bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of Endogenous Neurotrophic Factors Prevents the Androgenic Rescue of Rat Spinal Motoneurons
Authors: Xu Jun , Gingras Karen M. , Bengston Lynn , Di Marco Annalise , Forger Nancy G.
Published: April 2018

Target-derived neurotrophic factors are assumed to regulate motoneuron cell death during development but remain unspecified. Motoneuron cell death in the spinal nucleus of the bulbocavernosus (SNB) of rats extends postnatally and is controlled by androgens. We exploited these features of the SNB system to identify endogenously produced trophic factors regulating motoneuron survival. Newborn female rat pups were treated with the androgen, testosterone propionate, or the oil vehicle alone. In addition, females received trophic factor antagonists delivered either into the perineum (the site of SNB target muscles) or systemically. Fusion molecules that bind and sequester the neurotrophins (trkA-IgG, trkB-IgG, and trkC-IgG) were used to block activation of neurotrophin receptors, and AADH-CNTF was used to antagonize signaling through the ciliary neurotrophic factor receptor-α (CNTFRα). An acute blockade of trkB, trkC, or CNTFRα prevented the androgenic sparing of SNB motoneurons when antagonists were delivered to the perineum. Trophic factor antagonists did not significantly reduce SNB motoneuron number when higher doses were injected systemically. These findings demonstrate a requirement for specific, endogenously produced trophic factors in the androgenic rescue of SNB motoneurons and further suggest that trophic factor interactions at the perineum play a crucial role in masculinization of this neural system.
Morphine-Induced Dependence and Sensitization Are Altered in Mice Deficient in AMPA-Type Glutamate Receptor-A Subunits
Authors: Vekovischeva Olga Y. , Zamanillo Daniel , Echenko Oxana , Seppälä Timo , Uusi-Oukari Mikko , Honkanen Aapo , Seeburg Peter H. , Sprengel Rolf , Korpi Esa R.
Published: April 2018

AMPA-type glutamate receptors have been suggested to be involved in the neurobiological mechanisms of drug addiction. We have made use of two mouse lines, which both have modulated AMPA receptor responses. The first line is entirely deficient in glutamate receptor-A (GluR-A) subunits (A−/− knock-out line) and, in the second one, the Q582 residue of GluR-A subunits is replaced by an arginine residue (R/R mutants), which reduces the calcium permeability and channel conductance of the receptors containing this mutated subunit. Mice of both lines are healthy, but they show slightly increased locomotor activity. Acute morphine administration enhanced locomotor activity of the GluR-A−/− and GluR-A(R/R) mice, at least as much as that of their wild-type littermates. Only in the GluR-A−/− mice did we observe reduced tolerance development in tail-flick antinociception and less severe naloxone-precipitated withdrawal symptoms after treatment with increasing morphine doses, without differences in plasma and brain morphine levels when compared with wild type. Repeated daily morphine administration sensitized the locomotor activity responses in the GluR-A−/− and GluR-A(R/R) mice only when given in the measuring cages, whereas the wild-type mice showed slightly increased responses also when the repeated treatment was given in their home cages. Normal or even enhanced context-dependent sensitization was observed also with repeated amphetamine administration in the GluR-A subunit-deficient mice. The results indicate that AMPA receptors are involved in the acute and chronic effects of morphine, including context-independent sensitization, and that the GluR-A subunit itself is important for morphine tolerance and dependence.
Influence of the Direction of Elemental Luminance Gradients on the Responses of V4 Cells to Textured Surfaces
Authors: Hanazawa Akitoshi , Komatsu Hidehiko
Published: April 2018

The texture of an object provides important cues for its recognition; however, little is known about the neural representation of texture. To investigate the representation of texture in the visual cortex, we recorded single-cell activities in area V4 of macaque monkeys. To distinguish the sensitivity of the cells to texture parameters such as density and element size from that to spatial frequency, we used texture stimuli mimicking shaded granular surfaces. We varied the size and density of the texture elements and the direction of elemental luminance gradients (apparent shadings) as stimulus parameters. Most macaque V4 cells (151 of 170; 89%) exhibited sensitivity to the texture parameters. Interestingly, 21of these cells were tuned to single shading directions (unidirectional tuning). This unidirectional tuning cannot be explained by complex-cell-like tuning for spectral power of spatial frequency, because texture stimuli with a shading direction and its opposite have almost the same spectral power. Unidirectional tunings of these cells were invariant for the position of the texture elements. Thus, this tuning cannot be explained by simple-cell-like phase-dependent spatial frequency tuning or selectivity to a particular arrangement of the elements. Moreover, the unidirectional tuning had a bias toward vertical directions, consistent with an anisotropy in the perception of three-dimensional shape from shading. This novel spatial property suggests that V4 cells are involved in extracting texture features from objects, including their three-dimensionality.
Impaired Recognition of the Goal Location during Spatial Navigation in Rats with Hippocampal Lesions
Authors: Hollup Stig A. , Kjelstrup Kirsten G. , Hoff Joakim , Moser May-Britt , Moser Edvard I.
Published: April 2018

Converging evidence suggests that the hippocampus is essential for goal-directed spatial navigation. Successful navigation requires not only the ability to compute an appropriate path toward the target but is also guided by recognition of places along the trajectory between start and goal. To determine whether the hippocampus contributes to place recognition, we trained rats with hippocampal lesions in an annular water maze with a remotely controlled escape platform at a constant location in the corridor. The platform remained submerged and unavailable until the rat had swum at least one full lap. Probe trials with the platform unavailable for 60 sec were inserted at regular intervals. In these trials, the rat would swim over the platform several times, regardless of its navigational abilities. After a few training sessions, all sham-operated control animals reduced their swim velocity when they approached the platform, indicating that they recognized the target location. Rats with hippocampal lesions, in contrast, swam at the same velocity as elsewhere in the corridor. Preoperative training or prolonged postoperative training did not alleviate the deficit. Rats with hippocampal lesions were able to learn a cued version of the task, which implies that the failure to slow down was not attributable to motor inflexibility. Thus, hippocampal lesions caused a severe but selective deficit in the identification of a location, suggesting that the hippocampus may be essential for image recognition during spatial navigation.
Activation of the Nuclear Factor-κB Is a Key Event in Brain Tolerance
Authors: Blondeau Nicolas , Widmann Catherine , Lazdunski Michel , Heurteaux Catherine
Published: April 2018

The transcription factor nuclear factor-κB (NFκB) is an ubiquitously expressed inducible regulator of a broad range of genes and plays a pivotal role in cell death and survival pathways. Three models of brain tolerance (ischemic, epileptic, and polyunsaturated fatty acid-induced preconditioning), known to confer resistance to neurons against ischemia or status epilepticus, were used to determine whether NFκB mediated the late preconditioning. A sublethal 3 min ischemia, a dose of 5 mg/kg kainic acid (KA5) or 500 nmol of linolenic acid (LIN500) led to a rapid increase of NFκB DNA-binding activity and nuclear translocation of p65 and p50 subunits of NFκB in neurons. Pretreatment with the NFκB inhibitor diethyldithiocarbamate or κB decoy DNA blocked the increased DNA-binding activity and the nuclear translocation of NFκB and abolished the neuroprotective effects of different delayed preconditionings against severe ischemia or epilepsy. The inhibition of NFκB observed in rats preconditioned with 3 min ischemia, KA5 or LIN500 treatments compared with ischemic or epileptic controls was correlated with the prevention of the inducible degradation of the inhibitory protein IκBα. Preconditioning probably inhibits the activation of NFκB by interfering with a pathway that leads to the direct transcriptional activation of IκBα by NFκB itself. The present work provides evidence that activation of NFκB is a crucial step in the signal transduction pathway that underlies the development of brain tolerance and may open new strategies in the prevention of cerebral diseases, such as ischemia or epilepsy.
NMDA Receptor and Nitric Oxide Synthase Activation Regulate Polysialylated Neural Cell Adhesion Molecule Expression in Adult Brainstem Synapses
Authors: Bouzioukh Farima , Tell Fabien , Jean André , Rougon Geneviève
Published: April 2018

Here we report that synapses in the adult dorsal vagal complex, a gateway for many primary afferent fibers, express a high level of the polysialylated neural cell adhesion molecule (PSA-NCAM). We show that electrical stimulation of the vagal afferents causes a rapid decrease of PSA-NCAM expression bothin vivoand in acute slices. Inhibition of NMDA receptor activity completely prevented the decrease. Blockade of calmodulin activation, neuronal nitric oxide (NO) synthase, or soluble guanylyl cyclase and chelation of extracellular NO mimicked this inhibition. Our data provide a mechanistic framework for understanding how activity-linked stimulation of the NMDA–NO–cGMP pathway induces rapid changes in PSA-NCAM expression, which may be associated with long-term depression.
Contrasting Effects of Ibotenate Lesions of the Paraventricular Nucleus and Subparaventricular Zone on Sleep–Wake Cycle and Temperature Regulation
Authors: Lu J. , Zhang Y.-H. , Chou T. C. , Gaus S. E. , Elmquist J. K. , Shiromani P. , Saper C. B.
Published: April 2018

The suprachiasmatic nucleus (SCN), the circadian pacemaker for the brain, provides a massive projection to the subparaventricular zone (SPZ), but the role of the SPZ in circadian processes has received little attention. We examined the effects on circadian rhythms of sleep, body temperature, and activity in rats of restricted ibotenic acid lesions of the ventral or dorsal SPZ that spared the immediately adjacent paraventricular hypothalamic nucleus (PVH) and the SCN. Ventral SPZ lesions caused profound reduction of measures of circadian index of sleep (by 90%) and locomotor activity (75% reduction) but had less effect on body temperature (50% reduction); dorsal SPZ lesions caused greater reduction of circadian index of body temperature (by 70%) but had less effect on circadian index of locomotor activity (45% reduction) or sleep (<5% reduction). The loss of circadian regulation of body temperature or sleep was replaced by a strong ultradian rhythm (period ∼3 hr). Lesions of the PVH, immediately dorsal to the SPZ, had no significant effect on any circadian rhythms that we measured, nor did the lesions affect the baseline body temperature. However, the fever response after intravenous injection of lipopolysaccharide (5 μg/kg) was markedly decreased in the rats with PVH lesions (66.6%) but not dorsal SPZ lesions. These results indicate that circadian rhythms of sleep and body temperatures are regulated by separate neuronal populations in the SPZ, and different aspects of thermoregulation (circadian rhythm and fever response) are controlled by distinct anatomical substrates.
Expression of Striatal Preprotachykinin mRNA in Symptomatic and Asymptomatic 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Exposed Monkeys Is Related to Parkinsonian Motor Signs
Authors: Wade Timothy V. , Schneider Jay S.
Published: April 2018

Striatal preprotachykinin (PPT) gene expression and [3H]mazindol binding were examined in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Some animals (n= 5) became moderately to severely parkinsonian after receiving large doses of MPTP over 9–30 d and remained symptomatic for a relatively short time (3 weeks to 3 months; acutely symptomatic group). A second group of animals (n= 5) received low doses of MPTP (1.5–12 months), developed cognitive impairments but displayed no gross motor deficits (asymptomatic group), and were killed 3–12 months after their final dose of MPTP. Other animals became moderately to severely parkinsonian after receiving escalating doses of MPTP (>6 months;n= 4) or high doses of MPTP (<1 month;n= 1) and remained symptomatic for 2.5–5.75 years (chronically symptomatic group). All MPTP-treated animals had extensive losses of [3H]mazindol binding in dorsal striatal sensorimotor regions with asymptomatic animals generally having a lesser degree of damage. However, PPT mRNA levels differed sharply among treatment groups. Symptomatic animals (acutely and chronically parkinsonian) had significantly decreased PPT mRNA levels in most striatal regions. In asymptomatic animals, PPT mRNA expression was not significantly different from that measured in control animals, despite decreases in [3H]mazindol binding in some striatal regions of similar magnitude to those observed in symptomatic animals. These observations suggest that PPT gene expression may be directly related to expression of parkinsonian motor symptomatology regardless of duration of MPTP exposure, duration of the parkinsonism, or extent of dopamine denervation. These results imply that the direct striatal output circuit may have a greater contribution to expression of parkinsonian symptomatology than proposed previously.
Distinct Changes in Cortical Acetylcholine and Noradrenaline Efflux during Contingent and Noncontingent Performance of a Visual Attentional Task
Authors: Dalley Jeffrey W. , McGaughy Jill , O'Connell Mark T. , Cardinal Rudolf N. , Levita Liat , Robbins Trevor W.
Published: April 2018

Optimization of cognitive processing may depend on specific and distinct functions of the cortical cholinergic and noradrenergic systems. This investigation dissociates functions of cortical acetylcholine (ACh) and noradrenaline (NA) in arousal and visual attention by simultaneously measuring ACh and NA efflux in the rat prefrontal cortex during sustained attentional performance. The five-choice serial reaction time task was used to provide a continuous assessment of visuospatial attention. Previous studies using this task have established a critical role for the cortical cholinergic system in the detection of visual targets. However, selective lesions of the locus coeruleus noradrenergic system impair performance only when additional attentional demands are placed on the subject by distractors or temporally unpredictable targets. To test the hypothesis that the cortical noradrenergic system is particularly sensitive to novel task contingencies, we also assessed NA and ACh efflux in rats that been trained previously on the task but for whom the instrumental contingency coupling responding with stimulus detection and reward was abolished. Cortical ACh efflux showed a robust and task-related increase during established contingent performance. This response was significantly attenuated in noncontingent subjects, although it still exceeded pretask values. In contrast, NA efflux only increased transiently in contingent subjects after task onset but showed sustained elevations in noncontingent subjects on the first day when contingencies were changed. These data also implicate cortical ACh in aspects of attentional functioning but highlight a specific involvement of the cortical noradrenergic system in detecting shifts in the predictive relationship between instrumental action and reinforcement.
Glutamatergic Afferents from the Hippocampus to the Nucleus Accumbens Regulate Activity of Ventral Tegmental Area Dopamine Neurons
Authors: Floresco Stan B. , Todd Christopher L. , Grace Anthony A.
Published: April 2018

Several studies have shown that the mesolimbic dopamine (DA) system is strongly influenced by the ventral subiculum (vSub) of the hippocampus. To examine whether this occurs by activation of DA neuron firing, the effects of chemical stimulation of the vSub on ventral tegmental area (VTA) DA neuron activity were examined using extracellular single-unit recordings. Infusions of NMDA into the vSub increased the number of spontaneously firing DA cells recorded per electrode track, while having no effect on firing rate or burst firing. This response was abolished by intranucleus accumbens (NAc) infusions of the glutamate receptor antagonist kynurenic acid. This effect did not involve the prefrontal cortex, because infusions of tetrodotoxin into the prefrontal cortex did not affect the increase in spontaneously active DA cells. Infusions of either kynurenic acid into the NAc or tetrodotoxin into the vSub decreased the firing rate and burst firing of DA neurons without altering the number of spontaneously active DA neurons. These data show that glutamatergic afferents from the vSub to the NAc exert a potent excitatory effect on VTA DA neurons, influencing both DA neuron population activity and the regulation of the firing properties of these neurons. As a result, dysfunctions in hippocampal circuitries may contribute to the hyperexcitable state of the DA system that is present in schizophrenia.
Cyclic Nucleotide-Gated Channels Contribute to the Cholinergic Plateau Potential in Hippocampal CA1 Pyramidal Neurons
Authors: Kuzmiski J. Brent , MacVicar Brian A.
Published: April 2018

Plateau potentials are prolonged membrane depolarizations that are observed in hippocampal pyramidal neurons when spiking and Ca2+entry occur in combination with muscarinic receptor activation. In this study, we used whole-cell voltage clamping to study the current underlying the plateau potential and to determine the cellular signaling pathways contributing to this current. When combined with muscarinic stimulation, depolarizing command potentials that evoked Ca2+influx elicited a prolonged tail current (Itail) that had an extrapolated reversal potential of −20 mV.Itailwas not observed when intracellular Ca2+levels were chelated with 10 mmintracellular BAPTA, andItailwas reversibly depressed in low external sodium. WhenItailwas evoked at intervals >3 min, current amplitudes were stable for up to 1 hr. However, at shorter intervals,Itailwas refractory, with a time constant of recovery of 43.5 sec. The inhibitors of soluble guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and 6-anilino-5,8-quinolinequinone depressedItailand zaprinast, which blocks cGMP-specific phosphodiesterase, enhancedItail, suggesting that a component ofItailwas activated by cGMP. The inhibitors of cyclic nucleotide-gated (CNG) channelsl-cis-diltiazem and 2′,4′-dichlorobenzamil reversibly depressedItail. However, protein kinase G inhibition had no effect. Therefore, these results indicate that a component ofItailis attributable to activation of CNG channels. We conclude that Ca2+influx when combined with muscarinic receptor activation activates soluble guanylate cyclase and increases cGMP levels. The increased cGMP activates CNG channels and leads to prolonged depolarization. The cation conductance of the CNG channel contributes to the prolonged depolarization of the plateau potential.
Presynaptic R-Type Calcium Channels Contribute to Fast Excitatory Synaptic Transmission in the Rat Hippocampus
Authors: Gasparini Sonia , Kasyanov Alexander M. , Pietrobon Daniela , Voronin Leon L. , Cherubini Enrico
Published: April 2018

The possibility that R-type calcium channels contribute to fast glutamatergic transmission in the hippocampus has been assessed using low concentrations of NiCl2and the peptide toxin SNX 482, a selective antagonist of the pore-forming α1Esubunit of R-type calcium channel. EPSPs or EPSCs were recorded in the whole-cell configuration of the patch-clamp technique mainly from CA3 hippocampal neurons. Effects of both NiCl2and SNX 482 were tested on large (composite) EPSCs evoked by mossy and associative–commissural fiber stimulation. NiCl2effects were also tested on minimal EPSPs–EPSCs. Both substances reduced the amplitude of EPSPs–EPSCs. This effect was associated with an increase in the number of response failures of minimal EPSPs–EPSCs, an enhancement of the paired-pulse facilitation ratios of both minimal and composite EPSCs, and a reduction of the inverse squared coefficient of variation (CV−2). The reduction of CV−2was positively correlated with the decrease in EPSC amplitude. The inhibitory effect of NiCl2was occluded by SNX 482 but not by ω-conotoxin-MVIIC, a broad-spectrum antagonist thought to interact with N- and P/Q-type calcium channels, supporting a specific action of low concentrations of NiCl2on R-type calcium channels. Together, these observations indicate that both NiCl2and SNX 482 act at presynaptic sites and block R-type calcium channels with pharmacological properties similar to those encoded by the α1Egene. These channels are involved in fast glutamatergic transmission at hippocampal synapses.
Proteasomal-Dependent Aggregate Reversal and Absence of Cell Death in a Conditional Mouse Model of Huntington's Disease
Authors: Martı́n-Aparicio Ester , Yamamoto Ai , Hernández Félix , Hen René , Avila Jesús , Lucas José J.
Published: April 2018

Neuronal intranuclear inclusions are a histopathological hallmark of Huntington's disease. Nevertheless, the precise mechanism by which they are formed and their relevance to neuronal cell death and/or dysfunction remains unclear. We recently generated a conditional mouse model of Huntington's disease (HD94) in which silencing expression of mutated huntingtin led to the disappearance of intranuclear aggregates and amelioration of the behavioral phenotype. Here, we analyze primary striatal neuronal cultures from HD94 mice to explore the dynamics of aggregate formation and reversal, the possible mechanisms involved, and the correlation between aggregates and neuronal death. In parallel, we examine symptomatic adult HD94 mice in similar studies and explored the relationship between aggregate clearance and behavioral reversal. We report that, in culture, aggregate formation and reversal were rapid processes, such that 2 d of transgene expression led to aggregate formation, and 5 d of transgene suppression led to aggregate disappearance. In mice, full reversal of aggregates and intranuclear mutant huntingtin was more rapid than reported previously and preceded the motor recovery by several weeks. Furthermore, the proteasome inhibitor lactacystin inhibited the aggregate clearance observed in culture, thus indicating that aggregate formation is a balance between the rate of huntingtin synthesis and its degradation by the proteasome. Finally, neither expression of the mutant huntingtin nor aggregates compromised the viability of HD94 cultures. This correlated with the lack of cell death in symptomatic HD94 mice, thus demonstrating that neuronal dysfunction, and not cell loss, triggered by mutant huntingtin underlies symptomatology.
An Activity-Dependent Neurotrophin-3 Autocrine Loop Regulates the Phenotype of Developing Hippocampal Pyramidal Neurons before Target Contact
Authors: Boukhaddaoui Hassan , Sieso Victor , Scamps Frederique , Valmier Jean
Published: April 2018

Neurotrophin-3 (NT-3), its cognate receptor trkC, and voltage-gated calcium channels are coexpressed by embryonic pyramidal neurons before target contact, but their functions at this stage of development are still unclear. We show here that,in vitro, anti-NT-3 and anti-trkC antibodies blocked the increase, and NT-3 reversed the decrease in the number of calbindin-D28k-positive pyramidal neurons induced by, respectively, calcium channel activations and blockades. Similar results were obtained with single-neuron microcultures. In addition, voltage-gated calcium channel inhibition downregulates the extracellular levels of NT-3 in high-density cultures. Moreover, electrophysiological experiments in single-cell cultures reveal a tetrodotoxin-sensitive spontaneous electrical activity allowing voltage-gated calcium channel activation. The mouse NT-3 (−/−) mutation decreases by 40% the number of developing calbindin-D28k-positive pyramidal neurons, without affecting neuronal survival, bothin vitroandin vivo. Thus, present results strongly support that an activity-dependent autocrine NT-3 loop provides a local, intrinsic mechanism by which, before target contact, hippocampal pyramidal-like neurons may regulate their own differentiation, a role that may be important during early CNS differentiation or after adult target disruption.
Nitric Oxide Is an Essential Negative Regulator of Cell Proliferation inXenopusBrain
Authors: Peunova Natalia , Scheinker Vladimir , Cline Hollis , Enikolopov Grigori
Published: April 2018

Mechanisms controlling the transition of a neural precursor cell from proliferation to differentiation during brain development determine the distinct anatomical features of the brain. Nitric oxide (NO) may mediate such a transition, because it can suppress DNA synthesis and cell proliferation. We cloned the gene encoding the neuronal isoform ofXenopusNO synthase (XNOS) and found that in the developing brain ofXenopustadpoles, a zone of XNOS-expressing cells lies adjacent to the zone of dividing neuronal precursors. Exogenous NO, supplied to the tadpole brain in vivo, decreased the number of proliferating cells and the total number of cells in the optic tectum. Conversely, inhibition of NOS activity in vivo increased the number of proliferating cells and the total number of cells in the optic tectum. NOS inhibition yielded larger brains with grossly perturbed organization. Our results indicate that NO is an essential negative regulator of neuronal precursor proliferation during vertebrate brain development.
Glutamine Uptake by Neurons: Interaction of Protons with System A Transporters
Authors: Chaudhry Farrukh A. , Schmitz Dietmar , Reimer Richard J. , Larsson Peter , Gray Andrew T. , Nicoll Roger , Kavanaugh Michael , Edwards Robert H.
Published: April 2018

Astrocytes provide the glutamine required by neurons to synthesize glutamate and GABA. However, the mechanisms involved in glutamine transfer from glia to neurons have remained poorly understood. Recent work has implicated the System N transporter SN1 in the efflux of glutamine from astrocytes and the very closely related System A transporters SA1 and SA2 in glutamine uptake by neurons. To understand how these closely related proteins mediate flux in different directions, we have examined their ionic coupling. In contrast to the electroneutral exchange of H+for Na+and neutral amino acid catalyzed by SN1, we now show that SA1 and SA2 do not couple H+movement to amino acid flux. As a result, SA1 and SA2 are electrogenic and do not mediate flux reversal as readily as SN1. Differences between System N and A transporters in coupling to H+thus contribute to the delivery of glutamine from glia to neurons. Nonetheless, although they are not transported, H+inhibit SA1 and SA2 by competing with Na+.
Protoplasmic Astrocytes in CA1 Stratum Radiatum Occupy Separate Anatomical Domains
Authors: Bushong Eric A. , Martone Maryann E. , Jones Ying Z. , Ellisman Mark H.
Published: April 2018

Protoplasmic astrocytes are increasingly thought to interact extensively with neuronal elements in the brain and to influence their activity. Recent reports have also begun to suggest that physiologically, and perhaps functionally, diverse forms of these cells may be present in the CNS. Our current understanding of astrocyte form and distribution is based predominately on studies that used the astrocytic marker glial fibrillary acidic protein (GFAP) and on studies using metal-impregnation techniques. The prevalent opinion, based on studies using these methods, is that astrocytic processes overlap extensively and primarily share the underlying neuropil. However, both of these techniques have serious shortcomings for visualizing the interactions among these structurally complex cells. In the present study, intracellular injection combined with immunohistochemistry for GFAP show that GFAP delineates only ∼15% of the total volume of the astrocyte. As a result, GFAP-based images have led to incorrect conclusions regarding the interaction of processes of neighboring astrocytes. To investigate these interactions in detail, groups of adjacent protoplasmic astrocytes in the CA1 stratum radiatum were injected with fluorescent intracellular tracers of distinctive emissive wavelengths and analyzed using three-dimensional (3D) confocal analysis and electron microscopy. Our findings show that protoplasmic astrocytes establish primarily exclusive territories. The knowledge of how the complex morphology of protoplasmic astrocytes affects their 3D relationships with other astrocytes, oligodendroglia, neurons, and vasculature of the brain should have important implications for our understanding of nervous system function.
From Spectrum to Space: The Contribution of Level Difference Cues to Spatial Receptive Fields in the Barn Owl Inferior Colliculus
Authors: Euston David R. , Takahashi Terry T.
Published: April 2018

Space-specific neurons in the owl's inferior colliculus have spatial receptive fields (RFs) computed from interaural time (ITD) and level (ILD) differences. Because of the shape of the owl's head, these cues vary with frequency in a manner specific for each location. We sought to determine the contribution of ILD to spatial selectivity. We measured the normal spatial receptive fields of space-specific neurons using virtual sound sources (i.e., noises filtered to simulate external sound sources, presented using headphones). The virtual-source filters were then altered so that ITD was fixed while frequency-specific ILDs varied according to location in the usual manner. The resulting “ILD-alone” RF typically revealed a horizontal band of excitation that included the normal RF. Above and below, the neurons were inhibited. Interestingly, the maxima of ILD-alone RFs were generally outside the normal RF, suggesting that space-specific neurons are not optimally tuned to the ILD spectrum occurring at the normal RF location. Congruously, frequency-specific ILD tuning, assessed with tones, better matched the ILDs at the peak of the ILD-alone RF than those at the peak of the normal RF. The firing evoked from the normal RF may thus reflect the balance of excitatory and inhibitory inputs needed to appropriately restrict the receptive field.

Frequency-specific ILD tuning curves were combined with measured head-filtering characteristics to predict responses to the frequency-specific ILDs at each location. The predicted ILD-alone RFs, which are based on a simple sum of frequency-specific inputs, accounted for 56% of the variance in our measured ILD-alone RFs.
Extraclassical Receptive Field Properties of Parvocellular, Magnocellular, and Koniocellular Cells in the Primate Lateral Geniculate Nucleus
Authors: Solomon Samuel G. , White Andrew J. R. , Martin Paul R.
Published: April 2018

Descriptions of receptive fields at subcortical levels of the visual system have mostly considered only the classical receptive field (CRF). A suppressive extraclassical receptive field (ECRF) has been demonstrated in relay cells within the primate lateral geniculate nucleus (LGN), but the quantitative properties and specific influence of the ECRF on the distinct magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways are not known. Here we quantified the effect of ECRF stimulation on visually responsive cells in the LGN of a diurnal New World primate, the marmoset. We show that for all cells, visually evoked responses are reduced by stimulation of the ECRF. The magnitude of the suppression is greatest for MC cells and smallest for PC cells. The effect of ECRF stimulation on KC cells is variable but always suppressive. We refer to these effects as extraclassical inhibition (ECI). The contrast–response relationship of the ECI parallels that of CRF-induced excitation for each cell class: for MC cells, ECI contrast threshold is close to 10% and the ECI saturates at 50% contrast, but the contrast dependence of ECI on PC cells is more linear. The ECI also contributes to contrast-dependent changes in spatial summation: on average for all LGN cells the radius of the excitatory spatial summation field (measured from aperture-tuning curves) at low contrast is 1.31 times that at high contrast. No consistent effects of orientation on ECI were seen. The data suggest that the suppressive component of the ECRF seen in cortical neurons could primarily be inherited from subcortical input streams.
Role of Melanocortin-4 Receptors in Mediating Renal Sympathoactivation to Leptin and Insulin
Authors: Rahmouni Kamal , Haynes William G. , Morgan Donald A. , Mark Allyn L.
Published: April 2018

Central melanocortin signaling plays an important role in regulation of energy homeostasis by leptin and insulin. We investigated the interaction between leptin, insulin, and melanocortin-4 receptors (MC-4Rs) in the control of renal sympathetic nerve activity (RSNA) in mice. We compared the effects of intracerebroventricular (ICV) administration of leptin, insulin, MC-3/4R agonist (MTII), and corticotrophin-releasing factor (CRF) on RSNA in leptin receptor-deficient (db/db) mice, MC-4R knock-out mice, and their wild-type controls. ICV administration of leptin and MTII caused a significant and dose-dependent increase in RSNA in control mice. As expected, leptin had no significant effect on RSNA in the db/db mice. Interestingly, db/db mice exhibited markedly attenuated RSNA responses to ICV administration of MTII. However, the increase in RSNA induced by insulin and CRF was comparable between db/db and control mice. In the heterozygous and homozygous MC-4R knock-out mice, the RSNA response to MTII was attenuated and abolished, respectively. The RSNA response to ICV leptin and insulin was also attenuated and abolished in the heterozygous and homozygous MC-4R knock-out mice, respectively. In contrast, CRF induced a similar increase in RSNA in the MC-4R knock-out and wild-type mice. Our data demonstrate that in the absence of leptin receptors, the sympathoexcitatory effects of melanocortin system stimulation are attenuated. In addition, the renal sympathoexcitatory responses to leptin and insulin are dependent on the MC-4R, demonstrating an important role for the MC-4R in the regulation of renal sympathetic nerve outflow by leptin and insulin.
The Visual Grasp of the Fragmented Landscape
Authors: Kwa Chunglin
Published: April 2018

Between 1925 and 1980, landscape ecology underwent important changes through the gradual imposition of the view from above, through the uses of aerial photography. A new concept emerged, “the smallest unit of landscape,” also called ecotope and land unit, expressing a direct visual grasp of the landscape. This article compares the view from above as introduced and promoted by geographers Carl Troll and Isaak Zonneveld, with its (problematic) history vis-à-vis a school of ecology, i.e., plant sociology, led by Josias Braun-Blanquet and Reinhold Tüxen. This school’s internal struggles with balancing the physiognomic gaze (at the ground) and numerical methods are discussed. In comparison, the geographers based themselves on the mechanical objectivity of standardized aerial surveys, whereas the plant sociologists relied on their subjective expert judgment of plant recognition together with the structural objectivity of their numerical methods. An important communality of both schools was their inductive building of a landscape from its constituent landscape fragments. Landscape fragments were identified through abstraction and categorization, emanating from a taxonomical style of science.
SYNTHESIS AND OPTIMIZATION OF CARBON NANOPARTICLES (C-DOTS) AS ABSORBER MATERIALS FOR SOLAR DISTILLATION APPLICATIONS
Authors: Nuryadin B. W. , Qulsum U. , Mahen E. C. S. , Nuryantini A. Y. , Aliah H. , Perkasa Y. S.
Published: April 2018

Carbon nanoparticles (C-Dots) were synthesized using citric acid and urea as carbon and fuel source, and combustion reaction methods. The absorption spectral and morphology particles of C-Dots were investigated. The morphology describes the synthesis of small (<1 ?m) and monodispersedC-Dots. Thus, the C-Dots solutions has absorption spectral range of about 86% at visible light spectral. This study suggests that the as-prepared carbon nanoparticles (C-Dots) with particle size and absorption spectral tunability might be utilized as solar energy absorber material.Karbon nanopartikel (C-Dots) disintesis menggunakan asam sitrat dan urea sebagai sumber karbon dan bahan bakar, melalui reaksi pembakaran sederhana. Spektrum absorpsi dan morfologi partikel C-Dots diinvestigasi menggunakan UV-Vis Spectrometry dan analisis SEM. Hasil SEM menunjukan bahwa morfologi partikel C-Dots sangat kecil (<1 ?m) dan seragam. Selain itu, larutan C-Dots memiliki spektrum absopsi pada rentang sekitar 86% pada daerah cahaya tampak. Hasil studi ini menunjukan bahwa karbon nanopartikel (C-Dots) dengan ukuran partikel dan spektrum absorpsi yang dapat diatur, sehingga dapat digunakan sebagai material penyerap sinar matahari.
The Use of Numbered Heads Together (NHT) Learning Model with Science, Environment, Technology, Society (SETS) Approach to Improve Student Learning Motivation of Senior High School
Authors: Sutipnyo B. , Mosik M.
Published: April 2018

This research was aimed to determine the increasing of students' motivation that has been applied by Numbered Heads Together (NHT) learning model with Science, Environment, Technology, Society (SETS) approach. The design of this study was quasi experiment with One Group Pretest-Posttest Design. The data of students’ learning motivation obtained through questionnaire administered before and after NHT learning model with SETS approach. In this research, the indicators of learning-motivation were facing tasks diligently, showing interest in variety of problems, prefering to work independently, keeping students’ opinions, and feeling happy to find and solve problems. Increasing of the students’ learning motivation was analyzed by using a gain test. The results showed that applying NHT learning model with SETS approach could increase the students’ learning motivation in medium categories.
Isolation of a multipotent mesenchymal stem cell-like population from human adrenal cortex
Authors: Gan Earn H , Robson Wendy , Murphy Peter , Pickard Robert , Pearce Simon , Oldershaw Rachel
Published: April 2018

Background

The highly plastic nature of adrenal cortex suggests the presence of adrenocortical stem cells (ACSC), but the exact in vivo identity of ACSC remains elusive. A few studies have demonstrated the differentiation of adipose or bone marrow-derived mesenchymal stem cells (MSC) into steroid-producing cells. We therefore investigated the isolation of multipotent MSC from human adrenal cortex.

Methods

Human adrenals were obtained as discarded surgical material. Single-cell suspensions from human adrenal cortex (n = 3) were cultured onto either complete growth medium (CM) or MSC growth promotion medium (MGPM) in hypoxic condition. Following ex vivo expansion, their multilineage differentiation capacity was evaluated. Phenotype markers were analysed by immunocytochemistry and flow cytometry for cell-surface antigens associated with bone marrow MSCs and adrenocortical-specific phenotype. Expression of mRNAs for pluripotency markers was assessed by q-PCR.

Results

The formation of colony-forming unit fibroblasts comprising adherent cells with fibroblast-like morphology were observed from the monolayer cell culture, in both CM and MGPM. Cells derived from MGPM revealed differentiation towards osteogenic and adipogenic cell lineages. These cells expressed cell-surface MSC markers (CD44, CD90, CD105 and CD166) but did not express the haematopoietic, lymphocytic or HLA-DR markers. Flow cytometry demonstrated significantly higher expression of GLI1 in cell population harvested from MGPM, which were highly proliferative. They also exhibited increased expression of the pluripotency markers.

Conclusion

Our study demonstrates that human adrenal cortex harbours a mesenchymal stem cell-like population. Understanding the cell biology of adrenal cortex- derived MSCs will inform regenerative medicine approaches in autoimmune Addison’s disease.
Role of RAB5A in FSHR-mediated signal transduction in human granulosa cells
Authors: Zhu Kai , Li Shang , Liu Jiansheng , Hong Yan , Chen Zi-Jiang , Du Yanzhi
Published: April 2018

Polycystic ovary syndrome, a common condition characterized by endocrine dysfunction, menstrual irregularity, anovulation and polycystic ovaries, affects 5–7% of reproductive-age women. RAB5B, which is identified by a genome-wide association study as a risk locus for this syndrome, encodes a small GTPase involved in control of receptor internalization and early endosome fusion. We found that RAB5A mRNA levels in luteinized granulosa cells of obese patients with polycystic ovary syndrome were lower than in those of obese women without the syndrome. RAB5A regulated follicle-stimulating hormone (FSH)-mediated translocation of the FSH receptor (FSHR) from the membrane to the cytoplasm and the subsequent FSH–FSHR signaling pathway. We showed that RAB5A negatively regulated aromatase expression and estradiol synthesis in human granulosa cells in association with changes in FSHR levels by way of the cAMP/PKA/CREB pathway. The regulation of FSHR by RAB5A may have been associated with two transcription factors, USF1 and USF2. In conclusion, RAB5A gene was abnormally expressed in luteinized granulosa cells of obese patients with polycystic ovary syndrome, which may help explain high FSHR levels found in this syndrome.
The Pseudokinase Domain of Saccharomyces cerevisiae Tra1 Is Required for Nuclear Localization and Incorporation into the SAGA and NuA4 Complexes
Authors: Berg Matthew D , Genereaux Julie , Karagiannis Jim , Brandl Christopher J
Published: April 2018

Tra1 is an essential component of the SAGA/SLIK and NuA4 complexes in S. cerevisiae, recruiting these co-activator complexes to specific promoters. As a PIKK family member, Tra1 is characterized by a C-terminal phosphoinositide 3-kinase (PI3K) domain. Unlike other PIKK family members (e.g., Tor1, Tor2, Mec1, Tel1), Tra1 has no demonstrable kinase activity. We identified three conserved arginine residues in Tra1 that reside proximal or within the cleft between the N- and C-terminal subdomains of the PI3K domain. To establish a function for Tra1’s PI3K domain and specifically the cleft region, we characterized a tra1 allele where these three arginine residues are mutated to glutamine. The half-life of the Tra1Q3 protein is reduced but its steady state level is maintained at near wild-type levels by a transcriptional feedback mechanism. The tra1Q3 allele results in slow growth under stress and alters the expression of genes also regulated by other components of the SAGA complex. Tra1Q3 is less efficiently transported to the nucleus than the wild-type protein. Likely related to this, Tra1Q3 associates poorly with SAGA/SLIK and NuA4. The ratio of Spt7SLIK to Spt7SAGA increases in the tra1Q3 strain and truncated forms of Spt20 become apparent upon isolation of SAGA/SLIK. Intragenic suppressor mutations of tra1Q3 map to the cleft region further emphasizing its importance. We propose that the PI3K domain of Tra1 is directly or indirectly important for incorporating Tra1 into SAGA and NuA4 and thus the biosynthesis and/or stability of the intact complexes.
Presentation with Personality changes and Tinnitus to a Vascular Intervention: Rare case of Carotid Body Paraganglioma
Authors: Zil-E-Ali Ahsan , Ahmed Zubair , Faquih Amber Ehsan , Ishaq Muhammad , Aadil Muhammad
Published: April 2018

Background: Carotid body paragangliomas are rare neuroendocrine neoplasms of chromaffin negative glomus cells. This case report explains an atypical case with unusual presentation and treatment.

Case Report: A healthy smoker technician by profession was brought to the emergency room (ER) with coprolalia. The general physical exam did not reveal any information. His history revealed unilateral tinnitus and odynophagia leading to a consultation by the neurologist with head imaging. Acoustic neuroma was ruled out and the caregiver was asked to elaborate the events mentioned in the history and a psychiatric examination was done. The personality changes were evaluated by the psychiatrist that showed overlapping of delirium and depression. The patient was further examined by a vascular surgeon. After careful revisiting of the history, examination and indication of tender mass in the neck by the patient's vascular surgeon, the diagnosis of carotid body paraganglioma was made which was followed by surgical resection for treatment.

Conclusion: Carotid Body Paragangliomas are very vascular structures and their manipulation in a surgery setting requires expertise. This case presented with personality changes and tinnitus, a very less likely event to occur in a carotid body tumor. The present care report, thus adds on to the literature of carotid body tumors and its presenting symptoms.
Prediction of sweet corn yield depending on cultivation technology parameters by using linear regression and artificial neural network methods
Authors: Lykhovyd P. V.
Published: April 2018

Artificial neural networks and linear regression are widely used in particularly all branches of science for modeling and prediction. Linear regression is an old data processing tool, and artificial neural networks are a comparatively new one. The goal of the study was to determine whether artificial neural networks are more accurate than linear regression in sweet corn yield prediction. In the study we used a dataset obtained from field experiments on the technological improvement of sweet corn cultivation. The field experiments were conducted during the period from 2014 to 2016 on dark-chestnut soil under drip irrigated conditions in the Steppe Zone of Ukraine. We studied the impact of the moldboard plowing depths, mineral fertilizer application rates and plant densities on the crop yield. A significant impact of all the studied factors on the sweet corn productivity was proved by using the analysis of variance. The highest yield of sweet corn ears without husks (10.93 t ha–1) was under the moldboard plowing at the depth of 20–22 cm, mineral fertilizers application rate of N120P120, plant density of 65,000 plants ha–1. Data processing by using the linear regression and artificial neural network methods showed that the latter is a great deal better than linear regression in sweet corn yield prediction. Higher accuracy of the artificial neural network prediction was proved by the higher value of the coefficient of determination (R2) – 0.978, in comparison to 0.897 for the linear regression prediction model. We conclude that artificial neural networks are a much better data processing tool, especially, in the life sciences and for prediction of the non-linear natural processes and phenomena. The main disadvantage of the neural network models is their “black box” nature. However, linear regression will not lose its popularity among scientists in the nearest future. Linear regression is a much simpler data analysis tool, it is easier to perform the prediction, but it still provides a sufficiently high level of accuracy.