protein 2 gene encodes a protein specific for the nucleolus. It is assumed that it plays a role in the synthesis of ribosomes and regulation of the cell cycle. Due to its link to cell proliferation, higher expression of Nop2 indicates a worse tumor prognosis. In this work we used Nop2(gt1gaj) gene trap mouse strain. While lethality of homozygous animals suggested a vital role of this gene, heterozygous animals allowed the detection of expression of Nop2 in various tissues, including mouse brain. Histochemistry, immunohistochemistry and immunoelectron microscopy techniques, applied to a mature mouse brain, human brain and on mouse neural stem cells revealed expression of Nop2 in differentiating cells, including astrocytes, as well as in mature neurons. Nop2 was detected in various regions of mouse and human brain, mostly in large pyramidal neurons. In the human, Nop2 was strongly expressed in supragranular and infragranular layers of the somatosensory cortex and in layer III of the cingulate cortex. Also, Nop2 was detected in CA1 and the subiculum of the hippocampus. Subcellular analyses revealed predominant location of Nop2 within the dense fibrillar component of the nucleolus. To test if Nop2 expression correlates to cell proliferation occurring during tissue regeneration, we induced strokes in mice by middle cerebral artery occlusion. Two weeks after stroke, the number of Nop2/nestin double positive cells in the region affected by ischemia and the periventricular zone substantially increased. Our findings suggest a newly discovered role of Nop2 in both mature neurons and in cells possibly involved in the regeneration of nervous tissue. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Cartography and Connectomes Perspective article for Neuron 25th Anniversary Issue

PubMed Central

Van Essen, David C.

2013-01-01

The past 25 years have seen great progress in parcellating the cerebral cortex into a mosaic of many distinct areas in mice, monkeys, and humans. Quantitative studies of inter-areal connectivity have revealed unexpectedly many pathways and a wide range of connection strengths in mouse and macaque cortex. In humans, advances in analyzing ‘structural’ and ‘functional’ connectivity using powerful but indirect noninvasive neuroimaging methods are yielding intriguing insights about brain circuits, their variability across individuals, and their relationship to behavior. PMID:24183027

eGFP expression under the Uchl1 promoter labels corticospinal motor neurons and a subpopulation of degeneration resistant spinal motor neurons in ALS mouse models

NASA Astrophysics Data System (ADS)

Yasvoina, Marina V.

Current understanding of basic cellular and molecular mechanisms for motor neuron vulnerability during motor neuron disease initiation and progression is incomplete. The complex cytoarchitecture and cellular heterogeneity of the cortex and spinal cord greatly impedes our ability to visualize, isolate, and study specific neuron populations in both healthy and diseased states. We generated a novel reporter line, the Uchl1-eGFP mouse, in which cortical and spinal components of motor neuron circuitry are genetically labeled with eGFP under the Uchl1 promoter. A series of cellular and anatomical analyses combined with retrograde labeling, molecular marker expression, and electrophysiology were employed to determine identity of eGFP expressing cells in the motor cortex and the spinal cord of novel Uchl1-eGFP reporter mice. We conclude that eGFP is expressed in corticospinal motor neurons (CSMN) in the motor cortex and a subset of S-type alpha and gamma spinal motor neurons (SMN) in the spinal cord. hSOD1G93A and Alsin-/- mice, mouse models for amyotrophic lateral sclerosis (ALS), were bred to Uchl1-eGFP reporter mouse line to investigate the pathophysiology and underlying mechanisms of CSMN degeneration in vivo. Evidence suggests early and progressive degeneration of CSMN and SMN in the hSOD1G93A transgenic mice. We show an early increase of autophagosome formation in the apical dendrites of vulnerable CSMN in hSOD1G93A-UeGFP mice, which is localized to the apical dendrites. In addition, labeling S-type alpha and gamma SMN in the hSOD1G93A-UeGFP mice provide a unique opportunity to study basis of their resistance to degeneration. Mice lacking alsin show moderate clinical phenotype and mild CSMN axon degeneration in the spinal cord, which suggests vulnerability of CSMN. Therefore, we investigated the CSMN cellular and axon defects in aged Alsin-/- mice bred to Uchl1-eGFP reporter mouse line. We show that while CSMN are preserved and lack signs of degeneration, CSMN axons are vulnerable and show significant loss.

The mouse cortico-striatal projectome

PubMed Central

Hintiryan, Houri; Foster, Nicholas N.; Bowman, Ian; Bay, Maxwell; Song, Monica Y.; Gou, Lin; Yamashita, Seita; Bienkowski, Michael S.; Zingg, Brian; Zhu, Muye; Yang, X. William; Shih, Jean C.; Toga, Arthur W.; Dong, Hong-Wei

2017-01-01

Different cortical areas are organized into distinct intra-cortical subnetworks. How descending pathways from the entire cortex interact subcortically as a network remains unclear. Here, we report an open-access comprehensive mesoscale cortico-striatal projectome—a detailed connectivity projection map from the entire cerebral cortex to the dorsal striatum or caudoputamen (CP) in rodents. Based on these projections, we use novel computational neuroanatomical tools to identify 29 distinct functional striatal domains. Further, we characterize different cortico-striatal networks and how they reconfigure across the rostral-caudal extent of the CP. The workflow was also applied to select cortico-striatal connections in two different mouse models of disconnection syndromes to demonstrate its utility in characterizing circuitry-specific connectopathies. Together, this work provides the structural basis for studying the functional diversity of the dorsal striatum and disruptions of cortico-basal ganglia networks across a broad range of disorders. PMID:27322419

Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome

PubMed Central

Nomura, Toshihiro; Zhu, Yiwen; Remmers, Christine L.; Xu, Jian; Nicholson, Daniel A.

2017-01-01

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS. SIGNIFICANCE STATEMENT Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin signaling during early development in FXS. PMID:29038238

Small arms mini-fire control system: fiber-optic barrel deflection sensor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajic, Slobodan; Datskos, Panos G

Traditionally the methods to increase firearms accuracy, particularly at distance, have concentrated on barrel isolation (free floating) and substantial barrel wall thickening to gain rigidity. This barrel stiffening technique did not completely eliminate barrel movement but the problem was significantly reduced to allow a noticeable accuracy enhancement. This process, although highly successful, came at a very high weight penalty. Obviously the goal would be to lighten the barrel (firearm), yet achieve even greater accuracy. Thus, if lightweight barrels could ultimately be compensated for both their static and dynamic mechanical perturbations, the result would be very accurate, yet significantly lighter weight,more » weapons. We discuss our development of a barrel reference sensor system that is designed to accomplish this ambitious goal. Our optical fiber-based sensor monitors the barrel muzzle position and autonomously compensates for any induced perturbations. The reticle is electronically adjusted in position to compensate for the induced barrel deviation in real time.« less

Development and matching of binocular orientation preference in mouse V1.

PubMed

Bhaumik, Basabi; Shah, Nishal P

2014-01-01

Eye-specific thalamic inputs converge in the primary visual cortex (V1) and form the basis of binocular vision. For normal binocular perceptions, such as depth and stereopsis, binocularly matched orientation preference between the two eyes is required. A critical period of binocular matching of orientation preference in mice during normal development is reported in literature. Using a reaction diffusion model we present the development of RF and orientation selectivity in mouse V1 and investigate the binocular orientation preference matching during the critical period. At the onset of the critical period the preferred orientations of the modeled cells are mostly mismatched in the two eyes and the mismatch decreases and reaches levels reported in juvenile mouse by the end of the critical period. At the end of critical period 39% of cells in binocular zone in our model cortex is orientation selective. In literature around 40% cortical cells are reported as orientation selective in mouse V1. The starting and the closing time for critical period determine the orientation preference alignment between the two eyes and orientation tuning in cortical cells. The absence of near neighbor interaction among cortical cells during the development of thalamo-cortical wiring causes a salt and pepper organization in the orientation preference map in mice. It also results in much lower % of orientation selective cells in mice as compared to ferrets and cats having organized orientation maps with pinwheels.

15 CFR 241.2 - Legal standard barrels.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Legal standard barrels. 241.2 Section..., VEGETABLES AND OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.2 Legal standard barrels. (a) Any barrel... form or dimensions, is a legal standard barrel for fruits, vegetables, or other dry commodities other...

15 CFR 241.2 - Legal standard barrels.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Legal standard barrels. 241.2 Section..., VEGETABLES AND OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.2 Legal standard barrels. (a) Any barrel... form or dimensions, is a legal standard barrel for fruits, vegetables, or other dry commodities other...

Tapered-Tip Capillary Electrophoresis Nano-Electrospray Ionization Mass Spectrometry for Ultrasensitive Proteomics: the Mouse Cortex

NASA Astrophysics Data System (ADS)

Choi, Sam B.; Zamarbide, Marta; Manzini, M. Chiara; Nemes, Peter

2017-04-01

Ultrasensitive characterization of the proteome raises the potential to understand how differential gene expression orchestrates cell heterogeneity in the brain. Here, we report a microanalytical capillary electrophoresis nano-flow electrospray ionization (CE-nanoESI) interface for mass spectrometry to enable the measurement of limited amounts of proteins in the mouse cortex. Our design integrates a custom-built CE system to a tapered-tip metal emitter in a co-axial sheath-flow configuration. This interface can be constructed in <15 min using readily available components, facilitating broad adaptation. Tapered-tip CE-nanoESI generates stable electrospray by reproducibly anchoring the Taylor cone, minimizes sample dilution in the ion source, and ensures efficient ion generation by sustaining the cone-jet spraying regime. Parallel reaction monitoring provided a 260-zmol lower limit of detection for angiotensin II (156,000 copies). CE was able to resolve a complex mixture of peptides in 330,000 theoretical plates and identify 15 amol ( 1 pg) of BSA or cytochrome c. Over 30 min of separation, 1 ng protein digest from the mouse cortex yielded 217 nonredundant proteins encompassing a 3-log-order concentration range using a quadrupole time-of-flight mass spectrometer. Identified proteins included many products from genes that are traditionally used to mark oligodendrocytes, astrocytes, and microglia. Finally, key proteins involved in neurodegenerative disorders were detected (e.g., parkinsonism and spastic paraplegia). CE-nanoESI-HRMS delivers sufficient sensitivity to detect proteins in limited amounts of tissues and cell populations to help understand how gene expression differences maintain cell heterogeneity in the brain.

Spatial integration in mouse primary visual cortex.

PubMed

Vaiceliunaite, Agne; Erisken, Sinem; Franzen, Florian; Katzner, Steffen; Busse, Laura

2013-08-01

Responses of many neurons in primary visual cortex (V1) are suppressed by stimuli exceeding the classical receptive field (RF), an important property that might underlie the computation of visual saliency. Traditionally, it has proven difficult to disentangle the underlying neural circuits, including feedforward, horizontal intracortical, and feedback connectivity. Since circuit-level analysis is particularly feasible in the mouse, we asked whether neural signatures of spatial integration in mouse V1 are similar to those of higher-order mammals and investigated the role of parvalbumin-expressing (PV+) inhibitory interneurons. Analogous to what is known from primates and carnivores, we demonstrate that, in awake mice, surround suppression is present in the majority of V1 neurons and is strongest in superficial cortical layers. Anesthesia with isoflurane-urethane, however, profoundly affects spatial integration: it reduces the laminar dependency, decreases overall suppression strength, and alters the temporal dynamics of responses. We show that these effects of brain state can be parsimoniously explained by assuming that anesthesia affects contrast normalization. Hence, the full impact of suppressive influences in mouse V1 cannot be studied under anesthesia with isoflurane-urethane. To assess the neural circuits of spatial integration, we targeted PV+ interneurons using optogenetics. Optogenetic depolarization of PV+ interneurons was associated with increased RF size and decreased suppression in the recorded population, similar to effects of lowering stimulus contrast, suggesting that PV+ interneurons contribute to spatial integration by affecting overall stimulus drive. We conclude that the mouse is a promising model for circuit-level mechanisms of spatial integration, which relies on the combined activity of different types of inhibitory interneurons.

Computational Image Analysis Reveals Intrinsic Multigenerational Differences between Anterior and Posterior Cerebral Cortex Neural Progenitor Cells

PubMed Central

Winter, Mark R.; Liu, Mo; Monteleone, David; Melunis, Justin; Hershberg, Uri; Goderie, Susan K.; Temple, Sally; Cohen, Andrew R.

2015-01-01

Summary Time-lapse microscopy can capture patterns of development through multiple divisions for an entire clone of proliferating cells. Images are taken every few minutes over many days, generating data too vast to process completely by hand. Computational analysis of this data can benefit from occasional human guidance. Here we combine improved automated algorithms with minimized human validation to produce fully corrected segmentation, tracking, and lineaging results with dramatic reduction in effort. A web-based viewer provides access to data and results. The improved approach allows efficient analysis of large numbers of clones. Using this method, we studied populations of progenitor cells derived from the anterior and posterior embryonic mouse cerebral cortex, each growing in a standardized culture environment. Progenitors from the anterior cortex were smaller, less motile, and produced smaller clones compared to those from the posterior cortex, demonstrating cell-intrinsic differences that may contribute to the areal organization of the cerebral cortex. PMID:26344906

Odor identity coding by distributed ensembles of neurons in the mouse olfactory cortex

PubMed Central

Roland, Benjamin; Deneux, Thomas; Franks, Kevin M; Bathellier, Brice; Fleischmann, Alexander

2017-01-01

Olfactory perception and behaviors critically depend on the ability to identify an odor across a wide range of concentrations. Here, we use calcium imaging to determine how odor identity is encoded in olfactory cortex. We find that, despite considerable trial-to-trial variability, odor identity can accurately be decoded from ensembles of co-active neurons that are distributed across piriform cortex without any apparent spatial organization. However, piriform response patterns change substantially over a 100-fold change in odor concentration, apparently degrading the population representation of odor identity. We show that this problem can be resolved by decoding odor identity from a subpopulation of concentration-invariant piriform neurons. These concentration-invariant neurons are overrepresented in piriform cortex but not in olfactory bulb mitral and tufted cells. We therefore propose that distinct perceptual features of odors are encoded in independent subnetworks of neurons in the olfactory cortex. DOI: http://dx.doi.org/10.7554/eLife.26337.001 PMID:28489003

Assessment of undiscovered oil and gas resources of the Assam, Bombay, Cauvery, and Krishna-Godavari Provinces, South Asia, 2011

USGS Publications Warehouse

Klett, T.R.; Schenk, Christopher J.; Wandrey, Craig J.; Charpentier, Ronald R.; Cook, Troy A.; Brownfield, Michael E.; Pitman, Janet K.; Pollastro, Richard M.

2012-01-01

Using a geology-based assessment methodology, the U.S. Geological Survey estimated volumes of undiscovered, technically recoverable, conventional petroleum resources for the Assam, Bombay, Cauvery, and Krishna–Godavari Provinces, South Asia. The estimated mean volumes are as follows: (1) Assam Province, 273 million barrels of crude oil, 1,559 billion cubic feet of natural gas, and 43 million barrels of natural gas liquids; (2) Bombay Province, 1,854 million barrels of crude oil, 15,417 billion cubic feet of natural gas, and 498 million barrels of natural gas liquids; (3) Cauvery Province, 941 million barrels of crude oil, 25,208 billion cubic feet of natural gas, and 654 million barrels of natural gas liquids; and (4) Krishna–Godavari Province, 466 million barrels of crude oil, 37,168 billion cubic feet of natural gas, and 484 million barrels of natural gas liquids. The totals for the four provinces are 3,534 million barrels of crude oil, 79,352 billion cubic feet of natural gas, and 1,679 million barrels of natural gas liquids.

RNA sequencing from neural ensembles activated during fear conditioning in the mouse temporal association cortex

PubMed Central

Cho, Jin-Hyung; Huang, Ben S.; Gray, Jesse M.

2016-01-01

The stable formation of remote fear memories is thought to require neuronal gene induction in cortical ensembles that are activated during learning. However, the set of genes expressed specifically in these activated ensembles is not known; knowledge of such transcriptional profiles may offer insights into the molecular program underlying stable memory formation. Here we use RNA-Seq to identify genes whose expression is enriched in activated cortical ensembles labeled during associative fear learning. We first establish that mouse temporal association cortex (TeA) is required for remote recall of auditory fear memories. We then perform RNA-Seq in TeA neurons that are labeled by the activity reporter Arc-dVenus during learning. We identify 944 genes with enriched expression in Arc-dVenus+ neurons. These genes include markers of L2/3, L5b, and L6 excitatory neurons but not glial or inhibitory markers, confirming Arc-dVenus to be an excitatory neuron-specific but non-layer-specific activity reporter. Cross comparisons to other transcriptional profiles show that 125 of the enriched genes are also activity-regulated in vitro or induced by visual stimulus in the visual cortex, suggesting that they may be induced generally in the cortex in an experience-dependent fashion. Prominent among the enriched genes are those encoding potassium channels that down-regulate neuronal activity, suggesting the possibility that part of the molecular program induced by fear conditioning may initiate homeostatic plasticity. PMID:27557751

Transient effects of anesthetics on dendritic spines and filopodia in the living mouse cortex

PubMed Central

Yang, Guang; Chang, Paul C.; Bekker, Alex; Blanck, Thomas; Gan, Wen-Biao

2013-01-01

Background Anesthetics are widely used to induce unconsciousness, pain relief and immobility during surgery. It remains unclear whether the use of anesthetics has significant and long lasting effects on synapse development and plasticity in the brain. To address this question, we examined the formation and elimination of dendritic spines, postsynaptic sites of excitatory synapses, in the developing mouse cortex during and after anesthetics exposure. Methods Transgenic mice expressing yellow fluorescence protein in layer 5 pyramidal neurons were used in this study. Mice at 1 month of age underwent ketamine-xylazine and isoflurane anesthesia over a period of hours. The elimination and formation rates of dendritic spines and filopodia, the precursors of spines, were followed over hours to days in the primary somatosensory cortex using transcranial two-photon microscopy. 4–5 animals were examined under each experimental condition. Student's t-test and Mann-Whitney U-test were used to analyze the data. Results Administration of either ketamine-xylazine or isoflurane rapidly altered dendritic filopodial dynamics but had no significant effects on spine dynamics. Ketamine-xylazine increased filopodial formation while isoflurane decreased filopodial elimination during 4 hours of anesthesia. Both effects were transient and disappeared within a day after the animals woke up. Conclusion Our studies suggest that exposure to anesthetics transiently affects the dynamics of dendritic filopodia but has no significant effect on dendritic spine development and plasticity in the cortex of 1-month-old mice. PMID:21768874

La Deletion from Mouse Brain Alters Pre-tRNA Metabolism and Accumulation of Pre-5.8S rRNA, with Neuron Death and Reactive Astrocytosis

PubMed Central

Blewett, Nathan H.; Iben, James R.; Gaidamakov, Sergei

2017-01-01

ABSTRACT Human La antigen (Sjögren's syndrome antigen B [SSB]) is an abundant multifunctional RNA-binding protein. In the nucleoplasm, La binds to and protects from 3′ exonucleases, the ends of precursor tRNAs, and other transcripts synthesized by RNA polymerase III and facilitates their maturation, while a nucleolar isoform has been implicated in rRNA biogenesis by multiple independent lines of evidence. We showed previously that conditional La knockout (La cKO) from mouse cortex neurons results in defective tRNA processing, although the pathway(s) involved in neuronal loss thereafter was unknown. Here, we demonstrate that La is stably associated with a spliced pre-tRNA intermediate. Microscopic evidence of aberrant nuclear accumulation of 5.8S rRNA in La cKO is supported by a 10-fold increase in a pre-5.8S rRNA intermediate. To identify pathways involved in subsequent neurodegeneration and loss of brain mass in the cKO cortex, we employed mRNA sequencing (mRNA-Seq), immunohistochemistry, and other approaches. This revealed robust enrichment of immune and astrocyte reactivity in La cKO cortex. Immunohistochemistry, including temporal analyses, demonstrated neurodegeneration, followed by astrocyte invasion associated with immune response and decreasing cKO cortex size over time. Thus, deletion of La from postmitotic neurons results in defective pre-tRNA and pre-rRNA processing and progressive neurodegeneration with loss of cortical brain mass. PMID:28223366

Cholecystokinin levels in prohormone convertase 2 knock-out mouse brain regions reveal a complex phenotype of region-specific alterations.

PubMed

Beinfeld, Margery C; Blum, Alissa; Vishnuvardhan, Daesety; Fanous, Sanya; Marchand, James E

2005-11-18

Prohormone convertase 2 is widely co-localized with cholecystokinin in rodent brain. To examine its role in cholecystokinin processing, cholecystokinin levels were measured in dissected brain regions from prohormone convertase 2 knock-out mice. Cholecystokinin levels were lower in hippocampus, septum, thalamus, mesencephalon, and pons in knock-out mice than wild-type mice. In cerebral cortex, cortex-related structures and olfactory bulb, cholecystokinin levels were higher than wild type. Female mice were more affected by the loss of prohormone convertase 2 than male mice. The decrease in cholecystokinin levels in these brain regions shows that prohormone convertase 2 is important for cholecystokinin processing. Quantitative polymerase chain reaction measurements were performed to examine the relationship between peptide levels and cholecystokinin and enzyme expression. They revealed that cholecystokinin and prohormone convertase 1 mRNA levels in cerebral cortex and olfactory bulb were actually lower in knock-out than wild type, whereas their expression in other brain regions of knock-out mouse brain was the same as wild type. Female mice frequently had higher expression of cholecystokinin and prohormone convertase 1, 2, and 5 mRNA than male mice. The loss of prohormone convertase 2 alters CCK processing in specific brain regions. This loss also appears to trigger compensatory mechanisms in cerebral cortex and olfactory bulb that produce elevated levels of cholecystokinin but do not involve increased expression of cholecystokinin, prohormone convertase 1 or 5 mRNA.

Amyloid deposition in the hippocampus and entorhinal cortex: Quantitative analysis of a transgenic mouse model

PubMed Central

Reilly, John F.; Games, Dora; Rydel, Russell E.; Freedman, Stephen; Schenk, Dale; Young, Warren G.; Morrison, John H.; Bloom, Floyd E.

2003-01-01

Various transgenic mouse models of Alzheimer's disease (AD) have been developed that overexpress mutant forms of amyloid precursor protein in an effort to elucidate more fully the potential role of β-amyloid (Aβ) in the etiopathogenesis of the disease. The present study represents the first complete 3D reconstruction of Aβ in the hippocampus and entorhinal cortex of PDAPP transgenic mice. Aβ deposits were detected by immunostaining and thioflavin fluorescence, and quantified by using high-throughput digital image acquisition and analysis. Quantitative analysis of amyloid load in hippocampal subfields showed a dramatic increase between 12 and 15 months of age, with little or no earlier detectable deposition. Three-dimensional reconstruction in the oldest brains visualized previously unrecognized sheets of Aβ coursing through the hippocampus and cerebral cortex. In contrast with previous hypotheses, compact plaques form before significant deposition of diffuse Aβ, suggesting that different mechanisms are involved in the deposition of diffuse amyloid and the aggregation into plaques. The dentate gyrus was the hippocampal subfield with the greatest amyloid burden. Sublaminar distribution of Aβ in the dentate gyrus correlated most closely with the termination of afferent projections from the lateral entorhinal cortex, mirroring the selective vulnerability of this circuit in human AD. This detailed temporal and spatial analysis of Aβ and compact amyloid deposition suggests that specific corticocortical circuits express selective, but late, vulnerability to the pathognomonic markers of amyloid deposition, and can provide a basis for detecting prior vulnerability factors. PMID:12697936

Genetic Elimination of GABAergic Neurotransmission Reveals Two Distinct Pacemakers for Spontaneous Waves of Activity in the Developing Mouse Cortex

PubMed Central

Easton, Curtis R.; Weir, Keiko; Scott, Adina; Moen, Samantha P.; Barger, Zeke; Folch, Albert; Hevner, Robert F.

2014-01-01

Many structures of the mammalian CNS generate propagating waves of electrical activity early in development. These waves are essential to CNS development, mediating a variety of developmental processes, such as axonal outgrowth and pathfinding, synaptogenesis, and the maturation of ion channel and receptor properties. In the mouse cerebral cortex, waves of activity occur between embryonic day 18 and postnatal day 8 and originate in pacemaker circuits in the septal nucleus and the piriform cortex. Here we show that genetic knock-out of the major synthetic enzyme for GABA, GAD67, selectively eliminates the picrotoxin-sensitive fraction of these waves. The waves that remain in the GAD67 knock-out have a much higher probability of propagating into the dorsal neocortex, as do the picrotoxin-resistant fraction of waves in controls. Field potential recordings at the point of wave initiation reveal different electrical signatures for GABAergic and glutamatergic waves. These data indicate that: (1) there are separate GABAergic and glutamatergic pacemaker circuits within the piriform cortex, each of which can initiate waves of activity; (2) the glutamatergic pacemaker initiates waves that preferentially propagate into the neocortex; and (3) the initial appearance of the glutamatergic pacemaker does not require preceding GABAergic waves. In the absence of GAD67, the electrical activity underlying glutamatergic waves shows greatly increased tendency to burst, indicating that GABAergic inputs inhibit the glutamatergic pacemaker, even at stages when GABAergic pacemaker circuitry can itself initiate waves. PMID:24623764

Specific excitatory connectivity for feature integration in mouse primary visual cortex

PubMed Central

Molina-Luna, Patricia; Roth, Morgane M.

2017-01-01

Local excitatory connections in mouse primary visual cortex (V1) are stronger and more prevalent between neurons that share similar functional response features. However, the details of how functional rules for local connectivity shape neuronal responses in V1 remain unknown. We hypothesised that complex responses to visual stimuli may arise as a consequence of rules for selective excitatory connectivity within the local network in the superficial layers of mouse V1. In mouse V1 many neurons respond to overlapping grating stimuli (plaid stimuli) with highly selective and facilitatory responses, which are not simply predicted by responses to single gratings presented alone. This complexity is surprising, since excitatory neurons in V1 are considered to be mainly tuned to single preferred orientations. Here we examined the consequences for visual processing of two alternative connectivity schemes: in the first case, local connections are aligned with visual properties inherited from feedforward input (a ‘like-to-like’ scheme specifically connecting neurons that share similar preferred orientations); in the second case, local connections group neurons into excitatory subnetworks that combine and amplify multiple feedforward visual properties (a ‘feature binding’ scheme). By comparing predictions from large scale computational models with in vivo recordings of visual representations in mouse V1, we found that responses to plaid stimuli were best explained by assuming feature binding connectivity. Unlike under the like-to-like scheme, selective amplification within feature-binding excitatory subnetworks replicated experimentally observed facilitatory responses to plaid stimuli; explained selective plaid responses not predicted by grating selectivity; and was consistent with broad anatomical selectivity observed in mouse V1. Our results show that visual feature binding can occur through local recurrent mechanisms without requiring feedforward convergence, and that such a mechanism is consistent with visual responses and cortical anatomy in mouse V1. PMID:29240769

15 CFR 240.3 - Permissible sizes.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE STANDARDS FOR BARRELS BARRELS AND OTHER CONTAINERS FOR LIME § 240.3 Permissible sizes. Lime in barrels shall be packed only in barrels containing 280 pounds or 180...

Causal evidence for retina dependent and independent visual motion computations in mouse cortex

PubMed Central

Hillier, Daniel; Fiscella, Michele; Drinnenberg, Antonia; Trenholm, Stuart; Rompani, Santiago B.; Raics, Zoltan; Katona, Gergely; Juettner, Josephine; Hierlemann, Andreas; Rozsa, Balazs; Roska, Botond

2017-01-01

How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity – either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells – and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an overrepresentation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the overrepresentation of posterior-motion-preferring cortical cells disappeared, and their response at higher stimulus speeds was reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex. PMID:28530661

Oil burner nozzle

DOEpatents

Wright, Donald G.

1982-01-01

An oil burner nozzle for use with liquid fuels and solid-containing liquid fuels. The nozzle comprises a fuel-carrying pipe, a barrel concentrically disposed about the pipe, and an outer sleeve retaining member for the barrel. An atomizing vapor passes along an axial passageway in the barrel, through a bore in the barrel and then along the outer surface of the front portion of the barrel. The atomizing vapor is directed by the outer sleeve across the path of the fuel as it emerges from the barrel. The fuel is atomized and may then be ignited.

Laterodorsal nucleus of the thalamus: A processor of somatosensory inputs.

PubMed

Bezdudnaya, Tatiana; Keller, Asaf

2008-04-20

The laterodorsal (LD) nucleus of the thalamus has been considered a "higher order" nucleus that provides inputs to limbic cortical areas. Although its functions are largely unknown, it is often considered to be involved in spatial learning and memory. Here we provide evidence that LD is part of a hitherto unknown pathway for processing somatosensory information. Juxtacellular and extracellular recordings from LD neurons reveal that they respond to vibrissa stimulation with short latency (median = 7 ms) and large magnitude responses (median = 1.2 spikes/stimulus). Most neurons (62%) had large receptive fields, responding to six and more individual vibrissae. Electrical stimulation of the trigeminal nucleus interpolaris (SpVi) evoked short latency responses (median = 3.8 ms) in vibrissa-responsive LD neurons. Labeling produced by anterograde and retrograde neuroanatomical tracers confirmed that LD neurons receive direct inputs from SpVi. Electrophysiological and neuroanatomical analyses revealed also that LD projects upon the cingulate and retrosplenial cortex, but has only sparse projections to the barrel cortex. These findings suggest that LD is part of a novel processing stream involved in spatial orientation and learning related to somatosensory cues. (c) 2008 Wiley-Liss, Inc.

Spontaneous Fluctuations of PO2 in the Rabbit Somatosensory Cortex.

PubMed

Linsenmeier, Robert A; Aksenov, Daniil P; Faber, Holden M; Makar, Peter; Wyrwicz, Alice M

2016-01-01

In many tissues, PO2 fluctuates spontaneously with amplitudes of a few mmHg. Here we further characterized these oscillations. PO2 recordings were made from the whisker barrel cortex of six rabbits with acutely or chronically placed polarographic electrodes. Measurements were made while rabbits were awake and while anesthetized with isoflurane, during air breathing, and during 100% oxygen inspiration. In awake rabbits, 90% of the power was between 0 and 20 cycles per minute (cpm), not uniformly distributed over this range, but with a peak frequently near 10 cpm. This was much slower than heart or respiratory rhythms and is similar to the frequency content observed in other tissues. During hyperoxia, total power was higher than during air-breathing, and the dominant frequencies tended to shift toward lower values (0-10 cpm). These observations suggest that at least the lower frequency fluctuations represent efforts by the circulation to regulate local PO2. There were no consistent changes in total power during 0.5 or 1.5% isoflurane anesthesia, but the power shifted to lower frequencies. Thus, both hyperoxia and anesthesia cause characteristic, but distinct, changes in spontaneous fluctuations. These PO2 fluctuations may be caused by vasomotion, but other factors cannot be ruled out.

Contribution of cerebellar intracortical inhibition to Purkinje cell response during vestibulo-ocular reflex of alert rabbits.

PubMed Central

Miyashita, Y; Nagao, S

1984-01-01

Ionophoretic application of bicuculline, an antagonist of gamma-aminobutyric acid (GABA), was used to examine the contribution of intracortical inhibition to vestibular responses of Purkinje cells in the cerebellar flocculus of alert rabbits. Purkinje cells were sampled extracellularly (with triple-barrelled micropipettes) from the floccular area where electrical stimulation through the micro-electrode evoked abduction of the ipsilateral eye, indicating its close functional relationship to the horizontal vestibulo-ocular reflex. These cells exhibited frequency modulation of simple spike discharges in-phase or out-phase with sinusoidal head rotation (0.5 cycles/s, 5 degrees peak-to-peak) in the horizontal plane. Bicuculline was ejected ionophoretically through one barrel with a 20-60 nA current. The pharmacological effectiveness of the ejected bicuculline was confirmed for each Purkinje cell by its blocking action upon the depressant action of GABA applied ionophoretically through another barrel. Bicuculline usually shifted the simple spike modulation in the in-phase direction: it reduced the amplitude of out-phase modulation in three cells, converted out-phase modulation to the in-phase type in four cells, and increased in-phase modulation in five cells. In three other cells, however, bicuculline shifted the modulation in the out-phase direction. Because bicuculline application usually increased the resting discharge level of a Purkinje cell, ionophoretic application of DL-homocysteate was used in ten Purkinje cells to control for the effect of a generalized increase in excitability. In contrast to bicuculline, DL-homocysteate generally induced a slight increase of the simple spike modulation regardless of the phase relationship. Since frequency modulation of the simple spike discharges of flocculus Purkinje cells is presumed to contribute to the control of vestibulo-ocular reflexes, these results point to an important functional role of intracortical post-synaptic inhibition in the cerebellar cortex. PMID:6611408

De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy

PubMed Central

Parmeggiani, Fabio; Velasco, D. Alejandro Fernandez; Höcker, Birte; Baker, David

2015-01-01

Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of 4-fold symmetrical (β/α)8-barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of sidechain-backbone hydrogen bonding for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical with the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has only sampled a subset of the sequence space available to the TIM-barrel fold. The ability to de novo design TIM-barrels opens new possibilities for custom-made enzymes. PMID:26595462

Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals

PubMed Central

Chery, Romain; L'Heureux, Barbara; Bendahmane, Mounir; Renaud, Rémi; Martin, Claire; Pain, Frédéric; Gurden, Hirac

2011-01-01

In the brain, sensory stimulation activates distributed populations of neurons among functional modules which participate to the coding of the stimulus. Functional optical imaging techniques are advantageous to visualize the activation of these modules in sensory cortices with high spatial resolution. In this context, endogenous optical signals that arise from molecular mechanisms linked to neuroenergetics are valuable sources of contrast to record spatial maps of sensory stimuli over wide fields in the rodent brain. Here, we present two techniques based on changes of endogenous optical properties of the brain tissue during activation. First the intrinsic optical signals (IOS) are produced by a local alteration in red light reflectance due to: (i) absorption by changes in blood oxygenation level and blood volume (ii) photon scattering. The use of in vivo IOS to record spatial maps started in the mid 1980's with the observation of optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex1. IOS imaging of the surface of the rodent main olfactory bulb (OB) in response to odorants was later demonstrated by Larry Katz's group2. The second approach relies on flavoprotein autofluorescence signals (FAS) due to changes in the redox state of these mitochondrial metabolic intermediates. More precisely, the technique is based on the green fluorescence due to oxidized state of flavoproteins when the tissue is excited with blue light. Although such signals were probably among the first fluorescent molecules recorded for the study of brain activity by the pioneer studies of Britton Chances and colleagues3, it was not until recently that they have been used for mapping of brain activation in vivo. FAS imaging was first applied to the somatosensory cortex in rodents in response to hindpaw stimulation by Katsuei Shibuki's group4. The olfactory system is of central importance for the survival of the vast majority of living species because it allows efficient detection and identification of chemical substances in the environment (food, predators). The OB is the first relay of olfactory information processing in the brain. It receives afferent projections from the olfactory primary sensory neurons that detect volatile odorant molecules. Each sensory neuron expresses only one type of odorant receptor and neurons carrying the same type of receptor send their nerve processes to the same well-defined microregions of ˜100μm3 constituted of discrete neuropil, the olfactory glomerulus (Fig. 1). In the last decade, IOS imaging has fostered the functional exploration of the OB5, 6, 7 which has become one of the most studied sensory structures. The mapping of OB activity with FAS imaging has not been performed yet. Here, we show the successive steps of an efficient protocol for IOS and FAS imaging to map odor-evoked activities in the mouse OB. PMID:22064685

The Bat as a New Model of Cortical Development.

PubMed

Martínez-Cerdeño, Verónica; Camacho, Jasmin; Ariza, Jeanelle; Rogers, Hailee; Horton-Sparks, Kayla; Kreutz, Anna; Behringer, Richard; Rasweiler, John J; Noctor, Stephen C

2017-11-09

The organization of the mammalian cerebral cortex shares fundamental features across species. However, while the radial thickness of grey matter varies within one order of magnitude, the tangential spread of the cortical sheet varies by orders of magnitude across species. A broader sample of model species may provide additional clues for understanding mechanisms that drive cortical expansion. Here, we introduce the bat Carollia perspicillata as a new model species. The brain of C. perspicillata is similar in size to that of mouse but has a cortical neurogenic period at least 5 times longer than mouse, and nearly as long as that of the rhesus macaque, whose brain is 100 times larger. We describe the development of laminar and regional structures, neural precursor cell identity and distribution, immune cell distribution, and a novel population of Tbr2+ cells in the caudal ganglionic eminence of the developing neocortex of C. perspicillata. Our data indicate that unique mechanisms guide bat cortical development, particularly concerning cell cycle length. The bat model provides new perspective on the evolution of developmental programs that regulate neurogenesis in mammalian cerebral cortex, and offers insight into mechanisms that contribute to tangential expansion and gyri formation in the cerebral cortex. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antidepressant-like effects of ferulic acid: involvement of serotonergic and norepinergic systems.

PubMed

Chen, Jianliang; Lin, Dan; Zhang, Chong; Li, Gaowen; Zhang, Nianping; Ruan, Lina; Yan, Qizhi; Li, Jianxin; Yu, Xuefeng; Xie, Xupei; Pang, Cong; Cao, Liang; Pan, Jianchun; Xu, Ying

2015-02-01

Ferulic acid is a polyphenol that has antioxidant, anti-inflammatory and anticancer properties. The present study analyzed the antidepressant-like potential of ferulic acid using two well-validated mouse models of despair test, tail suspension and forced swim tests. The results suggested that ferulic acid treatment at doses of 10, 20, 40 and 80 mg/kg (p.o.) significantly reduced the immobility time in both of these two tests. These doses that affected the depressive-like behaviors did now show any effect on locomotion counts. The further neurochemical assays suggested that ferulic acid increased monoamine neurotransmitter levels in the brain regions that are relative to mood disorders: the hippocampus and frontal cortex. The increased tend to serotonin and norepinephrine was also found in the hypothalamus after higher dose of ferulic acid treatment. The subsequent study suggested that monoamine oxidase A (MAO-A) activity was inhibited in the frontal cortex and hippocampus when treatment with 40 and 80 mg/kg ferulic acid; while MAO-B activity did not change significantly. The current study provides the first lines of evidence that serotonin and norepinephrine, but not dopamine levels were elevated in mouse hippocampus and frontal cortex after ferulic acid treatment. These changes may be attributable to the inhibition of MAO-A activities in the same brain regions.

Local and Global Spatial Organization of Interaural Level Difference and Frequency Preferences in Auditory Cortex

PubMed Central

Panniello, Mariangela; King, Andrew J; Dahmen, Johannes C; Walker, Kerry M M

2018-01-01

Abstract Despite decades of microelectrode recordings, fundamental questions remain about how auditory cortex represents sound-source location. Here, we used in vivo 2-photon calcium imaging to measure the sensitivity of layer II/III neurons in mouse primary auditory cortex (A1) to interaural level differences (ILDs), the principal spatial cue in this species. Although most ILD-sensitive neurons preferred ILDs favoring the contralateral ear, neurons with either midline or ipsilateral preferences were also present. An opponent-channel decoder accurately classified ILDs using the difference in responses between populations of neurons that preferred contralateral-ear-greater and ipsilateral-ear-greater stimuli. We also examined the spatial organization of binaural tuning properties across the imaged neurons with unprecedented resolution. Neurons driven exclusively by contralateral ear stimuli or by binaural stimulation occasionally formed local clusters, but their binaural categories and ILD preferences were not spatially organized on a more global scale. In contrast, the sound frequency preferences of most neurons within local cortical regions fell within a restricted frequency range, and a tonotopic gradient was observed across the cortical surface of individual mice. These results indicate that the representation of ILDs in mouse A1 is comparable to that of most other mammalian species, and appears to lack systematic or consistent spatial order. PMID:29136122

Early network activity propagates bidirectionally between hippocampus and cortex.

PubMed

Barger, Zeke; Easton, Curtis R; Neuzil, Kevin E; Moody, William J

2016-06-01

Spontaneous activity in the developing brain helps refine neuronal connections before the arrival of sensory-driven neuronal activity. In mouse neocortex during the first postnatal week, waves of spontaneous activity originating from pacemaker regions in the septal nucleus and piriform cortex propagate through the neocortex. Using high-speed Ca(2+) imaging to resolve the spatiotemporal dynamics of wave propagation in parasagittal mouse brain slices, we show that the hippocampus can act as an additional source of neocortical waves. Some waves that originate in the hippocampus remain restricted to that structure, while others pause at the hippocampus-neocortex boundary and then propagate into the neocortex. Blocking GABAergic neurotransmission decreases the likelihood of wave propagation into neocortex, whereas blocking glutamatergic neurotransmission eliminates spontaneous and evoked hippocampal waves. A subset of hippocampal and cortical waves trigger Ca(2+) waves in astrocytic networks after a brief delay. Hippocampal waves accompanied by Ca(2+) elevation in astrocytes are more likely to propagate into the neocortex. Finally, we show that two structures in our preparation that initiate waves-the hippocampus and the piriform cortex-can be electrically stimulated to initiate propagating waves at lower thresholds than the neocortex, indicating that the intrinsic circuit properties of those regions are responsible for their pacemaker function. © 2015 Wiley Periodicals, Inc.

An improved method for constructing and selectively silanizing double-barreled, neutral liquid-carrier, ion-selective microelectrodes

PubMed Central

Deveau, Jason S.T.; Grodzinski, Bernard

2005-01-01

We describe an improved, efficient and reliable method for the vapour-phase silanization of multi-barreled, ion-selective microelectrodes of which the silanized barrel(s) are to be filled with neutral liquid ion-exchanger (LIX). The technique employs a metal manifold to exclusively and simultaneously deliver dimethyldichlorosilane to only the ion-selective barrels of several multi-barreled microelectrodes. Compared to previously published methods the technique requires fewer procedural steps, less handling of individual microelectrodes, improved reproducibility of silanization of the selected microelectrode barrels and employs standard borosilicate tubing rather than the less-conventional theta-type glass. The electrodes remain stable for up to 3 weeks after the silanization procedure. The efficacy of a double-barreled electrode containing a proton ionophore in the ion-selective barrel is demonstrated in situ in the leaf apoplasm of pea (Pisum) and sunflower (Helianthus). Individual leaves were penetrated to depth of ~150 μm through the abaxial surface. Microelectrode readings remained stable after multiple impalements without the need for a stabilizing PVC matrix. PMID:16136222

Combining Microdialysis and Electrophysiology in Cerebral Cortex to Delineate Functional Implications of Acetylcholine Gradients

NASA Astrophysics Data System (ADS)

Nelson, Kari L.

The neuronal network in cerebral cortex is a dynamic system that can undergo changes in collective neural activity as the organism changes its behavior. For example, during sleep and quiet restful awake state, many neurons tend to fire together in synchrony. In contrast, during alert awake states, firing patterns of neurons tend to be more asynchronous, firing more independently. These changes in population-level synchrony are defined as changes in cortical state. Response to sensory input is state-dependent, i.e., change in cortical state can impact the sensory information processing in cortex and introduce trial-to-trial variability in response to the same repeated stimuli. How the brain maintains reliable perception in spite of such trial-to-trial variability is a longstanding important question in neuroscience research. This dissertation is centered on two hypotheses. The first hypothesis is that different parts of the cortex can be in different states simultaneously. The second hypothesis is that inhomogeneity in cortical states can benefit the system by enabling the cortical network to maintain reliable sensory detection. If one part of the system is in a state that is not good for detection, then another part of the system could be in a different state that is good for detection, thus compensating and maintaining good detection for the system as a whole. These hypotheses were tested on anesthetized rats and awake mice. In anesthetized rats, cholinergic neuromodulation via microdialysis (muD) probes was used to induce cortical state changes in the somatosensory barrel cortex. Changes in cortical state and response to whisker stimulus was recorded with a microelectrode array (MEA). In awake mice, nucleus basalis was optogenetically stimulated by inserting an optic fiber in basal forebrain and response to visual stimulus was analyzed. The results demonstrated heterogeneity in cortical state across the spatial extent of cortical network. Changes in sensory response followed this heterogeneity and sensory detection was not reliable at the level of single neurons or small regions of cortex. The greater population of neurons, on the other hand, maintained reliable sensory detection, suggesting that heterogeneous state can be functionally beneficial for the cortical network.

Development and matching of binocular orientation preference in mouse V1

PubMed Central

Bhaumik, Basabi; Shah, Nishal P.

2014-01-01

Eye-specific thalamic inputs converge in the primary visual cortex (V1) and form the basis of binocular vision. For normal binocular perceptions, such as depth and stereopsis, binocularly matched orientation preference between the two eyes is required. A critical period of binocular matching of orientation preference in mice during normal development is reported in literature. Using a reaction diffusion model we present the development of RF and orientation selectivity in mouse V1 and investigate the binocular orientation preference matching during the critical period. At the onset of the critical period the preferred orientations of the modeled cells are mostly mismatched in the two eyes and the mismatch decreases and reaches levels reported in juvenile mouse by the end of the critical period. At the end of critical period 39% of cells in binocular zone in our model cortex is orientation selective. In literature around 40% cortical cells are reported as orientation selective in mouse V1. The starting and the closing time for critical period determine the orientation preference alignment between the two eyes and orientation tuning in cortical cells. The absence of near neighbor interaction among cortical cells during the development of thalamo-cortical wiring causes a salt and pepper organization in the orientation preference map in mice. It also results in much lower % of orientation selective cells in mice as compared to ferrets and cats having organized orientation maps with pinwheels. PMID:25104927

Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

PubMed Central

Chang, Chia-Yu; Guo, How-Ran; Tsai, Wan-Chen; Yang, Kai-Lin; Lin, Li-Chuan

2015-01-01

Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression. PMID:26114099

Matrix Metalloproteinase (MMP) 9 Transcription in Mouse Brain Induced by Fear Learning*

PubMed Central

Ganguly, Krishnendu; Rejmak, Emilia; Mikosz, Marta; Nikolaev, Evgeni; Knapska, Ewelina; Kaczmarek, Leszek

2013-01-01

Memory formation requires learning-based molecular and structural changes in neurons, whereas matrix metalloproteinase (MMP) 9 is involved in the synaptic plasticity by cleaving extracellular matrix proteins and, thus, is associated with learning processes in the mammalian brain. Because the mechanisms of MMP-9 transcription in the brain are poorly understood, this study aimed to elucidate regulation of MMP-9 gene expression in the mouse brain after fear learning. We show here that contextual fear conditioning markedly increases MMP-9 transcription, followed by enhanced enzymatic levels in the three major brain structures implicated in fear learning, i.e. the amygdala, hippocampus, and prefrontal cortex. To reveal the role of AP-1 transcription factor in MMP-9 gene expression, we have used reporter gene constructs with specifically mutated AP-1 gene promoter sites. The constructs were introduced into the medial prefrontal cortex of neonatal mouse pups by electroporation, and the regulation of MMP-9 transcription was studied after contextual fear conditioning in the adult animals. Specifically, −42/-50- and −478/-486-bp AP-1 binding motifs of the mouse MMP-9 promoter sequence have been found to play a major role in MMP-9 gene activation. Furthermore, increases in MMP-9 gene promoter binding by the AP-1 transcription factor proteins c-Fos and c-Jun have been demonstrated in all three brain structures under investigation. Hence, our results suggest that AP-1 acts as a positive regulator of MMP-9 transcription in the brain following fear learning. PMID:23720741

Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning.

PubMed

Ganguly, Krishnendu; Rejmak, Emilia; Mikosz, Marta; Nikolaev, Evgeni; Knapska, Ewelina; Kaczmarek, Leszek

2013-07-19

Memory formation requires learning-based molecular and structural changes in neurons, whereas matrix metalloproteinase (MMP) 9 is involved in the synaptic plasticity by cleaving extracellular matrix proteins and, thus, is associated with learning processes in the mammalian brain. Because the mechanisms of MMP-9 transcription in the brain are poorly understood, this study aimed to elucidate regulation of MMP-9 gene expression in the mouse brain after fear learning. We show here that contextual fear conditioning markedly increases MMP-9 transcription, followed by enhanced enzymatic levels in the three major brain structures implicated in fear learning, i.e. the amygdala, hippocampus, and prefrontal cortex. To reveal the role of AP-1 transcription factor in MMP-9 gene expression, we have used reporter gene constructs with specifically mutated AP-1 gene promoter sites. The constructs were introduced into the medial prefrontal cortex of neonatal mouse pups by electroporation, and the regulation of MMP-9 transcription was studied after contextual fear conditioning in the adult animals. Specifically, -42/-50- and -478/-486-bp AP-1 binding motifs of the mouse MMP-9 promoter sequence have been found to play a major role in MMP-9 gene activation. Furthermore, increases in MMP-9 gene promoter binding by the AP-1 transcription factor proteins c-Fos and c-Jun have been demonstrated in all three brain structures under investigation. Hence, our results suggest that AP-1 acts as a positive regulator of MMP-9 transcription in the brain following fear learning.

Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression.

PubMed

Chang, Chia-Yu; Guo, How-Ran; Tsai, Wan-Chen; Yang, Kai-Lin; Lin, Li-Chuan; Cheng, Tain-Junn; Chuu, Jiunn-Jye

2015-01-01

Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

Astringency, bitterness and color changes in dry red wines before and during oak barrel aging: An updated phenolic perspective review.

PubMed

Li, Si-Yu; Duan, Chang-Qing

2018-01-30

To understand effects of using oak barrels on the astringency, bitterness and color of dry red wines, phenolic reactions in wines before and after barrel aging are reviewed in this paper, which has been divided into three sections. The first section includes an introduction to chemical reactivities of grape-derived phenolic compounds, a summary of the phenolic reactions that occur in dry red wines before barrel aging, and a discussion of the effects of these reactions on wine astringency, bitterness and color. The second section introduces barrel types that determine the oak barrel constituents in wines (primarily oak aldehydes and ellagitannins) and presents reactions between the oak constituents and grape-derived phenolic compounds that may modulate wine astringency, bitterness and color. The final section illustrates the chemical differences between basic oxidation and over-oxidation in wines, discusses oxygen consumption kinetics in wines during barrel aging by comparing different oxygen consumption kinetics observed previously by others, and speculates on the possible preliminary phenolic reactions that occur in dry red wines during oak barrel aging that soften tannins and stabilize pigments via basic oxidation. Additionally, sulfur dioxide (SO 2 ) addition during barrel aging and suitability of adopting oak barrels for aging wines are briefly discussed.

Recovery from ketamine-induced amnesia by blockade of GABA-A receptor in the medial prefrontal cortex of mice.

PubMed

Farahmandfar, Maryam; Akbarabadi, Ardeshir; Bakhtazad, Atefeh; Zarrindast, Mohammad-Reza

2017-03-06

Ketamine and other noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists are known to induce deficits in learning and cognitive performance sensitive to prefrontal cortex (PFC) functions. The interaction of a glutamatergic and GABAergic systems is essential for many cognitive behaviors. In order to understand the effect of γ-aminobutyric acid (GABA)/glutamate interactions on learning and memory, we investigated the effects of intra medial prefrontal cortex (mPFC) injections of GABAergic agents on ketamine-induced amnesia using a one-trial passive avoidance task in mice. Pre-training systemic administration of ketamine (5, 10 and 15mg/kg, i.p.) dose-dependently decreased the memory acquisition of a one-trial passive avoidance task. Pre-training intra-mPFC injection of muscimol, GABAA receptor agonist (0.05, 0.1 and 0.2μg/mouse) and baclofen GABAB receptor agonist (0.05, 0.1, 0.5 and 1μg/mouse), impaired memory acquisition. However, co-pretreatment of different doses of muscimol and baclofen with a lower dose of ketamine (5mg/kg), which did not induce amnesia by itself, caused inhibition of memory formation. Our data showed that sole pre-training administration of bicuculline, GABA-A receptor antagonist and phaclofen GABA-B receptor antagonist into the mPFC, did not affect memory acquisition. In addition, the amnesia induced by pre-training ketamine (15mg/kg) was significantly decreased by the pretreatment of bicuculline (0.005, 0.1 and 0.5μg/mouse). It can be concluded that GABAergic system of the mPFC is involved in the ketamine-induced impairment of memory acquisition. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Retinal lesions induce fast intrinsic cortical plasticity in adult mouse visual system.

PubMed

Smolders, Katrien; Vreysen, Samme; Laramée, Marie-Eve; Cuyvers, Annemie; Hu, Tjing-Tjing; Van Brussel, Leen; Eysel, Ulf T; Nys, Julie; Arckens, Lutgarde

2016-09-01

Neuronal activity plays an important role in the development and structural-functional maintenance of the brain as well as in its life-long plastic response to changes in sensory stimulation. We characterized the impact of unilateral 15° laser lesions in the temporal lower visual field of the retina, on visually driven neuronal activity in the afferent visual pathway of adult mice using in situ hybridization for the activity reporter gene zif268. In the first days post-lesion, we detected a discrete zone of reduced zif268 expression in the contralateral hemisphere, spanning the border between the monocular segment of the primary visual cortex (V1) with extrastriate visual area V2M. We could not detect a clear lesion projection zone (LPZ) in areas lateral to V1 whereas medial to V2M, agranular and granular retrosplenial cortex showed decreased zif268 levels over their full extent. All affected areas displayed a return to normal zif268 levels, and this was faster in higher order visual areas than in V1. The lesion did, however, induce a permanent LPZ in the retinorecipient layers of the superior colliculus. We identified a retinotopy-based intrinsic capacity of adult mouse visual cortex to recover from restricted vision loss, with recovery speed reflecting the areal cortical magnification factor. Our observations predict incomplete visual field representations for areas lateral to V1 vs. lack of retinotopic organization for areas medial to V2M. The validation of this mouse model paves the way for future interrogations of cortical region- and cell-type-specific contributions to functional recovery, up to microcircuit level. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Effects of ubiquitin C-terminal hydrolase L1 deficiency on mouse ova.

PubMed

Koyanagi, Sayaka; Hamasaki, Hiroko; Sekiguchi, Satoshi; Hara, Kenshiro; Ishii, Yoshiyuki; Kyuwa, Shigeru; Yoshikawa, Yasuhiro

2012-03-01

Maternal proteins are rapidly degraded by the ubiquitin-proteasome system during oocyte maturation in mice. Ubiquitin C-terminal hydrolase L1 (UCHL1) is highly and specifically expressed in mouse ova and is involved in the polyspermy block. However, the role of UCHL1 in the underlying mechanism of polyspermy block is poorly understood. To address this issue, we performed a comprehensive proteomic analysis to identify maternal proteins that were relevant to the role of UCHL1 in mouse ova using UCHL1-deficient gad. Furthermore, we assessed morphological features in gad mouse ova using transmission electron microscopy. NACHT, LRR, and PYD domain-containing (NALP) family proteins and endoplasmic reticulum (ER) chaperones were identified by proteomic analysis. We also found that the 'maternal antigen that embryos require' (NLRP5 (MATER)) protein level increased significantly in gad mouse ova compared with that in wild-type mice. In an ultrastructural study, gad mouse ova contained less ER in the cortex than in wild-type mice. These results provide new insights into the role of UCHL1 in the mechanism of polyspermy block in mouse ova.

15 CFR 240.1 - Title of act.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE STANDARDS FOR BARRELS BARRELS AND OTHER CONTAINERS FOR LIME... U.S.C. 237-242), entitled “An Act to standardize lime barrels,” shall be known and referred to as the “Standard Lime-Barrel Act.” ...

Reduction of Gun Erosion and Correlation of Gun Erosion Measurements

NASA Technical Reports Server (NTRS)

Bogdanoff, Dave; Wercinski, Paul (Technical Monitor)

1997-01-01

Gun barrel erosion is serious problem with two-stage light gas guns. Excessive barrel erosion can lead to poor or failed launches and frequent barrel changes, with the corresponding down time. Also, excessive barrel erosion can limit the maximum velocity obtainable by loading down the hydrogen working gas with eroded barrel material. Guided by a CFD code, the operating conditions of the Ames 0.5-inch gun were modified to reduce barrel erosion. The changes implemented included: (1) reduction in the piston mass, powder mass and hydrogen fill pressure; and (2) reduction in pump tube volume, while maintaining hydrogen mass. The latter change was found, in particular, to greatly reduce barrel erosion. For muzzle velocity ranges of 6.1 - 6.9 km/sec, the barrel erosion was reduced by a factor of 10. Even for the higher muzzle velocity range of 7.0 - 8.2 km/sec, the barrel erosion was reduced by a factor of 4. Gun erosion data from the Ames 0.5-inch, 1.0-inch, and 1.5-inch guns operated over a wide variety of launch conditions was examined and it was found that this data could be correlated using four different parameters: normalized powder charge energy, normalized hydrogen energy density, normalized pump tube volume and barrel diameter. The development of the correlation and the steps used to collapse the experimental data are presented. Over a certain parameter range in the correlation developed, the barrel erosion per shot is found to increase very rapidly. The correlation should prove useful in the selection of gun operating conditions and the design of new guns. Representative shapes of eroded gun barrels are also presented.

Spatial embedding of structural similarity in the cerebral cortex

PubMed Central

Song, H. Francis; Kennedy, Henry; Wang, Xiao-Jing

2014-01-01

Recent anatomical tracing studies have yielded substantial amounts of data on the areal connectivity underlying distributed processing in cortex, yet the fundamental principles that govern the large-scale organization of cortex remain unknown. Here we show that functional similarity between areas as defined by the pattern of shared inputs or outputs is a key to understanding the areal network of cortex. In particular, we report a systematic relation in the monkey, human, and mouse cortex between the occurrence of connections from one area to another and their similarity distance. This characteristic relation is rooted in the wiring distance dependence of connections in the brain. We introduce a weighted, spatially embedded random network model that robustly gives rise to this structure, as well as many other spatial and topological properties observed in cortex. These include features that were not accounted for in any previous model, such as the wide range of interareal connection weights. Connections in the model emerge from an underlying distribution of spatially embedded axons, thereby integrating the two scales of cortical connectivity—individual axons and interareal pathways—into a common geometric framework. These results provide insights into the origin of large-scale connectivity in cortex and have important implications for theories of cortical organization. PMID:25368200

Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex.

PubMed

Corcoba, Alberto; Gruetter, Rolf; Do, Kim Q; Duarte, João M N

2017-09-01

Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations of N-acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine-to-glutamate (Gln/Glu), and by a reduction in levels of myo-inositol and choline-containing compounds in the frontal cortex of -/- animals with respect to wild-type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower myo-inositol concentration (-8.4%, p < 0.05) and larger Gln/Glu (+7.6%, p < 0.05), relative to those in group housing. Furthermore, glutathione deficiency caused a reduction in whole brain volume and enlargement of ventricles, but social isolation had no effect on these parameters. We conclude that social isolation caused neurochemical alterations that may add to those associated to impaired glutathione synthesis. © 2017 International Society for Neurochemistry.

Connexin31.1 deficiency in the mouse impairs object memory and modulates open-field exploration, acetylcholine esterase levels in the striatum, and cAMP response element-binding protein levels in the striatum and piriform cortex.

PubMed

Dere, E; Zheng-Fischhöfer, Q; Viggiano, D; Gironi Carnevale, U A; Ruocco, L A; Zlomuzica, A; Schnichels, M; Willecke, K; Huston, J P; Sadile, A G

2008-05-02

Neuronal gap junctions in the brain, providing intercellular electrotonic signal transfer, have been implicated in physiological and behavioral correlates of learning and memory. In connexin31.1 (Cx31.1) knockout (KO) mice the coding region of the Cx31.1 gene was replaced by a LacZ reporter gene. We investigated the impact of Cx31.1 deficiency on open-field exploration, the behavioral response to an odor, non-selective attention, learning and memory performance, and the levels of memory-related proteins in the hippocampus, striatum and the piriform cortex. In terms of behavior, the deletion of the Cx31.1 coding DNA in the mouse led to increased exploratory behaviors in a novel environment, and impaired one-trial object recognition at all delays tested. Despite strong Cx31.1 expression in the peripheral and central olfactory system, Cx31.1 KO mice exhibited normal behavioral responses to an odor. We found increased levels of acetylcholine esterase (AChE) and cAMP response element-binding protein (CREB) in the striatum of Cx31.1 KO mice. In the piriform cortex the Cx31.1 KO mice had an increased heterogeneity of CREB expression among neurons. In conclusion, gap-junctions featuring the Cx31.1 protein might be involved in open-field exploration as well as object memory and modulate levels of AChE and CREB in the striatum and piriform cortex.

Stream-related preferences of inputs to the superior colliculus from areas of dorsal and ventral streams of mouse visual cortex.

PubMed

Wang, Quanxin; Burkhalter, Andreas

2013-01-23

Previous studies of intracortical connections in mouse visual cortex have revealed two subnetworks that resemble the dorsal and ventral streams in primates. Although calcium imaging studies have shown that many areas of the ventral stream have high spatial acuity whereas areas of the dorsal stream are highly sensitive for transient visual stimuli, there are some functional inconsistencies that challenge a simple grouping into "what/perception" and "where/action" streams known in primates. The superior colliculus (SC) is a major center for processing of multimodal sensory information and the motor control of orienting the eyes, head, and body. Visual processing is performed in superficial layers, whereas premotor activity is generated in deep layers of the SC. Because the SC is known to receive input from visual cortex, we asked whether the projections from 10 visual areas of the dorsal and ventral streams terminate in differential depth profiles within the SC. We found that inputs from primary visual cortex are by far the strongest. Projections from the ventral stream were substantially weaker, whereas the sparsest input originated from areas of the dorsal stream. Importantly, we found that ventral stream inputs terminated in superficial layers, whereas dorsal stream inputs tended to be patchy and either projected equally to superficial and deep layers or strongly preferred deep layers. The results suggest that the anatomically defined ventral and dorsal streams contain areas that belong to distinct functional systems, specialized for the processing of visual information and visually guided action, respectively.

Coring device with a improved core sleeve and anti-gripping collar with a collective core catcher

DOE Office of Scientific and Technical Information (OSTI.GOV)

Story, A.L.; Filshtinsky, M.

1986-01-28

This patent describes an improved coring apparatus used in combination with a coring bit and drill string. This device consists of: an outer driving structure adapted to be connected at one end to the coring bit for cutting a core in a borehole, and at the other end to the lower end of the drill string in telescoping and co-rotatable manner therewith; an inner barrel disposed within the outer driving structure and including a lower end portion adjacent to the bit; first means supporting the inner barrel in spaced relationship to the outer driving structure while permitting rotation of themore » driving structure with respect to the inner barrel; a woven metal mesh sleeve mounted in surrounding relation on at least a portion of the exterior surface of the inner barrel; second means, connected to a free end of the sleeve opposite the leading portion of the sleeve, for maintaining the portion of the sleeve which surrounds the inner barrel in compression and to maintain an inside diameter greater than the outside diameter of the inner barrel of the portion of the sleeve surrounding the inner barrel while the portion of the sleeve positioned inside the inner barrel being in tension to grip and compress a core received within the sleeve and having an outside diameter less than the inside diameter of the inner barrel when in tension, wherein the second means is also for engaging the core when the means is drawn into the inner barrel, and third means positioned within the inner barrel and connected to the leading portion of the sleeve to draw the sleeve within the inner barrel and to apply tension to the portion of the sleeve within the barrel to encase and grip the core as it is cut.« less

Platelets are responsible for the accumulation of β-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis.

PubMed

Kucheryavykh, Lilia Y; Dávila-Rodríguez, Josué; Rivera-Aponte, David E; Zueva, Lidia V; Washington, A Valance; Sanabria, Priscilla; Inyushin, Mikhail Y

2017-01-01

Platelets contain beta-amyloid precursor protein (APP) as well as Aβ peptide (Aβ) that can be released upon activation. During thrombosis, platelets are concentrated in clots and activated. We used in vivo fluorescent analysis and electron microscopy in mice to determine to what degree platelets are concentrated in clots. We used immunostaining to visualize Aβ after photothrombosis in mouse brains. Both in vivo results and electron microscopy revealed that platelets were 300-500 times more concentrated in clots than in non-clotted blood. After thrombosis in control mice, but not in thrombocytopenic animals, Aβ immunofluorescence was present inside blood vessels in the visual cortex and around capillaries in the entorhinal cortex. The increased concentration of platelets allows enhanced release of Aβ during thrombosis, suggesting an additional source of Aβ in the brains of Alzheimer's patients that may arise if frequent micro-thrombosis events occur in their brains. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

PubMed

Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-11-01

Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular Regulation of DNA Damage-Induced Apoptosis in Neurons of Cerebral Cortex

PubMed Central

Liu, Zhiping; Pipino, Jacqueline; Chestnut, Barry; Landek, Melissa A.

2009-01-01

Cerebral cortical neuron degeneration occurs in brain disorders manifesting throughout life, but the mechanisms are understood poorly. We used cultured embryonic mouse cortical neurons and an in vivo mouse model to study mechanisms of DNA damaged-induced apoptosis in immature and differentiated neurons. p53 drives apoptosis of immature and differentiated cortical neurons through its rapid and prominent activation stimulated by DNA strand breaks induced by topoisomerase-I and -II inhibition. Blocking p53-DNA transactivation with α-pifithrin protects immature neurons; blocking p53-mitochondrial functions with μ-pifithrin protects differentiated neurons. Mitochondrial death proteins are upregulated in apoptotic immature and differentiated neurons and have nonredundant proapoptotic functions; Bak is more dominant than Bax in differentiated neurons. p53 phosphorylation is mediated by ataxia telangiectasia mutated (ATM) kinase. ATM inactivation is antiapoptotic, particularly in differentiated neurons, whereas inhibition of c-Abl protects immature neurons but not differentiated neurons. Cell death protein expression patterns in mouse forebrain are mostly similar to cultured neurons. DNA damage induces prominent p53 activation and apoptosis in cerebral cortex in vivo. Thus, DNA strand breaks in cortical neurons induce rapid p53-mediated apoptosis through actions of upstream ATM and c-Abl kinases and downstream mitochondrial death proteins. This molecular network operates through variations depending on neuron maturity. PMID:18820287

15 CFR 240.2 - Application.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE STANDARDS FOR BARRELS BARRELS AND OTHER CONTAINERS FOR LIME... to lime in barrels, or other containers packed, sold, or offered for sale for shipment from any State...; and to lime in containers of less capacity than the standard small barrel sold in interstate or...

Regulation of embryonic neurotransmitter and tyrosine hydroxylase protein levels by ascorbic acid

PubMed Central

Meredith, M. Elizabeth; May, James M.

2013-01-01

Scope: Ascorbic acid (ascorbate) is required to recycle tetrahydrobiopterin, which is necessary for neurotransmitter synthesis by the rate-limiting enzymes tyrosine and tryptophan hydroxylases. We sought to determine whether ascorbate might regulate embryonic brain cortex monoamine synthesis utilizing transgenic mouse models with varying intracellular ascorbate levels. Methods and Results: In embryos lacking the sodium-dependent vitamin C transporter 2 (SVCT2), very low levels of brain ascorbate decreased cortex levels of norepinephrine and dopamine by approximately 33%, but had no effect on cortex serotonin or its metabolite, 5-hydroxyindole acetic acid. This decrease in ascorbate also led to a decrease in protein levels of tyrosine hydroxylase, but not of tryptophan hydroxylase. Increased cortex ascorbate in embryos carrying extra copies of the SVCT2 resulted in increased levels of dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), as well as serotonin and 5-hydroxyindole acetic acid. Conclusion: The dependence of embryonic brain cortex neurotransmitter synthesis and tyrosine hydroxylase expression on intracellular ascorbate emphasizes the importance of receiving adequate ascorbate during development. PMID:24095796

Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model.

PubMed

Toonen, Lodewijk J A; Overzier, Maurice; Evers, Melvin M; Leon, Leticia G; van der Zeeuw, Sander A J; Mei, Hailiang; Kielbasa, Szymon M; Goeman, Jelle J; Hettne, Kristina M; Magnusson, Olafur Th; Poirel, Marion; Seyer, Alexandre; 't Hoen, Peter A C; van Roon-Mom, Willeke M C

2018-06-22

Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by expansion of the polyglutamine repeat in the ataxin-3 protein. Expression of mutant ataxin-3 is known to result in transcriptional dysregulation, which can contribute to the cellular toxicity and neurodegeneration. Since the exact causative mechanisms underlying this process have not been fully elucidated, gene expression analyses in brains of transgenic SCA3 mouse models may provide useful insights. Here we characterised the MJD84.2 SCA3 mouse model expressing the mutant human ataxin-3 gene using a multi-omics approach on brain and blood. Gene expression changes in brainstem, cerebellum, striatum and cortex were used to study pathological changes in brain, while blood gene expression and metabolites/lipids levels were examined as potential biomarkers for disease. Despite normal motor performance at 17.5 months of age, transcriptional changes in brain tissue of the SCA3 mice were observed. Most transcriptional changes occurred in brainstem and striatum, whilst cerebellum and cortex were only modestly affected. The most significantly altered genes in SCA3 mouse brain were Tmc3, Zfp488, Car2, and Chdh. Based on the transcriptional changes, α-adrenergic and CREB pathways were most consistently altered for combined analysis of the four brain regions. When examining individual brain regions, axon guidance and synaptic transmission pathways were most strongly altered in striatum, whilst brainstem presented with strongest alterations in the pi-3 k cascade and cholesterol biosynthesis pathways. Similar to other neurodegenerative diseases, reduced levels of tryptophan and increased levels of ceramides, di- and triglycerides were observed in SCA3 mouse blood. The observed transcriptional changes in SCA3 mouse brain reveal parallels with previous reported neuropathology in patients, but also shows brain region specific effects as well as involvement of adrenergic signalling and CREB pathway changes in SCA3. Importantly, the transcriptional changes occur prior to onset of motor- and coordination deficits.

Locomotion Enhances Neural Encoding of Visual Stimuli in Mouse V1

PubMed Central

2017-01-01

Neurons in mouse primary visual cortex (V1) are selective for particular properties of visual stimuli. Locomotion causes a change in cortical state that leaves their selectivity unchanged but strengthens their responses. Both locomotion and the change in cortical state are thought to be initiated by projections from the mesencephalic locomotor region, the latter through a disinhibitory circuit in V1. By recording simultaneously from a large number of single neurons in alert mice viewing moving gratings, we investigated the relationship between locomotion and the information contained within the neural population. We found that locomotion improved encoding of visual stimuli in V1 by two mechanisms. First, locomotion-induced increases in firing rates enhanced the mutual information between visual stimuli and single neuron responses over a fixed window of time. Second, stimulus discriminability was improved, even for fixed population firing rates, because of a decrease in noise correlations across the population. These two mechanisms contributed differently to improvements in discriminability across cortical layers, with changes in firing rates most important in the upper layers and changes in noise correlations most important in layer V. Together, these changes resulted in a threefold to fivefold reduction in the time needed to precisely encode grating direction and orientation. These results support the hypothesis that cortical state shifts during locomotion to accommodate an increased load on the visual system when mice are moving. SIGNIFICANCE STATEMENT This paper contains three novel findings about the representation of information in neurons within the primary visual cortex of the mouse. First, we show that locomotion reduces by at least a factor of 3 the time needed for information to accumulate in the visual cortex that allows the distinction of different visual stimuli. Second, we show that the effect of locomotion is to increase information in cells of all layers of the visual cortex. Third, we show that the means by which information is enhanced by locomotion differs between the upper layers, where the major effect is the increasing of firing rates, and in layer V, where the major effect is the reduction in noise correlations. PMID:28264980

Experience-dependent development of perineuronal nets and chondroitin sulfate proteoglycan receptors in mouse visual cortex.

PubMed

Ye, Qian; Miao, Qing-Long

2013-08-08

Perineuronal nets (PNNs) are extracellular matrix structures consisting of chondroitin sulfate proteoglycans (CSPGs), hyaluronan, link proteins and tenascin-R (Tn-R). They enwrap a subset of GABAergic inhibitory interneurons in the cerebral cortex and restrict experience-dependent cortical plasticity. While the expression profile of PNN components has been widely studied in many areas of the central nervous system of various animal species, it remains unclear how these components are expressed during the postnatal development of mouse primary visual cortex (V1). In the present study, we characterized the developmental time course of the formation of PNNs in the mouse primary visual cortex, using the specific antibodies against the two PNN component proteins aggrecan and tenascin-R, or the lectin Wisteria floribunda agglutinin (WFA) that directly binds to glycosaminoglycan chains of chondroitin sulfate proteoglycans (CSPGs). We found that the fluorescence staining signals of both the WFA staining and the antibody against aggrecan rapidly increased in cortical neurons across layers 2-6 during postnatal days (PD) 10-28 and reached a plateau around PD42, suggesting a full construction of PNNs by the end of the critical period. Co-staining with antibodies to Ca(2+) binding protein parvalbumin (PV) demonstrated that the majority of PNN-surrounding cortical neurons are immunoreactive to PV. Similar expression profile of another PNN component tenascin-R was observed in the development of V1. Dark rearing of mice from birth significantly reduced the density of PNN-surrounding neurons. In addition, the expression of two recently identified CSPG receptors - Nogo receptor (NgR) and leukocyte common antigen-related phosphatase (LAR), showed significant increases from PD14 to PD70 in layer 2-6 of cortical PV-positive interneurons in normal reared mice, but decreased significantly in dark-reared ones. Taken together, these results suggest that PNNs form preferentially in cortical PV-positive interneurons in an experience-dependent manner, and reach full maturation around the end of the critical period of V1 development. © Elsevier B.V. All rights reserved.

Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome.

PubMed

Nomura, Toshihiro; Musial, Timothy F; Marshall, John J; Zhu, Yiwen; Remmers, Christine L; Xu, Jian; Nicholson, Daniel A; Contractor, Anis

2017-11-22

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS ( Fmr1 KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS. SIGNIFICANCE STATEMENT Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS ( Fmr1 KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin signaling during early development in FXS. Copyright © 2017 the authors 0270-6474/17/3711298-13$15.00/0.

Analysis of multiplex gene expression maps obtained by voxelation.

PubMed

An, Li; Xie, Hongbo; Chin, Mark H; Obradovic, Zoran; Smith, Desmond J; Megalooikonomou, Vasileios

2009-04-29

Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological disease. Researchers have previously used voxelation in combination with microarrays for acquisition of genome-wide atlases of expression patterns in the mouse brain. On the other hand, some work has been performed on studying gene functions, without taking into account the location information of a gene's expression in a mouse brain. In this paper, we present an approach for identifying the relation between gene expression maps obtained by voxelation and gene functions. To analyze the dataset, we chose typical genes as queries and aimed at discovering similar gene groups. Gene similarity was determined by using the wavelet features extracted from the left and right hemispheres averaged gene expression maps, and by the Euclidean distance between each pair of feature vectors. We also performed a multiple clustering approach on the gene expression maps, combined with hierarchical clustering. Among each group of similar genes and clusters, the gene function similarity was measured by calculating the average gene function distances in the gene ontology structure. By applying our methodology to find similar genes to certain target genes we were able to improve our understanding of gene expression patterns and gene functions. By applying the clustering analysis method, we obtained significant clusters, which have both very similar gene expression maps and very similar gene functions respectively to their corresponding gene ontologies. The cellular component ontology resulted in prominent clusters expressed in cortex and corpus callosum. The molecular function ontology gave prominent clusters in cortex, corpus callosum and hypothalamus. The biological process ontology resulted in clusters in cortex, hypothalamus and choroid plexus. Clusters from all three ontologies combined were most prominently expressed in cortex and corpus callosum. The experimental results confirm the hypothesis that genes with similar gene expression maps might have similar gene functions. The voxelation data takes into account the location information of gene expression level in mouse brain, which is novel in related research. The proposed approach can potentially be used to predict gene functions and provide helpful suggestions to biologists.

Whisker row deprivation affects the flow of sensory information through rat barrel cortex.

PubMed

Jacob, Vincent; Mitani, Akinori; Toyoizumi, Taro; Fox, Kevin

2017-01-01

Whisker trimming causes substantial reorganization of neuronal response properties in barrel cortex. However, little is known about experience-dependent rerouting of sensory processing following sensory deprivation. To address this, we performed in vivo intracellular recordings from layers 2/3 (L2/3), layer 4 (L4), layer 5 regular-spiking (L5RS), and L5 intrinsically bursting (L5IB) neurons and measured their multiwhisker receptive field at the level of spiking activity, membrane potential, and synaptic conductance before and after sensory deprivation. We used Chernoff information to quantify the "sensory information" contained in the firing patterns of cells in response to spared and deprived whisker stimulation. In the control condition, information for flanking-row and same-row whiskers decreased in the order L4, L2/3, L5IB, L5RS. However, after whisker-row deprivation, spared flanking-row whisker information was reordered to L4, L5RS, L5IB, L2/3. Sensory information from the trimmed whiskers was reduced and delayed in L2/3 and L5IB neurons, whereas sensory information from spared whiskers was increased and advanced in L4 and L5RS neurons. Sensory information from spared whiskers was increased in L5IB neurons without a latency change. L5RS cells exhibited the largest changes in sensory information content through an atypical plasticity combining a significant decrease in spontaneous activity and an increase in a short-latency excitatory conductance. Sensory cortical plasticity is usually quantified by changes in evoked firing rate. In this study we quantified plasticity by changes in sensory detection performance using Chernoff information and receiver operating characteristic analysis. We found that whisker deprivation causes a change in information flow within the cortical layers and that layer 5 regular-spiking cells, despite showing only a small potentiation of short-latency input, show the greatest increase in information content for the spared input partly by decreasing their spontaneous activity. Copyright © 2017 the American Physiological Society.

Explosively driven hypervelocity launcher: Second-stage augmentation techniques

NASA Technical Reports Server (NTRS)

Baum, D. W.

1973-01-01

The results are described of a continuing study aimed at developing a two-stage explosively driven hypervelocity launcher capable of achieving projectile velocities between 15 and 20 km/sec. The testing and evaluation of a new cylindrical impact technique for collapsing the barrel of two-stage launcher are reported. Previous two-stage launchers have been limited in ultimate performance by incomplete barrel collapse behind the projectile. The cylindrical impact technique explosively collapses a steel tube concentric with and surrounding the barrel of the launcher. The impact of the tube on the barrel produces extremely high stresses which cause the barrel to collapse. The collapse rate can be adjusted by appropriate variation of the explosive charge and tubing parameters. Launcher experiments demonstrated that the technique did achieve complete barrel collapse and form a second-stage piston. However, jetting occurred in the barrel collapse process and was responsible for severe projectile damage.

Barrel maturation, oak alternatives and micro-oxygenation: influence on red wine aging and quality.

PubMed

Oberholster, A; Elmendorf, B L; Lerno, L A; King, E S; Heymann, H; Brenneman, C E; Boulton, R B

2015-04-15

The impact of micro-oxygenation (MOX) in conjunction with a variety of oak alternatives on phenolic composition and red wine aging was investigated and compared with traditional barrel aging. Although several studies concluded that MOX give similar results to barrel aging, few have compared them directly and none directly compared MOX with and without wood alternatives and barrel aging. Results confirmed that MOX had a positive effect on colour density, even after 5 months of bottle aging. This is supported by an increase in polymeric phenol and pigment content not only with aging but in the MOX compared to barrel matured wine treatments. Descriptive analysis showed that MOX in combination with wood alternatives such as oak chips and staves could mimic short term (six months) barrel aging in new American and French oak barrels in regards to sensory characteristics. Published by Elsevier Ltd.

Development of explosively driven launcher for meteoroid studies

NASA Technical Reports Server (NTRS)

Baum, D. W.

1973-01-01

The results of a continuing program to develop an explosively driven 2-stage hypervelocity launcher capable of achieving velocities between 15 and 20 km/sec are described. Previous efforts had identified incomplete barrel collapse as a limiting factor in launcher performance. Correlation of experimental and computational results obtained in the present study indicate that boundary-layer gases within the barrel act to prevent complete closure. Simplified calculations suggest that in-contact explosives may have insufficient energy densities to collapse the barrel against a developed boundary layer. Higher energy densities, sufficient to produce complete closure, were obtained with the use of steel flyer plates accelerated by a phased explosive lens. However, when flat flyer plates were impacted on the barrel, the sides of the barrel were observed to rupture and leak gas prior to barrel closure. A promising solution to this problem (untested) is to produce a symmetrical collapse with a cylindrical tube around the barrel.

15 CFR 240.4 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE STANDARDS FOR BARRELS BARRELS AND OTHER CONTAINERS FOR LIME... container not in barrel form containing therein a net weight of lime of less than 180 pounds. (b) The term... matter upon the surface of a barrel or other container of lime subject to the provisions of this act, or...

Tapered laser rods as a means of minimizing the path length of trapped barrel mode rays

DOEpatents

Beach, Raymond J.; Honea, Eric C.; Payne, Stephen A.; Mercer, Ian; Perry, Michael D.

2005-08-30

By tapering the diameter of a flanged barrel laser rod over its length, the maximum trapped path length of a barrel mode can be dramatically reduced, thereby reducing the ability of the trapped spontaneous emission to negatively impact laser performance through amplified spontaneous emission (ASE). Laser rods with polished barrels and flanged end caps have found increasing application in diode array end-pumped laser systems. The polished barrel of the rod serves to confine diode array pump light within the rod. In systems utilizing an end-pumping geometry and such polished barrel laser rods, the pump light that is introduced into one or both ends of the laser rod, is ducted down the length of the rod via the total internal reflections (TIRs) that occur when the light strikes the rod's barrel. A disadvantage of using polished barrel laser rods is that such rods are very susceptible to barrel mode paths that can trap spontaneous emission over long path lengths. This trapped spontaneous emission can then be amplified through stimulated emission resulting in a situation where the stored energy available to the desired lasing mode is effectively depleted, which then negatively impacts the laser's performance, a result that is effectively reduced by introducing a taper onto the laser rod.

Paroxetine and Low-dose Risperidone Induce Serotonin 5-HT1A and Dopamine D2 Receptor Heteromerization in the Mouse Prefrontal Cortex.

PubMed

Kolasa, Magdalena; Solich, Joanna; Faron-Górecka, Agata; Żurawek, Dariusz; Pabian, Paulina; Łukasiewicz, Sylwia; Kuśmider, Maciej; Szafran-Pilch, Kinga; Szlachta, Marta; Dziedzicka-Wasylewska, Marta

2018-05-01

Recently, it has been shown that serotonin 5-HT 1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT 1A -D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT 1A -D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.05 mg/kg). Receptor heteromerization was visualized and quantified in the mouse brain by in situ proximity ligation assay (PLA). Additionally, we aimed to determine the cellular localization of 5-HT 1A -D2 receptor heteromers in mouse adult primary neuronal cells by immunofluorescent staining with markers for astrocytes (GFAP) and neurons (NeuN and MAP2). The results from the current study demonstrated that 5-HT 1A and D2 receptor co-localization and heteromerization occurred in the mouse prefrontal cortex. Counterstaining after PLA confirmed neuronal (pyramidal and GABAergic) as well as astrocytal localization of 5-HT 1A -D2 receptor heteromers. Chronic administration of paroxetine or risperidone increased the level of 5-HT 1A -D2 receptor heteromers in the prefrontal cortex. These changes were not accompanied by any changes in the expression of mRNAs (measured by in situ hybridization) or densities of 5-HT 1A and D2 receptors (quantified by receptor autoradiography with [3H]8-OH-DPAT and [3H]domperidone, respectively), what all indicated that paroxetine and risperidone facilitated 5-HT 1A -D2 heteromer formation independently of the receptor expression. In vitro homogenous time-resolved FRET (HTRF) study confirmed the ability of tested drugs to influence the human 5-HT 1A -D2 heteromer formation. The obtained data indicate that the increase in 5-HT 1A -D2 receptor heteromerization is a common molecular characteristic of paroxetine and low-dose risperidone treatment. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse

PubMed Central

Radulovic, Jelena

2016-01-01

Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections onto M2 pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2–6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control. SIGNIFICANCE STATEMENT Corticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we show that a posterior part of secondary motor cortex receives corticocortical axons from the rostral retrosplenial cortex (RSC) and these form monosynaptic excitatory connections onto a wide spectrum of excitatory projection neurons in this area. Our results define a cellular basis for direct communication from RSC to this medial frontal area, suggesting a direct link from dorsal hippocampal networks involved in spatial cognition and navigation (the “map”) to sensorimotor networks involved the control of movement (the “motor”). PMID:27605612

Modulation of 3H-noradrenaline release by presynaptic opioid, cannabinoid and bradykinin receptors and β-adrenoceptors in mouse tissues

PubMed Central

Trendelenburg, A U; Cox, S L; Schelb, V; Klebroff, W; Khairallah, L; Starke, K

2000-01-01

Release-modulating opioid and cannabinoid (CB) receptors, β-adrenoceptors and bradykinin receptors at noradrenergic axons were studied in mouse tissues (occipito-parietal cortex, heart atria, vas deferens and spleen) preincubated with 3H-noradrenaline. Experiments using the OP1 receptor-selective agonists DPDPE and DSLET, the OP2-selective agonists U50488H and U69593, the OP3-selective agonist DAMGO, the ORL1 receptor-selective agonist nociceptin, and a number of selective antagonists showed that the noradrenergic axons innervating the occipito-parietal cortex possess release-inhibiting OP3 and ORL1 receptors, those innervating atria OP1, ORL1 and possibly OP3 receptors, and those innervating the vas deferens all four opioid receptor types. Experiments using the non-selective CB agonists WIN 55,212-2 and CP 55,940 and the CB1-selective antagonist SR 141716A indicated that the noradrenergic axons of the vas deferens possess release-inhibiting CB1 receptors. Presynaptic CB receptors were not found in the occipito-parietal cortex, in atria or in the spleen. Experiments using the non-selective β-adrenoceptor agonist isoprenaline and the β2-selective agonist salbutamol, as well as subtype-selective antagonists, demonstrated the occurrence of release-enhancing β2-adrenoceptors at the sympathetic axons of atria and the spleen, but demonstrated their absence in the occipito-parietal cortex and the vas deferens. Experiments with bradykinin and the B2-selective antagonist Hoe 140 showed the operation of release-enhancing B2 receptors at the sympathetic axons of atria, the vas deferens and the spleen, but showed their absence in the occipito-parietal cortex. The experiments document a number of new presynaptic receptor locations. They confirm and extend the existence of marked tissue and species differences in presynaptic receptors at noradrenergic neurons. PMID:10807669

A mouse model of pre-pregnancy maternal obesity combined with offspring exposure to a high-fat diet resulted in cognitive impairment in male offspring.

PubMed

Zhu, Chen; Han, Ting-Li; Zhao, Yalan; Zhou, Xiaobo; Mao, Xun; Qi, Hongbo; Baker, Philip N; Zhang, Hua

2018-04-23

Cognitive impairment is a brain dysfunction characterized by neuropsychological deficits in attention, working memory, and executive function. Maternal obesity and consumption of a high-fat diet (HFD) in the offspring has been suggested to have detrimental consequences for offspring cognitive function through its effect on the hippocampus and prefrontal cortex. Therefore, our study aimed to investigate the effects of maternal obesity and offspring HFD exposure on the brain metabolome of the offspring. In our pilot study, a LepRdb/+ mouse model was used to model pre-pregnancy maternal obesity and the c57bl/6 wildtype was used as a control group. Offspring were fed either a HFD or a low-fat control diet (LFD) after weaning (between 8 and 10 weeks). The Mirrors water maze was performed between 28 and 30 weeks to measure cognitive function. Fatty acid metabolomic profiles of the prefrontal cortex and hippocampus from the offspring at 30-32 weeks were analyzed using gas chromatography-mass spectrometry. The memory of male offspring from obese maternal mice, consuming a HFD post-weaning, was significantly impaired when compared to the control offspring mice. No significant differences were observed in female offspring. In male mice, the fatty acid metabolites in the prefrontal cortex were most affected by maternal obesity, whereas, the fatty acid metabolites in the hippocampus were most affected by the offspring's diet. Hexadecanoic acid and octadecanoic acid were significantly affected in both the hippocampus and pre-frontal cortex, as a result of maternal obesity and a HFD in the offspring. Our findings suggest that the combination of maternal obesity and HFD in the offspring can result in spatial cognitive deficiency in the male offspring, by influencing the fatty acid metabolite profiles in the prefrontal cortex and hippocampus. Further research is needed to validate the results of our pilot study. Copyright © 2018 Elsevier Inc. All rights reserved.

Barrels XXX meeting report: Barrels in Baltimore.

PubMed

Shin, Hyeyoung; Bitzidou, Malamati; Palaguachi, Fernando; Brumberg, Joshua C

2018-03-01

The Barrels meeting annually brings together researchers focused on the rodent whisker to cortical barrel system prior to the Society for Neuroscience meeting. The 2017 meeting focused on the classification of cortical interneurons, the role interneurons have in shaping brain dynamics, and finally on the circuitry underlying oral sensations. The meeting highlighted the latest advancements in this rapidly advancing field.

A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor.

PubMed

Bernard, Clémence; Vincent, Clémentine; Testa, Damien; Bertini, Eva; Ribot, Jérôme; Di Nardo, Ariel A; Volovitch, Michel; Prochiantz, Alain

2016-05-01

During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment. In the visual cortex, critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor, which regulates the maturation of parvalbumin-expressing inhibitory interneurons (PV cells). In adult mice, the maintenance of a non-plastic adult state requires continuous Otx2 import by PV cells. An important source of extra-cortical Otx2 is the choroid plexus, which secretes Otx2 into the cerebrospinal fluid. Otx2 secretion and internalization requires two small peptidic domains that are part of the DNA-binding domain. Thus, mutating these "transfer" sequences also modifies cell autonomous transcription, precluding this approach to obtain a cell autonomous-only mouse. Here, we develop a mouse model with inducible secretion of an anti-Otx2 single-chain antibody to trap Otx2 in the extracellular milieu. Postnatal secretion of this single-chain antibody by PV cells delays PV maturation and reduces plasticity gene expression. Induced adult expression of this single-chain antibody in cerebrospinal fluid decreases Otx2 internalization by PV cells, strongly induces plasticity gene expression and reopens physiological plasticity. We provide the first mammalian genetic evidence for a signaling mechanism involving intercellular transfer of a homeoprotein transcription factor. Our single-chain antibody mouse model is a valid strategy for extracellular neutralization that could be applied to other homeoproteins and signaling molecules within and beyond the nervous system.

A different regional response by mouse oligodendrocyte progenitor cells (OPCs) to high-dose X-irradiation has consequences for repopulating OPC-depleted normal tissue.

PubMed

Irvine, Karen-Amanda; Blakemore, William F

2007-01-01

This study was designed to investigate whether the residual, dysfunctional oligodendrocyte progenitor cells (OPCs) observed following X-irradiation of the mouse spinal cord [D. M. Chari et al. (2003) Exp. Neurol., 198, 145-153], the presence of which prevented the endogenous repopulation of these areas from normal tissue, reflects a general response of OPCs in the mouse central nervous system (CNS) to X-irradiation. The brains of adult mice were exposed to 40 Gy of X-irradiation and the effect of X-irradiation on the OPCs was assessed up to 4 weeks post-irradiation using anti-NG2 antibodies. X-irradiation resulted in almost complete depletion of OPCs within the telencephalon (cortex, corpus callosum and hippocampus) by 7 days post-irradiation, which was followed by progressive repopulation of OPCs from non-irradiated areas of the cortex. By contrast, within the lower brain centres (the diencephalon and mesencephalon) OPC loss occurred much more slowly so that 26% of the OPCs still remained 4 weeks after X-irradiation. The consequence of this heterogeneous response to X-irradiation was that whereas transplanted and endogenous OPCs rapidly established themselves in the OPC-depleted telencephalon this did not occur in the areas where there was incomplete depletion of endogenous OPCs. Our findings confirm not only the requirement for almost complete OPC depletion in order to establish transplanted OPCs in normal tissue but also highlight a heterogeneity of progenitor populations in different areas of the mouse CNS.

Treatment of hypoxic-ischemic encephalopathy in mouse by transplantation of embryonic stem cell-derived cells.

PubMed

Ma, Jie; Wang, Yu; Yang, Jianhua; Yang, Min; Chang, Keun-A; Zhang, Linhua; Jiang, Feng; Li, Yi; Zhang, Zhonggong; Heo, Chaejeong; Suh, Yoo-Hun

2007-07-01

A 7-day-old hypoxic-ischemic encephalopathy (HIE) mouse model was used to study the effect of transplantation of embryonic stem (ES) cell-derived cells on the HIE. After the inducement in vitro, the ES cell-derived cells expressed Nestin and MAP-2, rather than GFAP mRNA. After transplantation, ES cell-derived cells can survive, migrate into the injury site, and specifically differentiate into neurons, showing improvement of the learning ability and memory of the HIE mouse at 8 months post-transplantation. The non-grafted HIE mouse brain showed typical pathological changes in the hippocampus and cerebral cortex, where the number of neurons was reduced, while in the cell graft group, number of the neurons increased in the same regions. Although further study is necessary to elucidate the precise mechanisms responsible for this functional recovery, we believe that ES cells have advantages for use as a donor source in HIE.

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

PubMed

Bárez-López, Soledad; Obregon, Maria Jesus; Bernal, Juan; Guadaño-Ferraz, Ana

2018-05-01

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.

Reduced expression of conditioned fear in the R6/2 mouse model of Huntington’s disease is related to abnormal activity in prelimbic cortex

PubMed Central

Walker, Adam G.; Ummel, Jason R.; Rebec, George V.

2011-01-01

Prefrontal cortex (PFC) dysfunction is common in patients with Huntington’s disease (HD), a dominantly inherited neurological disorder, and has been linked to cognitive disruption. We previously reported alterations in neuronal firing patterns recorded from PFC of the R6/2 mouse model of HD. To determine if PFC dysfunction results in behavioral impairments, we evaluated performance of wild-type (WT) and R6/2 mice in a fear conditioning and extinction behavioral task. Fear conditioning and extinction retrieval were similar in both genotypes, but R6/2s exhibited less fear during extinction by freezing less than WTs. A fear reinstatement test after extinction retrieval indicated that faster extinction was not due to poor memory for conditioning. During initial extinction and extinction retrieval training, neuronal activity was recorded from prelimbic (PL) cortex, a subregion of PFC known to be important for fear expression. In WTs, a large number of neurons were activated by the conditioned stimulus during initial extinction and this activation was significantly impaired in R6/2s. Notably, there was no genotype difference in PFC activity during extinction retrieval. Thus, altered extinction is likely a result of reduced fear expression due to impairments in PL activation. Collectively, our results suggest that PFC dysfunction may play a key role in R6/2 cognitive impairments. PMID:21515374

LIS1 controls mitosis and mitotic spindle organization via the LIS1–NDEL1–dynein complex

PubMed Central

Moon, Hyang Mi; Youn, Yong Ha; Pemble, Hayley; Yingling, Jessica; Wittmann, Torsten; Wynshaw-Boris, Anthony

2014-01-01

Heterozygous LIS1 mutations are responsible for the human neuronal migration disorder lissencephaly. Mitotic functions of LIS1 have been suggested from many organisms throughout evolution. However, the cellular functions of LIS1 at distinct intracellular compartments such as the centrosome and the cell cortex have not been well defined especially during mitotic cell division. Here, we used detailed cellular approaches and time-lapse live cell imaging of mitosis from Lis1 mutant mouse embryonic fibroblasts to reveal critical roles of LIS1 in mitotic spindle regulation. We found that LIS1 is required for the tight control of chromosome congression and segregation to dictate kinetochore–microtubule (MT) interactions and anaphase progression. In addition, LIS1 is essential for the establishment of mitotic spindle pole integrity by maintaining normal centrosome number. Moreover, LIS1 plays crucial roles in mitotic spindle orientation by increasing the density of astral MT plus-end movements toward the cell cortex, which enhances cortical targeting of LIS1–dynein complex. Overexpression of NDEL1–dynein and MT stabilization rescues spindle orientation defects in Lis1 mutants, demonstrating that mouse LIS1 acts via the LIS1–NDEL1–dynein complex to regulate astral MT plus-ends dynamics and establish proper contacts of MTs with the cell cortex to ensure precise cell division. PMID:24030547

Differential Receptive Field Properties of Parvalbumin and Somatostatin Inhibitory Neurons in Mouse Auditory Cortex.

PubMed

Li, Ling-Yun; Xiong, Xiaorui R; Ibrahim, Leena A; Yuan, Wei; Tao, Huizhong W; Zhang, Li I

2015-07-01

Cortical inhibitory circuits play important roles in shaping sensory processing. In auditory cortex, however, functional properties of genetically identified inhibitory neurons are poorly characterized. By two-photon imaging-guided recordings, we specifically targeted 2 major types of cortical inhibitory neuron, parvalbumin (PV) and somatostatin (SOM) expressing neurons, in superficial layers of mouse auditory cortex. We found that PV cells exhibited broader tonal receptive fields with lower intensity thresholds and stronger tone-evoked spike responses compared with SOM neurons. The latter exhibited similar frequency selectivity as excitatory neurons. The broader/weaker frequency tuning of PV neurons was attributed to a broader range of synaptic inputs and stronger subthreshold responses elicited, which resulted in a higher efficiency in the conversion of input to output. In addition, onsets of both the input and spike responses of SOM neurons were significantly delayed compared with PV and excitatory cells. Our results suggest that PV and SOM neurons engage in auditory cortical circuits in different manners: while PV neurons may provide broadly tuned feedforward inhibition for a rapid control of ascending inputs to excitatory neurons, the delayed and more selective inhibition from SOM neurons may provide a specific modulation of feedback inputs on their distal dendrites. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Optogenetic noise-photostimulation on the brain increases somatosensory spike firing responses.

PubMed

Huidobro, Nayeli; De la Torre-Valdovinos, Braniff; Mendez, Abraham; Treviño, Mario; Arias-Carrion, Oscar; Chavez, Fermin; Gutierrez, Ranier; Manjarrez, Elias

2018-01-18

We examined whether the optogenetic noise-photostimulation (ONP) of the barrel cortex (BC) of anesthetized Thy1-ChR2-YFP transgenic mice increases the neuronal multiunit-activity response evoked by whisker mechanical stimulation (whisker-evoked MUA). In all transgenic mice, we found that the signal-to-noise ratio (SNR) of such whisker-evoked MUA signals exhibited an inverted U-like shape as a function of the ONP level. Numerical simulations of a ChR2-expressing neuron model qualitatively support our experimental data. These results show that the application of an intermediate intensity of ONP in the brain can increase cortical somatosensory spike responses to whisker protraction. These findings suggest that ONP of the mice-BC could produce improvements in somatosensory perception to whisker stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Subcortical barrelette-like and barreloid-like structures in the prosimian galago (Otolemur garnetti)

PubMed Central

Sawyer, Eva Kille; Liao, Chia-Chi; Qi, Hui-Xin; Balaram, Pooja; Matrov, Denis; Kaas, Jon H.

2015-01-01

Galagos are prosimian primates that resemble ancestral primates more than most other extant primates. As in many other mammals, the facial vibrissae of galagos are distributed across the upper and lower jaws and above the eye. In rats and mice, the mystacial macrovibrissae are represented throughout the ascending trigeminal pathways as arrays of cytoarchitecturally distinct modules, with each module having a nearly one-to-one relationship with a specific facial whisker. The macrovibrissal representations are termed barrelettes in the trigeminal somatosensory brainstem, barreloids in the ventroposterior medial subnucleus of the thalamus, and barrels in primary somatosensory cortex. Despite the presence of facial whiskers in all nonhuman primates, barrel-like structures have not been reported in primates. By staining for cytochrome oxidase, Nissl, and vesicular glutamate transporter proteins, we show a distinct array of barrelette-like and barreloid-like modules in the principal sensory nucleus, the spinal trigeminal nucleus, and the ventroposterior medial subnucleus of the galago, Otolemur garnetti. Labeled terminals of primary sensory neurons in the brainstem and cell bodies of thalamocortically projecting neurons demonstrate that barrelette-like and barreloid-like modules are located in areas of these somatosensory nuclei that are topographically consistent with their role in facial touch. Serendipitously, the plane of section that best displays the barreloid-like modules reveals a remarkably distinct homunculus-like patterning which, we believe, is one of the clearest somatotopic maps of an entire body surface yet found. PMID:26038561

A periodic network of neurochemical modules in the inferior colliculus.

PubMed

Chernock, Michelle L; Larue, David T; Winer, Jeffery A

2004-02-01

A new organization has been found in shell nuclei of rat inferior colliculus. Chemically specific modules with a periodic distribution fill about half of layer 2 of external cortex and dorsal cortex. Modules contain clusters of small glutamic acid decarboxylase-positive neurons and large boutons at higher density than in other inferior colliculus subdivisions. The modules are also present in tissue stained for parvalbumin, cytochrome oxidase, nicotinamide adenine dinucleotide phosphate-diaphorase, and acetylcholinesterase. Six to seven bilaterally symmetrical modules extend from the caudal extremity of the external cortex of the inferior colliculus to its rostral pole. Modules are from approximately 800 to 2200 microm long and have areas between 5000 and 40,000 microm2. Modules alternate with immunonegative regions. Similar modules are found in inbred and outbred strains of rat, and in both males and females. They are absent in mouse, squirrel, cat, bat, macaque monkey, and barn owl. Modules are immunonegative for glycine, calbindin, serotonin, and choline acetyltransferase. The auditory cortex and ipsi- and contralateral inferior colliculi project to the external cortex. Somatic sensory influences from the dorsal column nuclei and spinal trigeminal nucleus are the primary ascending sensory input to the external cortex; ascending auditory input to layer 2 is sparse. If the immunopositive modular neurons receive this input, the external cortex could participate in spatial orientation and somatic motor control through its intrinsic and extrinsic projections.

Descending projections from the dysgranular zone of rat primary somatosensory cortex processing deep somatic input.

PubMed

Lee, Taehee; Kim, Uhnoh

2012-04-01

In the mammalian somatic system, peripheral inputs from cutaneous and deep receptors ascend via different subcortical channels and terminate in largely separate regions of the primary somatosensory cortex (SI). How these inputs are processed in SI and then projected back to the subcortical relay centers is critical for understanding how SI may regulate somatic information processing in the subcortex. Although it is now relatively well understood how SI cutaneous areas project to the subcortical structures, little is known about the descending projections from SI areas processing deep somatic input. We examined this issue by using the rodent somatic system as a model. In rat SI, deep somatic input is processed mainly in the dysgranular zone (DSZ) enclosed by the cutaneous barrel subfields. By using biotinylated dextran amine (BDA) as anterograde tracer, we characterized the topography of corticostriatal and corticofugal projections arising in the DSZ. The DSZ projections terminate mainly in the lateral subregions of the striatum that are also known as the target of certain SI cutaneous areas. This suggests that SI processing of deep and cutaneous information may be integrated, to a certain degree, in this striatal region. By contrast, at both thalamic and prethalamic levels as far as the spinal cord, descending projections from DSZ terminate in areas largely distinguishable from those that receive input from SI cutaneous areas. These subcortical targets of DSZ include not only the sensory but also motor-related structures, suggesting that SI processing of deep input may engage in regulating somatic and motor information flow between the cortex and periphery. Copyright © 2011 Wiley-Liss, Inc.

Effect of Barrel Material on Critical Current Measurements of High-Jc RRP Nb3Sn Wires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, A.

Nb{sub 3}Sn strands extracted from a 20-strand rectangular Rutherford cable were reacted on either stainless steel or Ti-alloy barrels and the critical current, I{sub c}, in the field range of 8-11.5 T was measured on ITER-type barrels made from Ti-6Al-4V alloy, 304 stainless steel and G-10. Measurements on the 'standard' Ti-alloy barrel using the test procedure employed at BNL are shown to reproduce I{sub c} for extracted strands to {+-}2%. The I{sub c} data for the sample mounted on the 'standard' Ti-alloy are fit to the deviatoric strain scaling model developed for Nb{sub 3}Sn by the University of Twente groupmore » using an arbitrary pre-strain. Using the parameters for this fit, the I{sub c} data for the other barrels are fitted by only adjusting the strain. Using this procedure, the strain difference due to the barrel material is determined. Assuming a thermal pre-strain of -0.2% for the sample measured on the Ti-alloy barrel, the use of stainless steel barrel increases the compressive strain by -0.07%, that of G-10 by -0.10%. With the wire soldered to the stainless steel barrel, the strain increases to -0.15%. Details of this study are presented.« less

Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex.

PubMed

McClure-Begley, Tristan D; Esterlis, Irina; Stone, Kathryn L; Lam, TuKiet T; Grady, Sharon R; Colangelo, Christopher M; Lindstrom, Jon M; Marks, Michael J; Picciotto, Marina R

2016-01-01

Nicotinic acetylcholine receptors (nAChRs) support the initiation and maintenance of smoking, but the long-term changes occurring in the protein complex as a result of smoking and the nicotine in tobacco are not known. Human studies and animal models have also demonstrated that increasing cholinergic tone increases behaviors related to depression, suggesting that the nAChR-associated proteome could be altered in individuals with mood disorders. We therefore immunopurified nAChRs and associated proteins for quantitative proteomic assessment of changes in protein-protein interactions of high-affinity nAChRs containing the β2 subunit (β2*-nAChRs) from either cortex of mice treated with saline or nicotine, or postmortem human temporal cortex tissue from tobacco-exposed and nonexposed individuals, with a further comparison of diagnosed mood disorder to control subjects. We observed significant effects of nicotine exposure on the β2*-nAChR-associated proteome in human and mouse cortex, particularly in the abundance of the nAChR subunits themselves, as well as putative interacting proteins that make up core components of neuronal excitability (Na/K ATPase subunits), presynaptic neurotransmitter release (syntaxins, SNAP25, synaptotagmin), and a member of a known nAChR protein chaperone family (14-3-3ζ). These findings identify candidate-signaling proteins that could mediate changes in cholinergic signaling via nicotine or tobacco use. Further analysis of identified proteins will determine whether these interactions are essential for primary function of nAChRs at presynaptic terminals. The identification of differences in the nAChR-associated proteome and downstream signaling in subjects with various mood disorders may also identify novel etiological mechanisms and reveal new treatment targets.

Molecular analysis of neocortical layer structure in the ferret

PubMed Central

Rowell, Joanna J.; Mallik, Atul K.; Dugas-Ford, Jennifer; Ragsdale, Clifton W.

2010-01-01

Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals is, however, unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for fifteen layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: (1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; (2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layer 5 and 6 into 5a, 5b, 6a and 6b are also conserved between rodents and carnivores. (3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; (4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals. PMID:20575059

Model-based analysis of pattern motion processing in mouse primary visual cortex

PubMed Central

Muir, Dylan R.; Roth, Morgane M.; Helmchen, Fritjof; Kampa, Björn M.

2015-01-01

Neurons in sensory areas of neocortex exhibit responses tuned to specific features of the environment. In visual cortex, information about features such as edges or textures with particular orientations must be integrated to recognize a visual scene or object. Connectivity studies in rodent cortex have revealed that neurons make specific connections within sub-networks sharing common input tuning. In principle, this sub-network architecture enables local cortical circuits to integrate sensory information. However, whether feature integration indeed occurs locally in rodent primary sensory areas has not been examined directly. We studied local integration of sensory features in primary visual cortex (V1) of the mouse by presenting drifting grating and plaid stimuli, while recording the activity of neuronal populations with two-photon calcium imaging. Using a Bayesian model-based analysis framework, we classified single-cell responses as being selective for either individual grating components or for moving plaid patterns. Rather than relying on trial-averaged responses, our model-based framework takes into account single-trial responses and can easily be extended to consider any number of arbitrary predictive models. Our analysis method was able to successfully classify significantly more responses than traditional partial correlation (PC) analysis, and provides a rigorous statistical framework to rank any number of models and reject poorly performing models. We also found a large proportion of cells that respond strongly to only one stimulus class. In addition, a quarter of selectively responding neurons had more complex responses that could not be explained by any simple integration model. Our results show that a broad range of pattern integration processes already take place at the level of V1. This diversity of integration is consistent with processing of visual inputs by local sub-networks within V1 that are tuned to combinations of sensory features. PMID:26300738

In vivo binding of /sup 125/I-LSD to serotonin 5-HT/sub 2/ receptors in mouse brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartig, P.R.; Scheffel, U., Frost, J.J.; Wagner, H.N. Jr.

The binding of /sup 125/I-LSD (2-(/sup 125/I)-lysergic acid diethylamide) was studied in various mouse brain regions following intravenous injection of the radioligand. The high specific activity of /sup 125/I-LSD enabled the injection of low mass doses (14ng/kg), which are well below the threshold for induction of any known physiological effect of the probe. The highest levels of /sup 125/I-LSD binding were found in the frontal cortex, olfactory tubercles, extra-frontal cortex and striatum while the lowest level was found in the cerebellum. Binding was saturable in the frontal cortex but increased linearly in the cerebellum with increasing doses of /sup 125/I-LSD.more » Serotonergic compounds potently inhibited /sup 125/I-LSD binding in cortical regions, olfactory tubercles, and hypothalamus but had no effect in the cerebellum. Dopaminergic compounds caused partial inhibition of binding in the striatum while adrenergic compounds were inactive. From these studies the authors conclude that /sup 125/I-LSD labels serotonin 5-HT/sub 2/ receptor sites in cortical regions with no indication that other receptor sites are labeled. In the olfactory tubercles and hypothalamus, /sup 125/I-LSD labeling occurs predominantly or entirely at serotonic 5-HT/sub 2/ sites. In the striatum, /sup 125/I-LSD labels approximately equal proportions of serotonergic and dopaminergic sites. These data indicate that /sup 125/I-LSD labels serotonin receptors in vivo and suggests that appropriate derivatives of 2I-LSD may prove useful for tomographic imaging of serotonin 5-HT/sub 2/ receptors in the mammalian cortex.« less

Molecular analysis of neocortical layer structure in the ferret.

PubMed

Rowell, Joanna J; Mallik, Atul K; Dugas-Ford, Jennifer; Ragsdale, Clifton W

2010-08-15

Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals, however, is unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for 15 layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: 1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; 2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layers 5 and 6 into 5a, 5b, 6a, and 6b are also conserved between rodents and carnivores; 3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; 4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals. (c) 2010 Wiley-Liss, Inc.

7. View north at back (canal side) of culvert inlet, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. View north at back (canal side) of culvert inlet, with canal bank completely removed. Background to foreground: back of inlet headwall with tops of high inlet barrels exposed; vertical transition wall between high inlet barrels and low, interior, inlet barrels; tops of low interior barrels; vertical heartening planks and low cutoff wall at site of former canal edge of canal bank; dewatered canal bed and plank sheathing on top of culvert barrels beneath canal bed. - Delaware & Raritan Canal, Ten Mile Run Culvert, 1.5 miles South of Blackwells Road, East Millstone, Somerset County, NJ

Relationships between structure, in vivo function and long-range axonal target of cortical pyramidal tract neurons.

PubMed

Rojas-Piloni, Gerardo; Guest, Jason M; Egger, Robert; Johnson, Andrew S; Sakmann, Bert; Oberlaender, Marcel

2017-10-11

Pyramidal tract neurons (PTs) represent the major output cell type of the neocortex. To investigate principles of how the results of cortical processing are broadcasted to different downstream targets thus requires experimental approaches, which provide access to the in vivo electrophysiology of PTs, whose subcortical target regions are identified. On the example of rat barrel cortex (vS1), we illustrate that retrograde tracer injections into multiple subcortical structures allow identifying the long-range axonal targets of individual in vivo recorded PTs. Here we report that soma depth and dendritic path lengths within each cortical layer of vS1, as well as spiking patterns during both periods of ongoing activity and during sensory stimulation, reflect the respective subcortical target regions of PTs. We show that these cellular properties result in a structure-function parameter space that allows predicting a PT's subcortical target region, without the need to inject multiple retrograde tracers.The major output cell type of the neocortex - pyramidal tract neurons (PTs) - send axonal projections to various subcortical areas. Here the authors combined in vivo recordings, retrograde tracings, and reconstructions of PTs in rat somatosensory cortex to show that PT structure and activity can predict specific subcortical targets.

Feedforward inhibitory control of sensory information in higher-order thalamic nuclei.

PubMed

Lavallée, Philippe; Urbain, Nadia; Dufresne, Caroline; Bokor, Hajnalka; Acsády, László; Deschênes, Martin

2005-08-17

Sensory stimuli evoke strong responses in thalamic relay cells, which ensure a faithful relay of information to the neocortex. However, relay cells of the posterior thalamic nuclear group in rodents, despite receiving significant trigeminal input, respond poorly to vibrissa deflection. Here we show that sensory transmission in this nucleus is impeded by fast feedforward inhibition mediated by GABAergic neurons of the zona incerta. Intracellular recordings of posterior group neurons revealed that the first synaptic event after whisker deflection is a prominent inhibition. Whisker-evoked EPSPs with fast rise time and longer onset latency are unveiled only after lesioning the zona incerta. Excitation survives barrel cortex lesion, demonstrating its peripheral origin. Electron microscopic data confirm that trigeminal axons make large synaptic terminals on the proximal dendrites of posterior group cells and on the somata of incertal neurons. Thus, the connectivity of the system allows an unusual situation in which inhibition precedes ascending excitation resulting in efficient shunting of the responses. The dominance of inhibition over excitation strongly suggests that the paralemniscal pathway is not designed to relay inputs triggered by passive whisker deflection. Instead, we propose that this pathway operates through disinhibition, and that the posterior group forwards to the cerebral cortex sensory information that is contingent on motor instructions.

Cortical Local Field Potential Power Is Associated with Behavioral Detection of Near-threshold Stimuli in the Rat Whisker System: Dissociation between Orbitofrontal and Somatosensory Cortices.

PubMed

Rickard, Rachel E; Young, Andrew M J; Gerdjikov, Todor V

2018-01-01

There is growing evidence that ongoing brain oscillations may represent a key regulator of attentional processes and as such may contribute to behavioral performance in psychophysical tasks. OFC appears to be involved in the top-down modulation of sensory processing; however, the specific contribution of ongoing OFC oscillations to perception has not been characterized. Here we used the rat whiskers as a model system to further characterize the relationship between cortical state and tactile detection. Head-fixed rats were trained to report the presence of a vibrotactile stimulus (frequency = 60 Hz, duration = 2 sec, deflection amplitude = 0.01-0.5 mm) applied to a single vibrissa. We calculated power spectra of local field potentials preceding the onset of near-threshold stimuli from microelectrodes chronically implanted in OFC and somatosensory cortex. We found a dissociation between slow oscillation power in the two regions in relation to detection probability: Higher OFC but not somatosensory delta power was associated with increased detection probability. Furthermore, coherence between OFC and barrel cortex was reduced preceding successful detection. Consistent with the role of OFC in attention, our results identify a cortical network whose activity is differentially modulated before successful tactile detection.

FoxP2 protein levels regulate cell morphology changes and migration patterns in the vertebrate developing telencephalon.

PubMed

Garcia-Calero, Elena; Botella-Lopez, Arancha; Bahamonde, Olga; Perez-Balaguer, Ariadna; Martinez, Salvador

2016-07-01

In the mammalian telencephalon, part of the progenitor cells transition from multipolar to bipolar morphology as they invade the mantle zone. This associates with changing patterns of radial migration. However, the molecules implicated in these morphology transitions are not well known. In the present work, we analyzed the function of FoxP2 protein in this process during telencephalic development in vertebrates. We analyzed the expression of FoxP2 protein and its relation with cell morphology and migratory patterns in mouse and chicken developing striatum. We observed FoxP2 protein expressed in a gradient from the subventricular zone to the mantle layer in mice embryos. In the FoxP2 low domain cells showed multipolar migration. In the striatal mantle layer where FoxP2 protein expression is higher, cells showed locomoting migration and bipolar morphology. In contrast, FoxP2 showed a high and homogenous expression pattern in chicken striatum, thus bipolar morphology predominated. Elevation of FoxP2 in the striatal subventricular zone by in utero electroporation promoted bipolar morphology and impaired multipolar radial migration. In mouse cerebral cortex we obtained similar results. FoxP2 promotes transition from multipolar to bipolar morphology by means of gradiental expression in mouse striatum and cortex. Together these results indicate a role of FoxP2 differential expression in cell morphology control of the vertebrate telencephalon.

Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?

PubMed Central

Janecek, S.

1996-01-01

The question of parallel (alpha/beta)8-barrel fold evolution remains unclear, owing mainly to the lack of sequence homology throughout the amino acid sequences of (alpha/beta)8-barrel enzymes. The "classical" approaches used in the search for homologies among (alpha/beta)8-barrels (e.g., production of structurally based alignments) have yielded alignments perfect from the structural point of view, but the approaches have been unable to reveal the homologies. These are proposed to be "hidden" in (alpha/beta)8-barrel enzymes. The term "hidden homology" means that the alignment of sequence stretches proposed to be homologous need not be structurally fully satisfactory. This is due to the very long evolutionary history of all (alpha/beta)8-barrels. This work identifies so-called hidden homology around the strand beta 2 that is flanked by loops containing invariant glycines and prolines in 17 different (alpha/beta)8-barrel enzymes, i.e., roughly in half of all currently known (alpha/beta)8-barrel proteins. The search was based on the idea that a conserved sequence region of an (alpha/beta)8-barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif, given their mutual evolutionary relatedness. For this purpose, the sequence region around the well-conserved second beta-strand of alpha-amylase flanked by the invariant glycine and proline (56_GFTAIWITP, Aspergillus oryzae alpha-amylase numbering), was used as the sequence-structural template. The proposal that the second beta-strand of (alpha/beta)8-barrel fold is important from the evolutionary point of view is strongly supported by the increasing trend of the observed beta 2-strand structural similarity for the pairs of (alpha/beta)8-barrel enzymes: alpha-amylase and the alpha-subunit of tryptophan synthase, alpha-amylase and mandelate racemase, and alpha-amylase and cyclodextrin glycosyltransferase. This trend is also in agreement with the existing evolutionary division of the entire family of (alpha/beta)8-barrel proteins. PMID:8762144

Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?

PubMed

Janecek, S

1996-06-01

The question of parallel (alpha/beta)8-barrel fold evolution remains unclear, owing mainly to the lack of sequence homology throughout the amino acid sequences of (alpha/beta)8-barrel enzymes. The "classical" approaches used in the search for homologies among (alpha/beta)8-barrels (e.g., production of structurally based alignments) have yielded alignments perfect from the structural point of view, but the approaches have been unable to reveal the homologies. These are proposed to be "hidden" in (alpha/beta)8-barrel enzymes. The term "hidden homology" means that the alignment of sequence stretches proposed to be homologous need not be structurally fully satisfactory. This is due to the very long evolutionary history of all (alpha/beta)8-barrels. This work identifies so-called hidden homology around the strand beta 2 that is flanked by loops containing invariant glycines and prolines in 17 different (alpha/beta)8-barrel enzymes, i.e., roughly in half of all currently known (alpha/beta)8-barrel proteins. The search was based on the idea that a conserved sequence region of an (alpha/beta)8-barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif, given their mutual evolutionary relatedness. For this purpose, the sequence region around the well-conserved second beta-strand of alpha-amylase flanked by the invariant glycine and proline (56_GFTAIWITP, Aspergillus oryzae alpha-amylase numbering), was used as the sequence-structural template. The proposal that the second beta-strand of (alpha/beta)8-barrel fold is important from the evolutionary point of view is strongly supported by the increasing trend of the observed beta 2-strand structural similarity for the pairs of (alpha/beta)8-barrel enzymes: alpha-amylase and the alpha-subunit of tryptophan synthase, alpha-amylase and mandelate racemase, and alpha-amylase and cyclodextrin glycosyltransferase. This trend is also in agreement with the existing evolutionary division of the entire family of (alpha/beta)8-barrel proteins.

Inhibitory effect of a Microcystis sp (cyanobacteria) toxin on development of preimplantation mouse embryos.

PubMed

Sepulveda, M S; Rojas, M; Zambrano, F

1992-07-01

1. A soluble toxin, purified from the algae bloom of an eutrophic lake dominated by Microcystis, is a very effective inhibitor of early embryo development in a dose-response relationship. 2. Two- and 8-cell mouse embryos under the influence of Microcystis toxin do not reach the developmental stages of morula and blastocyst, respectively. 3. Actin cortex is disorganized without change in the microtubules structure. 4. Results are discussed in terms of the possible mechanisms by which the toxin arrests development considering, specifically, effects on the cytoskeleton and/or on voltage-insensitive transmembrane Ca2+ channels.

Creation of active TIM barrel enzymes through genetic fusion of half-barrel domain constructs derived from two distantly related glycosyl hydrolases.

PubMed

Sharma, Prerna; Kaila, Pallavi; Guptasarma, Purnananda

2016-12-01

Diverse unrelated enzymes that adopt the beta/alpha (or TIM) barrel topology display similar arrangements of beta/alpha units placed in a radial eight-fold symmetry around the barrel's axis. The TIM barrel was originally thought to be a single structural domain; however, it is now thought that TIM barrels arose from duplication and fusion of smaller half-barrels consisting of four beta/alpha units. We describe here the design, expression and purification, as well as characterization of folding, activity and stability, of chimeras of two TIM barrel glycosyl hydrolases, made by fusing different half-barrel domains derived from an endoglucanase from Clostridium cellulolyticum, CelCCA and a beta-glucosidase from Pyrococcus furiosus, CelB. We show that after refolding following purification from inclusion bodies, the two half-barrel fusion chimeras (CelCCACelB and CelBCelCCA) display catalytic activity although they assemble into large soluble oligomeric aggregated species containing chains of mixed beta and alpha structure. CelBCelCCA displays hyperthermophile-like structural stability as well as significant stability to chemical denaturation (C m of 2.6 m guanidinium hydrochloride), whereas CelCCACelB displays mesophile-like stability (T m of ~ 71 °C). The endoglucanase activities of both chimeras are an order of magnitude lower than those of CelB or CelCCA, whereas the beta-glucosidase activity of CelBCelCCA is about two orders of magnitude lower than that of CelB. The chimera CelCCACelB shows no beta-glucosidase activity. Our results demonstrate that half-barrel domains from unrelated sources can fold, assemble and function, with scope for improvement. Pyrococcus furiosus beta-glucosidase (CelB, EC: 3.2.1.21). Clostridium cellulolyticum endoglucanase A (CelCCA, EC: 3.2.1.4). © 2016 Federation of European Biochemical Societies.

Assembly of 5.5-Meter Diameter Developmental Barrel Segments for the Ares I Upper Stage

NASA Technical Reports Server (NTRS)

Carter, Robert W.

2011-01-01

Full scale assembly welding of Ares I Upper Stage 5.5-Meter diameter cryogenic tank barrel segments has been performed at the Marshall Space Flight Center (MSFC). One full-scale developmental article produced under the Ares 1 Upper Stage project is the Manufacturing Demonstration Article (MDA) Barrel. This presentation will focus on the welded assembly of this barrel section, and associated lessons learned. Among the MDA articles planned on the Ares 1 Program, the Barrel was the first to be completed, primarily because the process of manufacture from piece parts (barrel panels) utilized the most mature friction stir process planned for use on the Ares US program: Conventional fixed pin Friction Stir Welding (FSW). This process is in use on other space launch systems, including the Shuttle s External Tank, the Delta IV common booster core, the Delta II, and the Atlas V rockets. The goals for the MDA Barrel development were several fold: 1) to prove out Marshall Space Flight Center s new Vertical Weld Tool for use in manufacture of cylindrical barrel sections, 2) to serve as a first run for weld qualification to a new weld specification, and 3) to provide a full size cylindrical section for downstream use in precision cleaning and Spray-on Foam Insulation development. The progression leading into the welding of the full size barrel included sub scale panel welding, subscale cylinder welding, a full length confidence weld, and finally, the 3 seamed MDA barrel processing. Lessons learned on this MDA program have been carried forward into the production tooling for the Ares 1 US Program, and in the use of the MSFC VWT in processing other large scale hardware, including two 8.4 meter diameter Shuttle External Tank barrel sections that are currently being used in structural analysis to validate shell buckling models.

The structure of the β-barrel assembly machinery complex

DOE PAGES

Bakelar, Jeremy; Buchanan, Susan K.; Noinaj, Nicholas

2016-01-08

β-Barrel outer membrane proteins (OMPs) are found in the outer membranes of Gram-negative bacteria and are essential for nutrient import, signaling, and adhesion. A 200-kilodalton five-component complex called the β-barrel assembly machinery (BAM) complex has been implicated in the biogenesis of OMPs. In this paper, we report the structure of the BAM complex from Escherichia coli, revealing that binding of BamCDE modulates the conformation of BamA, the central component, which may serve to regulate the BAM complex. The periplasmic domain of BamA was in a closed state that prevents access to the barrel lumen, which indicates substrate OMPs may notmore » be threaded through the barrel during biogenesis. Finally and further, conformational shifts in the barrel domain lead to opening of the exit pore and rearrangement at the lateral gate.« less

The structure of the β-barrel assembly machinery complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakelar, Jeremy; Buchanan, Susan K.; Noinaj, Nicholas

β-Barrel outer membrane proteins (OMPs) are found in the outer membranes of Gram-negative bacteria and are essential for nutrient import, signaling, and adhesion. A 200-kilodalton five-component complex called the β-barrel assembly machinery (BAM) complex has been implicated in the biogenesis of OMPs. In this paper, we report the structure of the BAM complex from Escherichia coli, revealing that binding of BamCDE modulates the conformation of BamA, the central component, which may serve to regulate the BAM complex. The periplasmic domain of BamA was in a closed state that prevents access to the barrel lumen, which indicates substrate OMPs may notmore » be threaded through the barrel during biogenesis. Finally and further, conformational shifts in the barrel domain lead to opening of the exit pore and rearrangement at the lateral gate.« less

System for supporting a bundled tube fuel injector within a combustor

DOE Office of Scientific and Technical Information (OSTI.GOV)

LeBegue, Jeffrey Scott; Melton, Patrick Benedict; Westmoreland, III, James Harold

A combustor includes an end cover having an outer side and an inner side, an outer barrel having a forward end that is adjacent to the inner side of the end cover and an aft end that is axially spaced from the forward end. An inner barrel is at least partially disposed concentrically within the outer barrel and is fixedly connected to the outer barrel. A fluid conduit extends downstream from the end cover. A first bundled tube fuel injector segment is disposed concentrically within the inner barrel. The bundled tube fuel injector segment includes a fuel plenum that ismore » in fluid communication with the fluid conduit and a plurality of parallel tubes that extend axially through the fuel plenum. The bundled tube fuel injector segment is fixedly connected to the inner barrel.« less

Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder

DTIC Science & Technology

2013-06-01

mouse brain Phospho-S6 staining revealed a striking dysmorphic appearance and increased cell size in the TSC1CKO cortex (Figs. 3). These enlarged...TSC1CKO mice. B A 11 6. Increased cell size of TSC1CKO astrocytes Increased numbers of astrocytes, many with enlarged and dysmorphic shapes, have

Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex

PubMed Central

Hulsman, Marc; Lelieveldt, Boudewijn P. F.; de Ridder, Jeroen; Reinders, Marcel

2015-01-01

The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains challenging. We address this by characterizing the topology of the cortical chromatin interaction network using scale-aware topological measures. We demonstrate that based on these characterizations it is possible to accurately predict spatial co-expression between genes in the mouse cortex. Consistent with previous findings, we find that the chromatin interaction profile of a gene-pair is a good predictor of their spatial co-expression. However, the accuracy of the prediction can be substantially improved when chromatin interactions are described using scale-aware topological measures of the multi-resolution chromatin interaction network. We conclude that, for co-expression prediction, it is necessary to take into account different levels of chromatin interactions ranging from direct interaction between genes (i.e. small-scale) to chromatin compartment interactions (i.e. large-scale). PMID:25965262

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

PubMed

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.

Daam1 regulates fascin for actin assembly in mouse oocyte meiosis.

PubMed

Lu, Yujie; Zhang, Yu; Pan, Meng-Hao; Kim, Nam-Hyung; Sun, Shao-Chen; Cui, Xiang-Shun

2017-07-18

As a formin protein, Daam1 (Dishevelled-associated activator of morphogenesis 1) is reported to regulate series of cell processes like endocytosis, cell morphology and migration via its effects on actin assembly in mitosis. However, whether Daam1 plays roles in female meiosis remains uncertain. In this study, we investigated the expression and functions of Daam1 during mouse oocyte meiosis. Our results indicated that Daam1 localized at the cortex of oocytes, which was similar with actin filaments. After Daam1 morpholino (MO) microinjection, the expression of Daam1 significantly decreased, which resulted in the failure of oocyte polar body extrusion. These results might be due to the defects of actin assembly, since the decreased fluorescence intensity of actin filaments in oocyte cortex and cytoplasm were observed. However, Daam1 knockdown seemed not to affect the meiotic spindle movement. In addition, we found that fascin might be the down effector of Daam1, since the protein expression of fascin decreased after Daam1 knockdown. Thus, our data suggested that Daam1 affected actin assembly during oocyte meiotic division via the regulation of fascin expression.

Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

PubMed Central

Portmann, Thomas; Ellegood, Jacob; Dolen, Gul; Bader, Patrick L.; Grueter, Brad A.; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Kalikhman, David; Loureiro, Darren; Saw, Nay L.; Zhengqui, Zhou; Miller, Michael A.; Lerch, Jason P.; Henkelman, Mark; Shamloo, Mehrdad; Malenka, Robert C.; Crawley, Jacqueline N.; Dolmetsch, Ricardo E.

2014-01-01

Summary A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11+/−). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2+) and fewer dopamine-sensitive (Drd1+) neurons in deep layers of cortex. Electrophysiological recordings of Drd2+ MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11+/− mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11+/− mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism. PMID:24794428

Induction of c-Fos immunoreactivity in the amygdala of mice expressing anxiety-like behavior after local perfusion of veratrine in the prelimbic medial prefrontal cortex.

PubMed

Yamada, Misa; Saitoh, Akiyoshi; Ohashi, Masanori; Suzuki, Satoshi; Oka, Jun-Ichiro; Yamada, Mitsuhiko

2015-08-01

Local perfusion of the sodium channel activator veratrine in mouse prelimbic medial prefrontal cortex (PL) induced c-Fos immunoreactivity in the sub-regions of amygdala. Co-perfusion of the NMDA receptor antagonist MK-801 diminished the c-Fos expression. Significant correlations were observed between c-Fos immunoreactivity and behavioral measures in the open-field test. The PL stimulation activates a neural network projecting to the amygdala via NMDA receptor-mediated glutamatergic neurotransmission. Anxiety-like behavior induced after the PL stimulation may be partly mediated through the activation of amygdala.

Cobalt-Base Alloy Gun Barrel Study

DTIC Science & Technology

2014-07-01

Cobalt-Base Alloy Gun Barrel Study by William S. de Rosset and Jonathan S. Montgomery ARL-RP-0491 July 2014 A reprint...21005-5069 ARL-RP-0491 July 2014 Cobalt-Base Alloy Gun Barrel Study William S. de Rosset and Jonathan S. Montgomery Weapons and Materials... Gun Barrel Study 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) William S. de Rosset and Jonathan S. Montgomery

Cooling of weapons with graphite foam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klett, James W.; Trammell, Michael P.

Disclosed are examples of an apparatus for cooling a barrel 12 of a firearm 10 and examples of a cooled barrel assembly 32 for installation into an existing firearm 10. When assembled with the barrel 12, a contact surface 16 of a shell 14 is proximate to, and in thermal communication with, the outer surface of the barrel 18. The shell 14 is formed of commercially available or modified graphite foam.

Assembly of the β-Barrel Outer Membrane Proteins in Gram-Negative Bacteria, Mitochondria, and Chloroplasts

PubMed Central

Misra, Rajeev

2012-01-01

In the last decade, there has been an explosion of publications on the assembly of β-barrel outer membrane proteins (OMPs), which carry out diverse cellular functions, including solute transport, protein secretion, and assembly of protein and lipid components of the outer membrane. Of the three outer membrane model systems—Gram-negative bacteria, mitochondria and chloroplasts—research on bacterial and mitochondrial systems has so far led the way in dissecting the β-barrel OMP assembly pathways. Many exciting discoveries have been made, including the identification of β-barrel OMP assembly machineries in bacteria and mitochondria, and potentially the core assembly component in chloroplasts. The atomic structures of all five components of the bacterial β-barrel assembly machinery (BAM) complex, except the β-barrel domain of the core BamA protein, have been solved. Structures reveal that these proteins contain domains/motifs known to facilitate protein-protein interactions, which are at the heart of the assembly pathways. While structural information has been valuable, most of our current understanding of the β-barrel OMP assembly pathways has come from genetic, molecular biology, and biochemical analyses. This paper provides a comparative account of the β-barrel OMP assembly pathways in Gram-negative bacteria, mitochondria, and chloroplasts. PMID:27335668

Effect of extrusion conditions on the physico-chemical properties and in vitro protein digestibility of canola meal.

PubMed

Zhang, Bo; Liu, Guo; Ying, Danyang; Sanguansri, Luz; Augustin, Mary Ann

2017-10-01

Canola meal has potential as a high protein food ingredient. The extrusion-induced changes in color, pH, extractable protein and in vitro protein digestibility of canola meal under different extrusion conditions was assessed. The extrusion barrel moisture (24%, 30% or 36%) and screw kneading block length (0, 30 or 60mm) were used as independent process parameters. Extrusion at high barrel moisture (36%) favored protein aggregation resulting in lower extractable protein compared to extrusion at the lowest barrel moisture (24%). At lower barrel moisture contents (24% and 30%), a longer kneading block length increased extractable protein but this was not the case at 36% barrel moisture. Canola protein digestibility was improved upon extrusion at 30% barrel moisture but there was no significant change at lower (24%) or higher (36%) barrel moisture. The kneading block length of the screw had no significant effect on the canola protein digestibility within the same barrel moisture level. The relationship between the physico-chemical parameters and in vitro digestibility was examined. This study highlighted the complex interplay of extrusion processing variables that affect protein degradation and the interaction of components, with consequent effects on protein digestibility. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nuclear reactor downcomer flow deflector

DOEpatents

Gilmore, Charles B [Greensburg, PA; Altman, David A [Pittsburgh, PA; Singleton, Norman R [Murrysville, PA

2011-02-15

A nuclear reactor having a coolant flow deflector secured to a reactor core barrel in line with a coolant inlet nozzle. The flow deflector redirects incoming coolant down an annulus between the core barrel and the reactor vessel. The deflector has a main body with a front side facing the fluid inlet nozzle and a rear side facing the core barrel. The rear side of the main body has at least one protrusion secured to the core barrel so that a gap exists between the rear side of the main body adjacent the protrusion and the core barrel. Preferably, the protrusion is a relief that circumscribes the rear side of the main body.

Evolutions of volatile sulfur compounds of Cabernet Sauvignon wines during aging in different oak barrels.

PubMed

Ye, Dong-Qing; Zheng, Xiao-Tian; Xu, Xiao-Qing; Wang, Yun-He; Duan, Chang-Qing; Liu, Yan-Lin

2016-07-01

The evolution of volatile sulfur compounds (VSCs) in Cabernet Sauvignon wines from seven regions of China during maturation in oak barrels was investigated. The barrels were made of different wood grains (fine and medium) and toasting levels (light and medium). Twelve VSCs were quantified by GC/FPD, with dimethyl sulfide (DMS) and methionol exceeding their sensory thresholds. Most VSCs tended to decline during the aging, while DMS was found to increase. After one year aging, the levels of DMS, 2-methyltetrahy-drothiophen-3-one and sulfur-containing esters were lower in the wines aged in oak barrels than in stainless steel tanks. The wood grain and toasting level of oak barrels significantly influenced the concentration of S-methyl thioacetate and 2-methyltetrahy-drothiophen-3-one. This study reported the evolution of VSCs in wines during oak barrel aging for the first time and evaluated the influence of barrel types, which would provide wine-makers with references in making proposals about wine aging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assembly of β-barrel proteins in the mitochondrial outer membrane.

PubMed

Höhr, Alexandra I C; Straub, Sebastian P; Warscheid, Bettina; Becker, Thomas; Wiedemann, Nils

2015-01-01

Mitochondria evolved through endosymbiosis of a Gram-negative progenitor with a host cell to generate eukaryotes. Therefore, the outer membrane of mitochondria and Gram-negative bacteria contain pore proteins with β-barrel topology. After synthesis in the cytosol, β-barrel precursor proteins are first transported into the mitochondrial intermembrane space. Folding and membrane integration of β-barrel proteins depend on the mitochondrial sorting and assembly machinery (SAM) located in the outer membrane, which is related to the β-barrel assembly machinery (BAM) in bacteria. The SAM complex recognizes β-barrel proteins by a β-signal in the C-terminal β-strand that is required to initiate β-barrel protein insertion into the outer membrane. In addition, the SAM complex is crucial to form membrane contacts with the inner mitochondrial membrane by interacting with the mitochondrial contact site and cristae organizing system (MICOS) and shares a subunit with the endoplasmic reticulum-mitochondria encounter structure (ERMES) that links the outer mitochondrial membrane to the endoplasmic reticulum (ER). Copyright © 2014 Elsevier B.V. All rights reserved.

Research on vibration characteristics of gun barrel based on contact model

NASA Astrophysics Data System (ADS)

Zhao, Yang; Zhou, Qizheng; Yue, Pengfei

2017-04-01

In order to study vibration characteristics of the gun barrel under the action of moving projectile, the gun barrel is simplified to cross sectional cantilever beam such as Euler. Considering contact conditions of inertia effect and projectile with the gun barrel, the equation of lateral vibration of the gun barrel is established under the projectile-gun coupling effect; the modal analysis method is used to give the analytic solutions of equation series. The effect of the motion parameters the projectile on the vibration of gun barrel is discussed, and characteristics of vibration of gun barrel are further studied under two conditions of repeating and projectile with mass eccentricity. The research results show that reasonable control of the acceleration of the projectile in the gun bore, and reduction of projectile mass eccentricity can help reduce the muzzle vibration at the gun firing. The research results can provide reference for overall design of the gun, and the modeling and analysis method used in the paper can be promoted for the solution of vibration of other related projects under the moving excitation.

An Intranasal Formulation of Erythropoietin (Neuro-EPO) Prevents Memory Deficits and Amyloid Toxicity in the APPSwe Transgenic Mouse Model of Alzheimer's Disease.

PubMed

Rodríguez Cruz, Yamila; Strehaiano, Manon; Rodríguez Obaya, Teresita; García Rodríguez, Julío César; Maurice, Tangui

2017-01-01

Erythropoietin (EPO) is a cytokine known to have effective cytoprotective action in the brain, particularly in ischemic, traumatic, inflammatory, and neurodegenerative conditions. We previously reported the neuroprotective effect of a low sialic form of EPO, Neuro-EPO, applied intranasally in rodent models of stroke or cerebellar ataxia and in a non-transgenic mouse model of Alzheimer's disease (AD). Here we analyzed the protective effect of Neuro-EPO in APPSwe mice, a reference transgenic mouse model of AD. Mice were administered 3 times a day, 3 days in the week with Neuro-EPO (125, 250 μg/kg) intranasally, between 12 and 14 months of age. Motor responses, general activity, and memory responses were analyzed during and after treatment. The deficits in spontaneous alternation, place learning in the water-maze, and novel object recognition observed in APPSwe mice were alleviated by the low dose of Neuro-EPO. Oxidative stress, neuroinflammation, trophic factor levels, and a synaptic marker were analyzed in the hippocampus or cortex of the animals. The increases in lipid peroxidation or in GFAP and Iba-1 contents in APPSwe mice were significantly reduced after Neuro-EPO. Activation of intrinsic and extrinsic apoptotic pathways was analyzed. The increases in Bax/Bcl-2 ratio, TNFα, or Fas ligand levels observed in APPSwe mice were reduced by Neuro-EPO. Finally, immunohistochemical and ELISA analyses of Aβ1-42 levels in the APPSwe mouse cortex and hippocampus showed a marked reduction in Aβ deposits and in soluble and insoluble Aβ1-42 forms. This study therefore confirmed the neuroprotective activity of EPO, particularly for an intranasally deliverable formulation, devoid of erythropoietic side effects, in a transgenic mouse model of AD. Neuro-EPO alleviated memory alterations, oxidative stress, neuroinflammation, apoptosis induction, and amyloid load in 14-month-old APPSwe mice.

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

PubMed

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.

Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions.

PubMed

Li, Hongyun; Ruberu, Kalani; Karl, Tim; Garner, Brett

2016-01-01

Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein.

8. View southwest at the northeastern end of culvert inlet, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. View southwest at the northeastern end of culvert inlet, with canal bank completely removed. Left to right: back of curved wingwall; tops of high inlet barrels; vertical transition wall between high inlet barrels and low interior barrels; tops of low, interior barrels; vertical heartening planks at former canal edge of canal bank. - Delaware & Raritan Canal, Ten Mile Run Culvert, 1.5 miles South of Blackwells Road, East Millstone, Somerset County, NJ

6. View southwest, culvert inlet with canal bank completely removed. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. View southwest, culvert inlet with canal bank completely removed. Left to right: back of headwall; tops of high inlet barrels; vertical transition wall between high inlet barrels and low, interior, inlet barrels; tops of low interior barrels; vertical heartening planks and low cutoff wall along former edge of canal bank; dewatered canal bed. - Delaware & Raritan Canal, Ten Mile Run Culvert, 1.5 miles South of Blackwells Road, East Millstone, Somerset County, NJ

46th Annual Gun and Missile Systems Conference and Exhibition. Volume 3 - Thursday

DTIC Science & Technology

2011-09-01

Grade Sensors Through Use of Accelerated Aging Principles Mr. Scott Gift 11657 Modeling of the Autofrettage Processes of a Gun Barrel Mr. Sudhir...Emissions Measured on the Outer Portion of a Composite Barrel Ms. Rushie Ghimire GUN & MISSILE SYSTEMS ADDITIONAL AUTHORS GUN & MISSILE SYSTEMS...Transportation – Loading – Gun Fire to Barrel Exit – After Barrel Exit • Passing: Fuze safety devices remain safe; safe for disposal or safe for

Sequential injection gas guns for accelerating projectiles

DOEpatents

Lacy, Jeffrey M [Idaho Falls, ID; Chu, Henry S [Idaho Falls, ID; Novascone, Stephen R [Idaho Falls, ID

2011-11-15

Gas guns and methods for accelerating projectiles through such gas guns are described. More particularly, gas guns having a first injection port located proximate a breech end of a barrel and a second injection port located longitudinally between the first injection port and a muzzle end of the barrel are described. Additionally, modular gas guns that include a plurality of modules are described, wherein each module may include a barrel segment having one or more longitudinally spaced injection ports. Also, methods of accelerating a projectile through a gas gun, such as injecting a first pressurized gas into a barrel through a first injection port to accelerate the projectile and propel the projectile down the barrel past a second injection port and injecting a second pressurized gas into the barrel through the second injection port after passage of the projectile and to further accelerate the projectile are described.

Prejunctional angiotensin receptors involved in the facilitation of noradrenaline release in mouse tissues

PubMed Central

Cox, S L; Trendelenburg, A U; Starke, K

1999-01-01

The effect of angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1–7) on the electrically induced release of noradrenaline was studied in preparations of mouse atria, spleen, hippocampus, occipito-parietal cortex and hypothalamus preincubated with [3H]-noradrenaline. The prejunctional angiotensin receptor type was investigated using the non-selective receptor antagonist saralasin (AT1/AT2) and the AT1 and AT2 selective receptor antagonists losartan and PD 123319, respectively. In atrial and splenic preparations, angiotensin II (0.01 nM–0.1 μM) and angiotensin III (0.01 and 0.1 nM–1 μM) increased the stimulation-induced overflow of tritium in a concentration-dependent manner. Angiotensin IV, only at high concentrations (1 and 10 μM), enhanced tritium overflow in the atria, while angiotensin-(1–7) (0.1 nM–10 μM) was without effect in both preparations. In preparations of hippocampus, occipito-parietal cortex and hypothalamus, none of the angiotensin peptides altered the evoked overflow of tritium. In atrial and splenic preparations, saralasin (0.1 μM) and losartan (0.1 and 1 μM), but not PD 123319 (0.1 μM), shifted the concentration-response curves of angiotensin II and angiotensin III to the right. In conclusion, in mouse atria and spleen, angiotensin II and angiotensin III facilitate the action potential induced release of noradrenaline via a prejunctional AT1 receptor. Only high concentrations of angiotensin IV are effective in the atria and angiotensin-(1–7) is without effect in both preparations. In mouse brain areas, angiotensin II, angiotensin III, angiotensin IV and angiotensin-(1–7) do not modulate the release of noradrenaline. PMID:10455273

Glutamatergic and GABAergic TCA cycle and neurotransmitter cycling fluxes in different regions of mouse brain.

PubMed

Tiwari, Vivek; Ambadipudi, Susmitha; Patel, Anant B

2013-10-01

The (13)C nuclear magnetic resonance (NMR) studies together with the infusion of (13)C-labeled substrates in rats and humans have provided important insight into brain energy metabolism. In the present study, we have extended a three-compartment metabolic model in mouse to investigate glutamatergic and GABAergic tricarboxylic acid (TCA) cycle and neurotransmitter cycle fluxes across different regions of the brain. The (13)C turnover of amino acids from [1,6-(13)C2]glucose was monitored ex vivo using (1)H-[(13)C]-NMR spectroscopy. The astroglial glutamate pool size, one of the important parameters of the model, was estimated by a short infusion of [2-(13)C]acetate. The ratio Vcyc/VTCA was calculated from the steady-state acetate experiment. The (13)C turnover curves of [4-(13)C]/[3-(13)C]glutamate, [4-(13)C]glutamine, [2-(13)C]/[3-(13)C]GABA, and [3-(13)C]aspartate from [1,6-(13)C2]glucose were analyzed using a three-compartment metabolic model to estimate the rates of the TCA cycle and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The glutamatergic TCA cycle rate was found to be highest in the cerebral cortex (0.91 ± 0.05 μmol/g per minute) and least in the hippocampal region (0.64 ± 0.07 μmol/g per minute) of the mouse brain. In contrast, the GABAergic TCA cycle flux was found to be highest in the thalamus-hypothalamus (0.28 ± 0.01 μmol/g per minute) and least in the cerebral cortex (0.24 ± 0.02 μmol/g per minute). These findings indicate that the energetics of excitatory and inhibitory function is distinct across the mouse brain.

The p38 mitogen-activated protein kinase signaling pathway is involved in regulating low-density lipoprotein receptor-related protein 1-mediated β-amyloid protein internalization in mouse brain.

PubMed

Ma, Kai-Ge; Lv, Jia; Hu, Xiao-Dan; Shi, Li-Li; Chang, Ke-Wei; Chen, Xin-Lin; Qian, Yi-Hua; Yang, Wei-Na; Qu, Qiu-Min

2016-07-01

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Recently, increasing evidence suggests that intracellular β-amyloid protein (Aβ) alone plays a pivotal role in the progression of AD. Therefore, understanding the signaling pathway and proteins that control Aβ internalization may provide new insight for regulating Aβ levels. In the present study, the regulation of Aβ internalization by p38 mitogen-activated protein kinases (MAPK) through low-density lipoprotein receptor-related protein 1 (LRP1) was analyzed in vivo. The data derived from this investigation revealed that Aβ1-42 were internalized by neurons and astrocytes in mouse brain, and were largely deposited in mitochondria and lysosomes, with some also being found in the endoplasmic reticulum. Aβ1-42-LRP1 complex was formed during Aβ1-42 internalization, and the p38 MAPK signaling pathway was activated by Aβ1-42 via LRP1. Aβ1-42 and LRP1 were co- localized in the cells of parietal cortex and hippocampus. Furthermore, the level of LRP1-mRNA and LRP1 protein involved in Aβ1-42 internalization in mouse brain. The results of this investigation demonstrated that Aβ1-42 induced an LRP1-dependent pathway that related to the activation of p38 MAPK resulting in internalization of Aβ1-42. These results provide evidence supporting a key role for the p38 MAPK signaling pathway which is involved in the regulation of Aβ1-42 internalization in the parietal cortex and hippocampus of mouse through LRP1 in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thalamic input to auditory cortex is locally heterogeneous but globally tonotopic

PubMed Central

Vasquez-Lopez, Sebastian A; Weissenberger, Yves; Lohse, Michael; Keating, Peter; King, Andrew J

2017-01-01

Topographic representation of the receptor surface is a fundamental feature of sensory cortical organization. This is imparted by the thalamus, which relays information from the periphery to the cortex. To better understand the rules governing thalamocortical connectivity and the origin of cortical maps, we used in vivo two-photon calcium imaging to characterize the properties of thalamic axons innervating different layers of mouse auditory cortex. Although tonotopically organized at a global level, we found that the frequency selectivity of individual thalamocortical axons is surprisingly heterogeneous, even in layers 3b/4 of the primary cortical areas, where the thalamic input is dominated by the lemniscal projection. We also show that thalamocortical input to layer 1 includes collaterals from axons innervating layers 3b/4 and is largely in register with the main input targeting those layers. Such locally varied thalamocortical projections may be useful in enabling rapid contextual modulation of cortical frequency representations. PMID:28891466

Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly

PubMed Central

de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor

2015-01-01

Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ∼80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices. PMID:25916825

Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction and Spatial Memory Deficits Reminiscent of Early Alzheimer's Disease

PubMed Central

Fu, Hongjun; Rodriguez, Gustavo A.; Herman, Mathieu; Emrani, Sheina; Nahmani, Eden; Barrett, Geoffrey; Figueroa, Helen Y.; Goldberg, Eliana

2017-01-01

Summary The earliest stages of Alzheimer's disease (AD) are characterized by the formation of mature tangles in the entorhinal cortex and disorientation and confusion navigating familiar places. The medial entorhinal cortex (MEC) contains specialized neurons called grid cells that form part of the spatial navigation system. Here we show in a transgenic mouse model expressing mutant human tau predominantly in the EC that the formation of mature tangles in old mice was associated with excitatory cell loss and deficits in grid cell function, including destabilized grid fields and reduced firing rates, as well as altered network activity. Overt tau pathology in the aged mice was accompanied by spatial memory deficits. Therefore, tau pathology initiated in the entorhinal cortex could lead to deficits in grid cell firing and underlie the deterioration of spatial cognition seen in human AD. PMID:28111080

Deficient plasticity in the primary visual cortex of alpha-calcium/calmodulin-dependent protein kinase II mutant mice.

PubMed

Gordon, J A; Cioffi, D; Silva, A J; Stryker, M P

1996-09-01

The recent characterization of plasticity in the mouse visual cortex permits the use of mutant mice to investigate the cellular mechanisms underlying activity-dependent development. As calcium-dependent signaling pathways have been implicated in neuronal plasticity, we examined visual cortical plasticity in mice lacking the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha CaMKII). In wild-type mice, brief occlusion of vision in one eye during a critical period reduces responses in the visual cortex. In half of the alpha CaMKII-deficient mice, visual cortical responses developed normally, but visual cortical plasticity was greatly diminished. After intensive training, spatial learning in the Morris water maze was severely impaired in a similar fraction of mutant animals. These data indicate that loss of alpha CaMKII results in a severe but variable defect in neuronal plasticity.

Control of Intermale Aggression by Medial Prefrontal Cortex Activation in the Mouse

PubMed Central

Takahashi, Aki; Nagayasu, Kazuki; Nishitani, Naoya; Kaneko, Shuji; Koide, Tsuyoshi

2014-01-01

Aggressive behavior is widely observed throughout the animal kingdom because of its adaptiveness for social animals. However, when aggressive behavior exceeds the species-typical level, it is no longer adaptive, so there should be a mechanism to control excessive aggression to keep it within the adaptive range. Using optogenetics, we demonstrate that activation of excitatory neurons in the medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits inter-male aggression in mice. At the same time, optogenetic silencing of mPFC neurons causes an escalation of aggressive behavior both quantitatively and qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces the intensity of aggressive behavior, but does not change the duration of the aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role in the initiation and execution, but not the termination, of aggressive behavior, and maintains such behavior within the adaptive range. PMID:24740241

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

PubMed

McCarthy, Deirdre M; Bhide, Pradeep G

2012-01-01

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

Peptidomics of Cpefat/fat mouse brain regions: Implications for neuropeptide processing

PubMed Central

Zhang, Xin; Che, Fa-Yun; Berezniuk, Iryna; Sonmez, Kemal; Toll, Lawrence; Fricker, Lloyd D.

2009-01-01

SUMMARY Quantitative peptidomics was used to compare levels of peptides in wild type and Cpefat/fat mice, which lack carboxypeptidase E (CPE) activity due to a point mutation. Six different brain regions were analyzed: amygdala, hippocampus, hypothalamus, prefrontal cortex, striatum, and thalamus. Altogether, 111 neuropeptides or other peptides derived from secretory pathway proteins were identified in wild type mouse brain extracts by tandem mass spectrometry, and another 47 peptides were tentatively identified based on mass and other criteria. Most secretory pathway peptides were much lower in Cpefat/fat mouse brain, relative to wild type mouse brain, indicating that CPE plays a major role in their biosynthesis. Other peptides were only partially reduced in the Cpefat/fat mice, indicating that another enzyme (presumably carboxypeptidase D) contributes to their biosynthesis. Approximately 10% of the secretory pathway peptides were present in the Cpefat/fat mouse brain at levels similar to those in wild type mouse brain. Many peptides were greatly elevated in the Cpefat/fat mice; these peptide processing intermediates with C-terminal Lys and/or Arg were generally not detectable in wild type mice. Taken together, these results indicate that CPE contributes, either directly or indirectly, to the production of the majority of neuropeptides. PMID:19014391

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

PubMed Central

Kerr, Abigail L.; Tennant, Kelly A.

2014-01-01

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. The present protocol describes a skilled motor task for use in mouse models of stroke. The Pasta Matrix Reaching Task functions as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies (i.e., learned non-use) and focused rehabilitative training. When combined with neuroanatomical tools, this task also permits researchers to explore the mechanisms that support behavioral recovery of function (or lack thereof) following stroke. The task is both simple and affordable to set up and conduct, offering a variety of training and testing options for numerous research questions concerning functional outcome following injury. Though the task has been applied to mouse models of stroke, it may also be beneficial in studies of functional outcome in other upper extremity injury models. PMID:25045916

Core drilling apparatus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gusman, M.T.; Konstantinov, L.P.; Malkin, B.D.

1974-04-16

Mounted on the exterior of a nonrotatable core barrel is an end of a resilient tape, the other end of which extends inward into the barrel and is connected to a device for pulling the tape inward into the barrel. The apparatus also is provided with an arrangement which forms a sleeve from the tape as this is being pulled into the core barrel. During the coring operation, the tape is being pulled inward into the barrel and a sleeve is formed from the tape with the aid of the arrangement to encase and protect the core from disturbance. Themore » coring apparatus is intended for core drilling in soft, unconsolidated, and fractured formations. (3 claims)« less

Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3 complex-driven cytoplasmic streaming in mouse oocytes

PubMed Central

Yi, Kexi; Unruh, Jay R.; Deng, Manqi; Slaughter, Brian D.; Rubinstein, Boris; Li, Rong

2012-01-01

Mature mammalian oocytes are poised for the completion of second polar body extrusion upon fertilization by positioning the metaphase spindle in close proximity to an actomyosin-rich cortical cap. Loss of this spindle position asymmetry is often associated with poor oocyte quality and infertility 1–3. Here, we report a novel role for the Arp2/3 actin nucleation complex in the maintenance of asymmetric spindle position in mature mouse oocytes. The Arp2/3 complex localizes to the cortical cap in a Ran GTPase-dependent manner and accounts for the nucleation of the majority of actin filaments in both the cortical cap and a cytoplasmic actin network. Inhibition of Arp2/3 complex activity or localization leads to rapid dissociation of the spindle from the cortex. High resolution live imaging and spatiotemporal image correlation spectroscopy (STICS) analysis reveal that in normal oocytes actin filaments flow continuously away from the Arp2/3-rich cortex, generating a cytoplamic streaming that results in a net pushing force on the spindle toward the actomyosin cap. Arp2/3 inhibition not only diminishes this actin flow and cytoplamic streaming but also enables a reverse streaming driven by myosin-II-based cortical contraction, leading to spindle movement away from the cortex. We conclude that the Arp2/3 complex maintains asymmetric meiotic spindle position by generating an actin polymerization-driven cytoplamic streaming and by suppressing a counteracting force from myosin-II-based contractility. PMID:21874009

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex.

PubMed

García-Díaz, Beatriz; Riquelme, Raquel; Varela-Nieto, Isabel; Jiménez, Antonio Jesús; de Diego, Isabel; Gómez-Conde, Ana Isabel; Matas-Rico, Elisa; Aguirre, José Ángel; Chun, Jerold; Pedraza, Carmen; Santín, Luis Javier; Fernández, Oscar; Rodríguez de Fonseca, Fernando; Estivill-Torrús, Guillermo

2015-11-01

Lysophosphatidic acid (LPA) is an intercellular signaling lipid that regulates multiple cellular functions, acting through specific G-protein coupled receptors (LPA(1-6)). Our previous studies using viable Malaga variant maLPA1-null mice demonstrated the requirement of the LPA1 receptor for normal proliferation, differentiation, and survival of the neuronal precursors. In the cerebral cortex LPA1 is expressed extensively in differentiating oligodendrocytes, in parallel with myelination. Although exogenous LPA-induced effects have been investigated in myelinating cells, the in vivo contribution of LPA1 to normal myelination remains to be demonstrated. This study identified a relevant in vivo role for LPA1 as a regulator of cortical myelination. Immunochemical analysis in adult maLPA1-null mice demonstrated a reduction in the steady-state levels of the myelin proteins MBP, PLP/DM20, and CNPase in the cerebral cortex. The myelin defects were confirmed using magnetic resonance spectroscopy and electron microscopy. Stereological analysis limited the defects to adult differentiating oligodendrocytes, without variation in the NG2+ precursor cells. Finally, a possible mechanism involving oligodendrocyte survival was demonstrated by the impaired intracellular transport of the PLP/DM20 myelin protein which was accompanied by cellular loss, suggesting stress-induced apoptosis. These findings describe a previously uncharacterized in vivo functional role for LPA1 in the regulation of oligodendrocyte differentiation and myelination in the CNS, underlining the importance of the maLPA1-null mouse as a model for the study of demyelinating diseases.

Ballistics of the 30-06 Rifle Cartridge

DTIC Science & Technology

2012-11-30

manuals for common bullet weights. Hodgdon, Nosler, and Barnes report velocities for 24" barrels . Hornady and Speer report velocoties for 22" barrels ...The data are all for barrels with a twist rate of 1 turn in 10” which is needed to stabilize the heaviest bullets. The higher muzzle velocities...are available that provide 2900 fps for 150 grain bullets, 2800 fps for 165 grain bullets, and 2700 fps for 180 grain bullets (in a 24 inch barrel

Effect of oak wood barrel capacity and utilization time on phenolic and sensorial profile evolution of an Encruzado white wine.

PubMed

Nunes, Paulo; Muxagata, Sara; Correia, Ana C; Nunes, Fernando M; Cosme, Fernanda; Jordão, António M

2017-11-01

Several studies have reported the influence of diverse winemaking technologies in white wine characteristics. However, the impact of the use of different oak wood barrel capacities and utilization time on the evolution of white wine phenolic content and sensorial characteristics are not usually considered. Thus the aim of this work was to evaluate the effect of oak wood barrel capacity and utilization time on the evolution of phenolic compounds, browning potential index and sensorial profile of an Encruzado white wine. For the 180 aging days considered, the use of new oak wood barrels induced a greater increase in global phenolic composition, including several individual compounds, such as gallic and ellagic acid, independently of the barrel capacity. Tendency for a lesser increase of the browning potential index values was detected for white wines aged in new oak wood barrels. The sensorial profile evolution, showed significant differences only for the aroma descriptors, namely for 'wood aroma' and 'aroma intensity', white wine aged in 225 L new oak wood barrels being the highest scored. The results show that, in general, the use of different capacities and utilization time of oak wood barrels used for white wine aging could play an important role in white wine quality. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

PubMed

Goldman, Aaron David; Beatty, Joshua T; Landweber, Laura F

2016-01-01

The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

A Supercomplex Spanning the Inner and Outer Membranes Mediates the Biogenesis of β-Barrel Outer Membrane Proteins in Bacteria.

PubMed

Wang, Yan; Wang, Rui; Jin, Feng; Liu, Yang; Yu, Jiayu; Fu, Xinmiao; Chang, Zengyi

2016-08-05

β-barrel outer membrane proteins (OMPs) are ubiquitously present in Gram-negative bacteria, mitochondria and chloroplasts, and function in a variety of biological processes. The mechanism by which the hydrophobic nascent β-barrel OMPs are transported through the hydrophilic periplasmic space in bacterial cells remains elusive. Here, mainly via unnatural amino acid-mediated in vivo photo-crosslinking studies, we revealed that the primary periplasmic chaperone SurA interacts with nascent β-barrel OMPs largely via its N-domain but with β-barrel assembly machine protein BamA mainly via its satellite P2 domain, and that the nascent β-barrel OMPs interact with SurA via their N- and C-terminal regions. Additionally, via dual in vivo photo-crosslinking, we demonstrated the formation of a ternary complex involving β-barrel OMP, SurA, and BamA in cells. More importantly, we found that a supercomplex spanning the inner and outer membranes and involving the BamA, BamB, SurA, PpiD, SecY, SecE, and SecA proteins appears to exist in living cells, as revealed by a combined analyses of sucrose-gradient ultra-centrifugation, Blue native PAGE and mass spectrometry. We propose that this supercomplex integrates the translocation, transportation, and membrane insertion events for β-barrel OMP biogenesis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A Supercomplex Spanning the Inner and Outer Membranes Mediates the Biogenesis of β-Barrel Outer Membrane Proteins in Bacteria*

PubMed Central

Wang, Yan; Wang, Rui; Jin, Feng; Liu, Yang; Yu, Jiayu; Fu, Xinmiao; Chang, Zengyi

2016-01-01

β-barrel outer membrane proteins (OMPs) are ubiquitously present in Gram-negative bacteria, mitochondria and chloroplasts, and function in a variety of biological processes. The mechanism by which the hydrophobic nascent β-barrel OMPs are transported through the hydrophilic periplasmic space in bacterial cells remains elusive. Here, mainly via unnatural amino acid-mediated in vivo photo-crosslinking studies, we revealed that the primary periplasmic chaperone SurA interacts with nascent β-barrel OMPs largely via its N-domain but with β-barrel assembly machine protein BamA mainly via its satellite P2 domain, and that the nascent β-barrel OMPs interact with SurA via their N- and C-terminal regions. Additionally, via dual in vivo photo-crosslinking, we demonstrated the formation of a ternary complex involving β-barrel OMP, SurA, and BamA in cells. More importantly, we found that a supercomplex spanning the inner and outer membranes and involving the BamA, BamB, SurA, PpiD, SecY, SecE, and SecA proteins appears to exist in living cells, as revealed by a combined analyses of sucrose-gradient ultra-centrifugation, Blue native PAGE and mass spectrometry. We propose that this supercomplex integrates the translocation, transportation, and membrane insertion events for β-barrel OMP biogenesis. PMID:27298319

Identification of Intracellular β-Barrel Residues Involved in Ion Selectivity in the Mechanosensitive Channel of Thermoanaerobacter tengcongensis

PubMed Central

Song, Yingcai; Zhang, Bing; Guo, Fei; Yang, Maojun; Li, Yang; Liu, Zhi-Qiang

2017-01-01

The mechanosensitive channel of small conductance (MscS) is a bacterial membrane pore that senses membrane tension and protects cells from lysis by releasing osmolytes. MscS is a homoheptameric channel with a cytoplasmic domain with seven portals and a β-barrel opening to the cytoplasm. TtMscS, an MscS channel from Thermoanaerobacter tengcongensis, is an anion-selective channel. A previous study from our laboratory has defined the crucial role of β-barrel in the anion selectivity of TtMscS (Zhang et al., 2012). However, the mechanistic details by which the β-barrel determines anion selectivity remain unclear. Here, using mutagenesis and patch-clamp recordings, we investigated the function and structural correlations between β-barrels and the anion selectivity of TtMscS at the atomic level. Our results indicated that mutation of V274, a residue at the center of the inner wall of the β-barrel in TtMscS, caused the anion selectivity of TtMscS reverse to cation selectivity. Moreover, the electrostatic potential (T272) and physical size (L276) of residues in the inner wall of β-barrel also determine the anion selectivity of TtMscS. In summary, the present study confirmed that the β-barrel region of TtMscS acts as a “selective filter” that renders TtMscS anion selectivity. PMID:29118717

Measurement of wavefront aberrations in cortex and peripheral nerve using a two-photon excitation guidestar

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Fontaine, Arjun; McCullough, Connor; Ozbay, Baris N.; George, Nickolas M.; Caldwell, John; Restrepo, Diego; Weir, Richard; Gibson, Emily A.

2018-02-01

Neural-machine interfaces using optogenetics are of interest due to their minimal invasiveness and potential for parallel read in and read out of activity. One possible biological target for such an interface is the peripheral nerve, where axonlevel imaging or stimulation could greatly improve interfacing with artificial limbs or enable neuron/fascicle level neuromodulation in the vagus nerve. Two-photon imaging has been successful in imaging brain activity using genetically encoded calcium or voltage indicators, but in the peripheral nerve, this is severely limited by scattering and aberrations from myelin. We employ a Shack-Hartman wavefront sensor and two-photon excitation guidestar to quantify optical scattering and aberrations in peripheral nerves and cortex. The sciatic and vagus nerves, and cortex from a ChAT-Cre ChR-eYFP transgenic mouse were excised and imaged directly. In peripheral nerves, defocus was the strongest aberration followed by astigmatism and coma. Peripheral nerve had orders of magnitude higher aberration compared with cortex. These results point to the potential of adaptive optics for increasing the depth of two-photon access into peripheral nerves.

Coevolution of radial glial cells and the cerebral cortex

PubMed Central

De Juan Romero, Camino

2015-01-01

Abstract Radial glia cells play fundamental roles in the development of the cerebral cortex, acting both as the primary stem and progenitor cells, as well as the guides for neuronal migration and lamination. These critical functions of radial glia cells in cortical development have been discovered mostly during the last 15 years and, more recently, seminal studies have demonstrated the existence of a remarkable diversity of additional cortical progenitor cell types, including a variety of basal radial glia cells with key roles in cortical expansion and folding, both in ontogeny and phylogeny. In this review, we summarize the main cellular and molecular mechanisms known to be involved in cerebral cortex development in mouse, as the currently preferred animal model, and then compare these with known mechanisms in other vertebrates, both mammal and nonmammal, including human. This allows us to present a global picture of how radial glia cells and the cerebral cortex seem to have coevolved, from reptiles to primates, leading to the remarkable diversity of vertebrate cortical phenotypes. GLIA 2015;63:1303–1319 PMID:25808466

Fitting neuron models to spike trains.

PubMed

Rossant, Cyrille; Goodman, Dan F M; Fontaine, Bertrand; Platkiewicz, Jonathan; Magnusson, Anna K; Brette, Romain

2011-01-01

Computational modeling is increasingly used to understand the function of neural circuits in systems neuroscience. These studies require models of individual neurons with realistic input-output properties. Recently, it was found that spiking models can accurately predict the precisely timed spike trains produced by cortical neurons in response to somatically injected currents, if properly fitted. This requires fitting techniques that are efficient and flexible enough to easily test different candidate models. We present a generic solution, based on the Brian simulator (a neural network simulator in Python), which allows the user to define and fit arbitrary neuron models to electrophysiological recordings. It relies on vectorization and parallel computing techniques to achieve efficiency. We demonstrate its use on neural recordings in the barrel cortex and in the auditory brainstem, and confirm that simple adaptive spiking models can accurately predict the response of cortical neurons. Finally, we show how a complex multicompartmental model can be reduced to a simple effective spiking model.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

PubMed

Lazic, Stanley E; Goodman, Anna O G; Grote, Helen E; Blakemore, Colin; Morton, A Jennifer; Hannan, Anthony J; van Dellen, Anton; Barker, Roger A

2007-06-02

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

Motor learning in animal models of Parkinson’s Disease: Aberrant synaptic plasticity in the motor cortex

PubMed Central

Xu, Tonghui; Wang, Shaofang; Lalchandani, Rupa R.; Ding, Jun B

2017-01-01

In Parkinson’s disease (PD), dopamine depletion causes dramatic changes in the brain resulting in debilitating cognitive and motor deficits. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time point of PD progression. Models of PD where dopamine tone in the brain are chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD. However, the etiology of the cognitive dysfunctions that are comorbid in PD patients has remained unclear until now. In this paper, we review recent studies exploring how dopamine depletion affects the motor cortex at the synaptic level. In particular, we highlight our recent findings on abnormal spine dynamics in the motor cortex of PD mouse models through in vivo, time-lapse imaging and motor-skill behavior assays. In combination with previous studies, a role of the motor cortex in skill-learning, and the impairment of this ability with the loss of dopamine, is becoming more apparent. Taken together, we conclude with a discussion on the potential role for the motor cortex in the motor-skill learning and cognitive impairments of PD, with the possibility of targeting the motor cortex for future PD therapeutics. PMID:28343366

Cobalamin-Independent Methionine Synthase (MetE): A Face-to-Face Double Barrel that Evolved by Gene Duplication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pejcha, Robert; Ludwig, Martha L.

2010-03-08

Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two ({beta}{alpha}){sub 8} barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domainmore » evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys){sub 3}Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E {center_dot} Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.« less

Final Report of the Rifling Profile Push Test

DTIC Science & Technology

2007-06-01

barrel lands through the copper alloy jacket, as shown in figure 6. As a result, compression of the jacket material above the steel core will occur...resistance pressure of the M855 projectile in an M16A2 barrel section. The M855 test projectiles were tested in a 2 × 2 matrix, two different M16A2 barrel ...1 Figure 2. M16A2 barrel machined section. The units of measure are in cm.................................2 Figure 3

COUNTERMEASURE: Army Ground Risk-Management Information. Volume 24, Number 3

DTIC Science & Technology

2003-03-01

damp rag, or a dry, clean cloth. Underwear crew members and maintenance personnel must should be changed frequently and foot powder wear gloves to...only p rolem oh the unlined barrel due to the probability of firing ugly things can happen with unlined barrels. If SLAP ammo. SLAP ammo will cause the...unlined you chamber a SLAP round in an unlined barrel barrel to wear significantly faster than the lined and don’t fire the round, there is a good

Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine Sepsis Survivors

PubMed Central

Zaghloul, Nahla; Addorisio, Meghan E.; Silverman, Harold A.; Patel, Hardik L.; Valdés-Ferrer, Sergio I.; Ayasolla, Kamesh R.; Lehner, Kurt R.; Olofsson, Peder S.; Nasim, Mansoor; Metz, Christine N.; Wang, Ping; Ahmed, Mohamed; Chavan, Sangeeta S.; Diamond, Betty; Tracey, Kevin J.; Pavlov, Valentin A.

2017-01-01

Sepsis, a complex disorder characterized by immune, metabolic, and neurological dysregulation, is the number one killer in the intensive care unit. Mortality remains alarmingly high even in among sepsis survivors discharged from the hospital. There is no clear strategy for managing this lethal chronic sepsis illness, which is associated with severe functional disabilities and cognitive deterioration. Providing insight into the underlying pathophysiology is desperately needed to direct new therapeutic approaches. Previous studies have shown that brain cholinergic signaling importantly regulates cognition and inflammation. Here, we studied the relationship between peripheral immunometabolic alterations and brain cholinergic and inflammatory states in mouse survivors of cecal ligation and puncture (CLP)-induced sepsis. Within 6 days, CLP resulted in 50% mortality vs. 100% survival in sham-operated controls. As compared to sham controls, sepsis survivors had significantly lower body weight, higher serum TNF, interleukin (IL)-1β, IL-6, CXCL1, IL-10, and HMGB1 levels, a lower TNF response to LPS challenge, and lower serum insulin, leptin, and plasminogen activator inhibitor-1 levels on day 14. In the basal forebrain of mouse sepsis survivors, the number of cholinergic [choline acetyltransferase (ChAT)-positive] neurons was significantly reduced. In the hippocampus and the cortex of mouse sepsis survivors, the activity of acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, as well as the expression of its encoding gene were significantly increased. In addition, the expression of the gene encoding the M1 muscarinic acetylcholine receptor was decreased in the hippocampus. In parallel with these forebrain cholinergic alterations, microglial activation (in the cortex) and increased Il1b and Il6 gene expression (in the cortex), and Il1b gene expression (in the hippocampus) were observed in mouse sepsis survivors. Furthermore, microglial activation was linked to decreased cortical ChAT protein expression and increased AChE activity. These results reinforce the notion of persistent inflammation-immunosuppression and catabolic syndrome in sepsis survivors and characterize a previously unrecognized relationship between forebrain cholinergic dysfunction and neuroinflammation in sepsis survivors. This insight is of interest for new therapeutic approaches that focus on brain cholinergic signaling for patients with chronic sepsis illness, a problem with no specific treatment. PMID:29326685

Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity.

PubMed

Yee, Yohan; Fernandes, Darren J; French, Leon; Ellegood, Jacob; Cahill, Lindsay S; Vousden, Dulcie A; Spencer Noakes, Leigh; Scholz, Jan; van Eede, Matthijs C; Nieman, Brian J; Sled, John G; Lerch, Jason P

2018-05-18

An organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings. Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed. We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the visceral area. Additionally, this pattern of explained variation differed spatially across the brain, with transcriptomic similarity playing a larger role in the cortex than subcortex, while connectivity explains structural covariance best in parts of the cortex, midbrain, and hindbrain. These results suggest that both gene expression and connectivity underlie structural volume covariance, albeit to different extents depending on brain region, and this relationship is modulated by distance. Copyright © 2018. Published by Elsevier Inc.

Neurotoxicity profiles of substituted amphetamines in the C57BL/6J mouse.

PubMed

O'Callaghan, J P; Miller, D B

1994-08-01

Dopaminergic (DA) and serotonergic (5-HT) projections to striatum and cortex have been implicated as the primary targets of substituted amphetamine (AMP)-induced neurotoxicity, largely on the basis of the propensity of these compounds to cause protracted decrements in DA and 5-HT rather than on the basis of AMP-induced alterations of indices linked to neural damage. Moreover, most studies of AMP-induced neurotoxicity, regardless of the endpoints assessed, have been conducted using a rat model; relatively little attention has been focused on the effects of these compounds in the mouse. Here, we evaluated the potential neurotoxic effects of d-methamphetamine (d-METH), d-methylenedioxyamphetamine (d-MDA), d-methylene-dioxymethamphetamine (d-MDMA) and d-fenfluramine (d-FEN) in the C57BL6/J mouse. Astrogliosis, assessed by quantification of glial fibrillary acidic protein (GFAP), was taken as the main index of AMP-induced neural damage. A silver degeneration stain also was used to obtain direct evidence of AMP-induced neuronal damage. Assays of tyrosine hydroxylase (TH), DA and 5-HT were used to assess effects on DA and 5-HT systems. Mice received d-METH (10 mg/kg), d-MDA (20 mg/kg), d-MDMA (20 mg/kg) or d-FEN (25 mg/kg) every 2 hr for a total of four s.c. injections. d-METH, d-MDA and d-MDMA caused a large (300%) increase in striatal GFAP that resolved by 3 weeks and a 50 to 75% decrease in TH and DA that did not resolve. d-METH, d-MDA and d-MDMA also caused fiber and terminal degeneration in striatum as revealed by silver staining. d-FEN did not affect any parameters in striatum. d-METH, d-MDA and d-MDMA also increased GFAP in cortex, effects that were associated with small (10-25%) and transient decrements in cortical 5-HT. d-FEN caused prolonged (weeks) decrements (20%) in cortical 5-HT but did not affect cortical GFAP. The effects of d-METH, d-MDA and d-MDMA were stereoselective and were blocked by pretreatment with MK-801. Core temperature was slightly elevated by d-METH, d-MDA and d-MDMA but was dramatically lowered by d-FEN. The data suggest that d-METH, d-MDA and d-MDMA, but not d-FEN, produce damage to neural elements of mouse striatum and cortex.

The TonB-dependent Transporter FhuA in Planar Lipid Bilayers: partial exit of its plug from the barrel

PubMed Central

Udho, Eshwar; Jakes, Karen S.; Finkelstein, Alan

2012-01-01

TonB-dependent transporters (TBDTs), which transport iron-chelating siderophores and vitamin B12 across the outer membrane of gram negative bacteria, share a conserved architecture of a 22-stranded beta-barrel with an amino-terminal plug domain occluding the barrel. We previously reported that we could induce TBDTs to reversibly open in planar lipid bilayers via the use of urea and that these channels were responsive to physiological concentrations of ligands. Here we report that in the presence of urea, trypsin can cleave the amino-terminal 67 residues of the plug of the TonB-dependent transporter FhuA, as assessed by gel shift and mass spectrometry assays. On the bilayer, trypsin treatment in the presence of urea resulted in the induced conductance no longer being reversed upon removal of urea, suggesting that urea opens intact FhuA channels by pulling the plug at least partly out of the barrel, and that removal of the urea then allows reinsertion of the plug into the barrel. When expressed separately, the FhuA plug domain was found to be a mostly unfolded structure that was able to occlude isolated FhuA beta-barrels inserted into the membrane. Thus, although folded in the barrel, the plug need not be folded upon exiting the barrel. The rate of insertion of the beta-barrels into the membrane was tremendously increased in the presence of an osmotic gradient provided by either urea or glycerol. Negative staining electron microscopy showed that FhuA in a detergent solution formed vesicles, thus explaining why an osmotic gradient promoted the insertion of FhuA into membranes. PMID:22846061

Water-Soluble Pd8L4 Self-assembled Molecular Barrel as an Aqueous Carrier for Hydrophobic Curcumin.

PubMed

Bhat, Imtiyaz Ahmad; Jain, Ruchi; Siddiqui, Mujahuddin M; Saini, Deepak K; Mukherjee, Partha Sarathi

2017-05-01

A tetrafacial water-soluble molecular barrel (1) was synthesized by coordination driven self-assembly of a symmetrical tetrapyridyl donor (L) with a cis-blocked 90° acceptor [cis-(en)Pd(NO 3 ) 2 ] (en = ethane-1,2-diamine). The open barrel structure of (1) was confirmed by single crystal X-ray diffraction. The presence of a hydrophobic cavity with large windows makes it an ideal candidate for encapsulation and carrying hydrophobic drug like curcumin in an aqueous medium. The barrel (1) encapsulates curcumin inside its molecular cavity and protects highly photosensitive curcumin from photodegradation. The photostability of encapsulated curcumin is due to the absorption of a high proportion of the incident photons by the aromatic walls of 1 with a high absorption cross-sectional area, which helps the walls to shield the guest even against sunlight/UV radiations. As compared to free curcumin in water, we noticed a significant increase in solubility as well as cellular uptake of curcumin upon encapsulation inside the water-soluble molecular barrel (1) in aqueous medium. Fluorescence imaging confirmed that curcumin was delivered into HeLa cancer cells by the aqueous barrel (1) with the retention of its potential anticancer activity. While free curcumin is inactive toward cancer cells in aqueous medium at room temperature due to negligible solubility, the determined IC 50 value of ∼14 μM for curcumin in aqueous medium in the presence of the barrel (1) reflects the efficiency of the barrel as a potential curcumin carrier in aqueous medium without any other additives. Thus, two major challenges of increasing the bioavailability and stability of curcumin in aqueous medium even in the presence of UV light have been addressed by using a new supramolecular water-soluble barrel (1) as a drug carrier.

Diffuse traumatic brain injury initially attenuates and later expands activation of the rat somatosensory whisker circuit concomitant with neuroplastic responses.

PubMed

Hall, Kelley D; Lifshitz, Jonathan

2010-04-06

Traumatic brain injury can initiate an array of chronic neurological deficits, effecting executive function, language and sensorimotor integration. Mechanical forces produce the diffuse pathology that disrupts neural circuit activation across vulnerable brain regions. The present manuscript explores the hypothesis that the extent of functional activation of brain-injured circuits is a consequence of initial disruption and consequent reorganization. In the rat, enduring sensory sensitivity to whisker stimulation directs regional analysis to the whisker barrel circuit. Adult, male rats were subjected to midline fluid percussion brain or sham injury and evaluated between 1day and 42days post-injury. Whisker somatosensory regions of the cortex and thalamus maintained cellular composition as visualized by Nissl stain. Within the first week post-injury, quantitatively less cFos activation was elicited by whisker stimulation, potentially due to axotomy within and surrounding the whisker circuit as visualized by amyloid precursor protein immunohistochemistry. Over six weeks post-injury, cFos activation after whisker stimulation showed a significant linear correlation with time in the cortex (r(2)=0.545; p=0.015), non-significant correlation in the thalamus (r(2)=0.326) and U-shaped correlation in the dentate gyrus (r(2)=0.831), all eventually exceeding sham levels. Ongoing neuroplastic responses in the cortex are evidenced by accumulating growth associated protein and synaptophysin gene expression. In the thalamus, the delayed restoration of plasticity markers may explain the broad distribution of neuronal activation extending into the striatum and hippocampus with whisker stimulation. The sprouting of diffuse-injured circuits into diffuse-injured tissue likely establishes maladaptive circuits responsible for behavioral morbidity. Therapeutic interventions to promote adaptive circuit restructuring may mitigate post-traumatic morbidity. Copyright 2010 Elsevier B.V. All rights reserved.

49 CFR 178.510 - Standards for wooden barrels.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Standards for wooden barrels. 178.510 Section 178.510 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS...-bulk Performance-Oriented Packaging Standards § 178.510 Standards for wooden barrels. (a) The following...

49 CFR 178.510 - Standards for wooden barrels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for wooden barrels. 178.510 Section 178.510 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.510 Standards for wooden barrels. (a) The...

Real-time monitoring of barrel thickness and barrel/screw separation using ultrasound

NASA Astrophysics Data System (ADS)

Jen, Cheng-Kuei; Zun, Zhigang; Kobayashi, Makiko

2005-03-01

Ultrasonic sensors together with a fast data acquisition system have been used to monitor the barrel thickness and barrel/screw separation during low-density polyethylene as well as high-density polyethylene extrusion in 30 mm and 50 mm twin-screw extruders. The sensors include sol-gel sprayed high temperature (HT) piezoelectric thick ceramic film ultrasonic transducers (UTs), stand-alone HTUTs and air-cooled buffer rod type sensors consisting of a room temperature UT and a non-clad or clad buffer rod to which the room temperature UT is attached. The installation and use of these sensors are non-intrusive to the extruder and non-destructive to the polymers being processed. This study has demonstrated the capability of appropriately designed ultrasonic sensors in monitoring the barrel and screw integrity at the melting, mixing and pumping zones of the extruder via barrel or flange. The merits and limitations of these sensors are discussed. The measurement speed and analysis of the sensitivity for quantitative wear measurements are also presented.

Autotransporter structure reveals intra-barrel cleavage followed by conformational changes.

PubMed

Barnard, Travis J; Dautin, Nathalie; Lukacik, Petra; Bernstein, Harris D; Buchanan, Susan K

2007-12-01

Autotransporters are virulence factors produced by Gram-negative bacteria. They consist of two domains, an N-terminal 'passenger' domain and a C-terminal beta-domain. beta-domains form beta-barrel structures in the outer membrane while passenger domains are translocated into the extracellular space. In some autotransporters, the two domains are separated by proteolytic cleavage. Using X-ray crystallography, we solved the 2.7-A structure of the post-cleavage state of the beta-domain of EspP, an autotransporter produced by Escherichia coli strain O157:H7. The structure consists of a 12-stranded beta-barrel with the passenger domain-beta-domain cleavage junction located inside the barrel pore, approximately midway between the extracellular and periplasmic surfaces of the outer membrane. The structure reveals an unprecedented intra-barrel cleavage mechanism and suggests that two conformational changes occur in the beta-domain after cleavage, one conferring increased stability on the beta-domain and another restricting access to the barrel pore.

Effect of Friction on Barreling during cold Upset Forging of Aluminium 6082 Alloy Solid cylinders

NASA Astrophysics Data System (ADS)

Priyadarshini, Amrita; Kiran, C. P.; Suresh, K.

2018-03-01

Friction is one of the significant factors in forging operations since it affects metal flow in the die, forming load, strain distribution, tool and die life, surface quality of the product etc. In upset forging, the frictional forces at the die-workpiece interface oppose the outward flow of the material due to which the specimen develops a barrel shape. As a result, the deformation becomes non-uniform or inhomogeneous which is undesirable. Barreling can be reduced by applying effective lubricant on the surface of the platens. The objective of the present work is to study experimentally the effect of various frictional conditions (dry, grease, mineral oil) on barreling during upset forging of aluminum 6082 solid cylinders of different aspect ratio (length/diameter: 0.5, 0.75, 1). The friction coefficients are determined using the ring compression test. Curvature of barrel is determined based on the assumption that the curvature of the barrel follows the geometry of circular arc.

Consumer demand for green stormwater management technology in an urban setting: The case of Chicago rain barrels

NASA Astrophysics Data System (ADS)

Ando, Amy W.; Freitas, Luiz P. C.

2011-12-01

Hydrological disruption and water pollution from urbanization can be reduced if households in urban areas adopt decentralized storm water controls. We study a citywide municipal subsidized rain-barrel program in the third biggest city in the United States, Chicago, to explore what factors influence whether households purchase this sort of green storm water management technology in an urban setting. Specifically, we regress census-tract level data on the number of rain barrels adopted in different parts of the city on socioeconomic variables, data on local flood frequency, and features of the housing stock. We find that rain-barrel purchases are not correlated with local levels of flooding, even though city residents were told by program managers that rain barrels could alleviate local flooding. Instead, rain barrels are heavily concentrated in places with high-income attitudinally green populations. We do find more rain barrels were adopted in places close to rain-barrel distribution points and near sites of hydrological information campaigns; thus, policy makers might increase green-technology adoption in areas where they can do the most good by reducing transaction costs and providing education programs to those areas. Finally, our results indicate that owner occupancy is positively correlated with green-technology adoption. Low-rise rental housing may have inefficiently low levels of adoption, such that city managers might want to develop programs to encourage storm water management investments by landlords who do not live in their own properties.

Globally intertwined evolutionary history of giant barrel sponges

NASA Astrophysics Data System (ADS)

Swierts, Thomas; Peijnenburg, Katja T. C. A.; de Leeuw, Christiaan A.; Breeuwer, Johannes A. J.; Cleary, Daniel F. R.; de Voogd, Nicole J.

2017-09-01

Three species of giant barrel sponge are currently recognized in two distinct geographic regions, the tropical Atlantic and the Indo-Pacific. In this study, we used molecular techniques to study populations of giant barrel sponges across the globe and assessed whether the genetic structure of these populations agreed with current taxonomic consensus or, in contrast, whether there was evidence of cryptic species. Using molecular data, we assessed whether giant barrel sponges in each oceanic realm represented separate monophyletic lineages. Giant barrel sponges from 17 coral reef systems across the globe were sequenced for mitochondrial (partial CO1 and ATP6 genes) and nuclear (ATPsβ intron) DNA markers. In total, we obtained 395 combined sequences of the mitochondrial CO1 and ATP6 markers, which resulted in 17 different haplotypes. We compared a phylogenetic tree constructed from 285 alleles of the nuclear intron ATPsβ to the 17 mitochondrial haplotypes. Congruent patterns between mitochondrial and nuclear gene trees of giant barrel sponges provided evidence for the existence of multiple reproductively isolated species, particularly where they occurred in sympatry. The species complexes in the tropical Atlantic and the Indo-Pacific, however, do not form separate monophyletic lineages. This rules out the scenario that one species of giant barrel sponge developed into separate species complexes following geographic separation and instead suggests that multiple species of giant barrel sponges already existed prior to the physical separation of the Indo-Pacific and tropical Atlantic.

Network analysis of corticocortical connections reveals ventral and dorsal processing streams in mouse visual cortex

PubMed Central

Wang, Quanxin; Sporns, Olaf; Burkhalter, Andreas

2012-01-01

Much of the information used for visual perception and visually guided actions is processed in complex networks of connections within the cortex. To understand how this works in the normal brain and to determine the impact of disease, mice are promising models. In primate visual cortex, information is processed in a dorsal stream specialized for visuospatial processing and guided action and a ventral stream for object recognition. Here, we traced the outputs of 10 visual areas and used quantitative graph analytic tools of modern network science to determine, from the projection strengths in 39 cortical targets, the community structure of the network. We found a high density of the cortical graph that exceeded that previously shown in monkey. Each source area showed a unique distribution of projection weights across its targets (i.e. connectivity profile) that was well-fit by a lognormal function. Importantly, the community structure was strongly dependent on the location of the source area: outputs from medial/anterior extrastriate areas were more strongly linked to parietal, motor and limbic cortex, whereas lateral extrastriate areas were preferentially connected to temporal and parahippocampal cortex. These two subnetworks resemble dorsal and ventral cortical streams in primates, demonstrating that the basic layout of cortical networks is conserved across species. PMID:22457489

40 CFR 52.987 - Control of hydrocarbon emissions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... control systems on a 37,500 barrel capacity crude oil storage tank at Cities Service Pipeline Company, Oil... a 25,000 barrel capacity crude oil storage tank at Cities Service Pipeline Company, Haynesville... barrel capacity crude oil storage tank at Cities Service Pipeline Company, Summerfield, Louisiana with...

40 CFR 52.987 - Control of hydrocarbon emissions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... control systems on a 37,500 barrel capacity crude oil storage tank at Cities Service Pipeline Company, Oil... a 25,000 barrel capacity crude oil storage tank at Cities Service Pipeline Company, Haynesville... barrel capacity crude oil storage tank at Cities Service Pipeline Company, Summerfield, Louisiana with...

40 CFR 52.987 - Control of hydrocarbon emissions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... control systems on a 37,500 barrel capacity crude oil storage tank at Cities Service Pipeline Company, Oil... a 25,000 barrel capacity crude oil storage tank at Cities Service Pipeline Company, Haynesville... barrel capacity crude oil storage tank at Cities Service Pipeline Company, Summerfield, Louisiana with...

Infectious Progression of Canine Distemper Virus from Circulating Cerebrospinal Fluid into the Central Nervous System.

PubMed

Takenaka, Akiko; Sato, Hiroki; Ikeda, Fusako; Yoneda, Misako; Kai, Chieko

2016-10-15

In the current study, we generated recombinant chimeric canine distemper viruses (CDVs) by replacing the hemagglutinin (H) and/or phosphoprotein (P) gene in an avirulent strain expressing enhanced green fluorescent protein (EGFP) with those of a mouse-adapted neurovirulent strain. An in vitro experimental infection indicated that the chimeric CDVs possessing the H gene derived from the mouse-adapted CDV acquired infectivity for neural cells. These cells lack the CDV receptors that have been identified to date (SLAM and nectin-4), indicating that the H protein defines infectivity in various cell lines. The recombinant viruses were administered intracerebrally to 1-week-old mice. Fatal neurological signs of disease were observed only with a recombinant CDV that possessed both the H and P genes of the mouse-adapted strain, similar to the parental mouse-adapted strain, suggesting that both genes are important to drive virulence of CDV in mice. Using this recombinant CDV, we traced the intracerebral propagation of CDV by detecting EGFP. Widespread infection was observed in the cerebral hemispheres and brainstems of the infected mice. In addition, EGFP fluorescence in the brain slices demonstrated a sequential infectious progression in the central nervous system: CDV primarily infected the neuroependymal cells lining the ventricular wall and the neurons of the hippocampus and cortex adjacent to the ventricle, and it then progressed to an extensive infection of the brain surface, followed by the parenchyma and cortex. In the hippocampal formation, CDV spread in a unidirectional retrograde pattern along neuronal processes in the hippocampal formation from the CA1 region to the CA3 region and the dentate gyrus. Our mouse model demonstrated that the main target cells of CDV are neurons in the acute phase and that the virus spreads via neuronal transmission pathways in the hippocampal formation. CDV is the etiological agent of distemper in dogs and other carnivores, and in many respects, the pathogenesis of CDV infection in animals resembles that of measles virus infection in humans. We successfully generated a recombinant CDV containing the H and P genes from a mouse-adapted neurovirulent strain and expressing EGFP. The recombinant CDV exhibited severe neurovirulence with high mortality, comparable to the parental mouse-adapted strain. The mouse-infectious model could become a useful tool for analyzing CDV infection of the central nervous system subsequent to passing through the blood-cerebrospinal fluid barrier and infectious progression in the target cells in acute disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Infectious Progression of Canine Distemper Virus from Circulating Cerebrospinal Fluid into the Central Nervous System

PubMed Central

Takenaka, Akiko; Sato, Hiroki; Ikeda, Fusako; Yoneda, Misako

2016-01-01

ABSTRACT In the current study, we generated recombinant chimeric canine distemper viruses (CDVs) by replacing the hemagglutinin (H) and/or phosphoprotein (P) gene in an avirulent strain expressing enhanced green fluorescent protein (EGFP) with those of a mouse-adapted neurovirulent strain. An in vitro experimental infection indicated that the chimeric CDVs possessing the H gene derived from the mouse-adapted CDV acquired infectivity for neural cells. These cells lack the CDV receptors that have been identified to date (SLAM and nectin-4), indicating that the H protein defines infectivity in various cell lines. The recombinant viruses were administered intracerebrally to 1-week-old mice. Fatal neurological signs of disease were observed only with a recombinant CDV that possessed both the H and P genes of the mouse-adapted strain, similar to the parental mouse-adapted strain, suggesting that both genes are important to drive virulence of CDV in mice. Using this recombinant CDV, we traced the intracerebral propagation of CDV by detecting EGFP. Widespread infection was observed in the cerebral hemispheres and brainstems of the infected mice. In addition, EGFP fluorescence in the brain slices demonstrated a sequential infectious progression in the central nervous system: CDV primarily infected the neuroependymal cells lining the ventricular wall and the neurons of the hippocampus and cortex adjacent to the ventricle, and it then progressed to an extensive infection of the brain surface, followed by the parenchyma and cortex. In the hippocampal formation, CDV spread in a unidirectional retrograde pattern along neuronal processes in the hippocampal formation from the CA1 region to the CA3 region and the dentate gyrus. Our mouse model demonstrated that the main target cells of CDV are neurons in the acute phase and that the virus spreads via neuronal transmission pathways in the hippocampal formation. IMPORTANCE CDV is the etiological agent of distemper in dogs and other carnivores, and in many respects, the pathogenesis of CDV infection in animals resembles that of measles virus infection in humans. We successfully generated a recombinant CDV containing the H and P genes from a mouse-adapted neurovirulent strain and expressing EGFP. The recombinant CDV exhibited severe neurovirulence with high mortality, comparable to the parental mouse-adapted strain. The mouse-infectious model could become a useful tool for analyzing CDV infection of the central nervous system subsequent to passing through the blood-cerebrospinal fluid barrier and infectious progression in the target cells in acute disease. PMID:27489268

15 CFR 240.5 - Required marking.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE STANDARDS FOR BARRELS BARRELS AND OTHER CONTAINERS FOR LIME § 240.5 Required marking. (a) The lettering required upon barrels of lime by section 2 of the law shall... lime and where manufactured, and, if imported, the name of the country from which it is imported, shall...

75 FR 6706 - In the Matter of Certain Foldable Stools; Notice of Commission Decision Not To Review an Initial...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-10

... Distributing and Crate & Barrel with ``LTD Commodities, LLC, d/b/a abc Distributing'' and ``Euromarket Designs... of investigation named several respondents including the following: abc Distributing Inc. (``abc Distributing'') of Bannockburn, Illinois; Crate & Barrel, Inc. (``Crate & Barrel'') of Northbrook, Illinois...

27 CFR 25.141 - Barrels and kegs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Barrels and kegs. 25.141 Section 25.141 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Marks, Brands, and Labels § 25.141 Barrels and kegs. (a) General...

10. OBLIQUE VIEW, PORTION OF SPANDREL WALL AND ARCH BARREL, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. OBLIQUE VIEW, PORTION OF SPANDREL WALL AND ARCH BARREL, FROM SOUTHEAST, SHOWING INTRADOS AND EXTRADOS, JUNCTURE OF BRICK BARREL AND CUT STONE MASONRY FACING STONES, TIE ROD CAPS, AND CONCRETE PARAPET EXTENSION - Boston Street Bridge, Spanning Harris Creek Sewer at Boston Street, Baltimore, Independent City, MD

Parallel beta/alpha-barrels of alpha-amylase, cyclodextrin glycosyltransferase and oligo-1,6-glucosidase versus the barrel of beta-amylase: evolutionary distance is a reflection of unrelated sequences.

PubMed

Janecek, S

1994-10-17

The structures of functionally related beta/alpha-barrel starch hydrolases, alpha-amylase, beta-amylase, cyclodextrin glycosyltransferase and oligo-1,6-glucosidase, are discussed, their mutual sequence similarities being emphasized. Since these enzymes (except for beta-amylase) along with the predicted set of more than ten beta/alpha-barrels from the alpha-amylase enzyme superfamily fulfil the criteria characteristic of the products of divergent evolution, their unrooted distance tree is presented.

Role of Hydrophobic Clusters and Long-Range Contact Networks in the Folding of (α/β)8 Barrel Proteins

PubMed Central

Selvaraj, S.; Gromiha, M. Michael

2003-01-01

Analysis on the three dimensional structures of (α/β)8 barrel proteins provides ample light to understand the factors that are responsible for directing and maintaining their common fold. In this work, the hydrophobically enriched clusters are identified in 92% of the considered (α/β)8 barrel proteins. The residue segments with hydrophobic clusters have high thermal stability. Further, these clusters are formed and stabilized through long-range interactions. Specifically, a network of long-range contacts connects adjacent β-strands of the (α/β)8 barrel domain and the hydrophobic clusters. The implications of hydrophobic clusters and long-range networks in providing a feasible common mechanism for the folding of (α/β)8 barrel proteins are proposed. PMID:12609894

Stress-opioid interactions: a comparison of morphine and methadone.

PubMed

Taracha, Ewa; Mierzejewski, Paweł; Lehner, Małgorzata; Chrapusta, Stanisław J; Kała, Maria; Lechowicz, Wojciech; Hamed, Adam; Skórzewska, Anna; Kostowski, Wojciech; Płaźnik, Adam

2009-01-01

The utility of methadone and morphine for analgesia and of methadone for substitution therapy for heroin addiction is a consequence of these drugs acting as opioid receptor agonists.We compared the cataleptogenic and antinociceptive effects of single subcutaneous doses of methadone hydrochloride (1-4 mg/kg) and morphine sulfate (2.5-10 mg/kg) using catalepsy and hot-plate tests, and examined the effects of the highest doses of the drugs on Fos protein expression in selected brain regions in male Sprague-Dawley rats. Methadone had greater cataleptogenic and analgesic potency than morphine. Fos immunohistochemistry revealed substantial effects on the Fos response of both the stress induced by the experimental procedures and of the drug exposure itself. There were three response patterns identified: 1) drug exposure, but not stress, significantly elevated Fos-positive cell counts in the caudate-putamen; 2) stress alone and stress combined with drug exposure similarly elevated Fos-positive cell counts in the nucleus accumbens and cingulate cortex; and 3) methadone and morphine (to a lesser extent) counteracted the stimulatory effect of nonpharmacological stressors on Fos protein expression in the somatosensory cortex barrel field, and Fos-positive cell counts in this region correlated negatively with both the duration of catalepsy and the latency time in the hot-plate test. The overlap between brain regions reacting to nonpharmacological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation.

Cortico-fugal output from visual cortex promotes plasticity of innate motor behaviour.

PubMed

Liu, Bao-Hua; Huberman, Andrew D; Scanziani, Massimo

2016-10-20

The mammalian visual cortex massively innervates the brainstem, a phylogenetically older structure, via cortico-fugal axonal projections. Many cortico-fugal projections target brainstem nuclei that mediate innate motor behaviours, but the function of these projections remains poorly understood. A prime example of such behaviours is the optokinetic reflex (OKR), an innate eye movement mediated by the brainstem accessory optic system, that stabilizes images on the retina as the animal moves through the environment and is thus crucial for vision. The OKR is plastic, allowing the amplitude of this reflex to be adaptively adjusted relative to other oculomotor reflexes and thereby ensuring image stability throughout life. Although the plasticity of the OKR is thought to involve subcortical structures such as the cerebellum and vestibular nuclei, cortical lesions have suggested that the visual cortex might also be involved. Here we show that projections from the mouse visual cortex to the accessory optic system promote the adaptive plasticity of the OKR. OKR potentiation, a compensatory plastic increase in the amplitude of the OKR in response to vestibular impairment, is diminished by silencing visual cortex. Furthermore, targeted ablation of a sparse population of cortico-fugal neurons that specifically project to the accessory optic system severely impairs OKR potentiation. Finally, OKR potentiation results from an enhanced drive exerted by the visual cortex onto the accessory optic system. Thus, cortico-fugal projections to the brainstem enable the visual cortex, an area that has been principally studied for its sensory processing function, to plastically adapt the execution of innate motor behaviours.

Gene expression in the rat cerebral cortex: comparison of recovery sleep and hypnotic-induced sleep.

PubMed

Wisor, J P; Morairty, S R; Huynh, N T; Steininger, T L; Kilduff, T S

2006-08-11

Most hypnotic medications currently on the market target some aspect of GABAergic neurotransmission. Although all such compounds increase sleep, these drugs differentially affect the activity of the cerebral cortex as measured by the electroencephalogram. Whereas benzodiazepine medications such as triazolam tend to suppress slow wave activity in the cortex, the GABA(B) ligand gamma-hydroxybutyrate greatly enhances slow wave activity and the non-benzodiazepine, zolpidem, which binds to the omega1 site on the GABA(A) receptor/Cl(-) ionophore complex, is intermediate in this regard. Our previous studies have demonstrated that a small number of genes exhibit increased expression in the cerebral cortex of the mouse and rat during recovery sleep after sleep deprivation: egr-3, fra-2, grp78, grp94, ngfi-b, and nr4a3. Using these genes as a panel of biomarkers associated with sleep, we asked whether hypnotic medications induce similar molecular changes in the rat cerebral cortex to those observed when both sleep continuity and slow wave activity are enhanced during recovery sleep. We find that, although each drug increases the expression of a subset of genes in the panel of biomarkers, no drug fully replicates the molecular changes in the cortex associated with recovery sleep. Furthermore, high levels of slow wave activity in the cortex are correlated with increased expression of fra-2 whereas the expression of grp94 is correlated with body temperature. These results demonstrate that sleep-related changes in gene expression may be affected by physiological covariates of sleep and wakefulness rather than by vigilance state per se.

Demonstration of neuron-glia transfer of precursors for GABA biosynthesis in a co-culture system of dissociated mouse cerebral cortex.

PubMed

Leke, Renata; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

2008-12-01

Co-cultures of neurons and astrocytes were prepared from dissociated embryonic mouse cerebral cortex and cultured for 7 days. To investigate if these cultures may serve as a functional model system to study neuron-glia interaction with regard to GABA biosynthesis, the cells were incubated either in media containing [U-(13)C]glutamine (0.1, 0.3 and 0.5 mM) or 1 mM acetate plus 2.5 mM glucose plus 1 mM lactate. In the latter case one of the 3 substrates was uniformly (13)C labeled. Cellular contents and (13)C labeling of glutamate, GABA, aspartate and glutamine were determined in the cells after an incubation period of 2.5 h. The GABA biosynthetic machinery exhibited the expected complexity with regard to metabolic compartmentation and involvement of TCA cycle activity as seen in other culture systems containing GABAergic neurons. Metabolism of acetate clearly demonstrated glial synthesis of glutamine and its transfer to the neuronal compartment. It is concluded that this co-culture system serves as a reliable model in which functional and pharmacological aspects of GABA biosynthesis can be investigated.

Microvascular basis for growth of small infarcts following occlusion of single penetrating arterioles in mouse cortex

PubMed Central

Taylor, Zachary J; Hui, Edward S; Watson, Ashley N; Nie, Xingju; Deardorff, Rachael L; Jensen, Jens H; Helpern, Joseph A

2015-01-01

Small cerebral infarcts, i.e. microinfarcts, are common in the aging brain and linked to vascular cognitive impairment. However, little is known about the acute growth of these minute lesions and their effect on blood flow in surrounding tissues. We modeled microinfarcts in the mouse cortex by inducing photothrombotic clots in single penetrating arterioles. The resultant hemodynamic changes in tissues surrounding the occluded vessel were then studied using in vivo two-photon microscopy. We were able to generate a spectrum of infarct volumes by occluding arterioles that carried a range of blood fluxes. Those resulting from occlusion of high-flux penetrating arterioles (flux of 2 nL/s or higher) exhibited a radial outgrowth that encompassed unusually large tissue volumes. The gradual expansion of these infarcts was propagated by an evolving insufficiency in capillary flow that encroached on territories of neighboring penetrating arterioles, leading to the stagnation and recruitment of their perfusion domains into the final infarct volume. Our results suggest that local collapse of microvascular function contributes to tissue damage incurred by single penetrating arteriole occlusions in mice, and that a similar mechanism may add to pathophysiology induced by microinfarcts of the human brain. PMID:26661182

Target dependence of orientation and direction selectivity of corticocortical projection neurons in the mouse V1

PubMed Central

Matsui, Teppei; Ohki, Kenichi

2013-01-01

Higher order visual areas that receive input from the primary visual cortex (V1) are specialized for the processing of distinct features of visual information. However, it is still incompletely understood how this functional specialization is acquired. Here we used in vivo two photon calcium imaging in the mouse visual cortex to investigate whether this functional distinction exists at as early as the level of projections from V1 to two higher order visual areas, AL and LM. Specifically, we examined whether sharpness of orientation and direction selectivity and optimal spatial and temporal frequency of projection neurons from V1 to higher order visual areas match with that of target areas. We found that the V1 input to higher order visual areas were indeed functionally distinct: AL preferentially received inputs from V1 that were more orientation and direction selective and tuned for lower spatial frequency compared to projection of V1 to LM, consistent with functional differences between AL and LM. The present findings suggest that selective projections from V1 to higher order visual areas initiates parallel processing of sensory information in the visual cortical network. PMID:24068987

H3 and H4 Lysine Acetylation Correlates with Developmental and Experimentally Induced Adult Experience-Dependent Plasticity in the Mouse Visual Cortex

PubMed Central

Vierci, Gabriela; Pannunzio, Bruno; Bornia, Natalia; Rossi, Francesco M.

2016-01-01

Histone posttranslational modifications play a fundamental role in orchestrating gene expression. In this work, we analyzed the acetylation of H3 and H4 histones (AcH3–AcH4) and its modulation by visual experience in the mouse visual cortex (VC) during normal development and in two experimental conditions that restore juvenile-like plasticity levels in adults (fluoxetine treatment and enriched environment). We found that AcH3–AcH4 declines with age and is upregulated by treatments restoring plasticity in the adult. We also found that visual experience modulates AcH3–AcH4 in young and adult plasticity-restored mice but not in untreated ones. Finally, we showed that the transporter vGAT is downregulated in adult plasticity-restored models. In summary, we identified a dynamic regulation of AcH3–AcH4, which is associated with high plasticity levels and enhanced by visual experience. These data, along with recent ones, indicate H3–H4 acetylation as a central hub in the control of experience-dependent plasticity in the VC. PMID:27891053

Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism.

PubMed

Kumar, Manoj; Kim, Sungheon; Pickup, Stephen; Chen, Rong; Fairless, Andrew H; Ittyerah, Ranjit; Abel, Ted; Brodkin, Edward S; Poptani, Harish

2012-05-21

Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70 days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30 days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism

PubMed Central

Kumar, Manoj; Kim, Sungheon; Pickup, Stephen; Chen, Rong; Fairless, Andrew H.; Ittyerah, Ranjit; Abel, Ted; Brodkin, Edward S.; Poptani, Harish

2012-01-01

Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70 days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30 days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders. PMID:22513103

Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

PubMed

Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

2016-01-01

Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lever, J.R.; Hartig, P.R.; Wong, D.F.

1985-05-01

2-(/sup 125/1)-LSD binds selectively and with high affinity to serotonin S2 receptors in vitro. In the present study, the authors prepared 2-(/sup 123/1)-LSD as well as a carbon-11 labeled analog. They also characterized the in vivo binding of these tracers to receptor sites in mouse brain to assess their potential for tomographic imaging of S2 receptors in man. The temporal distribution of 2-(/sup 125/1)-LSD paralleled the density of S2 receptors. Regional selectivity was maximal after 15 minutes when tissue to cerebellum ratios were: frontal cortex (2.6), olfactory tubercles (2.4), striatum (2.3), and cortex (2.0). Preinjection of ketanserin, a potent S2more » antagonist, inhibited binding. 2-(/sup 123/1)-LSD, prepared in 20% yield from LSD and electrophilic I-123, gave similar results in vivo and may be useful for SPECT studies. The authors then synthesized N1-((/sup 11/C)-Me)-2-Br-LSD (/sup 11/C-MBL) from (/sup 11/C)-methyl iodide and 2-Br-LSD for PET imaging trials. /sup 11/C-MBL was isolated by HPLC in high chemical and radiochemical purity within 30 minutes from E.O.B. The average radiochemical yield was 20% and the specific activity was determined by U.V. spectroscopy to be up to 1300Ci/mMol (E.O.S.). 11C-MBL showed greater regional selectivity in vivo in mouse brain than 2-(/sup 125/1)-LSD. After 30 minutes, peak tissue to cerebellum ratios were: frontal cortex (5.4), olfactory tubercles (4.2), striatum (3.0), and cortex (2.8). Preinjection of ketanserin markedly inhibited /sup 11/C-MBL binding. /sup 11/C-MBL is a promising candidate for PET studies of S2 receptors.« less

Fabrication and Tests of M240 Machine Gun Barrels Lined with Stellite 25

DTIC Science & Technology

2016-04-01

ARL-TR-7662 ● APR 2016 US Army Research Laboratory Fabrication and Tests of M240 Machine Gun Barrels Lined with Stellite 25...Fabrication and Tests of M240 Machine Gun Barrels Lined with Stellite 25 by William S de Rosset and Sean Fudger Weapons and Materials Research...

Processing of Niobium-Lined M240 Machine Gun Barrels

DTIC Science & Technology

2014-11-01

different materials (the gun steel and the niobium liner). A large chunk of the niobium liner in barrel 2 was torn away from the end of the liner at...it to increase the frictional bond between the liner and gun steel . The barrels with liners were hammer forged by FN. FN experienced some...

Mutations in α-Tubulin Cause Abnormal Neuronal Migration in Mice and Lissencephaly in Humans

PubMed Central

Keays, David A.; Tian, Guoling; Poirier, Karine; Huang, Guo-Jen; Siebold, Christian; Cleak, James; Oliver, Peter L.; Fray, Martin; Harvey, Robert J.; Molnár, Zoltán; Piñon, Maria C.; Dear, Neil; Valdar, William; Brown, Steve D.M.; Davies, Kay E.; Rawlins, J. Nicholas P.; Cowan, Nicholas J.; Nolan, Patrick; Chelly, Jamel; Flint, Jonathan

2007-01-01

Summary The development of the mammalian brain is dependent on extensive neuronal migration. Mutations in mice and humans that affect neuronal migration result in abnormal lamination of brain structures with associated behavioral deficits. Here, we report the identification of a hyperactive N-ethyl-N-nitrosourea (ENU)-induced mouse mutant with abnormalities in the laminar architecture of the hippocampus and cortex, accompanied by impaired neuronal migration. We show that the causative mutation lies in the guanosine triphosphate (GTP) binding pocket of α-1 tubulin (Tuba1) and affects tubulin heterodimer formation. Phenotypic similarity with existing mouse models of lissencephaly led us to screen a cohort of patients with developmental brain anomalies. We identified two patients with de novo mutations in TUBA3, the human homolog of Tuba1. This study demonstrates the utility of ENU mutagenesis in the mouse as a means to discover the basis of human neurodevelopmental disorders. PMID:17218254

Lovastatin regulates brain spontaneous low-frequency brain activity in Neurofibromatosis type 1

PubMed Central

Chabernaud, Camille; Mennes, Maarten; Kardel, Peter G.; Gaillard, William D.; Kalbfleisch, M. Layne; VanMeter, John W.; Packer, Roger J.; Milham, Michael P.; Castellanos, Francisco X.; Acosta, Maria T.

2012-01-01

In the Neurofibromatosis type 1 (NF1) mouse model, lovastatin, used clinically for hypercholesterolemia, improves cognitive dysfunction. While such impairment has been studied in NF1, the neural substrates remain unclear. The aim of this imaging add-on to a phase-1 open-label trial was to examine the effect of lovastatin on Default Network (DN) resting state functional connectivity (RSFC). Seven children with NF1 (aged 11.9±2.2; 1 female) were treated with lovastatin once daily for 12 weeks. A 7-minute 3-Tesla echo-planar-imaging scan was collected one day before beginning treatment (off-drug) and the last day of treatment (on-drug) while performing a Flanker task. After regressing-out task-associated variance, we used the residual time series as “continuous resting-state data” for RSFC analyses using 11 DN regions of interest. For qualitative comparisons, we included a group of 19 typically developing children (TDC) collected elsewhere. In the on-drug condition, lovastatin increased long-range positive RSFC within DN core regions (i.e., anterior medial prefrontal cortex and posterior cingulate cortex, PCC). In addition, lovastatin produced less diffuse local RSFC in the dorsomedial prefrontal cortex and PCC. The pattern of RSFC observed in the NF1 participants when on-drug closely resembled the RSFC patterns exhibited by the TDC. Lovastatin administration in this open trial regulated anterior-posterior long-range and local RSFC within the DN. These preliminary results are consistent with a role for lovastatin in normalization of developmental processes and with apparent benefits in a mouse NF1 model. PMID:22433254

Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex123

PubMed Central

Phoumthipphavong, Victoria; Barthas, Florent; Hassett, Samantha

2016-01-01

Abstract A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal effects of ketamine on structural plasticity remain unclear. The purpose of the current study is to use subcellular resolution optical imaging to determine the time course of dendritic alterations in vivo following systemic ketamine administration in mice. We used two-photon microscopy to visualize repeatedly the same set of dendritic branches in the mouse medial frontal cortex (MFC) before and after a single injection of ketamine or saline. Compared to controls, ketamine-injected mice had higher dendritic spine density in MFC for up to 2 weeks. This prolonged increase in spine density was driven by an elevated spine formation rate, and not by changes in the spine elimination rate. A fraction of the new spines following ketamine injection was persistent, which is indicative of functional synapses. In a few cases, we also observed retraction of distal apical tuft branches on the day immediately after ketamine administration. These results indicate that following systemic ketamine administration, certain dendritic inputs in MFC are removed immediately, while others are added gradually. These dynamic structural modifications are consistent with a model of ketamine action in which the net effect is a rebalancing of synaptic inputs received by frontal cortical neurons. PMID:27066532

Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

PubMed

Ikeda, Ritsuko; Kurokawa, Manae S; Chiba, Shunmei; Yoshikawa, Hideshi; Hashimoto, Takuo; Tadokoro, Mamoru; Suzuki, Noboru

2004-10-01

Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

Knockdown of Myo-Inositol Transporter SMIT1 Normalizes Cholinergic and Glutamatergic Function in an Immortalized Cell Line Established from the Cerebral Cortex of a Trisomy 16 Fetal Mouse, an Animal Model of Human Trisomy 21 (Down Syndrome).

PubMed

Cárdenas, Ana María; Fernández-Olivares, Paola; Díaz-Franulic, Ignacio; González-Jamett, Arlek M; Shimahara, Takeshi; Segura-Aguilar, Juan; Caviedes, Raúl; Caviedes, Pablo

2017-11-01

The Na + /myo-inositol cotransporter (SMIT1) is overexpressed in human Down syndrome (DS) and in trisomy 16 fetal mice (Ts16), an animal model of the human condition. SMIT1 overexpression determines increased levels of intracellular myo-inositol, a precursor of phophoinositide synthesis. SMIT1 is overexpressed in CTb cells, an immortalized cell line established from the cerebral cortex of a Ts16 mouse fetus. CTb cells exhibit impaired cytosolic Ca 2+ signals in response to glutamatergic and cholinergic stimuli (increased amplitude and delayed time-dependent kinetics in the decay post-stimulation), compared to our CNh cell line, derived from the cerebral cortex of a euploid animal. Considering the role of myo-inositol in intracellular signaling, we normalized SMIT1 expression in CTb cells using specific mRNA antisenses. Forty-eight hours post-transfection, SMIT1 levels in CTb cells reached values comparable to those of CNh cells. At this time, decay kinetics of Ca 2+ signals induced by either glutamate, nicotine, or muscarine were accelerated in transfected CTb cells, to values similar to those of CNh cells. The amplitude of glutamate-induced cytosolic Ca 2+ signals in CTb cells was also normalized. The results suggest that SMIT1 overexpression contributes to abnormal cholinergic and glutamatergic Ca 2+ signals in the trisomic condition, and knockdown of DS-related genes in our Ts16-derived cell line could constitute a relevant tool to study DS-related neuronal dysfunction.

Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice.

PubMed

Hara, Yuta; Ago, Yukio; Taruta, Atsuki; Hasebe, Shigeru; Kawase, Haruki; Tanabe, Wataru; Tsukada, Shinji; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-11-01

Rodents exposed prenatally to valproic acid (VPA) exhibit autism spectrum disorder (ASD)-like behavioral abnormalities. We recently found that prenatal VPA exposure causes hypofunction of the prefrontal dopaminergic system in mice. This suggests that the dopaminergic system may be a potential pharmacological target for treatment of behavioral abnormalities in ASD patients. In the present study, we examined the effects of antipsychotic drugs, which affect the dopaminergic system, on the social interaction deficits, recognition memory impairment, and reduction in dendritic spine density in the VPA mouse model of ASD. Both acute and chronic administrations of the atypical antipsychotic drugs risperidone and aripiprazole increased prefrontal dopamine (DA) release, while the typical antipsychotic drug haloperidol did not. Chronic risperidone and aripiprazole, but not haloperidol, increased the expression of c-Fos in the prefrontal cortex, although they all increased c-Fos expression in the striatum. Chronic, but not acute, administrations of risperidone and aripiprazole improved the VPA-induced social interaction deficits and recognition memory impairment, as well as the reduction in dendritic spine density in the prefrontal cortex and hippocampus. In contrast, chronic administration of haloperidol did not ameliorate VPA-induced abnormalities in behaviors and dendritic spine density. These findings indicate that chronic risperidone and aripiprazole treatments improve VPA-induced abnormalities in behaviors and prefrontal dendritic spine density, which may be mediated by repeated elevation of extracellular DA in the prefrontal cortex. Our results also imply that loss of prefrontal dendritic spines may be involved in the abnormal behaviors in the VPA mouse model of ASD.

High performance railgun barrels for laboratory use

NASA Astrophysics Data System (ADS)

Bauer, David P.; Newman, Duane C.

1993-01-01

High performance low-cost, laboratory railgun barrels are now available, comprised of an inherently stiff containment structure which surrounds the bore components machined from 'off the-shelf' materials. The shape of the containment structure was selected to make the barrel inherently stiff. The structure consists of stainless steel laminations which do not compromise the electrical efficiency of the railgun. The modular design enhances the utility of the barrel, as it is easy to service between shots, and can be 're-cored' to produce different configurations and sizes using the same structure. We have produced barrels ranging from 15 mm to 90 mm square bore, a 30 mm round bore, and in lengths varying from 0.25 meters to 10 meters long. Successful tests with both plasma and solid metal armatures have demonstrated the versatility and performance of this design.

An outbreak of norovirus-associated acute gastroenteritis associated with contaminated barrelled water in many schools in Zhejiang, China

PubMed Central

Sheng, Minyang; Song, Jianqiang; He, Fan; Qiu, Yinwei; Wu, Haocheng; Lu, Qinbao; Feng, Yan; Lin, Junfen; Chen, Enfu; Chai, Chengliang

2017-01-01

Objectives More than 900 students and teachers at many schools in Jiaxing city developed acute gastroenteritis in February 2014. An immediate epidemiological investigation was conducted to identify the pathogen, infection sources and route of transmission. Methods The probable cases and confirmed cases were defined as students or teachers with diarrhoea or vomiting present since the term began in February 2014. An active search was conducted for undiagnosed cases among students and teachers. Details such as demographic characteristics, gastrointestinal symptoms, and drinking water preference and frequency were collected via a uniform epidemiological questionnaire. A case-control study was implemented, and odds ratios (ORs) and 95% confidence intervals were calculated. Rectal swabs from several patients, food handlers and barrelled water factory workers, as well as water and food samples, were collected to test for potential bacteria and viruses. Results A total of 924 cases fit the definition of the probable case, including 8 cases of laboratory-confirmed norovirus infection at 13 schools in Jiaxing city between February 12 and February 21, 2014. The case-control study demonstrated that barrelled water was a risk factor (OR: 20.15, 95% CI: 2.59–156.76) and that bottled water and boiled barrelled water were protective factors (OR: 0.31, 95% CI: 0.13–0.70, and OR: 0.36, 95% CI: 0.16–0.77). A total of 11 rectal samples and 8 barrelled water samples were detected as norovirus-positive, and the genotypes of viral strains were the same (GII). The norovirus that contaminated the barrelled water largely came from the asymptomatic workers. Conclusions This acute gastroenteritis outbreak was caused by barrelled water contaminated by norovirus. The outbreak was controlled after stopping the supply of barrelled water. The barrelled water supply in China represents a potential source of acute gastroenteritis outbreaks due to the lack of surveillance and supervision. Therefore, more attention should be paid to this area. PMID:28170414

An outbreak of norovirus-associated acute gastroenteritis associated with contaminated barrelled water in many schools in Zhejiang, China.

PubMed

Shang, Xiaopeng; Fu, Xiaofei; Zhang, Peng; Sheng, Minyang; Song, Jianqiang; He, Fan; Qiu, Yinwei; Wu, Haocheng; Lu, Qinbao; Feng, Yan; Lin, Junfen; Chen, Enfu; Chai, Chengliang

2017-01-01

More than 900 students and teachers at many schools in Jiaxing city developed acute gastroenteritis in February 2014. An immediate epidemiological investigation was conducted to identify the pathogen, infection sources and route of transmission. The probable cases and confirmed cases were defined as students or teachers with diarrhoea or vomiting present since the term began in February 2014. An active search was conducted for undiagnosed cases among students and teachers. Details such as demographic characteristics, gastrointestinal symptoms, and drinking water preference and frequency were collected via a uniform epidemiological questionnaire. A case-control study was implemented, and odds ratios (ORs) and 95% confidence intervals were calculated. Rectal swabs from several patients, food handlers and barrelled water factory workers, as well as water and food samples, were collected to test for potential bacteria and viruses. A total of 924 cases fit the definition of the probable case, including 8 cases of laboratory-confirmed norovirus infection at 13 schools in Jiaxing city between February 12 and February 21, 2014. The case-control study demonstrated that barrelled water was a risk factor (OR: 20.15, 95% CI: 2.59-156.76) and that bottled water and boiled barrelled water were protective factors (OR: 0.31, 95% CI: 0.13-0.70, and OR: 0.36, 95% CI: 0.16-0.77). A total of 11 rectal samples and 8 barrelled water samples were detected as norovirus-positive, and the genotypes of viral strains were the same (GII). The norovirus that contaminated the barrelled water largely came from the asymptomatic workers. This acute gastroenteritis outbreak was caused by barrelled water contaminated by norovirus. The outbreak was controlled after stopping the supply of barrelled water. The barrelled water supply in China represents a potential source of acute gastroenteritis outbreaks due to the lack of surveillance and supervision. Therefore, more attention should be paid to this area.

Ballooning in the constant sun of the South Pole summer

NASA Image and Video Library

2017-12-08

Researchers communicate with the BARREL ground station during preparations for launch. The white box in the background is the science payload and the orange and white parachute can be seen on the ground in front of it. On the left is BARREL Principal Investigator Robyn Millan of Dartmouth College in Hanover, N.H.; on the right is BARREL Co-Investigator Michael McCarthy of the University of Washington in Seattle. Credit: NASA/Goddard/BARREL/M. Krzysztofowicz Read more: www.nasa.gov/content/goddard/nasas-barrel-returns-success... -- Three months, 20 balloons, and one very successful campaign. The team for NASA's BARREL – short for Balloon Array for Radiation belt Relativistic Electron Losses -- mission returned from Antarctica in March 2014. BARREL's job is to help unravel the mysterious Van Allen belts, two gigantic donuts of radiation that surround Earth, which can shrink and swell in response to incoming energy and particles from the sun and sometimes expose satellites to harsh radiation. While in Antarctica, the team launched 20 balloons carrying instruments that sense charged particles that are scattered into the atmosphere from the belts, spiraling down the magnetic fields near the South Pole. Each balloon traveled around the pole for up to three weeks. The team will coordinate the BARREL data with observations from NASA's two Van Allen Probes to better understand how occurrences in the belts relate to bursts of particles funneling down toward Earth. BARREL team members will be on hand at the USA Science and Engineering Festival in DC on April 26 and 27, 2014 for the exhibit Space Balloons: Exploring the Extremes of Space Weather. NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Localization of PPAR isotypes in the adult mouse and human brain

PubMed Central

Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B.; Mayfield, R. Dayne; Harris, R. Adron

2016-01-01

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain. PMID:27283430

Localization of PPAR isotypes in the adult mouse and human brain.

PubMed

Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B; Mayfield, R Dayne; Harris, R Adron

2016-06-10

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain.

Comparison of frailty of primary neurons, embryonic, and aging mouse cortical layers.

PubMed

Fugistier, Patrick; Vallet, Philippe G; Leuba, Geneviève; Piotton, Françoise; Marin, Pascale; Bouras, Constantin; Savioz, Armand

2014-02-01

Superficial layers I to III of the human cerebral cortex are more vulnerable toward Aβ peptides than deep layers V to VI in aging. Three models of layers were used to investigate this pattern of frailty. First, primary neurons from E14 and E17 embryonic murine cortices, corresponding respectively to future deep and superficial layers, were treated either with Aβ(1-42), okadaic acid, or kainic acid. Second, whole E14 and E17 embryonic cortices, and third, in vitro separated deep and superficial layers of young and old C57BL/6J mice, were treated identically. We observed that E14 and E17 neurons in culture were prone to death after the Aβ and particularly the kainic acid treatment. This was also the case for the superficial layers of the aged cortex, but not for the embryonic, the young cortex, and the deep layers of the aged cortex. Thus, the aged superficial layers appeared to be preferentially vulnerable against Aβ and kainic acid. This pattern of vulnerability corresponds to enhanced accumulation of senile plaques in the superficial cortical layers with aging and Alzheimer's disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Evolution and development of the mammalian cerebral cortex.

PubMed

Molnár, Zoltán; Kaas, Jon H; de Carlos, Juan A; Hevner, Robert F; Lein, Ed; Němec, Pavel

2014-01-01

Comparative developmental studies of the mammalian brain can identify key changes that can generate the diverse structures and functions of the brain. We have studied how the neocortex of early mammals became organized into functionally distinct areas, and how the current level of cortical cellular and laminar specialization arose from the simpler premammalian cortex. We demonstrate the neocortical organization in early mammals, which helps to elucidate how the large, complex human brain evolved from a long line of ancestors. The radial and tangential enlargement of the cortex was driven by changes in the patterns of cortical neurogenesis, including alterations in the proportions of distinct progenitor types. Some cortical cell populations travel to the cortex through tangential migration whereas others migrate radially. A number of recent studies have begun to characterize the chick, mouse and human and nonhuman primate cortical transcriptome to help us understand how gene expression relates to the development and anatomical and functional organization of the adult neocortex. Although all mammalian forms share the basic layout of cortical areas, the areal proportions and distributions are driven by distinct evolutionary pressures acting on sensory and motor experiences during the individual ontogenies. © 2014 S. Karger AG, Basel.

GiniClust: detecting rare cell types from single-cell gene expression data with Gini index.

PubMed

Jiang, Lan; Chen, Huidong; Pinello, Luca; Yuan, Guo-Cheng

2016-07-01

High-throughput single-cell technologies have great potential to discover new cell types; however, it remains challenging to detect rare cell types that are distinct from a large population. We present a novel computational method, called GiniClust, to overcome this challenge. Validation against a benchmark dataset indicates that GiniClust achieves high sensitivity and specificity. Application of GiniClust to public single-cell RNA-seq datasets uncovers previously unrecognized rare cell types, including Zscan4-expressing cells within mouse embryonic stem cells and hemoglobin-expressing cells in the mouse cortex and hippocampus. GiniClust also correctly detects a small number of normal cells that are mixed in a cancer cell population.

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

PubMed

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.

Primary Auditory Cortex is Required for Anticipatory Motor Response.

PubMed

Li, Jingcheng; Liao, Xiang; Zhang, Jianxiong; Wang, Meng; Yang, Nian; Zhang, Jun; Lv, Guanghui; Li, Haohong; Lu, Jian; Ding, Ran; Li, Xingyi; Guang, Yu; Yang, Zhiqi; Qin, Han; Jin, Wenjun; Zhang, Kuan; He, Chao; Jia, Hongbo; Zeng, Shaoqun; Hu, Zhian; Nelken, Israel; Chen, Xiaowei

2017-06-01

The ability of the brain to predict future events based on the pattern of recent sensory experience is critical for guiding animal's behavior. Neocortical circuits for ongoing processing of sensory stimuli are extensively studied, but their contributions to the anticipation of upcoming sensory stimuli remain less understood. We, therefore, used in vivo cellular imaging and fiber photometry to record mouse primary auditory cortex to elucidate its role in processing anticipated stimulation. We found neuronal ensembles in layers 2/3, 4, and 5 which were activated in relationship to anticipated sound events following rhythmic stimulation. These neuronal activities correlated with the occurrence of anticipatory motor responses in an auditory learning task. Optogenetic manipulation experiments revealed an essential role of such neuronal activities in producing the anticipatory behavior. These results strongly suggest that the neural circuits of primary sensory cortex are critical for coding predictive information and transforming it into anticipatory motor behavior. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome.

PubMed

Huang, Wen-Chin; Chen, Youjun; Page, Damon T

2016-11-15

Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten +/- ), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten +/- mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits. The latter two phenotypes can be suppressed by pharmacological inhibition of S6K1 during early postnatal life or by reducing the activity of mPFC-BLA circuitry in adulthood. These findings identify a mechanism of altered connectivity that has potential relevance to the pathophysiology of macrocephaly/autism syndrome and autism spectrum disorders featuring dysregulated mTOR signalling.

Electrical activity controls area-specific expression of neuronal apoptosis in the mouse developing cerebral cortex.

PubMed

Blanquie, Oriane; Yang, Jenq-Wei; Kilb, Werner; Sharopov, Salim; Sinning, Anne; Luhmann, Heiko J

2017-08-21

Programmed cell death widely but heterogeneously affects the developing brain, causing the loss of up to 50% of neurons in rodents. However, whether this heterogeneity originates from neuronal identity and/or network-dependent processes is unknown. Here, we report that the primary motor cortex (M1) and primary somatosensory cortex (S1), two adjacent but functionally distinct areas, display striking differences in density of apoptotic neurons during the early postnatal period. These differences in rate of apoptosis negatively correlate with region-dependent levels of activity. Disrupting this activity either pharmacologically or by electrical stimulation alters the spatial pattern of apoptosis and sensory deprivation leads to exacerbated amounts of apoptotic neurons in the corresponding functional area of the neocortex. Thus, our data demonstrate that spontaneous and periphery-driven activity patterns are important for the structural and functional maturation of the neocortex by refining the final number of cortical neurons in a region-dependent manner.

Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis.

PubMed

Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

2007-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis.

Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome

PubMed Central

Huang, Wen-Chin; Chen, Youjun; Page, Damon T.

2016-01-01

Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten+/−), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten+/− mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits. The latter two phenotypes can be suppressed by pharmacological inhibition of S6K1 during early postnatal life or by reducing the activity of mPFC–BLA circuitry in adulthood. These findings identify a mechanism of altered connectivity that has potential relevance to the pathophysiology of macrocephaly/autism syndrome and autism spectrum disorders featuring dysregulated mTOR signalling. PMID:27845329

GABAergic neurons in ferret visual cortex participate in functionally specific networks

PubMed Central

Wilson, Daniel E.; Smith, Gordon B.; Jacob, Amanda; Walker, Theo; Dimidschstein, Jordane; Fishell, Gord J.; Fitzpatrick, David

2017-01-01

Summary Functional circuits in the visual cortex require the coordinated activity of excitatory and inhibitory neurons. Molecular genetic approaches in the mouse have led to the ‘local nonspecific pooling principle’ of inhibitory connectivity, in which inhibitory neurons are untuned for stimulus features due to the random pooling of local inputs. However, it remains unclear whether this principle generalizes to species with a columnar organization of feature selectivity such as carnivores, primates, and humans. Here we use virally-mediated GABAergic-specific GCaMP6f expression to demonstrate that inhibitory neurons in ferret visual cortex respond robustly and selectively to oriented stimuli. We find that the tuning of inhibitory neurons is inconsistent with the local non-specific pooling of excitatory inputs, and that inhibitory neurons exhibit orientation-specific noise correlations with local and distant excitatory neurons. These findings challenge the generality of the non-specific pooling principle for inhibitory neurons, suggesting different rules for functional excitatory-inhibitory interactions in non-murine species. PMID:28279352

Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis

PubMed Central

Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

2007-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1-deficient mice (Ppt1−/−) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression, but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1−/− mice, revealing the thalamus as an important early focus of INCL pathogenesis. PMID:17046272

Combining robotic training and inactivation of the healthy hemisphere restores pre-stroke motor patterns in mice

PubMed Central

Spalletti, Cristina; Alia, Claudia; Lai, Stefano; Panarese, Alessandro; Conti, Sara

2017-01-01

Focal cortical stroke often leads to persistent motor deficits, prompting the need for more effective interventions. The efficacy of rehabilitation can be increased by ‘plasticity-stimulating’ treatments that enhance experience-dependent modifications in spared areas. Transcallosal pathways represent a promising therapeutic target, but their role in post-stroke recovery remains controversial. Here, we demonstrate that the contralesional cortex exerts an enhanced interhemispheric inhibition over the perilesional tissue after focal cortical stroke in mouse forelimb motor cortex. Accordingly, we designed a rehabilitation protocol combining intensive, repeatable exercises on a robotic platform with reversible inactivation of the contralesional cortex. This treatment promoted recovery in general motor tests and in manual dexterity with remarkable restoration of pre-lesion movement patterns, evaluated by kinematic analysis. Recovery was accompanied by a reduction of transcallosal inhibition and ‘plasticity brakes’ over the perilesional tissue. Our data support the use of combinatorial clinical therapies exploiting robotic devices and modulation of interhemispheric connectivity. PMID:29280732

Ballooning in the constant sun of the South Pole summer

NASA Image and Video Library

2017-12-08

The Halley station team members assisted the BARREL team with the launches. Here, one gives the thumbs up to start inflating a BARREL balloon. Credit: NASA/Goddard/BARREL/M. Krzysztofowicz Read more: www.nasa.gov/content/nasas-barrel-returns-successful-from... -- Three months, 20 balloons, and one very successful campaign. The team for NASA's BARREL – short for Balloon Array for Radiation belt Relativistic Electron Losses -- mission returned from Antarctica in March 2014. BARREL's job is to help unravel the mysterious Van Allen belts, two gigantic donuts of radiation that surround Earth, which can shrink and swell in response to incoming energy and particles from the sun and sometimes expose satellites to harsh radiation. While in Antarctica, the team launched 20 balloons carrying instruments that sense charged particles that are scattered into the atmosphere from the belts, spiraling down the magnetic fields near the South Pole. Each balloon traveled around the pole for up to three weeks. The team will coordinate the BARREL data with observations from NASA's two Van Allen Probes to better understand how occurrences in the belts relate to bursts of particles funneling down toward Earth. BARREL team members will be on hand at the USA Science and Engineering Festival in DC on April 26 and 27, 2014 for the exhibit Space Balloons: Exploring the Extremes of Space Weather. NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

Four reindeer walk past the BARREL payload on the launch pad at Esrange Space Center near Kiruna, Sweden. The BARREL team is at Esrange Space Center launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Image credit: NASA/University of Houston/Samar Mathur NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

A member of the BARREL team prepares a payload for launch from Esrange Space Center on Aug. 29, 2016. Throughout August 2016, the BARREL team was at Esrange Space Center near Kiruna, Sweden, launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carried instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Credit: NASA/Dartmouth/Alexa Halford NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

The fourth BARREL balloon of this campaign sits on the launch pad shortly before it launched on Aug. 21, 2016. The BARREL team is at Esrange Space Center near Kiruna, Sweden, launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Credit: NASA/University of Houston/Michael Greer NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

The third BARREL balloon floats towards the stratosphere on Aug. 21, 2016. This payload flew for nearly 30 hours, measuring X-rays in Earth’s atmosphere. The BARREL team is at Esrange Space Center near Kiruna, Sweden, launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Credit: NASA/University of Houston/Michael Greer NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

A BARREL payload sits on the launch pad at Esrange Space Center near Kiruna, Sweden. The BARREL team is at Esrange Space Center launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Image credit: NASA/University of Houston/Edgar Bering NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

A BARREL team member recovers the second payload after it landed. The BARREL team is at Esrange Space Center near Kiruna, Sweden, launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Image credit: NASA/Montana State University/Arlo Johnson NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

Prior to launch, the BARREL team works on the payload from the launch pad at Esrange Space Center near Kiruna, Sweden. The BARREL team is at Esrange Space Center launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Image credit: NASA/Dartmouth/Robyn Millan NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

The BARREL team prepares to launch their third payload from Esrange Space Center near Kiruna, Sweden, on Aug. 21, 2016. The BARREL team is at Esrange Space Center launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Credit: NASA/University of Houston/Michael Greer NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

A BARREL team member watches as one of their payloads launches from Esrange Space Center on Aug. 29, 2016. Throughout August 2016, the BARREL team was at Esrange Space Center near Kiruna, Sweden, launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carried instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Credit: NASA/Dartmouth/Alexa Halford NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

A BARREL balloon inflates on the launch pad at Esrange Space Center on Aug. 29, 2016. Throughout August 2016, the BARREL team was at Esrange Space Center near Kiruna, Sweden, launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carried instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Credit: NASA/Dartmouth/Alexa Halford NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

The first BARREL balloon is inflated just before its launch on Aug. 13, 2016, from Esrange Space Center near Kiruna, Sweden. The BARREL team is at Esrange Space Center launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Image credit: NASA/University of Houston/Edgar Bering NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

The BARREL team inflates the balloon to launch their fifth scientific payload from Esrange Space Center near Kiruna, Sweden, on Aug. 24, 2016. The BARREL team is at Esrange Space Center launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Credit: NASA/University of Houston/Michael Greer NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

NASA's BARREL Mission in Sweden

NASA Image and Video Library

2017-12-08

A BARREL payload sits on the launch pad at Esrange Space Center near Kiruna, Sweden. The BARREL team is at Esrange Space Center launching a series of six scientific payloads on miniature scientific balloons. The NASA-funded BARREL – which stands for Balloon Array for Radiation-belt Relativistic Electron Losses – primarily measures X-rays in Earth’s atmosphere near the North and South Poles. These X-rays are produced by electrons raining down into the atmosphere from two giant swaths of radiation that surround Earth, called the Van Allen belts. Learning about the radiation near Earth helps us to better protect our satellites. Several of the BARREL balloons also carry instruments built by undergraduate students to measure the total electron content of Earth’s ionosphere, as well as the low-frequency electromagnetic waves that help to scatter electrons into Earth’s atmosphere. Though about 90 feet in diameter, the BARREL balloons are much smaller than standard football stadium-sized scientific balloons. This is the fourth campaign for the BARREL mission. BARREL is led by Dartmouth College in Hanover, New Hampshire. The undergraduate student instrument team is led by the University of Houston and funded by the Undergraduate Student Instrument Project out of NASA’s Wallops Flight Facility. For more information on NASA’s scientific balloon program, visit: www.nasa.gov/scientificballoons. Image credit: NASA/Dartmouth/Robyn Millan NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Extent and mechanism of phase separation during the extrusion of calcium phosphate pastes.

PubMed

O'Neill, Rory; McCarthy, Helen O; Cunningham, Eoin; Montufar, Edgar; Ginebra, Maria-Pau; Wilson, D Ian; Lennon, Alex; Dunne, Nicholas

2016-02-01

The aim of this study was to increase understanding of the mechanism and dominant drivers influencing phase separation during ram extrusion of calcium phosphate (CaP) paste for orthopaedic applications. The liquid content of extrudate was determined, and the flow of liquid and powder phases within the syringe barrel during extrusion were observed, subject to various extrusion parameters. Increasing the initial liquid-to-powder mass ratio, LPR, (0.4-0.45), plunger rate (5-20 mm/min), and tapering the barrel exit (45°-90°) significantly reduced the extent of phase separation. Phase separation values ranged from (6.22 ± 0.69 to 18.94 ± 0.69 %). However altering needle geometry had no significant effect on phase separation. From powder tracing and liquid content determination, static zones of powder and a non-uniform liquid distribution was observed within the barrel. Measurements of extrudate and paste LPR within the barrel indicated that extrudate LPR remained constant during extrusion, while LPR of paste within the barrel decreased steadily. These observations indicate the mechanism of phase separation was located within the syringe barrel. Therefore phase separation can be attributed to either; (1) the liquid being forced downstream by an increase in pore pressure as a result of powder consolidation due to the pressure exerted by the plunger or (2) the liquid being drawn from paste within the barrel, due to suction, driven by dilation of the solids matrix at the barrel exit. Differentiating between these two mechanisms is difficult; however results obtained suggest that suction is the dominant phase separation mechanism occurring during extrusion of CaP paste.

Energetics of side-chain partitioning of β-signal residues in unassisted folding of a transmembrane β-barrel protein

PubMed Central

Iyer, Bharat Ramasubramanian; Zadafiya, Punit; Vetal, Pallavi Vijay

2017-01-01

The free energy of water-to-interface amino acid partitioning is a major contributing factor in membrane protein folding and stability. The interface residues at the C terminus of transmembrane β-barrels form the β-signal motif required for assisted β-barrel assembly in vivo but are believed to be less important for β-barrel assembly in vitro. Here, we experimentally measured the thermodynamic contribution of all 20 amino acids at the β-signal motif to the unassisted folding of the model β-barrel protein PagP. We obtained the partitioning free energy for all 20 amino acids at the lipid-facing interface (ΔΔG0w,i(φ)) and the protein-facing interface (ΔΔG0w,i(π)) residues and found that hydrophobic amino acids are most favorably transferred to the lipid-facing interface, whereas charged and polar groups display the highest partitioning energy. Furthermore, the change in non-polar surface area correlated directly with the partitioning free energy for the lipid-facing residue and inversely with the protein-facing residue. We also demonstrate that the interface residues of the β-signal motif are vital for in vitro barrel assembly, because they exhibit a side chain–specific energetic contribution determined by the change in nonpolar accessible surface. We further establish that folding cooperativity and hydrophobic collapse are balanced at the membrane interface for optimal stability of the PagP β-barrel scaffold. We conclude that the PagP C-terminal β-signal motif influences the folding cooperativity and stability of the folded β-barrel and that the thermodynamic contributions of the lipid- and protein-facing residues in the transmembrane protein β-signal motif depend on the nature of the amino acid side chain. PMID:28592485

Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection.

PubMed

Bray, Natasha; Burrows, Fiona E; Jones, Myles; Berwick, Jason; Allan, Stuart M; Schiessl, Ingo

2016-08-24

Neurovascular coupling describes the mechanism by which the energy and oxygen demand arising from neuronal activity is met by an increase in regional blood flow, known as the haemodynamic response. Interleukin 1 (IL-1) is a pro-inflammatory cytokine and an important mediator of neuronal injury, though mechanisms through which IL-1 exerts its effects in the brain are not fully understood. In this study, we set out to investigate if increased cerebral levels of IL-1 have a negative effect on the neurovascular coupling in the cortex in response to sensory stimulation. We used two approaches to measure the neuronal activity and haemodynamic changes in the anaesthetised rat barrel somatosensory cortex in response to mechanical whisker stimulation, before and for 6 h after intra-striatal injection of interleukin-1β or vehicle. First, we used two-dimensional optical imaging spectroscopy (2D-OIS) to measure the size of the functional haemodynamic response, indicated by changes of oxyhaemoglobin (HbO2) and total haemoglobin (HbT) concentration. In the same animals, immunostaining of immunoglobulin G and SJC-positive extravasated neutrophils was used to confirm the pro-inflammatory effects of interleukin-1β (IL-1β). Second, to examine the functional coupling between neuronal activity and the haemodynamic response, we used a 'Clark-style' electrode combined with a single sharp electrode to simultaneously record local tissue oxygenation (partial pressure oxygen, pO2) in layer IV/V of the stimulated barrel cortex and multi-unit activity (MUA) together with local field potentials (LFPs), respectively. 2D-OIS data revealed that the size of the haemodynamic response to mechanical whisker stimulation declined over the 6 h following IL-1β injection whereas the vehicle group remained stable, significant differences being seen after 5 h. Moreover, the size of the transient increases of neuronal LFP activity in response to whisker stimulation decreased after IL-1β injection, significant changes compared to vehicle being seen for gamma-band activity after 1 h and beta-band activity after 3 h. The amplitude of the functional pO2 response similarly decreased after 3 h post-IL-1β injection, whereas IL-1β had no significant effect on the peak of whisker-stimulation-induced MUA. The stimulation-evoked increases in gamma power and pO2 correlated significantly throughout the 6 h in the vehicle group, but such a correlation was not observed in the IL-1β-injected group. We conclude that intra-striatal IL-1β decouples cortical neuronal activity from its haemodynamic response. This finding may have implications for neurological conditions where IL-1β plays a part, especially those involving reductions in cerebral blood flow (such as stroke).

Influence of aging conditions on the quality of red Sangiovese wine.

PubMed

Castellari, M; Piermattei, B; Arfelli, G; Amati, A

2001-08-01

A red Sangiovese wine was stored in barrels of different woods (oak and chestnut) and types (225-L "barriques" and 1000-L barrels) at 12 and 22 degrees C for 320 days to evaluate the effects of different aging conditions on wine quality. Chestnut barrels led to wines richer in phenolics, and which were more tannic, colored, and fruity. Oak barrels gave wines with more monomeric phenolics, but less astringent, with higher vanilla smell, and more harmonious. The type of barrel could be used as a parameter to regulate the extraction of wood components and the polymerization of monomeric phenolics. Storage at 22 degrees C favored the formation of polymerized phenolics and the increase of color density and color hue. The temperature produced less pronounced effects on aroma and taste, even if wines stored at 12 degrees C showed more harmony.

Nuclear reactor alignment plate configuration

DOEpatents

Altman, David A; Forsyth, David R; Smith, Richard E; Singleton, Norman R

2014-01-28

An alignment plate that is attached to a core barrel of a pressurized water reactor and fits within slots within a top plate of a lower core shroud and upper core plate to maintain lateral alignment of the reactor internals. The alignment plate is connected to the core barrel through two vertically-spaced dowel pins that extend from the outside surface of the core barrel through a reinforcement pad and into corresponding holes in the alignment plate. Additionally, threaded fasteners are inserted around the perimeter of the reinforcement pad and into the alignment plate to further secure the alignment plate to the core barrel. A fillet weld also is deposited around the perimeter of the reinforcement pad. To accomodate thermal growth between the alignment plate and the core barrel, a gap is left above, below and at both sides of one of the dowel pins in the alignment plate holes through with the dowel pins pass.

EXTERNAL BARREL TEMPERATURE OF A SMALL BORE OLYMPIC RIFLE AND SHOOTING PRECISION

PubMed Central

Gladyszewska, B.; Baranowski, P.; Mazurek, W.; Wozniak, J.

2013-01-01

Investigations on changes in a rifle's barrel temperature during shooting in a rhythm typical for practitioners of Olympic shooting sports are presented. Walther KK300 (cal. 5.6 mm), a typical rifle often used in Olympic competitions, R50 RWS ammunition and a high speed thermographic camera were used in the study. Altair version 5 software was used to process thermal images and a stationary wavelet transform was applied to denoise signals for all the studied points. It was found that the temperature of the rifle barrel does not exceed 0.3°C after one shot whereas the total temperature increase does not exceed 5°C after taking 40 shots and does not affect the position of the hitting point on a target. In fact, contrary to popular belief, the so-called “warming shots” are not done for barrel heating but for cleaning of remnants in the barrel. PMID:24744465

Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice.

PubMed

Massé, Ian O; Guillemette, Sonia; Laramée, Marie-Eve; Bronchti, Gilles; Boire, Denis

2014-11-07

Anophthalmia is a condition in which the eye does not develop from the early embryonic period. Early blindness induces cross-modal plastic modifications in the brain such as auditory and haptic activations of the visual cortex and also leads to a greater solicitation of the somatosensory and auditory cortices. The visual cortex is activated by auditory stimuli in anophthalmic mice and activity is known to alter the growth pattern of the cerebral cortex. The size of the primary visual, auditory and somatosensory cortices and of the corresponding specific sensory thalamic nuclei were measured in intact and enucleated C57Bl/6J mice and in ZRDCT anophthalmic mice (ZRDCT/An) to evaluate the contribution of cross-modal activity on the growth of the cerebral cortex. In addition, the size of these structures were compared in intact, enucleated and anophthalmic fourth generation backcrossed hybrid C57Bl/6J×ZRDCT/An mice to parse out the effects of mouse strains and of the different visual deprivations. The visual cortex was smaller in the anophthalmic ZRDCT/An than in the intact and enucleated C57Bl/6J mice. Also the auditory cortex was larger and the somatosensory cortex smaller in the ZRDCT/An than in the intact and enucleated C57Bl/6J mice. The size differences of sensory cortices between the enucleated and anophthalmic mice were no longer present in the hybrid mice, showing specific genetic differences between C57Bl/6J and ZRDCT mice. The post natal size increase of the visual cortex was less in the enucleated than in the anophthalmic and intact hybrid mice. This suggests differences in the activity of the visual cortex between enucleated and anophthalmic mice and that early in-utero spontaneous neural activity in the visual system contributes to the shaping of functional properties of cortical networks. Copyright © 2014 Elsevier B.V. All rights reserved.

Impaired Auditory and Contextual Fear Conditioning in Soman-Exposed Rats

DTIC Science & Technology

2011-01-01

include the piriform cortex, amygdala, thalamus and hippocampus (Carpentier et al., 1990; Petras , 1994; Shih et al., 2003). Often the resulting... Martin M, Shah R, Bertchume A, Colvin J, Dong H. Cholinesterase inhibitors ameliorate behavioral deficits induced by MK-801 in mice. Neuropsy...Csernansky CA, Martin MV, Bertchume A, Vallera D, Csernansky JG. Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse

Osthole confers neuroprotection against cortical stab wound injury and attenuates secondary brain injury.

PubMed

Xia, Yang; Kong, Liang; Yao, Yingjia; Jiao, Yanan; Song, Jie; Tao, Zhenyu; You, Zhong; Yang, Jingxian

2015-09-04

Neuroendoscopy is an innovative technique for neurosurgery that can nonetheless result in traumatic brain injury. The accompanying neuroinflammation may lead to secondary tissue damage, which is the major cause of delayed neuronal death after surgery. The present study investigated the capacity of osthole to prevent secondary brain injury and the underlying mechanism of action in a mouse model of stab wound injury. A mouse model of cortical stab wound injury was established by inserting a needle into the cerebral cortex for 20 min to mimic neuroendoscopy. Mice received an intraperitoneal injection of osthole 30 min after surgery and continued for 14 days. Neurological severity was evaluated 12 h and up to 21 days after the trauma. Brains were collected 3-21 days post-injury for histological analysis, immunocytochemistry, quantitative real-time PCR, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and enzyme-linked immunosorbent assays. Neurological function improved in mice treated with osthole and was accompanied by reduced brain water content and accelerated wound closure relative to untreated mice. Osthole treatment reduced the number of macrophages/microglia and peripheral infiltrating of neutrophils and lowered the level of the proinflammatory cytokines interleukin-6 and tumor necrosis factor α in the lesioned cortex. Osthole-treated mice had fewer TUNEL+ apoptotic neurons surrounding the lesion than controls, indicating increased neuronal survival. Osthole reduced secondary brain damage by suppressing inflammation and apoptosis in a mouse model of stab wound injury. These results suggest a new strategy for promoting neuronal survival and function after neurosurgery to improve long-term patient outcome.

Assessing cortical and subcortical changes in a western diet mouse model using spectral/Fourier domain OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bernucci, Marcel T.; Norman, Jennifer E.; Merkle, Conrad W.; Aung, Hnin H.; Rutkowsky, Jennifer; Rutledge, John C.; Srinivasan, Vivek J.

2017-02-01

The Western diet, causative in the development of atherosclerotic cardiovascular disease, has recently been associated with the development of diffuse white matter disease (WMD) and other subcortical changes. Yet, little is known about the pathophysiological mechanisms by which a high-fat diet can cause WMD. Mechanistic studies of deep brain regions in mice have been challenging due to a lack of non-invasive, high-resolution, and deep imaging technologies. Here we used Optical Coherence Tomography to study mouse cortical/subcortical structures noninvasively and in vivo. To better understand the role of Western Diet in the development of WMD, intensity and Doppler flow OCT images, obtained using a 1300 nm spectral / Fourier domain OCT system, were used to observe the structural and functional alterations in the cortex and corpus callosum of Western Diet and control diet mouse models. Specifically, we applied segmentation to the OCT images to identify the boundaries of the cortex/corpus callosum, and further quantify the layer thicknesses across animals between the two diet groups. Furthermore, microvasculature alterations such as changes in spatiotemporal flow profiles within diving arterioles, arteriole diameter, and collateral tortuosity were analyzed. In the current study, while the arteriole vessel diameters between the two diet groups was comparable, we show that collateral tortuosity was significantly higher in the Western diet group, compared to control diet group, possibly indicating remodeling of brain vasculature due to dietary changes. Moreover, there is evidence showing that the corpus callosum is thinner in Western diet mice, indicative of tissue atrophy.

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

PubMed Central

Krienen, Fenna M.; Yeo, B. T. Thomas; Ge, Tian; Buckner, Randy L.; Sherwood, Chet C.

2016-01-01

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute’s human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections. PMID:26739559

TLR4 Gene Expression and Pro-Inflammatory Cytokines in Alzheimer's Disease and in Response to Hippocampal Deafferentation in Rodents.

PubMed

Miron, Justin; Picard, Cynthia; Frappier, Josée; Dea, Doris; Théroux, Louise; Poirier, Judes

2018-01-01

One important aspect in Alzheimer's disease pathology is the presence of chronic inflammation. Considering its role as a key receptor in the microglial innate immune system, TLR4 was shown to regulate the binding and phagocytosis of amyloid plaques by microglia in several mouse models of amyloidosis, as well as the production of pro-inflammatory cytokines. To our knowledge, TLR4 and its association with cytokines have not been thoroughly examined in the brains of subjects affected with Alzheimer's disease. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in postmortem human brains, we observed increased expression for the TLR4 and TNF genes (p = 0.001 and p = 0.025, respectively), as well as a trend for higher IL6 gene expression in the frontal cortex of AD subjects when compared to age-matched controls. Similarly, using a mouse model of hippocampal deafferentation without amyloidosis, (i.e., the entorhinal cortex lesioned mouse), we observed significant increases in the expression of both the Tlr4 (p = 0.0367 and p = 0.0193 compared to sham-lesioned mice or to the contralateral side, respectively) and Il1b (p = 0.0055 and p = 0.0066 compared to sham-lesioned mice or to the contralateral side, respectively) genes in the deafferentation phase, but not during the ensuing reinnervation process. In conclusion, we suggest that the modulation of cytokines by TLR4 is differentially regulated whether by the presence of amyloid plaques or by the ongoing deafferentation process.

The mouse cerebellar cortex in organotypic slice cultures: an in vitro model to analyze the consequences of mutations and pathologies on neuronal survival, development, and function.

PubMed

Lonchamp, Etienne; Dupont, Jean-Luc; Beekenkamp, Huguette; Poulain, Bernard; Bossu, Jean-Louis

2006-01-01

Thin acute slices and dissociated cell cultures taken from different parts of the brain have been widely used to examine the function of the nervous system, neuron-specific interactions, and neuronal development (specifically, neurobiology, neuropharmacology, and neurotoxicology studies). Here, we focus on an alternative in vitro model: brain-slice cultures in roller tubes, initially introduced by Beat Gähwiler for studies with rats, that we have recently adapted for studies of mouse cerebellum. Cultured cerebellar slices afford many of the advantages of dissociated cultures of neurons and thin acute slices. Organotypic slice cultures were established from newborn or 10-15-day-old mice. After 3-4 weeks in culture, the slices flattened to form a cell monolayer. The main types of cerebellar neurons could be identified with immunostaining techniques, while their electrophysiological properties could be easily characterized with the patch-clamp recording technique. When slices were taken from newborn mice and cultured for 3 weeks, aspects of the cerebellar development were displayed. A functional neuronal network was established despite the absence of mossy and climbing fibers, which are the two excitatory afferent projections to the cerebellum. When slices were made from 10-15-day-old mice, which are at a developmental stage when cerebellum organization is almost established, the structure and neuronal pathways were intact after 3-4 weeks in culture. These unique characteristics make organotypic slice cultures of mouse cerebellar cortex a valuable model for analyzing the consequences of gene mutations that profoundly alter neuronal function and compromise postnatal survival.

Dietary DHA supplementation causes selective changes in phospholipids from different brain regions in both wild type mice and the Tg2576 mouse model of Alzheimer's disease

PubMed Central

Bascoul-Colombo, Cécile; Guschina, Irina A.; Maskrey, Benjamin H.; Good, Mark; O'Donnell, Valerie B.; Harwood, John L.

2016-01-01

Alzheimer's disease (AD) is of major concern in ageing populations and we have used the Tg2576 mouse model to understand connections between brain lipids and amyloid pathology. Because dietary docosahexaenoic acid (DHA) has been identified as beneficial, we compared mice fed with a DHA-supplemented diet to those on a nutritionally-sufficient diet. Major phospholipids from cortex, hippocampus and cerebellum were separated and analysed. Each phosphoglyceride had a characteristic fatty acid composition which was similar in cortex and hippocampus but different in the cerebellum. The biggest changes on DHA-supplementation were within ethanolamine phospholipids which, together with phosphatidylserine, had the highest proportions of DHA. Reciprocal alterations in DHA and arachidonate were found. The main diet-induced alterations were found in ethanolamine phospholipids, (and included their ether derivatives), as were the changes observed due to genotype. Tg mice appeared more sensitive to diet with generally lower DHA percentages when on the standard diet and higher relative proportions of DHA when the diet was supplemented. All four major phosphoglycerides analysed showed age-dependent decreases in polyunsaturated fatty acid contents. These data provide, for the first time, a detailed evaluation of phospholipids in different brain areas previously shown to be relevant to behaviour in the Tg2576 mouse model for AD. The lipid changes observed with genotype are consistent with the subtle alterations found in AD patients, especially for the ethanolamine phospholipid molecular species. They also emphasise the contrasting changes in fatty acid content induced by DHA supplementation within individual phospholipid classes. PMID:26968097

Local Diversity and Fine-Scale Organization of Receptive Fields in Mouse Visual Cortex

PubMed Central

Histed, Mark H.; Yurgenson, Sergey

2011-01-01

Many thousands of cortical neurons are activated by any single sensory stimulus, but the organization of these populations is poorly understood. For example, are neurons in mouse visual cortex—whose preferred orientations are arranged randomly—organized with respect to other response properties? Using high-speed in vivo two-photon calcium imaging, we characterized the receptive fields of up to 100 excitatory and inhibitory neurons in a 200 μm imaged plane. Inhibitory neurons had nonlinearly summating, complex-like receptive fields and were weakly tuned for orientation. Excitatory neurons had linear, simple receptive fields that can be studied with noise stimuli and system identification methods. We developed a wavelet stimulus that evoked rich population responses and yielded the detailed spatial receptive fields of most excitatory neurons in a plane. Receptive fields and visual responses were locally highly diverse, with nearby neurons having largely dissimilar receptive fields and response time courses. Receptive-field diversity was consistent with a nearly random sampling of orientation, spatial phase, and retinotopic position. Retinotopic positions varied locally on average by approximately half the receptive-field size. Nonetheless, the retinotopic progression across the cortex could be demonstrated at the scale of 100 μm, with a magnification of ∼10 μm/°. Receptive-field and response similarity were in register, decreasing by 50% over a distance of 200 μm. Together, the results indicate considerable randomness in local populations of mouse visual cortical neurons, with retinotopy as the principal source of organization at the scale of hundreds of micrometers. PMID:22171051

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain.

PubMed

Krienen, Fenna M; Yeo, B T Thomas; Ge, Tian; Buckner, Randy L; Sherwood, Chet C

2016-01-26

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.

Memory-enhancing effect of aspirin is mediated through opioid system modulation in an AlCl3-induced neurotoxicity mouse model

PubMed Central

RIZWAN, SAIMA; IDREES, AYESHA; ASHRAF, MUHAMMAD; AHMED, TOUQEER

2016-01-01

Neurodegenerative disorders such as Alzheimers disease (AD) are multifaceted and there are currently a limited number of therapeutic strategies available to treat them. Aspirin is known to act on multiple therapeutic targets and is a successful anti-inflammatory agent in various tissues. The present study aimed to ascertain the performance of aspirin when employed as a therapeutic agent to treat neurodegeneration on novel targets, including opioid system genes, in an AlCl3-induced neurotoxicity mouse model. The effects of two doses of aspirin (5 and 20 mg/kg aspirin for 12 days) were investigated in an AlCl3-induced neurotoxicity mouse model (150 mg/kg AlCl3 for 12 days). Neurological improvements were assessed through different behavioral tests and the effects of aspirin on opioid system gene expression levels were assessed by reverse transcription-polymerase chain reaction. Both doses resulted in improvements in cognitive behavior. A 5 mg/kg dose of aspirin was revealed to be effective for spatial memory improvement (7.14±0.84 sec), whilst a 20 mg/kg dose was superior for improving extinction learning (7.63±4.04%). Aspirin (5 mg/kg) also significantly improved contextual memory (48.05±10.6%) when compared with the AlCl3-treated group (1.49±0.62%; P<0.001). Aspirin was also observed to significantly decrease δ-opioid receptor expression in the cortex (1.09±0.08 and 1.27±0.08, respectively) at both doses (5 and 20 mg/kg) when compared with the AlCl3-treated group (3.69±1.43; P<0.05). Furthermore, aspirin at 5 mg/kg significantly reduced expression of prodynorphin in the cortex (0.57±0.20) when compared with the AlCl3-treated group (1.95±0.84; P<0.05). Notably, the effect of aspirin was significant in the cortex but not in the hippocampus. In summary, aspirin was effective in ameliorating the AD-like symptoms via the modulation of opioid systems. However, additional studies are required to determine the long term effects of aspirin on such conditions. PMID:27168835

Proteomic profiling of brain cortex tissues in a Tau transgenic mouse model of Alzheimer's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Seong-Hun; Jung, In-Soo; Han, Gi-Yeon

Highlights: Black-Right-Pointing-Pointer A transgenic mouse model expressing NSE-htau23 was used. Black-Right-Pointing-Pointer 2D-gel electrophoresis to analyze the cortex proteins of transgenic mice was used. Black-Right-Pointing-Pointer Differentially expressed spots in different stages of AD were identified. Black-Right-Pointing-Pointer GSTP1 and CAII were downregulated with the progression of AD. Black-Right-Pointing-Pointer SCRN1 and ATP6VE1 were up regulated and down regulated differentially. -- Abstract: Alzheimer's disease (AD) involves regionalized neuronal death, synaptic loss, and an accumulation of intracellular neurofibrillary tangles and extracellular senile plaques. Although there have been numerous studies on tau proteins and AD in various stages of neurodegenerative disease pathology, the relationship between taumore » and AD is not yet fully understood. A transgenic mouse model expressing neuron-specific enolase (NSE)-controlled human wild-type tau (NSE-htau23), which displays some of the typical Alzheimer-associated pathological features, was used to analyze the brain proteome associated with tau tangle deposition. Two-dimensional electrophoresis was performed to compare the cortex proteins of transgenic mice (6- and 12-month-old) with those of control mice. Differentially expressed spots in different stages of AD were identified with ESI-Q-TOF (electrospray ionization quadruple time-of-flight) mass spectrometry and liquid chromatography/tandem mass spectrometry. Among the identified proteins, glutathione S-transferase P 1 (GSTP1) and carbonic anhydrase II (CAII) were down-regulated with the progression of AD, and secerin-1 (SCRN1) and V-type proton ATPase subunit E 1 (ATP6VE1) were up-regulated only in the early stages, and down-regulated in the later stages of AD. The proteins, which were further confirmed by RT-PCR at the mRNA level and with western blotting at the protein level, are expected to be good candidates as drug targets for AD. The study of up- and down-regulation of proteins during the progression of AD helps to explain the mechanisms associated with neuronal degeneration in AD.« less

Brain Cholesterol Synthesis and Metabolism is Progressively Disturbed in the R6/1 Mouse Model of Huntington's Disease: A Targeted GC-MS/MS Sterol Analysis.

PubMed

Kreilaus, Fabian; Spiro, Adena S; Hannan, Anthony J; Garner, Brett; Jenner, Andrew M

2015-01-01

Cholesterol has essential functions in neurological processes that require tight regulation of synthesis and metabolism. Perturbed cholesterol homeostasis has been demonstrated in Huntington's disease, however the exact role of these changes in disease pathogenesis is not fully understood. This study aimed to comprehensively examine changes in cholesterol biosynthetic precursors, metabolites and oxidation products in the striatum and cortex of the R6/1 transgenic mouse model of Huntington's disease. We also aimed to characterise the progression of the physical phenotype in these mice. GC-MS/MS was used to quantify a broad range of sterols in the striatum and cortex of R6/1 and wild type mice at 6, 12, 20, 24 and 28 weeks of age. Motor dysfunction was assessed over 28 weeks using the RotaRod and the hind-paw clasping tests. 24(S)-Hydroxycholesterol and 27-hydroxycholesterol were the major cholesterol metabolites that significantly changed in R6/1 mice. These changes were specifically localised to the striatum and were detected at the end stages of the disease. Cholesterol synthetic precursors (lathosterol and lanosterol) were significantly reduced in the cortex and striatum by 6 weeks of age, prior to the onset of motor dysfunction, as well as the cognitive and affective abnormalities previously reported. Elevated levels of desmosterol, a substrate of delta(24)-sterol reductase (DHCR24), were also detected in R6/1 mice at the end time-point. Female R6/1 mice exhibited a milder weight loss and hind paw clasping phenotype compared to male R6/1 mice, however, no difference in the brain sterol profile was detected between sexes. Several steps in cholesterol biosynthetic and metabolic pathways are differentially altered in the R6/1 mouse brain as the disease progresses and this is most severe in the striatum. This provides further insights into early molecular mediators of HD onset and disease progression and identifies candidate molecular targets for novel therapeutic approaches.

Motor Experience Reprograms Development of a Genetically-Altered Bilateral Corticospinal Motor Circuit

PubMed Central

Serradj, Najet

2016-01-01

Evidence suggests that motor experience plays a role in shaping development of the corticospinal system and voluntary motor control, which is a key motor function of the system. Here we used a mouse model with conditional forebrain deletion of the gene for EphA4 (Emx1-Cre:EphA4tm2Kldr), which regulates development of the laterality of corticospinal tract (CST). We combined study of Emx1-Cre:EphA4tm2Kldr with unilateral forelimb constraint during development to expand our understanding of experience-dependent CST development from both basic and translational perspectives. This mouse develops dense ipsilateral CST projections, a bilateral motor cortex motor representation, and bilateral motor phenotypes. Together these phenotypes can be used as readouts of corticospinal system organization and function and the changes brought about by experience. The Emx1-Cre:EphA4tm2Kldr mouse shares features with the common developmental disorder cerebral palsy: bilateral voluntary motor impairments and bilateral CST miswiring. Emx1-Cre:EphA4tm2Kldr mice with typical motor experiences during development display the bilateral phenotype of “mirror” reaching, because of a strongly bilateral motor cortex motor representation and a bilateral CST. By contrast, Emx1-Cre:EphA4tm2Kldr mice that experienced unilateral forelimb constraint from P1 to P30 and tested at maturity had a more contralateral motor cortex motor representation in each hemisphere; more lateralized CST projections; and substantially more lateralized/independent reaching movements. Changes in CST organization and function in this model can be explained by reduced synaptic competition of the CST from the side without developmental forelimb motor experiences. Using this model we show that unilateral constraint largely abrogated the effects of the genetic mutation on CST projections and thus demonstrates how robust and persistent experience-dependent development can be for the establishment of corticospinal system connections and voluntary control. Further, our findings inform the mechanisms of and strategies for developing behavioral therapies to treat bilateral movement impairments and CST miswiring in cerebral palsy. PMID:27673329

Motor Experience Reprograms Development of a Genetically-Altered Bilateral Corticospinal Motor Circuit.

PubMed

Serradj, Najet; Martin, John H

Evidence suggests that motor experience plays a role in shaping development of the corticospinal system and voluntary motor control, which is a key motor function of the system. Here we used a mouse model with conditional forebrain deletion of the gene for EphA4 (Emx1-Cre:EphA4tm2Kldr), which regulates development of the laterality of corticospinal tract (CST). We combined study of Emx1-Cre:EphA4tm2Kldr with unilateral forelimb constraint during development to expand our understanding of experience-dependent CST development from both basic and translational perspectives. This mouse develops dense ipsilateral CST projections, a bilateral motor cortex motor representation, and bilateral motor phenotypes. Together these phenotypes can be used as readouts of corticospinal system organization and function and the changes brought about by experience. The Emx1-Cre:EphA4tm2Kldr mouse shares features with the common developmental disorder cerebral palsy: bilateral voluntary motor impairments and bilateral CST miswiring. Emx1-Cre:EphA4tm2Kldr mice with typical motor experiences during development display the bilateral phenotype of "mirror" reaching, because of a strongly bilateral motor cortex motor representation and a bilateral CST. By contrast, Emx1-Cre:EphA4tm2Kldr mice that experienced unilateral forelimb constraint from P1 to P30 and tested at maturity had a more contralateral motor cortex motor representation in each hemisphere; more lateralized CST projections; and substantially more lateralized/independent reaching movements. Changes in CST organization and function in this model can be explained by reduced synaptic competition of the CST from the side without developmental forelimb motor experiences. Using this model we show that unilateral constraint largely abrogated the effects of the genetic mutation on CST projections and thus demonstrates how robust and persistent experience-dependent development can be for the establishment of corticospinal system connections and voluntary control. Further, our findings inform the mechanisms of and strategies for developing behavioral therapies to treat bilateral movement impairments and CST miswiring in cerebral palsy.

Long-term continuous corticosterone treatment decreases VEGF receptor-2 expression in frontal cortex.

PubMed

Howell, Kristy R; Kutiyanawalla, Ammar; Pillai, Anilkumar

2011-01-01

Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated. We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecular mechanism of the neurobiological effects of chronic stress.

Assessment of undiscovered oil and gas resources of the Dnieper-Donets Basin Province and Pripyat Basin Province, Russia, Ukraine, and Belarus, 2010

USGS Publications Warehouse

Klett, T.R.

2011-01-01

The U.S. Geological Survey, using a geology-based assessment methodology, estimated mean volumes of technically recoverable, conventional, undiscovered petroleum resources at 84 million barrels of crude oil, 4.7 trillion cubic feet of natural gas, and 130 million barrels of natural gas liquids for the Dnieper-Donets Basin Province and 39 million barrels of crude oil, 48 billion cubic feet of natural gas, and 1 million barrels of natural gas liquids for the Pripyat Basin Province. The assessments are part of a program to estimate these resources for priority basins throughout the world.

Computer vision barrel inspection

NASA Astrophysics Data System (ADS)

Wolfe, William J.; Gunderson, James; Walworth, Matthew E.

1994-02-01

One of the Department of Energy's (DOE) ongoing tasks is the storage and inspection of a large number of waste barrels containing a variety of hazardous substances. Martin Marietta is currently contracted to develop a robotic system -- the Intelligent Mobile Sensor System (IMSS) -- for the automatic monitoring and inspection of these barrels. The IMSS is a mobile robot with multiple sensors: video cameras, illuminators, laser ranging and barcode reader. We assisted Martin Marietta in this task, specifically in the development of image processing algorithms that recognize and classify the barrel labels. Our subsystem uses video images to detect and locate the barcode, so that the barcode reader can be pointed at the barcode.

Experimental evidence that stripes do not cool zebras.

PubMed

Horváth, Gábor; Pereszlényi, Ádám; Száz, Dénes; Barta, András; Jánosi, Imre M; Gerics, Balázs; Åkesson, Susanne

2018-06-19

There are as many as 18 theories for the possible functions of the stripes of zebras, one of which is to cool the animal. We performed field experiments and thermographic measurements to investigate whether thermoregulation might work for zebra-striped bodies. A zebra body was modelled by water-filled metal barrels covered with horse, cattle and zebra hides and with various black, white, grey and striped patterns. The barrels were installed in the open air for four months while their core temperature was measured continuously. Using thermography, the temperature distributions of the barrel surfaces were compared to those of living zebras. The sunlit zebra-striped barrels reproduced well the surface temperature characteristics of sunlit zebras. We found that there were no significant core temperature differences between the striped and grey barrels, even on many hot days, independent of the air temperature and wind speed. The average core temperature of the barrels increased as follows: white cattle, grey cattle, real zebra, artificial zebra, grey horse, black cattle. Consequently, we demonstrate that zebra-striped coats do not keep the body cooler than grey coats challenging the hypothesis of a thermoregulatory role of zebra stripes.

Cortico-fugal output from visual cortex promotes plasticity of innate motor behaviour

PubMed Central

Liu, Bao-hua; Huberman, Andrew D.; Scanziani, Massimo

2017-01-01

The mammalian visual cortex massively innervates the brainstem, a phylogenetically older structure, via cortico-fugal axonal projections1. Many cortico-fugal projections target brainstem nuclei that mediate innate motor behaviours, but the function of these projections remains poorly understood1–4. A prime example of such behaviours is the optokinetic reflex (OKR), an innate eye movement mediated by the brainstem accessory optic system3,5,6, that stabilizes images on the retina as the animal moves through the environment and is thus crucial for vision5. The OKR is plastic, allowing the amplitude of this reflex to be adaptively adjusted relative to other oculomotor reflexes and thereby ensuring image stability throughout life7–11. Although the plasticity of the OKR is thought to involve subcortical structures such as the cerebellum and vestibular nuclei10–13, cortical lesions have suggested that the visual cortex might also be involved9,14,15. Here we show that projections from the mouse visual cortex to the accessory optic system promote the adaptive plasticity of the OKR. OKR potentiation, a compensatory plastic increase in the amplitude of the OKR in response to vestibular impairment11,16–18, is diminished by silencing visual cortex. Furthermore, targeted ablation of a sparse population of cortico-fugal neurons that specifically project to the accessory optic system severely impairs OKR potentiation. Finally, OKR potentiation results from an enhanced drive exerted by the visual cortex onto the accessory optic system. Thus, cortico-fugal projections to the brainstem enable the visual cortex, an area that has been principally studied for its sensory processing function19, to plastically adapt the execution of innate motor behaviours. PMID:27732573

Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.

PubMed

Baldo, Barbara; Soylu, Rana; Petersén, Asa

2013-01-01

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin protein. Neuropathology in the basal ganglia and in the cerebral cortex has been linked to the motor and cognitive symptoms whereas recent work has suggested that the hypothalamus might be involved in the metabolic dysfunction. Several mouse models of HD that display metabolic dysfunction have hypothalamic pathology, and expression of mutant huntingtin in the hypothalamus has been causally linked to the development of metabolic dysfunction in mice. Although the pathogenic mechanisms by which mutant huntingtin exerts its toxic functions in the HD brain are not fully known, several studies have implicated a role for the lysososomal degradation pathway of autophagy. Interestingly, changes in autophagy in the hypothalamus have been associated with the development of metabolic dysfunction in wild-type mice. We hypothesized that expression of mutant huntingtin might lead to changes in the autophagy pathway in the hypothalamus in mice with metabolic dysfunction. We therefore investigated whether there were changes in basal levels of autophagy in a mouse model expressing a fragment of 853 amino acids of mutant huntingtin selectively in the hypothalamus using a recombinant adeno-associate viral vector approach as well as in the transgenic BACHD mice. We performed qRT-PCR and Western blot to investigate the mRNA and protein expression levels of selected autophagy markers. Our results show that basal levels of autophagy are maintained in the hypothalamus despite the presence of metabolic dysfunction in both mouse models. Furthermore, although there were no major changes in autophagy in the striatum and cortex of BACHD mice, we detected modest, but significant differences in levels of some markers in mice at 12 months of age. Taken together, our results indicate that overexpression of mutant huntingtin in mice do not significantly perturb basal levels of autophagy.

Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation.

PubMed

Ji, Hua; Xu, Linhao; Wang, Zheng; Fan, Xinli; Wu, Lihui

2018-03-01

Glyphosate is the active ingredient in numerous herbicide formulations. The role of glyphosate in neurotoxicity has been reported in human and animal models. However, the detailed mechanism of the role of glyphosate in neuronal development remains unknown. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. The current group previously identified microRNAs (miRNAs) that are associated with the etiology of NDDs, but their expression levels in the developing brain following glyphosate exposure have not been characterized. In the present study, miRNA expression patterns were evaluated in the prefrontal cortex (PFC) of 28 postnatal day mouse offspring following glyphosate exposure during pregnancy and lactation. An miRNA microarray detected 55 upregulated and 19 downregulated miRNAs in the PFC of mouse offspring, and 20 selected deregulated miRNAs were further evaluated by quantitative polymerase chain reaction (PCR). A total of 11 targets of these selected deregulated miRNAs were analyzed using bioinformatics. Gene Ontology (GO) terms associated with the relevant miRNAs included neurogenesis (GO:0050769), neuron differentiation (GO:0030182) and brain development (GO:0007420). The genes Cdkn1a, Numbl, Notch1, Fosl1 and Lef1 are involved in the Wnt and Notch signaling pathways, which are closely associated with neural development. PCR arrays for the mouse Wnt and Notch signaling pathways were used to validate the effects of glyphosate on the expression pattern of genes involved in the Wnt and Notch pathways. Nr4a2 and Wnt7b were downregulated, while Dkk1, Dixdc1, Runx1, Shh, Lef-1 and Axin2 were upregulated in the PFC of mice offspring following glyphosate exposure during pregnancy and lactation. These results indicated abnormalities of the Wnt/β-catenin and Notch pathways. These findings may be of particular interest for understanding the mechanism of glyphosate-induced neurotoxicity, as well as helping to clarify the association between glyphosate and NDDs.

Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation

PubMed Central

Ji, Hua; Xu, Linhao; Wang, Zheng; Fan, Xinli; Wu, Lihui

2018-01-01

Glyphosate is the active ingredient in numerous herbicide formulations. The role of glyphosate in neurotoxicity has been reported in human and animal models. However, the detailed mechanism of the role of glyphosate in neuronal development remains unknown. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. The current group previously identified microRNAs (miRNAs) that are associated with the etiology of NDDs, but their expression levels in the developing brain following glyphosate exposure have not been characterized. In the present study, miRNA expression patterns were evaluated in the prefrontal cortex (PFC) of 28 postnatal day mouse offspring following glyphosate exposure during pregnancy and lactation. An miRNA microarray detected 55 upregulated and 19 downregulated miRNAs in the PFC of mouse offspring, and 20 selected deregulated miRNAs were further evaluated by quantitative polymerase chain reaction (PCR). A total of 11 targets of these selected deregulated miRNAs were analyzed using bioinformatics. Gene Ontology (GO) terms associated with the relevant miRNAs included neurogenesis (GO:0050769), neuron differentiation (GO:0030182) and brain development (GO:0007420). The genes Cdkn1a, Numbl, Notch1, Fosl1 and Lef1 are involved in the Wnt and Notch signaling pathways, which are closely associated with neural development. PCR arrays for the mouse Wnt and Notch signaling pathways were used to validate the effects of glyphosate on the expression pattern of genes involved in the Wnt and Notch pathways. Nr4a2 and Wnt7b were downregulated, while Dkk1, Dixdc1, Runx1, Shh, Lef-1 and Axin2 were upregulated in the PFC of mice offspring following glyphosate exposure during pregnancy and lactation. These results indicated abnormalities of the Wnt/β-catenin and Notch pathways. These findings may be of particular interest for understanding the mechanism of glyphosate-induced neurotoxicity, as well as helping to clarify the association between glyphosate and NDDs. PMID:29467848

Prefrontal cortical-specific differences in behavior and synaptic plasticity between adolescent and adult mice.

PubMed

Konstantoudaki, Xanthippi; Chalkiadaki, Kleanthi; Vasileiou, Elisabeth; Kalemaki, Katerina; Karagogeos, Domna; Sidiropoulou, Kyriaki

2018-03-01

Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty-seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC, particularly compared with other primary cortical areas. This study aims to understand the development of PFC-mediated, compared with non-PFC-mediated, cognitive functions. Toward this aim, we performed cognitive behavioral tasks in adolescent and adult mice and subsequently investigated synaptic plasticity in two different cortical areas. Our results showed that adolescent mice exhibit impaired performance in PFC-dependent cognitive tasks compared with adult mice, whereas their performance in non-PFC-dependent tasks is similar to that of adults. Furthermore, adolescent mice exhibited decreased long-term potentiation (LTP) within upper-layer synapses of the PFC but not the barrel cortex. Blocking GABA A receptor function significantly augments LTP in both the adolescent and adult PFC. No change in intrinsic excitability of PFC pyramidal neurons was observed between adolescent and adult mice. Finally, increased expression of the NR2A subunit of the N-methyl-d-aspartate receptors is found only in the adult PFC, a change that could underlie the emergence of LTP. In conclusion, our results demonstrate physiological and behavioral changes during adolescence that are specific to the PFC and could underlie the reduced cognitive control in adolescents. NEW & NOTEWORTHY This study reports that adolescent mice exhibit impaired performance in cognitive functions dependent on the prefrontal cortex but not in cognitive functions dependent on other cortical regions. The current results propose reduced synaptic plasticity in the upper layers of the prefrontal cortex as a cellular correlate of this weakened cognitive function. This decreased synaptic plasticity is due to reduced N-methyl-d-aspartate receptor expression but not due to dampened intrinsic excitability or enhanced GABAergic signaling during adolescence.

27 CFR 25.160 - Tax adjustment for brewers who produce more than 2,000,000 barrels of beer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... who produce more than 2,000,000 barrels of beer. 25.160 Section 25.160 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Determination of Tax § 25.160 Tax adjustment for brewers who produce more than 2,000,000 barrels of beer. Each...

27 CFR 25.160 - Tax adjustment for brewers who produce more than 2,000,000 barrels of beer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... who produce more than 2,000,000 barrels of beer. 25.160 Section 25.160 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Determination of Tax § 25.160 Tax adjustment for brewers who produce more than 2,000,000 barrels of beer. Each...

27 CFR 25.160 - Tax adjustment for brewers who produce more than 2,000,000 barrels of beer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... who produce more than 2,000,000 barrels of beer. 25.160 Section 25.160 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Tax on Beer Determination of Tax § 25.160 Tax adjustment for brewers who produce more than 2,000,000 barrels of beer. Each...

27 CFR 25.160 - Tax adjustment for brewers who produce more than 2,000,000 barrels of beer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... who produce more than 2,000,000 barrels of beer. 25.160 Section 25.160 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Tax on Beer Determination of Tax § 25.160 Tax adjustment for brewers who produce more than 2,000,000 barrels of beer. Each...

Design and development of a work robot to place ATLAS SCT modules onto barrel cylinders

NASA Astrophysics Data System (ADS)

Terada, S.; Kobayashi, H.; Sengoku, H.; Kato, Y.; Hara, K.; Honma, F.; Ikegami, Y.; Iwata, Y.; Kohriki, T.; Kondo, T.; Nakano, I.; Takashima, R.; Tanaka, R.; Ujiie, N.; Unno, Y.; Yasuda, S.

2005-04-01

More than 2000 silicon modules need to be placed and fastened on the ATLAS SCT barrel tracker. A semi-automatic pick-and-place work robot was designed and developed to cope with the module placement for the SCT barrel assembly. We found that this robot could place modules to a mechanical precision of better than 25 μm.

27 CFR 25.160 - Tax adjustment for brewers who produce more than 2,000,000 barrels of beer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... who produce more than 2,000,000 barrels of beer. 25.160 Section 25.160 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Determination of Tax § 25.160 Tax adjustment for brewers who produce more than 2,000,000 barrels of beer. Each...

40 CFR Table Nn-2 to Subpart Nn of... - Default Values for Calculation Methodology 2 of This Subpart

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Suppliers of Natural Gas and Natural Gas Liquids Pt. 98, Subpt. NN, Table NN-2 Table NN-2 to Subpart NN of Part 98.../Unit) 1 Natural Gas Mscf 0.0544 Propane Barrel 0.241 Normal butane Barrel 0.281 Ethane Barrel 0.170...

Infralimbic Neurotrophin-3 Infusion Rescues Fear Extinction Impairment in a Mouse Model of Pathological Fear.

PubMed

D'Amico, Davide; Gener, Thomas; de Lagrán, Maria Martínez; Sanchez-Vives, Maria V; Santos, Mónica; Dierssen, Mara

2017-01-01

The inability to properly extinguish fear memories constitutes the foundation of several anxiety disorders, including panic disorder. Recent findings show that boosting prefrontal cortex synaptic plasticity potentiates fear extinction, suggesting that therapies that augment synaptic plasticity could prove useful in rescue of fear extinction impairments in this group of disorders. Previously, we reported that mice with selective deregulation of neurotrophic tyrosine kinase receptor, type 3 expression (TgNTRK3) exhibit increased fear memories accompanied by impaired extinction, congruent with an altered activation pattern of the amygdala-hippocampus-medial prefrontal cortex fear circuit. Here we explore the specific role of neurotrophin 3 and its cognate receptor in the medial prefrontal cortex, and its involvement in fear extinction in a pathological context. In this study we combined molecular, behavioral, in vivo pharmacology and ex vivo electrophysiological recordings in TgNTRK3 animals during contextual fear extinction processes. We show that neurotrophin 3 protein levels are increased upon contextual fear extinction in wild-type animals but not in TgNTRK3 mice, which present deficits in infralimbic long-term potentiation. Importantly, infusion of neurotrophin 3 to the medial prefrontal cortex of TgNTRK3 mice rescues contextual fear extinction and ex vivo local application improves medial prefrontal cortex synaptic plasticity. This effect is blocked by inhibition of extracellular signal-regulated kinase phosphorylation through peripheral administration of SL327, suggesting that rescue occurs via this pathway. Our results suggest that stimulating neurotrophin 3-dependent medial prefrontal cortex plasticity could restore contextual fear extinction deficit in pathological fear and could constitute an effective treatment for fear-related disorders.

Evidence that primary visual cortex is required for image, orientation, and motion discrimination by rats.

PubMed

Petruno, Sarah K; Clark, Robert E; Reinagel, Pamela

2013-01-01

The pigmented Long-Evans rat has proven to be an excellent subject for studying visually guided behavior including quantitative visual psychophysics. This observation, together with its experimental accessibility and its close homology to the mouse, has made it an attractive model system in which to dissect the thalamic and cortical circuits underlying visual perception. Given that visually guided behavior in the absence of primary visual cortex has been described in the literature, however, it is an empirical question whether specific visual behaviors will depend on primary visual cortex in the rat. Here we tested the effects of cortical lesions on performance of two-alternative forced-choice visual discriminations by Long-Evans rats. We present data from one highly informative subject that learned several visual tasks and then received a bilateral lesion ablating >90% of primary visual cortex. After the lesion, this subject had a profound and persistent deficit in complex image discrimination, orientation discrimination, and full-field optic flow motion discrimination, compared with both pre-lesion performance and sham-lesion controls. Performance was intact, however, on another visual two-alternative forced-choice task that required approaching a salient visual target. A second highly informative subject learned several visual tasks prior to receiving a lesion ablating >90% of medial extrastriate cortex. This subject showed no impairment on any of the four task categories. Taken together, our data provide evidence that these image, orientation, and motion discrimination tasks require primary visual cortex in the Long-Evans rat, whereas approaching a salient visual target does not.

Assessment of undiscovered oil and gas resources of the Amu Darya Basin and Afghan-Tajik Basin Provinces, Afghanistan, Iran, Tajikistan, Turkmenistan, and Uzbekistan, 2011

USGS Publications Warehouse

Klett, T.R.; Schenk, Christopher J.; Wandrey, Craig J.; Charpentier, Ronald R.; Brownfield, Michael E.; Pitman, Janet K.; Pollastro, Richard M.; Cook, Troy A.; Tennyson, Marilyn E.

2012-01-01

Using a geology-based assessment methodology, the U.S. Geological Survey estimated volumes of undiscovered, technically recoverable, conventional petroleum resources for the Amu Darya Basin and Afghan–Tajik Basin Provinces of Afghanistan, Iran, Tajikistan, Turkmenistan, and Uzbekistan. The mean volumes were estimated at 962 million barrels of crude oil, 52 trillion cubic feet of natural gas, and 582 million barrels of natural gas liquids for the Amu Darya Basin Province and at 946 million barrels of crude oil, 7 trillion cubic feet of natural gas, and 85 million barrels of natural gas liquids for the Afghan–Tajik Basin Province.

Vesicular monoamine transporter-1 (VMAT-1) mRNA and immunoreactive proteins in mouse brain.

PubMed

Ashe, Karen M; Chiu, Wan-Ling; Khalifa, Ahmed M; Nicolas, Antoine N; Brown, Bonnie L; De Martino, Randall R; Alexander, Clayton P; Waggener, Christopher T; Fischer-Stenger, Krista; Stewart, Jennifer K

2011-01-01

Vesicular monoamine transporter 1 (VMAT-1) mRNA and protein were examined (1) to determine whether adult mouse brain expresses full-length VMAT-1 mRNA that can be translated to functional transporter protein and (2) to compare immunoreactive VMAT-1 proteins in brain and adrenal. VMAT-1 mRNA was detected in mouse brain with RT-PCR. The cDNA was sequenced, cloned into an expression vector, transfected into COS-1 cells, and cell protein was assayed for VMAT-1 activity. Immunoreactive proteins were examined on western blots probed with four different antibodies to VMAT-1. Sequencing confirmed identity of the entire coding sequences of VMAT-1 cDNA from mouse medulla oblongata/pons and adrenal to a Gen-Bank reference sequence. Transfection of the brain cDNA into COS-1 cells resulted in transporter activity that was blocked by the VMAT inhibitor reserpine and a proton ionophore, but not by tetrabenazine, which has a high affinity for VMAT-2. Antibodies to either the C- or N- terminus of VMAT-1 detected two proteins (73 and 55 kD) in transfected COS-1 cells. The C-terminal antibodies detected both proteins in extracts of mouse medulla/pons, cortex, hypothalamus, and cerebellum but only the 73 kD protein and higher molecular weight immunoreactive proteins in mouse adrenal and rat PC12 cells, which are positive controls for rodent VMAT-1. These findings demonstrate that a functional VMAT-1 mRNA coding sequence is expressed in mouse brain and suggest processing of VMAT-1 protein differs in mouse adrenal and brain.

Low Leachable Container System Consisting of a Polymer-Based Syringe with Chlorinated Isoprene Isobutene Rubber Plunger Stopper.

PubMed

Kiminami, Hideaki; Takeuchi, Katsuyuki; Nakamura, Koji; Abe, Yoshihiko; Lauwers, Philippe; Dierick, William; Yoshino, Keisuke; Suzuki, Shigeru

2015-01-01

A 36 month leachable study on water for injection in direct contact within a polymer-based prefillable syringe consisting of a cyclo olefin polymer barrel, a chlorinated isoprene isobutene rubber plunger stopper, a polymer label attached on the barrel, and a secondary packaging was conducted at 25 ± 2 °C and 60 ± 5% relative humidity. Through the various comparison studies, no difference in the leachable amounts was observed between this polymer-based prefilled syringe and a glass bottle as a blank sample reference by 36 months. No influence on the leachables study outcome was noted from the printed label and/or label adhesive or from the secondary packaging. In an additional study, no acrylic acid used as the label adhesive leachable was detected by an extended storage for 45 months at 25 ± 2 °C and 60 ± 5% relative humidity as a worst case. To obtain more details, a comparison extractable study was conducted between a cyclo olefin polymer barrel and a glass barrel. In addition, chlorinated isoprene isobutene rubber and bromo isoprene isobutene rubber were compared. As a result, no remarkable difference was found in the organic extractables for syringe barrels. On the other hand, in the case of element extractable analysis, the values for the cyclo olefin polymer barrel were lower than that for the glass barrel. For the plunger stoppers, the chlorinated isoprene isobutene rubber applied in this study was showing a lower extractable profile as compared to the bromo isoprene isobutene rubber, both for organic and element extractables. In conclusion, the proposed polymer-based prefillable syringe system has great potential and represents a novel alternative that can achieve very low level extractable profiles and can bring additional value to the highly sensitive biotech drug market. A 36 month leachable study on water for injection in direct contact within a cyclo olefin polymer barrel and chlorinated isoprene isobutene rubber plunger stopper that has a polymer label attached to the barrel and is wrapped into a secondary packaging was conducted at 25 °C and 60% relative humidity. Through the various comparison studies, no difference in the leachable amounts was observed between polymer-based prefilled syringes and a glass bottle as a blank sample reference by 36 months. No influences on the leachables study outcome were noted from the secondary packaging. To obtain more details, a comparison extractable study was conducted between the cyclo olefin polymer and the glass barrel. In addition, chlorinated isoprene isobutene rubber and bromo isoprene isobutene rubber plunger stoppers were compared as well. As a result, no remarkable difference was found in the organic extractables for barrels. As for element extractable analysis, the values for the cyclo olefin polymer barrel were lower than that for the glass barrel. For the plunger stoppers, the chlorinated isoprene isobutene rubber applied in this study was showing a lower extractable profile as compared to the bromo isoprene isobutene rubber, both for organic and element extractables. In conclusion, the proposed polymer-based prefillable syringe system has great potential and represents a novel alternative that can achieve very low level extractable profiles and can bring additional value to the highly sensitive biotech drug market. © PDA, Inc. 2015.

Alterations in neuronal cytoskeletal and astrocytic proteins content in the brain of the autistic-like mouse strain C58/J.

PubMed

Barón-Mendoza, Isabel; García, Octavio; Calvo-Ochoa, Erika; Rebollar-García, Jorge Omar; Garzón-Cortés, Daniel; Haro, Reyes; González-Arenas, Aliesha

2018-06-06

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficient social interaction, impaired communication as well as repetitive behaviors. ASD subjects present connectivity and neuroplasticity disturbances associated with morphological alterations in axons, dendrites, and dendritic spines. Given that the neuronal cytoskeleton and astrocytes have an essential role in regulating several mechanisms of neural plasticity, the aim of this work was to study alterations in the content of neuronal cytoskeletal components actin and tubulin and their associated proteins, as well as astrocytic proteins GFAP and TSP-1 in the brain of a C58/J mouse model of ASD. We determined the expression and regulatory phosphorylation state of cytoskeletal components in the prefrontal cortex, hippocampus, and cerebellum of C58/J mice by means of Western blotting. Our results show that autistic-like mice present: 1) region-dependent altered expression and phosphorylation patterns of Tau isoforms, associated with anomalous microtubule depolymerization; 2) reduced MAP2 A content in prefrontal cortex; 3) region-dependent changes in cofilin expression and phosphorylation, associated with abnormal actin filament depolymerizing dynamics; 4) diminished synaptopodin levels in the hippocampus; and 5) reduced content of the astrocyte-secreted protein TSP-1 in the prefrontal cortex and hippocampus. Our work demonstrates changes in the expression and phosphorylation of cytoskeletal proteins as well as in TSP-1 in the brain of the autistic-like mice C58/J, shedding light in one of the possible molecular mechanisms underpinning neuroplasticity alterations in the ASD brain and laying the foundation for future investigations in this topic. Copyright © 2018 Elsevier B.V. All rights reserved.

A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.

PubMed

Deng, Dazhi; Jian, Chongdong; Lei, Ling; Zhou, Yijing; McSweeney, Colleen; Dong, Fengping; Shen, Yilun; Zou, Donghua; Wang, Yonggang; Wu, Yuan; Zhang, Limin; Mao, Yingwei

2017-10-17

Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 ( DISC1 ), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life. We have established a new mouse model that specifically interrupts DISC1 functions in NPCs in vivo by a dominant-negative DISC1 (DN-DISC1) with a precise temporal and spatial regulation. Interestingly, prenatal interruption of mouse Disc1 function in NPCs leads to abnormal depression-like deficit in adult mice. Here we took a novel unbiased metabonomics approach to identify brain-specific metabolites that are significantly changed in DN-DISC1 mice. Surprisingly, the inhibitory neurotransmitter, GABA, is augmented. Consistently, parvalbumin (PV) interneurons are increased in the cingulate cortex, retrosplenial granular cortex, and motor cortex. Interestingly, somatostatin (SST) positive and neuropeptide Y (NPY) interneurons are decreased in some brain regions, suggesting that DN-DISC1 expression affects the localization of interneuron subtypes. To further explore the cellular mechanisms that cause this change, DN-DISC1 suppresses proliferation and promotes the cell cycle exit of progenitors in the medial ganglionic eminence (MGE), whereas it stimulates ectopic proliferation of neighboring cells through cell non-autonomous effect. Mechanistically, it modulates GSK3 activity and interrupts Dlx2 activity in the Wnt activation. In sum, our results provide evidence that specific genetic insults on NSCs at a short period of time could lead to prolonged changes of brain metabolism and development, eventually behavioral defects.

Age-dependent effects of esculetin on mood-related behavior and cognition from stressed mice are associated with restoring brain antioxidant status.

PubMed

Martín-Aragón, Sagrario; Villar, Ángel; Benedí, Juana

2016-02-04

Dietary antioxidants might exert an important role in the aging process by relieving oxidative damage, a likely cause of age-associated brain dysfunctions. This study aims to investigate the influence of esculetin (6,7-dihydroxycoumarin), a naturally occurring antioxidant in the diet, on mood-related behaviors and cognitive function and its relation with age and brain oxidative damage. Behavioral tests were employed in 11-, 17- and 22-month-old male C57BL/6J mice upon an oral 35day-esculetin treatment (25mg/kg). Activity of antioxidant enzymes, GSH and GSSG levels, GSH/GSSG ratio, and mitochondrial function were analyzed in brain cortex at the end of treatment in order to assess the oxidative status related to mouse behavior. Esculetin treatment attenuated the increased immobility time and enhanced the diminished climbing time in the forced swim task elicited by acute restraint stress (ARS) in the 11- and 17-month-old mice versus their counterpart controls. Furthermore, ARS caused an impairment of contextual memory in the step-through passive avoidance both in mature adult and aged mice which was partially reversed by esculetin only in the 11-month-old mice. Esculetin was effective to prevent the ARS-induced oxidative stress mostly in mature adult mice by restoring antioxidant enzyme activities, augmenting the GSH/GSSG ratio and increasing cytochrome c oxidase (COX) activity in cortex. Modulation of the mood-related behavior and cognitive function upon esculetin treatment in a mouse model of ARS depends on age and is partly due to the enhancement of redox status and levels of COX activity in cortex. Copyright © 2015. Published by Elsevier Inc.

An interspecies comparison of mercury inhibition on muscarinic acetylcholine receptor binding in the cerebral cortex and cerebellum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, Niladri; Department of Natural Resource Sciences, McGill University, Ste.-Anne-de-Bellevue, Quebec, H9X 3V9; Stamler, Christopher J.

2005-05-15

Mercury (Hg) is a ubiquitous pollutant that can disrupt neurochemical signaling pathways in mammals. It is well documented that inorganic Hg (HgCl{sub 2}) and methyl Hg (MeHg) can inhibit the binding of radioligands to the muscarinic acetylcholine (mACh) receptor in rat brains. However, little is known concerning this relationship in specific anatomical regions of the brain or in other species, including humans. The purpose of this study was to explore the inhibitory effects of HgCl{sub 2} and MeHg on [{sup 3}H]-quinuclidinyl benzilate ([{sup 3}H]-QNB) binding to the mACh receptor in the cerebellum and cerebral cortex regions from human, rat, mouse,more » mink, and river otter brain tissues. Saturation binding curves were obtained from each sample to calculate receptor density (B {sub max}) and ligand affinity (K {sub d}). Subsequently, samples were exposed to HgCl{sub 2} or MeHg to derive IC50 values and inhibition constants (K {sub i}). Results demonstrate that HgCl{sub 2} is a more potent inhibitor of mACh receptor binding than MeHg, and the receptors in the cerebellum are more sensitive to Hg-mediated mACh receptor inhibition than those in the cerebral cortex. Species sensitivities, irrespective of Hg type and brain region, can be ranked from most to least sensitive: river otter > rat > mink > mouse > humans. In summary, our data demonstrate that Hg can inhibit the binding [{sup 3}H]-QNB to the mACh receptor in a range of mammalian species. This comparative study provides data on interspecies differences and a framework for interpreting results from human, murine, and wildlife studies.« less

Quetiapine and aripiprazole signal differently to ERK, p90RSK and c-Fos in mouse frontal cortex and striatum: role of the EGF receptor

PubMed Central

2014-01-01

Background Signaling pathways outside dopamine D2 receptor antagonism may govern the variable clinical profile of antipsychotic drugs (APD) in schizophrenia. One postulated mechanism causal to APD action may regulate synaptic plasticity and neuronal connectivity via the extracellular signal-regulated kinase (ERK) cascade that links G-protein coupled receptors (GPCR) and ErbB growth factor signaling, systems disturbed in schizophrenia. This was based upon our finding that the low D2 receptor affinity APD clozapine induced initial down-regulation and delayed epidermal growth factor receptor (EGFR or ErbB1) mediated activation of the cortical and striatal ERK response in vivo distinct from olanzapine or haloperidol. Here we map whether the second generation atypical APDs aripiprazole and quetiapine affect the EGFR-ERK pathway and its substrates p90RSK and c-Fos in mouse brain, given their divergent agonist and antagonist properties on dopaminergic transmission, respectively. Results In prefrontal cortex, aripiprazole triggered triphasic ERK phosphorylation that was EGFR-independent but had no significant effect in striatum. Conversely quetiapine did not alter cortical ERK signaling but elevated striatal ERK levels in an EGFR-dependent manner. Induction of ERK by aripiprazole did not affect p90RSK signaling but quetiapine decreased RSK phosphorylation within 1-hour of administration. The transcription factor c-Fos by comparison was a direct target of ERK phosphorylation induced by aripiprazole in cortex and quetiapine in striatum with protein levels in temporal alignment with that of ERK. Conclusions These data indicate that aripiprazole and quetiapine signal to specific nuclear targets of ERK, which for quetiapine occurs via an EGFR-linked mechanism, possibly indicating involvement of this system in its action. PMID:24552586

Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues.

PubMed

de Cavanagh, E M; Inserra, F; Ferder, L; Fraga, C G

2000-03-01

The effect of enalapril and captopril on total glutathione content (GSSG + GSH) and selenium-dependent glutathione peroxidase (Se-GPx) and glutathione reductase (GSSG-Rd) activities was investigated in mouse tissues. CF-1 mice (4-mo-old females) received water containing enalapril (20 mg/l) or captopril (50 mg/l) for 11 wk. Enalapril increased GSSG + GSH content (P < 0.05) in erythrocytes (147%), brain (112%), and lung (67%), and captopril increased GSSG + GSH content in erythrocytes (190%) and brain (132%). Enalapril enhanced Se-GPx activity in kidney cortex (42%) and kidney medulla (23%) and captopril in kidney cortex (30%). GSSG-Rd activity was enhanced by enalapril in erythrocytes (21%), brain (21%), liver (18%), and kidney cortex (53%) and by captopril in erythrocytes (25%), brain (19%), and liver (34%). In vitro erythrocyte oxidant stress was evaluated by thiobarbituric acid-reactive substances (TBARS) production (control 365 +/- 11, enalapril 221 +/- 26, captopril 206 +/- 17 nmol TBARS x g Hb(-1) x h(-1); both P < 0.05 vs. control) and phenylhydrazine-induced methemoglobin (MetHb) formation (control 66.5 +/- 3.5, enalapril 52.9 +/- 0.4, captopril: 56.4 +/- 2.9 micromol MetHb/g Hb; both P < 0.05 vs. control). Both angiotensin-converting enzyme inhibitor treatments were associated with increased nitric oxide production, as assessed by plasma NO-(3) + NO-(2) level determination (control 9.22 +/- 0.64, enalapril 13.7 +/- 1.9, captopril 17.3 +/- 3.0 micromol NO-(3) + NO-(2)/l plasma; both P < 0.05 vs. control). These findings support our previous reports on the enalapril- and captopril-induced enhancement of endogenous antioxidant defenses and include new data on glutathione-dependent defenses, thus furthering current knowledge on the association of ACE inhibition and antioxidants.

Two waves of anisotropic growth generate enlarged follicles in the spiny mouse

PubMed Central

2014-01-01

Background Mammals exhibit a remarkable variety of phenotypes and comparative studies using novel model species are needed to uncover the evolutionary developmental mechanisms generating this diversity. Here, we undertake a developmental biology and numerical modeling approach to investigate the development of skin appendages in the spiny mouse, Acomys dimidiatus. Results We demonstrate that Acomys spines, possibly involved in display and protection, are enlarged awl hairs with a concave morphology. The Acomys spines originate from enlarged placodes that are characterized by a rapid downwards growth which results in voluminous follicles. The dermal condensation (dermal papilla) at the core of the follicle is very large and exhibits a curved geometry. Given its off-centered position, the dermal papilla generates two waves of anisotropic proliferation, first of the posterior matrix, then of the anterior inner root sheath (IRS). Higher in the follicle, the posterior and anterior cortex cross-section areas substantially decrease due to cortex cell elongation and accumulation of keratin intermediate filaments. Milder keratinization in the medulla gives rise to a foamy material that eventually collapses under the combined compression of the anterior IRS and elongation of the cortex cells. Simulations, using linear elasticity theory and the finite-element method, indicate that these processes are sufficient to replicate the time evolution of the Acomys spine layers and the final shape of the emerging spine shaft. Conclusions Our analyses reveal how hair follicle morphogenesis has been altered during the evolution of the Acomys lineage, resulting in a shift from ancestral awl follicles to enlarged asymmetrical spines. This study contributes to a better understanding of the evolutionary developmental mechanisms that generated the great diversity of skin appendage phenotypes observed in mammals. PMID:25705371

Cathepsin L plays a major role in cholecystokinin production in mouse brain cortex and in pituitary AtT-20 cells: protease gene knockout and inhibitor studies.

PubMed

Beinfeld, Margery C; Funkelstein, Lydiane; Foulon, Thierry; Cadel, Sandrine; Kitagawa, Kouki; Toneff, Thomas; Reinheckel, Thomas; Peters, Christoph; Hook, Vivian

2009-10-01

Cholecystokinin (CCK) is a peptide neurotransmitter whose production requires proteolytic processing of the proCCK precursor to generate active CCK8 neuropeptide in brain. This study demonstrates the significant role of the cysteine protease cathepsin L for CCK8 production. In cathepsin L knockout (KO) mice, CCK8 levels were substantially reduced in brain cortex by an average of 75%. To evaluate the role of cathepsin L in producing CCK in the regulated secretory pathway of neuroendocrine cells, pituitary AtT-20 cells that stably produce CCK were treated with the specific cathepsin L inhibitor, CLIK-148. CLIK-148 inhibitor treatment resulted in decreased amounts of CCK secreted from the regulated secretory pathway of AtT-20 cells. CLIK-148 also reduced cellular levels of CCK9 (Arg-CCK8), consistent with CCK9 as an intermediate product of cathepsin L, shown by the decreased ratio of CCK9/CCK8. The decreased CCK9/CCK8 ratio also suggests a shift in the production to CCK8 over CCK9 during inhibition of cathepsin L. During reduction of the PC1/3 processing enzyme by siRNA, the ratio of CCK9/CCK8 was increased, suggesting a shift to the cathepsin L pathway for the production of CCK9. The changes in ratios of CCK9 compared to CCK8 are consistent with dual roles of the cathepsin L protease pathway that includes aminopeptidase B to remove NH2-terminal Arg or Lys, and the PC1/3 protease pathway. These results suggest that cathepsin L functions as a major protease responsible for CCK8 production in mouse brain cortex, and participates with PC1/3 for CCK8 production in pituitary cells.

Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity.

PubMed

Roselli, Charles E; Finn, Timothy J; Ronnekleiv-Kelly, Sean M; Tanchuck, Michelle A; Kaufman, Katherine R; Finn, Deborah A

2011-12-01

Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined the activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone [WSP]) and found that Srd5a1 was downregulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity. Published by Elsevier Inc.

Localization of Brain 5α-Reductase Messenger RNA in Mice Selectively Bred for High Chronic Alcohol Withdrawal Severity

PubMed Central

Roselli, Charles E.; Finn, Tim J.; Ronnekleiv-Kelly, Sean M.; Tanchuck, Michelle A.; Kaufman, Katherine R.; Finn, Deborah A.

2011-01-01

Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone, WSP) and found that Srd5a1 was down-regulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72 h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity. PMID:21917407

Chronic Ketamine Reduces the Peak Frequency of Gamma Oscillations in Mouse Prefrontal Cortex Ex vivo.

PubMed

McNally, James M; McCarley, Robert W; Brown, Ritchie E

2013-01-01

Abnormalities in EEG gamma band oscillations (GBO, 30-80 Hz) serve as a prominent biomarker of schizophrenia (Sz), associated with positive, negative, and cognitive symptoms. Chronic, subanesthetic administration of antagonists of N-methyl-D-aspartate receptors (NMDAR), such as ketamine, elicits behavioral effects, and alterations in cortical interneurons similar to those observed in Sz. However, the chronic effects of ketamine on neocortical GBO are unknown. Thus, here we examine the effects of chronic (five daily i.p. injections) application of ketamine (5 and 30 mg/kg) and the more specific NMDAR antagonist, MK-801 (0.02, 0.5, and 2 mg/kg), on neocortical GBO ex vivo. Oscillations were generated by focal application of the glutamate receptor agonist, kainate (KA), in coronal brain slices containing the prelimbic cortex. This region constitutes the rodent analog of the human dorsolateral prefrontal cortex, a brain region strongly implicated in Sz-pathophysiology. Here we report the novel finding that chronic ketamine elicits a reduction in the peak oscillatory frequency of KA-elicited oscillations (from 47 to 40 Hz at 30 mg/kg). Moreover, the power of GBO in the 40-50 Hz band was reduced. These findings are reminiscent of both the reduced resonance frequency and power of cortical oscillations observed in Sz clinical studies. Surprisingly, MK-801 had no significant effect, suggesting care is needed when equating Sz-like behavioral effects elicited by different NMDAR antagonists to alterations in GBO activity. We conclude that chronic ketamine in the mouse mimics GBO abnormalities observed in Sz patients. Use of this ex vivo slice model may be useful in testing therapeutic compounds which rescue these GBO abnormalities.

Fitting Neuron Models to Spike Trains

PubMed Central

Rossant, Cyrille; Goodman, Dan F. M.; Fontaine, Bertrand; Platkiewicz, Jonathan; Magnusson, Anna K.; Brette, Romain

2011-01-01

Computational modeling is increasingly used to understand the function of neural circuits in systems neuroscience. These studies require models of individual neurons with realistic input–output properties. Recently, it was found that spiking models can accurately predict the precisely timed spike trains produced by cortical neurons in response to somatically injected currents, if properly fitted. This requires fitting techniques that are efficient and flexible enough to easily test different candidate models. We present a generic solution, based on the Brian simulator (a neural network simulator in Python), which allows the user to define and fit arbitrary neuron models to electrophysiological recordings. It relies on vectorization and parallel computing techniques to achieve efficiency. We demonstrate its use on neural recordings in the barrel cortex and in the auditory brainstem, and confirm that simple adaptive spiking models can accurately predict the response of cortical neurons. Finally, we show how a complex multicompartmental model can be reduced to a simple effective spiking model. PMID:21415925

Effects of anesthesia on the cerebral capillary blood flow in young and old mice

NASA Astrophysics Data System (ADS)

Moeini, Mohammad; Tabatabaei, Maryam S.; Bélanger, Samuel; Avti, Pramod; Castonguay, Alexandre; Pouliot, Philippe; Lesage, Frédéric

2015-03-01

Despite recent findings on the possible role of age-related cerebral microvasculature changes in cognition decline, previous studies of capillary blood flow in aging (using animal models) are scarce and limited to anesthetized conditions. Since anesthesia can have different effects in young and old animals, it may introduce a confounding effect in aging studies. The present study aimed to eliminate the potential confound introduced by anesthesia by measuring capillary blood flow parameters in both awake conditions and under isoflurane anesthesia. We used 2-photon laser scanning fluorescence microscopy to measure capillary diameter, red blood cell velocity and flux, hematocrit and capillary volumetric flow in individual capillaries in the barrel cortex of 6- and 24-month old C57Bl/6 mice. It was observed that microvascular properties are significantly affected by anesthesia leading to different trends in capillary blood flow parameters with aging when measured under awake or anesthetized conditions. The findings in this study suggest taking extra care in interpreting aging studies from anesthetized animals.

Variations in oxygen and ellagitannins, and organoleptic properties of red wine aged in French oak barrels classified by a near infrared system.

PubMed

Michel, Julien; Albertin, Warren; Jourdes, Michael; Le Floch, Alexandra; Giordanengo, Thomas; Mourey, Nicolas; Teissedre, Pierre-Louis

2016-08-01

During wine aging in barrels, antioxidant molecules from wood, such as ellagitannins, are solubilized and react with wine molecules and oxygen. However, their concentrations are highly variable. Oxygen is an important factor, as it plays a role in wine parameters and organoleptic perceptions. Five barrel modalities were used; three polyphenol indices (IP), classified using the NIRS procedure, and three grain qualities. Barrels were equipped with windows to measure the oxygen using luminescence technology. The ellagitannin concentrations in the wine and its organoleptic properties were monitored. Oxygen concentrations decreased quickly during the first 8days of aging and this phenomenon was significantly more marked in barrels with a higher IP and medium grain. The ellagitannin concentrations were believed to be correlated with wood classification and oxygen consumption. Furthermore, the organoleptic properties were significantly impacted, as the wine with the lowest ellagitannin level was described as less astringent, bitter, woody, and smoky/toasty. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ellagitannin content, volatile composition and sensory profile of wines from different countries matured in oak barrels subjected to different toasting methods.

PubMed

González-Centeno, M R; Chira, K; Teissedre, P-L

2016-11-01

Ellagitannins and aromatic compounds evolution in Cabernet Sauvignon wines macerated in oak barrels for a year was studied. Identical barrels with different toastings (medium toasting, medium toasting with watering, Noisette) were used in French, Italian and USA cellars. Ellagitannins increased by 84-96% with aging time, as did woody volatiles, by 86-91% in French wines and 23-35% in Italian wines, while fruity aroma compounds declined by 50-57% in the French and Italian wines over a 12-months period. Nevertheless, other behaviors and different kinetics rates for these compounds were observed depending on barrel toasting, wine matrix and their interactions. Perceived overall woody intensity was closely related to trans-whiskey lactone, guaiacol and vanillin, whereas astringency and bitterness were significantly linked to ellagitannins (p<0.05). This is the first study that evaluates the toasting effect on wines from different countries matured in the same oak barrels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Usage of FT-ICR-MS Metabolomics for Characterizing the Chemical Signatures of Barrel-Aged Whisky

PubMed Central

Roullier-Gall, Chloé; Signoret, Julie; Hemmler, Daniel; Witting, Michael A.; Kanawati, Basem; Schäfer, Bernhard; Gougeon, Régis D.; Schmitt-Kopplin, Philippe

2018-01-01

Whisky can be described as a complex matrix integrating the chemical history from the fermented cereals, the wooden barrels, the specific distillery processes, aging, and environmental factors. In this study, using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analyzed 150 whisky samples from 49 different distilleries, 7 countries, and ranging from 1 day new make spirit to 43 years of maturation with different types of barrel. Chemometrics revealed the unexpected impact of the wood history on the distillate's composition during barrel aging, regardless of the whisky origin. Flavonols, oligolignols, and fatty acids are examples of important chemical signatures for Bourbon casks, whereas a high number of polyphenol glycosides, including for instance quercetin-glucuronide or myricetin-glucoside as potential candidates, and carbohydrates would discriminate Sherry casks. However, the comparison of barrel aged rums and whiskies revealed specific signatures, highlighting the importance of the initial composition of the distillate and the distillery processes. PMID:29520358

Usage of FT-ICR-MS Metabolomics for characterizing the chemical signatures of barrel-aged whisky

NASA Astrophysics Data System (ADS)

Roullier-Gall, Chloé; Signoret, Julie; Hemmler, Daniel; Witting, Michael A.; Kanawati, Basem; Schäfer, Bernhard; Gougeon, Régis D.; Schmitt-Kopplin, Philippe

2018-02-01

Whisky can be described as a complex matrix integrating the chemical history from the fermented cereals, the wooden barrels, the specific distillery processes, ageing and environmental factors. In this study, using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analysed 150 whisky samples from 49 different distilleries, 7 countries, and ranging from 1 day new make spirit to 43 years of maturation with different types of barrel. Chemometrics revealed the unexpected impact of the wood history on the distillatés composition during barrel ageing, regardless of the whisky origin. Flavonols, oligolignols and fatty acids are examples of important chemical signatures for Bourbon casks, whereas a high number of polyphenol glycosides, including for instance quercetin-glucuronide or myricetin-glucoside as potential candidates, and carbohydrates would discriminate Sherry casks. However, the comparison of barrel aged rums and whiskies revealed specific signatures, highlighting the importance of the initial composition of the distillate and the distillery processes.

Characterization of the targeting signal in mitochondrial β-barrel proteins

PubMed Central

Jores, Tobias; Klinger, Anna; Groß, Lucia E.; Kawano, Shin; Flinner, Nadine; Duchardt-Ferner, Elke; Wöhnert, Jens; Kalbacher, Hubert; Endo, Toshiya; Schleiff, Enrico; Rapaport, Doron

2016-01-01

Mitochondrial β-barrel proteins are synthesized on cytosolic ribosomes and must be specifically targeted to the organelle before their integration into the mitochondrial outer membrane. The signal that assures such precise targeting and its recognition by the organelle remained obscure. In the present study we show that a specialized β-hairpin motif is this long searched for signal. We demonstrate that a synthetic β-hairpin peptide competes with the import of mitochondrial β-barrel proteins and that proteins harbouring a β-hairpin peptide fused to passenger domains are targeted to mitochondria. Furthermore, a β-hairpin motif from mitochondrial proteins targets chloroplast β-barrel proteins to mitochondria. The mitochondrial targeting depends on the hydrophobicity of the β-hairpin motif. Finally, this motif interacts with the mitochondrial import receptor Tom20. Collectively, we reveal that β-barrel proteins are targeted to mitochondria by a dedicated β-hairpin element, and this motif is recognized at the organelle surface by the outer membrane translocase. PMID:27345737

Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate

DTIC Science & Technology

2006-05-01

and significant changes in the pattern of expression of ionotropic glutamate receptors in the cortex and striatum. In addition, exercise resulted in...transporter number; (2) phos- phorylation activated through glutamate receptors such as the mGluR5 metabotropic receptor ; and (3) internaliza- tion...dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes

Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

PubMed Central

Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku

2014-01-01

Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620