bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained Visual Attention Performance-Associated Prefrontal Neuronal Activity: Evidence for Cholinergic Modulation
Authors: Gill T. Michael , Sarter Martin , Givens Ben
Published: April 2018

Cortical cholinergic inputs are hypothesized to mediate attentional functions. The present experiment was designed to determine the single unit activity of neurons within the medial prefrontal cortex (mPFC) of rats performing a sustained visual attention task. Demands on attentional performance were varied by the presentation of a visual distractor. The contribution of cholinergic afferents of the mPFC to performance-associated unit activity within this area was determined by recording neuronal activity before and after unilateral cholinergic deafferentation using intracortical infusion of the immunotoxin 192 IgG-saporin. Presentation of the visual distractor resulted in a decrease in the detection of brief, unpredictable visual signals. As predicted, the unilateral loss of cholinergic inputs within the recording area of the mPFC did not affect sustained attentional performance. Cholinergic deafferentation, however, resulted in a decrease in the overall firing rate of medial prefrontal neurons and a substantial reduction in the proportion of neurons whose firing patterns correlated with specific aspects of behavioral performance. Furthermore, cholinergic deafferentation attenuated the frequency and amplitude of increased mPFC neuronal firing rates that were associated with the presentation of the visual distractor. The main findings from this experiment suggest that cholinergic inputs to the mPFC strongly influence spontaneous and behaviorally correlated single unit activity and mediate increases in neuronal activity associated with enhanced demands for attentional processing, all of which may be fundamental aspects in the maintenance of attentional performance.
Sustained Activation of Hippocampal Lp-Type Voltage-Gated Calcium Channels by Tetanic Stimulation
Authors: Schjött Jessica M. , Plummer Mark R.
Published: April 2018

The molecular heterogeneity of voltage-gated calcium channels is mirrored by extensive biophysical diversity. Subtype-selective antagonists have been used to place different kinds of calcium channels in functional categories. Dihydropyridine (DHP) antagonists have been used, for example, to implicate L-type calcium channels in the induction of NMDA receptor-independent forms of synaptic plasticity. DHPs, however, do not discriminate between the recently identified Lp and Ls subtypes of L-type calcium channel. The different properties of the two kinds of L-type channels suggest that they may have different functional roles. Ls channels are comparable with cardiac L-type channels, whereas Lp channels show low-threshold voltage-dependent potentiation. To clarify the potential roles of Lp and Ls channels in the induction of synaptic plasticity, we studied the responses of these channels to trains of action potentials. The frequency and duration of the trains were chosen to mimic the stimuli used to induce changes in synaptic strength. Cell-attached single-channel recordings from cultured hippocampal neurons revealed that both Lp and Ls channels responded to these trains, but only Lp channels showed persistent activation that outlasted the train. The magnitude of Lp channel activity increased with increasing action potential frequency and train duration. Stimuli that reproduced the postsynaptic response to action potential trains were also examined, and Lp channels were found to show much greater responses than were Ls channels. These results suggest that the Lp channel may play a critical role in the induction of long-lasting changes in synaptic strength.
Excitatory Role of the Hyperpolarization-Activated Inward Current in Phasic and Tonic Firing of Rat Supraoptic Neurons
Authors: Ghamari-Langroudi Masoud , Bourque Charles W.
Published: April 2018

The properties and functional roles of the hyperpolarization-activated inward current (IH) in magnocellular neurosecretory cells (MNCs) were investigated during sharp microelectrode recordings from supraoptic neurons in superfused explants of rat hypothalamus. Under current clamp, voltage responses to hyperpolarizing current pulses featured depolarizing sags that were abolished by theIHblocker ZD 7288. Under voltage clamp, subtraction of current responses to hyperpolarizing steps recorded in the absence and presence of ZD 7288 was used to investigate the properties ofIH. Current-voltage analysis revealed that steady-stateIHamplitude increases with hyperpolarization, with half-maximal activation of the underlying conductance occurring at −78 mV. The time course of activation ofIHduring hyperpolarizing steps was monoexponential with time constants (100–800 msec) decreasing with hyperpolarization. The effects of ZD 7288 onIHwere slow (τ, ∼15 min), irreversible, and half-maximal at 1.8 μm. When tested on continuously active MNCs, application of 30–60 μmZD 7288 caused a significant reduction in firing rate. In phasically active MNCs, the drug decreased burst duration and intraburst firing frequency and caused an increase in the duration of interburst intervals. These effects were accompanied with a small hyperpolarization of the membrane potential. In contrast, ZD 7288 had no effect on spike duration, on the amplitude of calcium-dependent afterpotentials, or on the frequencies and amplitudes of spontaneous synaptic potentials. These results confirm the presence ofIHin MNCs of the rat supraoptic nucleus and suggest that the presence of this conductance provides an excitatory drive that contributes to phasic and tonic firing.
Coexpression of Rat P2X2and P2X6Subunits inXenopusOocytes
Authors: King B. F. , Townsend-Nicholson A. , Wildman S. S. , Thomas T. , Spyer K. M. , Burnstock G.
Published: April 2018

Transcripts for P2X2and P2X6subunits are present in rat CNS and frequently colocalize in the same brainstem nuclei. When rat P2X2(rP2X2) and rat P2X6(rP2X6) receptors were expressed individually inXenopusoocytes and studied under voltage-clamp conditions, only homomeric rP2X2receptors were fully functional and gave rise to large inward currents (2–3 μA) to extracellular ATP. Coexpression of rP2X2and rP2X6subunits inXenopusoocytes resulted in a heteromeric rP2X2/6receptor, which showed a significantly different phenotype from the wild-type rP2X2receptor. Differences included reduction in agonist potencies and, in some cases (e.g., Ap4A), significant loss of agonist activity. ATP-evoked inward currents were biphasic at the heteromeric rP2X2/6receptor, particularly when Zn2+ions were present or extracellular pH was lowered. The pH range was narrower for H+enhancement of ATP responses at the heteromeric rP2X2/6receptor. Also, H+ions inhibited ATP responses at low pH levels (<pH 6.3). The pH-dependent blocking activity of suramin was changed at this heteromeric receptor, although the potentiating effect of Zn2+on ATP responses was unchanged. Thus, the rP2X2/6receptor is a functionally modified P2X2-like receptor with a distinct pattern of pH modulation of ATP activation and suramin blockade. Although homomeric P2X6receptors function poorly, the P2X6subunit can contribute to functional heteromeric P2X channels and may influence the phenotype of native P2X receptors in those cells in which it is expressed.
Destabilization and Mislocalization of Myelin Basic Protein mRNAs inquakingDysmyelination Lacking the QKI RNA-Binding Proteins
Authors: Li Zhenzhong , Zhang Youyi , Li Daqing , Feng Yue
Published: April 2018

Quakingviable (qkv) is a well known dysmyelination mutation. Recently, the genetic lesion of qkvhas been defined as a deletion 5′ to the qkI gene, which results in the severe reduction of the qkI-encoded QKI RNA-binding proteins in myelin-producing cells. However, no comprehensive model has been proposed regarding how the lack of QKI leads to dysmyelination. We hypothesized that QKI binds to myelin protein mRNAs, and the lack of QKI causes posttranscriptional misregulation, which in turn leads to the loss of the corresponding myelin proteins. To test this hypothesis, we developed an RNase protection assay to directly measure the mRNA isoforms encoding the myelin basic proteins (MBPs) in the brain. Our result suggested that isoform-preferential destabilization of MBP mRNAs in the cytoplasm was responsible for the reduced MBPs in the qkv/qkvbrain during early myelination. In addition, we detected markedly reduced MBP mRNAs in the qkv/qkvmyelin fraction with concomitant accumulation of MBP mRNAs associated with membrane-free polyribosomes. Presumably, the impaired localization of MBP mRNAs to the myelin membrane may cause insufficient incorporation of the newly synthesized MBPs into the myelin sheath. Finally, we observed interactions between QKI and MBP mRNAs, and removing MBP 3′UTR significantly reduced QKI-binding. Taken together, these observations suggest that misregulation at multiple posttranscriptional steps is responsible for the severe reduction of MBPs in qkvdysmyelination, presumably because of the lack of interactions between MBP mRNAs and the QKI RNA-binding proteins.
GFRα1 Is Required for Development of Distinct Subpopulations of Motoneuron
Authors: Garcès A. , Haase G. , Airaksinen M. S. , Livet J. , Filippi P. , deLapeyrière O.
Published: April 2018

Glial cell-line derived neurotrophic factor (GDNF) and its relative neurturin (NTN) are potent trophic factors for motoneurons. They exert their biological effects by activating the RET tyrosine kinase in the presence of a glycosyl-phosphatidylinositol-linked co-receptor, either GFRα1 or GFRα2. By whole-mountin situhybridization on embryonic mouse spinal cord, we demonstrate that whereasRetis expressed by nearly all motoneurons,Gfra1 andGfra2 exhibit complex and distinct patterns of expression. Most motoneurons purified fromGfra1 null mutant mice had lost their responsiveness to both GDNF and NTN. However, a minority of them (∼25%) retained their ability to respond to both factors, perhaps because they express GFRα2. Surprisingly,Gfra2−/−motoneurons showed normal survival responses to both GDNF and NTN. Thus, GFRα1, but not GFRα2, is absolutely required for the survival response of a majority of motoneurons to both GDNF and NTN. In accordance with the phenotype of the mutant motoneurons observed in culture we found the loss of distinct groups of motoneurons, identified by several markers, in theGfra1−/−spinal cords but no gross defects in theGfra2−/−mutant. During their natural programmed cell death period, motoneurons in theGfra1−/−mutant mice undertook increased apoptosis. Taken together these findings support the existence of subpopulations of motoneuron with different trophic requirements, some of them being dependent on the GDNF family.
Multiple Oscillators Provide Metastability in Rhythm Generation
Authors: Chang Hong-Shiu , Staras Kevin , Gilbey Michael P.
Published: April 2018

Biological rhythms such as cardiac and circadian rhythms arise from activity of multiple oscillators with dispersed intrinsic frequencies. It has been proposed that a stable population rhythm, fundamental to normal physiological processes, can be achieved in these systems by synchronization, through mutual entrainment, of individual oscillators. Mutual entrainment, however, is unlikely to be the mechanism underlying the generation of a stable rhythm in a population of multiple weakly coupled or uncoupled oscillators. We have recently identified such a population that is involved in the sympathetic regulation of vascular tone in a thermoregulatory circulation. In this paper, we investigate the stability of the output rhythm of these sympathetic oscillators by subjecting the system to a periodic driving force (the lung inflation cycle-related activity). We show that a population rhythm coupled to the drive can remain stable over a much wider driving frequency range compared with that of any one of its constituent oscillators. This population rhythmicity still exists despite the fact that the dominant frequencies of individual oscillators are not necessarily 1:1 frequency-locked to the drive. We provide evidence to show that this population metastability is achieved through linear and nonlinear dynamic interactions between the driving force and single sympathetic oscillators. Our study suggests that the generation of a stable population rhythm can exist even in the absence of mutual entrainment of its constituents, and this allows the population to generate a stable and flexible patterned response.
Mutational Analysis of the Conserved Cysteines of the Rat P2X2Purinoceptor
Authors: Clyne J. Dylan , Wang Lin-Fang , Hume Richard I.
Published: April 2018

P2X receptors are ATP-gated cation channels that are widely expressed in the brain. The extracellular domains of all seven P2X receptors contain 10 conserved cysteines, which could form disulfide bonds or binding sites for transition metals that modulate P2X receptors. To test whether these cysteines are critical for receptor function, we studied wild-type rat P2X2receptors and 10 mutant P2X2receptors, each containing an alanine substituted for a cysteine. Nine mutants were functional but had reduced maximum currents compared with wild-type P2X2expressed in eitherXenopusoocytes or human embryonic kidney (HEK) 293 cells. The 10th mutant (C224A) did not respond to ATP when expressed in oocytes and gave very small currents in HEK 293 cells. Seven mutants (C113A, C124A, C130A, C147A, C158A, C164A, and C214A) showed rightward shifts (9- to 30-fold) in their ATP concentration–response relationships and very little potentiation by zinc. In contrast, C258A and C267A had EC50values similar to those of wild-type P2X2and were potentiated by zinc. Acidic pH potentiated wild-type and all mutant receptor currents. Despite the loss of zinc potentiation in seven mutants, these cysteines are unlikely to be exposed in the zinc-binding site, because [2-(trimethylammonium)ethyl] methanethiosulfonate bromide did not prevent zinc potentiation of wild-type receptor currents. On the basis of correlations in the maximum current, EC50, zinc potentiation, and pH potentiation, we suggest that the following cysteine pairs form disulfide bonds: C113–C164, C214–C224, and C258–C267. We also suggest that C124, C130, C147, and C158 form two disulfide bonds, but we are unable to assign specific cysteine pairs to these two bonds.
Activity-Dependent Change in AMPA Receptor Properties in Cerebellar Stellate Cells
Authors: Liu Siqiong June , Cull-Candy Stuart G.
Published: April 2018

High-frequency synaptic stimulation is thought to cause a rapid and lasting change in the expression of GluR2 subunit-containing AMPA receptors (AMPARs) at synapses in cerebellar stellate cells. We examined whether spontaneous synaptic activity affects the expression of GluR2-containing synaptic AMPARs and whether the change in AMPAR subtypes alters their Ca2+permeability and kinetic properties. We used intracellular spermine, which blocks GluR2-lacking receptors at depolarized potentials, to distinguish the presence of GluR2. In most cells, the spontaneous EPSC frequency was low, and evoked EPSCs displayed inwardly rectifyingI–Vrelationships, indicative of the presence of GluR2-lacking AMPARs. However, in cells that displayed a higher rate of spontaneous synaptic activity, EPSCs gave linearI–Vplots, suggesting the presence of GluR2-containingAMPARs. This is consistent with the idea that spontaneous synaptic activity increased the expression of GluR2-containing AMPARs at synapses. The Ca2+permeability of AMPARs that gave inwardly rectifying currents in outside-out patches from TTX-treated cells was six times higher than in control cells that gave linear or outwardly rectifyingI–Vplots. However, increased spontaneous synaptic activity did not significantly alter the EPSC decay time. Furthermore, the decay time course ofEPSCs mediated by GluR2-containing receptors was not different from that mediated by a mixed population of receptors at the same synapse. Our results suggest that the level of spontaneous synaptic activity can determine the subunit composition of postsynaptic receptors at this synapse. The activity-induced expression of GluR2-containing receptors significantly reduced the Ca2+permeability of AMPARs in stellate cells but did not slow the decay time course of synaptic currents.
Glial Cell Line-Derived Neurotrophic Factor is a Survival Factor for Isolectin B4-Positive, but not Vanilloid Receptor 1-Positive, Neurons in the Mouse
Authors: Zwick Melissa , Davis Brian M. , Woodbury C. Jeffrey , Burkett John N. , Koerber H. Richard , Simpson James F. , Albers Kathryn M.
Published: April 2018

Most, if not all, nociceptor sensory neurons are dependent on nerve growth factor (NGF) during early embryonic development. A large subpopulation of these sensory neurons loses NGF dependency between embryonic day 16 and postnatal day 14 and become responsive to glial cell line-derived growth factor (GDNF), a member of the transforming growth factor β (TGF-β) family. To examine the survival and phenotypic effects of GDNF on sensory neuronsin vivo, we generated transgenic mice that overexpress GDNF in the skin. GDNF-overexpresser mice had increased numbers of small unmyelinated sensory neurons that express the tyrosine kinase receptor Ret and bind the plant isolectin B4 (IB4). Surprisingly, in wild-type and transgenic mice, few (∼2%) IB4-positive neurons expressed the vanilloid receptor VR1, a heat-sensitive receptor expressed by many IB4-positive neurons of the rat. Thus, in mouse, GDNF-dependent IB4-positive neurons must use a non-VR1 heat receptor. In addition, the behavior of GDNF-overexpresser animals to noxious heat or mechanical stimuli was indistinguishable from wild-type animals, indicating that, on a behavioral level, peripherally applied GDNF does not alter the sensitivity of the somatosensory system.
Nonlinear Spectrotemporal Sound Analysis by Neurons in the Auditory Midbrain
Authors: Escabı́ Monty A. , Schreiner Christoph E.
Published: April 2018

The auditory system of humans and animals must process information from sounds that dynamically vary along multiple stimulus dimensions, including time, frequency, and intensity. Therefore, to understand neuronal mechanisms underlying acoustic processing in the central auditory pathway, it is essential to characterize how spectral and temporal acoustic dimensions are jointly processed by the brain. We use acoustic signals with a structurally rich time-varying spectrum to study linear and nonlinear spectrotemporal interactions in the central nucleus of the inferior colliculus (ICC). Our stimuli, the dynamic moving ripple (DMR) and ripple noise (RN), allow us to systematically characterize response attributes with the spectrotemporal receptive field (STRF) methods to a rich and dynamic stimulus ensemble. Theoretically, we expect that STRFs derived with DMR and RN would be identical for a linear integrating neuron, and we find that ∼60% of ICC neurons meet this basic requirement. We find that the remaining neurons are distinctly nonlinear; these could either respond selectively to DMR or produce no STRFs despite selective activation to spectrotemporal acoustic attributes. Our findings delineate rules for spectrotemporal integration in the ICC that cannot be accounted for by conventional linear–energy integration models.
Calcium–Calmodulin-Dependent Protein Kinase II Contributes to Spinal Cord Central Sensitization
Authors: Fang Li , Wu Jing , Lin Qing , Willis William D.
Published: April 2018

Calcium/calmodulin-dependent protein kinase II (CaMK II) is found throughout the CNS. It regulates calcium signaling in synaptic transmission by phosphorylating various proteins, including neuronal membrane receptors and intracellular transcription factors. Inflammation or injuries to peripheral tissues cause long-lasting increases in the responses of central nociceptive neurons to innocuous and noxious stimuli. This change can occur independently of alterations in the responsiveness of primary afferent neurons and has been termed central sensitization. Central sensitization is a form of activity-dependent plasticity and results from interactions in a set of intracellular signaling pathways, which modulate nociceptive transmission. Here we demonstrate an increased expression and phosphorylation of CaMK II in rat spinal dorsal horn neurons after noxious stimulation by intradermal injection of capsaicin. Local administration of a CaMK II inhibitor in the spinal cord significantly inhibits the enhancement of responses of spinal nociceptive neurons and changes in exploratory behavior evoked by capsaicin injection. In addition, spinal CaMK II activity enhances phosphorylation of AMPA receptor GluR1 subunits during central sensitization produced by capsaicin injection. This study reveals that CaMK II contributes to central sensitization in a manner similar to its role in the processes underlying long-term potentiation.
Identification of Calcineurin as a Key Signal in the Extinction of Fear Memory
Authors: Lin Chih-Hung , Yeh Shiu-Hwa , Leu Tzeng-Horng , Chang Wen-Chang , Wang Shan-Tair , Gean Po-Wu
Published: April 2018

Memory extinction refers to a gradual decrease of the previously acquired response when exposed to conditional stimulus without pairing with unconditional stimulus. Here we show for the first time that fear training-induced phosphorylation of specific substrates in the rat amygdala is reduced after extinction trials and is accompanied by an increase in the protein level and enzymatic activity of calcineurin. In parallel, calcineurin inhibitors prevented extinction-induced protein dephosphorylation as well as extinction of fear memory. Thus, extinction training increased phosphatase activity likely via an expression of calcineurin. Calcineurin then created a negative-feedback loop and directly or indirectly dephosphorylated specific substrates, which, in their phosphorylated state, were required for memory consolidation. Accordingly, in our experimental condition, extinction could be ascribed at least in part to a weakening of the original signaling.
Afterhyperpolarization Regulates Firing Rate in Neurons of the Suprachiasmatic Nucleus
Authors: Cloues Robin K. , Sather William A.
Published: April 2018

Cluster I neurons of the suprachiasmatic nucleus (SCN), which are thought to be pacemakers supporting circadian activity, fire spontaneous action potentials that are followed by a monophasic afterhyperpolarization (AHP). Using a brain slice preparation, we have found that the AHP has a shorter duration in cells firing at higher frequency, consistent with circadian modulation of the AHP. The AHP is supported by at least three subtypes of KCachannels, including apamin-sensitive channels, iberiotoxin-sensitive channels, and channels that are insensitive to both of these antagonists. The latter KCachannel subtype is involved in rate-dependent regulation of the AHP. Voltage-clamped, whole-cell Ca2+channel currents recorded from SCN neurons were dissected pharmacologically, revealing all of the major high-voltage activated subtypes: L-, N-, P/Q-, and R-type Ca2+channel currents. Application of Ca2+channel antagonists to spontaneously firing neurons indicated that predominantly L- and R-type currents trigger the AHP. Our findings suggest that apamin- and iberiotoxin-insensitive KCachannels are subject to diurnal modulation by the circadian clock and that this modulation either directly or indirectly leads to the expression of a circadian rhythm in spiking frequency.
Impaired Spinal Cord Glutamate Transport Capacity and Reduced Sensitivity to Riluzole in a Transgenic Superoxide Dismutase Mutant Rat Model of Amyotrophic Lateral Sclerosis
Authors: Dunlop John , Beal McIlvain H. , She Yijin , Howland David S.
Published: April 2018

We characterized synaptosomal glutamate transport activity in a recently developed transgenic rat model of amyotrophic lateral sclerosis (ALS) overexpressing the G93A Cu2+/Zn2+superoxide dismutase (SOD1) mutation. Using spinal cord synaptosomes, a significant reduction (43%) in the maximal velocity for high-affinity, Na+-dependent glutamate uptake was observed at disease end stage in G93A rats compared with age-matched controls. Similarly, a 27% reduction in maximum velocity (Vmax) was measured at disease onset, but no difference in spinal cordVmaxvalues were observed with presymptomatic animals compared with controls. In comparison, we observed no differences in theVmaxfor glutamate clearance at disease end stage with synaptosomes from cortex, hippocampus, striatum, cerebellum, and brainstem, indicating a specific deficit in the spinal cord. The pharmacological sensitivity of spinal cord uptake to dihydrokainate suggests that the GLT-1 (glutamate transporter-1) subtype primarily mediates the transport activity. Expression analysis revealed a loss of GLT-1 as well as qualitative changes in GLAST (glutamate/aspartate transporter) but no measurable changes in EAAC1 (excitatory amino acid carrier 1) in spinal cord of end-stage G93A rats, indicating that deficits in glutamate transporters in this rat model may be glial specific. Riluzole, a neuroprotective agent used clinically to slow the progression of ALS, produced an enhancement of spinal cord synaptosomal glutamate uptake in control animals and early-stage disease G93A rats, but this effect was lost in end-stage animals. Altered expression of astroglial glutamate transporters accompanied by reduced capacity for spinal cord clearance of extracellular glutamate in the G93A SOD1 transgenic rat may account for a dampened effect of riluzole to enhance glutamate uptake at end-stage disease.
Glycoprotein 130 Signaling RegulatesNotch1Expression and Activation in the Self-Renewal of Mammalian Forebrain Neural Stem Cells
Authors: Chojnacki Andrew , Shimazaki Takuya , Gregg Christopher , Weinmaster Gerry , Weiss Samuel
Published: April 2018

Glycoprotein130 (gp130) and Notch signaling are thought to participate in neural stem cell (NSC) self-renewal. We asked whether gp130 regulates Notch activity in forebrain epidermal growth factor (EGF)-responsive NSCs. Disruption ofNotch1using antisense or a γ-secretase inhibitor demonstrated a requirement forNotch1in the maintenance and proliferation of NSCs. Ciliary neurotrophic factor (CNTF) activation of gp130 in NSCs rapidly increasedNotch1expression. NOTCH1 activation, indicated by tumor necrosis factor α-converting enzyme (TACE)- andpresenilin-mediated processing, also increased. Infusion of EGF+CNTF into adult forebrain lateral ventricles increased periventricular NOTCH1 compared with EGF alone. NeitherHes1(hairyandenhancerofsplit) norHes5appeared to mediate gp130-enhanced NOTCH1 signaling that regulates NSC maintenance. This is the first example of a link between gp130 signaling and NOTCH1 in regulating NSC self-renewal.
Homeostatic Effects of Depolarization on Ca2+Influx, Synaptic Signaling, and Survival
Authors: Moulder Krista L. , Cormier Robert J. , Shute Amanda A. , Zorumski Charles F. , Mennerick Steven
Published: April 2018

Depolarization promotes neuronal survival through moderate increases in Ca2+influx, but the effects of survival-promoting depolarization (vs conventional trophic support) on neuronal signaling are poorly characterized. We found that chronic, survival-promoting depolarization, but not conventional trophic support, selectively decreased the somatic Ca2+current density in hippocampal and cerebellar granule neurons. Depolarization rearing depressed multiple classes of high-voltage activated Ca2+current. Consistent with the idea that these changes also affected synaptic Ca2+channels, chronic depolarization presynaptically depressed hippocampal neurotransmission. Six days of depolarization rearing completely abolished glutamate transmission but altered GABA transmission in a manner consistent with the alterations of Ca2+current. The continued survival of depolarization-reared neurons was extremely sensitive to the re-establishment of basal culture conditions and was correlated with the effects on intracellular Ca2+concentration. Thus, compared with cells reared on conventional trophic factors, depolarization evokes homeostatic changes in Ca2+influx and signaling that render neurons vulnerable to cell death on activity reduction.
Excitatory Actions of Endogenously Released GABA Contribute to Initiation of Ictal Epileptiform Activity in the Developing Hippocampus
Authors: Dzhala Volodymyr I. , Staley Kevin J.
Published: April 2018

In the developing rat hippocampus, ictal epileptiform activity can be elicited easilyin vitroduring the first three postnatal weeks. Changes in neuronal ion transport during this time cause the effects of GABAAreceptor (GABAA-R) activation to shift gradually from strongly depolarizing to hyperpolarizing. It is not known whether the depolarizing effects of GABA and the propensity for ictal activity are causally linked. A key question is whether the GABA-mediated depolarization is excitatory, which we defined operationally as being sufficient to trigger action potentials. We assessed the effect of endogenous GABA on ictal activity and neuronal firing rate in hippocampal slices from postnatal day 1 (P1) to P30. In extracellular recordings, there was a strong correlation between the postnatal age at which GABAA-R antagonists decreased action potential frequency (P23) and the age at which ictal activity could be induced by elevated potassium (P23). In addition, there was a strong correlation between the fraction of slices in which ictal activity was induced by elevated potassium concentrations and the fractional decrease in action potential firing when GABAA-Rs were blocked in the presence of ionotropic glutamate receptor antagonists. Finally, ictal activity induced by elevated potassium was blocked by the GABAA-R antagonists bicuculline and SR-95531 (gabazine) and increased in frequency and duration by GABAA-R agonists isoguvacine and muscimol. Thus, the propensity of the developing hippocampus for ictal activity is highly correlated with the effect of GABA on action potential probability and reversed by GABAAantagonists, indicating that GABA-mediated excitation is causally linked to ictal activity in this developmental window.
Norepinephrine in the Prefrontal Cortex Is Critical for Amphetamine-Induced Reward and Mesoaccumbens Dopamine Release
Authors: Ventura Rossella , Cabib Simona , Alcaro Antonio , Orsini Cristina , Puglisi-Allegra Stefano
Published: April 2018

Increasing evidence points to a major involvement of cortical areas in addictive mechanisms. Noradrenergic transmission in the medial prefrontal cortex (mpFC) has been shown to affect the motor effects of amphetamine, although there is no evidence of its involvement in the rewarding effects of this psychostimulant.

The present experiments were aimed at investigating the possibility of a selective involvement of prefrontal cortical norepinephrine (NE) in the rewarding–reinforcing effects of amphetamine. To do so, we evaluated the effects of mpFC NE selective depletion in mice of C57BL/6J inbred strain, a background commonly used in molecular approaches that is known to be highly susceptible to the rewarding effects of the psychostimulant. In a first set of experiments, we demonstrated the absence of amphetamine-induced conditioned place preference in mice bearing prefrontal NE depletion. In a second series of experiments, we demonstrated that the same lesion dramatically reduced amphetamine-induced mesoaccumbens dopamine release as measured by intracerebral microdialysis.

These results indicate that noradrenergic prefrontal transmission, by allowing increased dopamine release in the nucleus accumbens induced by amphetamine, is a critical factor for the rewarding–reinforcing effects of this drug.
One-Trial Memory for Object-Place Associations after Separate Lesions of Hippocampus and Posterior Parahippocampal Region in the Monkey
Authors: Malkova Ludise , Mishkin Mortimer
Published: April 2018

In earlier studies of one-trial spatial memory in monkeys (Parkinson et al., 1988; Angeli et al., 1993), severe and chronic memory impairment for both object-place association and place alone was found after ablation of the hippocampal formation. The results appeared to provide the first clear-cut evidence in the monkey of the essential role of the hippocampus in spatial memory, but that interpretation neglected the inclusion in the lesion of the underlying posterior parahippocampal region. To determine the separate contributions of the hippocampus and posterior parahippocampal region to these spatial forms of one-trial memory, we trained 10 rhesus monkeys, as before, to remember the spatial positions of either two different trial-unique objects overlying two of the wells in a three-well test tray (object-place trials) or simply two of the three wells (place trials). Six of the monkeys then received ibotenic acid lesions restricted to the hippocampal formation (group H), and the four others received selective ablations of the posterior parahippocampal region (group P), comprising mainly parahippocampal cortex, parasubiculum, and presubiculum. Group H was found to be completely unaffected postoperatively on both types of trials, whereas group P sustained an impairment on both types equal in magnitude to that observed after the combined lesions in the original studies. Thus, contrary to the previous interpretation, one-trial memory for object-place association and, perhaps more fundamentally, one-trial memory for two different places appear to be critically dependent not on the hippocampal formation but rather on the posterior parahippocampal region.
ÇİYA TOHUMUNDAN ULTRASON DESTEKLİ YAĞ EKSTRAKSİYONUNUN OPTİMİZASYONU
Authors: ARSLAN TONTUL Sultan , MUTLU Ceren , KOÇ Andaç , ERBAŞ Mustafa
Published: April 2018

Bu çalışmada çiya tohum yağının, ultrason destekli
ekstraksiyon sisteminde eldesi ve uygulama sırasındaki ekstraksiyon
parametrelerinin (ultrason gücü, ekstraksiyon sıcaklığı ve ekstraksiyon süresi)
cevap yüzey metodu kullanılarak optimizasyonu gerçekleştirilmiştir. Yapılan
istatistiksel analiz sonucuna göre, modelin sadece ekstraksiyon verimi üzerine
etkili olduğu ancak peroksit sayısı ve serbest yağ asitliği değerleri üzerinde
etkili olmadığı tespit edilmiştir. Çalışmada kullanılan deneme desenine göre
elde edilen ekstraksiyon verimi, peroksit değeri ve serbest yağ asitliği
değerlerinin sırasıyla 36.19-49.45/100 g yağ, 0.33-7.33 mEqnO2/kg ve
%1.13-2.26 arasında değiştiği belirlenmiştir. Optimizasyon sonucunda ise en
yüksek yağ verimi olan %49.45 değerine; yaklaşık %75 ultrason gücünde, 25
dakikalık ekstraksiyon süresinde ve 55°C ekstraksiyon sıcaklığında
ulaşılabileceği tespit edilmiştir.
İNÜLİN VE MALTODEKSTRİN İLAVESİNİN KEFİRLERİN KONJÜGE LİNOLEİK ASİT İÇERİĞİ ÜZERİNE ETKİSİ
Authors: Özbey Ayşe , Dinç Selin Özge , Erinç Özlem
Published: April 2018

Kefir tarihi yüzyıllar öncesine dayanan Kafkas dağları,
Tibet ve Moğolistan kökenli fermente bir süt ürünüdür. Bazı bakteriler gelişim
ve metabolizmalarının sonucu olarak süt ürünlerinde fermantasyon boyunca farklı
yağ asidi profilleri ve fonksiyonel yağ asitleri oluşturabilirler. Çalışmada
kefir üretimleri inek sütüne %1, %2 ve %3 oranlarında maltodekstrin ve inülin
eklendikten sonra gerçekleştirilmiştir. Kontrol olarak maltodekstrin ve inülin
eklenmemiş sütten kefir üretilmiştir. Kefir üretiminden önce çiğ sütte genel
kimyasal bileşim (kurumadde, yağ, protein ve kül analizi) ve konjüge linoleik
asit (KLA) analizi gerçekleştirilmiştir. Kefirlerde depolamanın 0, 2, 7, 14 ve
21. günlerinde KLA analizleri yapılmıştır. Bu çalışmanın sonuçları fermantasyon
işlemi ile KLA miktarının arttığını fakat maltodekstrin ve inülin ilavesinin
depolama boyunca KLA miktarı üzerine bir etkisinin olmadığını göstermiştir.
Removal of sialic acid from bull sperm decreases motility and mucus penetration ability but increases zona pellucida binding and polyspermic penetration in vitro
Authors: Fernandez-Fuertes B , Blanco-Fernandez A , Reid C J , Meade K G , Fair S , Lonergan P
Published: April 2018

This study tested the hypothesis that sperm sialic acid (Sia) is required to reach the site of fertilization, and that successful fertilization requires recognition of Sia from both the sperm and oocyte to occur. In addition, it has recently been reported that Siglecs (Sia-binding-immunoglobulin-like lectins) are present on the sperm surface. Thus, the possibility that the recognition of oocyte Sia was sperm-Siglec-mediated was also addressed. Sperm exposed to neuraminidase (NMase) exhibited lower overall and progressive motility, which translated to a decreased ability to swim through cervical mucus from cows in oestrus. In addition, when either sperm or cumulus–oocyte complexes (COCs) were treated with NMase, a decrease in cleavage and blastocyst rate was observed. However, incubation of sperm with increasing concentrations of anti-Siglec-2, -5, -6 and -10 antibodies prior to fertilization had no effect on their fertilizing ability. Interestingly, treatment with NMase increased the number of sperm bound to the ZP but also the rate of polyspermic fertilization. Flow cytometry analysis revealed no differences in the percentage of capacitated or acrosome-reacted sperm. These results suggest that Sia are required to reach the site of fertilization but need to be removed for sperm–oocyte interaction. However, fine regulation is needed to avoid abnormal fertilization which can lead to impaired embryo development.
Subtle Perturbations of the Maize Methylome Reveal Genes and Transposons Silenced by Chromomethylase or RNA-Directed DNA Methylation Pathways
Authors: Anderson Sarah N , Zynda Gregory J , Song Jawon , Han Zhaoxue , Vaughn Matthew W , Li Qing , Springer Nathan M
Published: April 2018

DNA methylation is a chromatin modification that can provide epigenetic regulation of gene and transposon expression. Plants utilize several pathways to establish and maintain DNA methylation in specific sequence contexts. The chromomethylase (CMT) genes maintain CHG (where H = A, C or T) methylation. The RNA-directed DNA methylation (RdDM) pathway is important for CHH methylation. Transcriptome analysis was performed in a collection of Zea mays lines carrying mutant alleles for CMT or RdDM-associated genes. While the majority of the transcriptome was not affected, we identified sets of genes and transposon families sensitive to context-specific decreases in DNA methylation in mutant lines. Many of the genes that are up-regulated in CMT mutant lines have high levels of CHG methylation, while genes that are differentially expressed in RdDM mutants are enriched for having nearby mCHH islands, implicating context-specific DNA methylation in the regulation of expression for a small number of genes. Many genes regulated by CMTs exhibit natural variation for DNA methylation and transcript abundance in a panel of diverse inbred lines. Transposon families with differential expression in the mutant genotypes show few defining features, though several families up-regulated in RdDM mutants show enriched expression in endosperm tissue, highlighting the potential importance for this pathway during reproduction. Taken together, our findings suggest that while the number of genes and transposon families whose expression is reproducibly affected by mild perturbations in context-specific methylation is small, there are distinct patterns for loci impacted by RdDM and CMT mutants.
Security and development: Shifting the focus to interpersonal violence
Authors: Hoeffler Anke
Published: April 2018

The focus in the security and development debate is on collective violence and the World Bank’s World Development Report  2017 is typical by mainly considering the effects of organized armed conflict. In this article I argue that interpersonal violence affects many more people globally and should receive more attention as well as aid. The adverse consequences from interpersonal violence on socioeconomic development are likely to be large but much of this violence is hidden in plain sight. Women and children are at particularly high risk of being victims of violence but since most of this violence is perpetrated in the domestic sphere it is less likely to affect the collective conscience.
The evolution of revolution: Is splintering inevitable?
Authors: Basuchoudhary Atin , Razzolini Laura
Published: April 2018

We use an evolutionary model to study splintering within rebel groups. We assume that rebels possess cultural traits that encourage cooperation, defection (splintering), or a trigger behavior like Tit-For-Tat. We characterize the dynamic process by which rebels’ discount rates determine whether splintering will occur in the rebel population even when cooperation is otherwise efficient. The results suggest that political action by governments that make rebels impatient also increases the likelihood of rebel group splintering. This may be counterproductive from a government’s point of view. Our article closes a gap in the literature by providing a theoretical model for how rebel groups form. Policies that affect the patience of rebels and change the cultural context within rebel groups influence the likelihood of rebel group splintering. This article’s contribution to the literature is twofold. First, it applies an established modeling approach to understand how even otherwise cohesive rebellions can splinter as a consequence of exogenous shocks that change rebels’ time horizons. Second, we highlight how cultural context can influence this splintering process.
The need to be governed: Governance and violence in conflict contexts
Authors: Justino Patricia
Published: April 2018

This article analyses the relationship between governance and violence in light of the World Development Report 2017 on Governance and the Law. The article discusses the approach taken by the Report to link governance and violence and highlights the importance of new research and findings on forms of wartime governance, and their implications for international politics and development interventions in conflict and postconflict contexts.
Desarrollo territorial de Guanacaste, Costa Rica desde el enfoque de sistemas territoriales de producción agroalimentaria
Authors: Porras Acevedo Stephanie
Published: April 2018

El objetivo de este artículo es identificar los factores territoriales que impulsan o frenan el establecimiento de un sistema territorial de producción agroalimentaria (STPA), bajo el enfoque de desarrollo territorial, en el cantón de Carrillo de la provincia de Guanacaste, Costa Rica. Debido al dinamismo que ha experimentado la provincia en los últimos años y al desplazamiento de la actividad agrícolas desde los 90, debido a la actividad terciaria, se busca investigar aquellos factores que promuevan el crecimiento considerando las condiciones que proyectos actuales, como la creación del Mercado Regional PIMA en Carrillo, la ampliación terminal de carga en el aeropuerto Daniel Oduber Quirós en Liberia y la construcción del canal seco de La Cruz hacia Puerto Limón pueden ofrecer. Como resultado del análisis se proponen los componentes de un sistema territorial de producción agroalimentaria para la provincia, considerando las características de las empresas y la sinergia que estos actores deben tener con las instituciones. El artículo concluye que los STPA promueven una alta asociatividad y encadenamientos entre empresas, gobierno y recursos disponibles. Además, incluye el medio ambiental como una variable a circunscribir en los procesos. En su conjunto, los STPA pueden considerarse una alternativa para promover la seguridad y soberanía alimentaria de las regiones, a través del abastecimiento de un mercado con productos locales.
Social representations of anorexia among university students and risk factors: possible relations
Authors: Polli Gislei Mocelin , Da Silva Jenifer Cristina Clementino , Pereira Marilisa Graner , Dos Reis Ramiliane Aparecida , Peruci Tamy Talita , Gelinski Eliana Motter Müller , Gebara Telma Souza e Silva
Published: April 2018

Anorexia is a serious disease, characterized by a distorted body image that leads to extreme behavior. It mainly affects young women. This study sought to identify the social representations of anorexia and the presence of risk factors for its development among female students from different university courses. It sought to establish relationships between anorexia risk factors, body mass index, study area, body satisfaction and social representations. A questionnaire composed by the EAT-26, scale of body silhouettes and open questions about what students knew about anorexia was applied. The data were subjected to statistical and lexicographic analysis. 29% of the students presented risk factors for anorexia. Increased BMI and body dissatisfaction are related to the presence of risk factors. Social representations of anorexia demonstrate the characterization of the disease, very close to scientific knowledge.
Assessment of executive functions and inhibitory control in alcohol and crack use disorders
Authors: Czermainski Fernanda Rasch , Ornell Felipe , Guimarães Luciano Santos Pinto , Kessler Félix , Von Diemen Lísia , De Almeida Rosa Maria Martins
Published: April 2018

This study assessed executive functions and inhibitory control in alcohol and crack users, as previous research suggests an association between substance-related disorders and impaired self-regulation and impulse control. In this study, 67 men aged 18-65 years completed the following instruments: sociodemographic questionnaire, Vocabulary and Matrix Reasoning (Wechsler Abbreviated Scale of Intelligence), Five Digit Test, and Behavioral Assessment of the Dysexecutive Syndrome. Alcohol and crack users showed deficits involving processing speed, response inhibition, flexibility, abstraction, planning, and monitoring. Analysis per type of drug revealed poorer cognitive performance among alcohol users. Years of drug use were associated with planning deficits. These findings are consistent with the hypothesis of an association between drug abuse and cognitive changes. In conclusion, impairments in executive functioning and inhibitory control were found in the study samples.***Avaliação das funções executivas e controle inibitório nos transtornos por uso de álcool e crack***Este estudo investigou as funções executivas e o controle inibitório em usuários de álcool e crack, pois pesquisas prévias sugerem associação entre os transtornos relacionados a substâncias e o comprometimento das capacidades de autorregulação e de controle dos impulsos. Neste estudo, 67 homens com idades entre 18-65 anos responderam aos seguintes instrumentos: questionário sociodemográfico, Vocabulário e Raciocínio Matricial (Wechsler Abbreviated Scale of Intelligence), Five Digit Test e Behavioural Assessment of the Dysexecutive Syndrome. Os usuários de álcool e crack apresentaram déficits envolvendo velocidade de processamento, inibição de respostas, flexibilidade, abstração, planejamento e monitoramento. A análise por droga de abuso revelou desempenho cognitivo inferior entre os alcoolistas. O tempo de abuso de drogas foi associado a déficits de planejamento. Esses achados são consistentes com a hipótese de associação do abuso de drogas com alterações cognitivas. Em conclusão, foram observadas alterações do funcionamento executivo e do controle inibitório nas amostras de usuários avaliadas.