bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of isometric exercise on endogenous pain modulation: comparing exercise-induced hypoalgesia and offset analgesia in young, active adults
Authors: Harris Samuel , Sterling Michele , Farrell Scott F. , Pedler Ashley , Smith Ashley D.
Published: April 2018

Background and aims

Impairment of endogenous analgesia has been associated with the development, maintenance and persistence of pain. Endogenous analgesia can be evaluated using exercise-induced hypoalgesia (EIH) and offset analgesia (OffA) paradigms, which measure temporal filtering of sensory information. It is not clear if these paradigms are underpinned by common mechanisms, as EIH and OffA have not previously been directly compared. A further understanding of the processes responsible for these clinically relevant phenomena may have future diagnostic and therapeutic utility in management of individuals with persistent pain conditions. The primary aim of this study was to investigate if there is a correlation between the magnitudes of EIH and OffA. The secondary aim of the study was to examine whether exercise influences OffA.

Methods

Thirty-six healthy, pain-free participants were recruited. EIH was evaluated using pressure pain thresholds (PPT) and pain ratings to suprathreshold pressure stimuli over tibialis anterior and the cervical spine. OffA evaluation utilised a three-step protocol, whereby individualised heat pain thermal stimuli [Numerical Rating Scale (NRS)=50/100] were applied (T1), before increasing 1 °C (T2), followed by 1 °C reduction (T3). The magnitude of OffA was calculated as the percentage reduction in the NRS from T2 to T3. PPT/suprathreshold pain ratings and OffA measures were recorded, before and after 5 min of isometric quadriceps exercise performed at 20–25% maximum voluntary contraction (MVC); and following a 15 min rest period. Data were analysed using repeated measures (RM) ANCOVA and correlational analyses.

Results

There was no correlation between EIH measures (PPTs or pain ratings to suprathreshold pressure stimuli over tibialis anterior or the cervical spine) and OffA (p>0.11 for all). OffA was induced and not modulated by exercise (p=0.28).

Conclusions

Five minutes of 20–25% MVC lower limb isometric exercise provided non-pharmacological pain modulation in young, active adults. Magnitude of EIH was not correlated with that of OffA, and exercise did not influence magnitude of OffA.

Implications

These results suggest that in young, pain-free individuals, separate testing of these two paradigms is required to comprehensively evaluate efficacy of endogenous analgesia. If these results are replicated in patient populations, alternative or complementary methods to exercise interventions may be required to modulate impaired OffA.
Wie nah ist uns die Zwischenkriegszeit?
Authors: Raithel Thomas
Published: April 2018

The interwar period was a phase of the formation of new states and of democratic awakening, but also a time of crises and the failure of democracies as well as the establishment of authoritarian and dictatorial systems. Until recently, it was largely overlooked by research and the general public. Given the recent increase of right-wing populist currents and authoritarian tendencies in Europe, interest has once again grown. The second “Contemporary History Podium” is thus dedicated to the question of how akin we are to the interwar period. How is it perceived in different countries which constituted themselves as democracies at the end of the First World War after the fall of the Romanov, Habsburg and Hohenzollern Empires? Also what is the relevance of this history for the present? Ota Konrád (Charles University Prague), Ekaterina Makhotina (University of Bonn), Anton Pelinka (Central European University Budapest), Thomas Raithel (Institute for Contemporary History Munich-Berlin) und Krzysztof Ruchniewicz (Willy Brandt Center, Wrocław University) look into these questions utilising the examples of Czechoslovakia, Lithuania, Austria, Germany and Poland.
n-Type Cu2O/α-Fe2O3 Heterojunctions by Electrochemical Deposition: Tuning of Cu2O Thickness for Maximum Photoelectrochemical Performance
Authors: Gahlawat Soniya , Rashid Nusrat , Ingole Pravin P.
Published: April 2018

Here, we report the enhanced photoelectrochemical performance of surface modified hematite thin films with n-type copper oxide nanostructures (Cu2O/Fe2O3) obtained through simple electrochemical deposition method. The thickness and amount of cuprous oxide layer were varied by simply changing the number of electrodeposition cycles (viz. 5, 10, 25, 50 and 100) in order to understand its thermodynamic and kinetic influence on the photoelectrochemical activity of the resultant nano-heterostructures. Structural and morphological characteristics of the obtained Cu2O/Fe2O3 films have been studied by absorption spectroscopy, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy analysis. Electrochemical investigations such as linear sweep voltammetry, Mott–Schottky analysis, and electrochemical impedance spectroscopy suggested the formation of n-type Cu2O layers over the hematite films with varying charge-carrier densities, ranging from 0.56×1019 to 3.94×1019 cm−3, that varies with the number of cycles of electrochemical deposition. Besides, the thickness of deposited cuprous oxide layer is noted to alter the net electrochemical and photo-electrochemical response of the base material. An interesting, peak event was recorded for a particular thickness of the cuprous oxide layer (obtained after 25 cycles of electrochemical deposition) below and above which the efficiency of catalyst was impaired. The heterojunction obtained thus, followed well known Z-scheme and gave appreciable increment in the photocurrent response.
ANÁLISE DO ESTADO DE DECOMPOSIÇÃO E FRAGMENTAÇÃO DA PAISAGEM COSTEIRA (ABORDAGEM GEOGRÁFICA) DO RIO GRANDE DO SUL – BRASIL / DECOMPOSITION AND FRAGMENTATION STATE ANALYSIS OF THE COASTAL LANDSCAPE (GEOGRAPHICAL APPROACH) OF RIO GRANDE DO SUL - BRAZIL
Authors: Silva Flávia Milão , Silva Marcelo Dutra da
Published: April 2018

A Planície Costeira do Rio Grande do Sul é composta de um mosaico de ecossistemas frágeis e sua resiliência está relacionada diretamente à conservação da estrutura e função dos sistemas ecológicos. Sendo assim, a não-fragmentação de remanescentes naturais é um pré-requisito para a manutenção da integridade ecológica. O presente trabalho analisou a estrutura espacial da paisagem da Planície Costeira do Rio Grande do Sul a partir de índices métricos de Tamanho Efetivo de Malha e Área Nuclear que agrupados e classificados em 5 limiares qualitativos, de -10 a +10, representaram o estado de uso e ocupação da terra na paisagem costeira em 50 janelas de atenção. A integração das métricas aqui apresentadas permitiram identificar as estruturas fragmentadoras predominantes e possíveis refinamentos metodológicos a partir da constatação de que cultivos agrícolas dominam os processos ecológicos em todas as regiões litorâneas e a tendência de compactação dos remanescentes naturais afeta o diagnóstico de intensidade de uso da terra.Abstract:The Rio Grande do Sul Coastal Plain is composed by a mosaic of fragile ecosystems and its resilience is directly related to the conservation of the ecological systems structures and functions. Thus, non-fragmentation of natural remnants is a prerequisite for maintaining ecological integrity. The present work analyzed the Rio Grande do Sul Coastal Plain spatial structure through the landscape metric indexes of Effective Mesh Size and Nuclear Area. They were grouped and classified into 5 qualitative thresholds, from -10 to +10, representing the coastal landscape use and occupation among 50 attention windows. The integration of metrics presented herein allowed to identify the predominant fragmenting feature and possible methodological refinements, since agricultural crops dominated ecological processes in all coastal regions, while a trend for compaction of natural fragments affects the land use intensity diagnosis.Keywords: Effective Mesh Size; Core Area; Ecological Connection Matrix; Land Use Intensity
NAS CORDAS, ANZÓIS, REDES E GAIOLAS: SEGUINDO OS MATERIAIS NA PESCA ARTESANAL
Authors: Silva Lucas Antonio
Published: April 2018

O estudo dos materiais é um campo vasto, que concentra diversas áreas do conhecimento. Esse caráter plural, sobretudo a partir da década de 1980, configurou a este campo um status de disciplina independente. Nele, a Arqueologia ganha destaque, especialmente por se tratar da ciência que se dedica com maior atenção ao estudo dos materiais em seus mais diversos contextos e tempos. A etnoarqueologia, por sua vez, considerada um campo da Arqueologia, busca, através da etnografia, a compreensão das dinâmicas materiais das populações atuais Nesse sentido, pretende-se, com este trabalho, compreender os fluxos de vida e as relações dos materiais na pesca artesanal, mais especificamente em uma comunidade de pescadores, do litoral do Rio Grande do Sul. Para isso, utilizar-se-á três exemplos de artefatos: o espinhel, a rede e a gaiola de pesca.
“SE ELA TÁ VENDO EU TAMBÉM POSSO VER”: A ETNOGRAFIA NA COLÔNIA DE PESCADORES Z-3, PELOTAS, RIO GRANDE DO SUL, BRASIL
Authors: Bittencourt Carolina Amorim da Silva , Rosa Rogerio Réus Gonçalves , Moura Gustavo Goulart Moureira
Published: April 2018

Este trabalho é de cunho etnológico e etnográfico e pretende identificar as categorias empíricas utilizadas pelos moradores da Colônia de Pescadores Z-3 para atribuir um sentido ao ambiente aquático. Os personagens mitológicos aquáticos desta colônia evidenciam o caráter ligado ao feminino, utilizado local e globalmente para representar as águas. Por outro lado, a partir da relação de reciprocidade que se estabelece entre a etnóloga e os pescadores, surge um personagem mítico masculino, chamado de tritão.
A regional analysis of estrogen binding to hypothalamic cell nuclei in relation to masculinization and defeminization
Authors: Nordeen EJ , Yahr P
Published: April 2018

Gonadal steroids masculinize and defeminize neuroendocrine development, including behavior. Defeminization makes males less sensitive than females to estrogen for showing female sexual behavior and cyclic gonadotropin secretion. Masculinization makes males more sensitive than females to estrogen for showing male sexual behavior. Thus masculinization and defeminization produce opposite effects on estrogen sensitivity. To study the relationship between estrogen sensitivity and estrogen binding, we studied sex differences in estrogen binding to hypothalamic cell nuclei on a regional and temporal basis. We measured the amount of estradiol (E2) bound to cell nuclei in the preoptic area (POA), mediobasal hypothalamus (MBH), corticomedial amygdala, and cortex of gonadectomized male and female rats 30 and 60 min after [3H]E2 was injected intravenously. In the MBH, males consistently bound less E2 than females did. In the POA, males bound less E2 than females after 60 min, but they bound more E2 than females after 30 min. Decreased estrogen binding in the MBH may underlie defeminized sexual behavior. Similarly, decreased estrogen binding in the POA at 60 min may be a correlate of defeminized gonadotropin secretion, whereas increased estrogen binding in the POA at 30 min may be a correlate of masculinized sexual behavior. To test the hypothesis that decreased estrogen binding in the MBH and POA are correlates of defeminization, we measured E2 binding at 60 min in female rats in which masculinization and defeminization were manipulated independently. Defeminization decreased E2 binding to cell nuclei in both the POA and MBH to the level seen in males at this time point. Masculinization had no effect at this time point. The data suggest that sex differences in E2 binding to hypothalamic cell nuclei correlate reliably with sex differences in estrogen sensitivity even though masculinization and defeminization produce opposing effects on these parameters.
Immunocytochemical localization of the neuron-specific form of the c- src gene product, pp60c-src(+), in rat brain
Authors: Sugrue MM , Brugge JS , Marshak DR , Greengard P , Gustafson EL
Published: April 2018

Neurons express high levels of a variant form of the c-src gene product, denoted pp60c-src(+), which contains a 6 amino acid insert in the amino-terminal half of the c-src protein. We have determined the localization of pp60c-src(+) in neurons using an affinity-purified anti- peptide antibody, referred to as affi-SB12, that exclusively recognizes this neuron-specific form of the c-src gene product. Using affi-SB12, we examined the distribution of pp60c-src(+) by immunoperoxidase staining of sections through adult rat brains, pp60c-src(+) was widely distributed in rat brain and appeared to be differentially expressed in subpopulations of neurons. The majority of immunoreactive neurons was found in the mesencephalon, cerebellum, pons, and medulla. Telencephalic structures that contained substantial populations of pp60c-src(+)-immunoreactive neurons included layer V of the cerebral cortex and the ventral pallidum. Within individual neurons, pp60c- src(+) immunoreactivity was localized to the cell soma and dendritic processes, while labeling of axons and nerve terminals (puncta) was not as readily detected. Dense accumulations of immunoreactive axons were rare, being most prominent in portions of the inferior and superior olive, and in the spinal trigeminal nucleus. While the regional distribution of pp60c-src(+) immunoreactivity does not correlate with any specific neuronal cell type or first messenger system, this unique pattern of expression of pp60c-src(+) suggests the existence of a previously uncharacterized functional organization within the brain. Furthermore, the localization of this neuron-specific tyrosine kinase in functionally important areas of the nerve cell, namely, dendritic processes, axons, and nerve terminals, suggests that pp60c-src(+) may regulate pleiotropic functions in specific classes of neurons in the adult central nervous system.
Context-dependent responses of primate nucleus basalis neurons in a go/no-go task
Authors: Richardson RT , DeLong MR
Published: April 2018

In previous studies involving monkeys performing behavioral tasks, neurons in the nucleus basalis frequently had significant changes in discharge rate when the animal made a movement in response to a sensory stimulus in order to obtain a reward. To determine whether such responses of basalis neurons are primarily sensory or motor in nature, the activity of single basalis neurons was recorded in monkeys performing a go/no-go (GNG) task which provided a dissociation between sensory and motor neuronal responses. In a sample of 425 basalis neurons, 326 (77%) had significant changes in firing in at least one phase of the GNG task. Most of the task-related neurons (70%) responded in the choice phase in which the animal either made an arm movement (go condition) or kept its arm motionless (no-go condition) in order to obtain a water reward. Of 253 neurons that responded in the choice phase, 88% had changes in firing in the no-go condition that were equal to or, in some cases, greater than the changes in firing in the go condition. Therefore, most responses of basalis neurons in the choice phase could not be specific for the arm movement because they occurred when there was no arm movement at all. The visual stimulus presented in the choice phase was also presented earlier on each trial in the cue phase. Although 70% of the task-related basalis neurons responded in the choice phase, only 5% had detectable changes in firing in the cue phase. Of 251 neurons responding in the cue or choice phase, 59% had significantly larger changes in firing in the choice phase than in the cue phase, whereas only one neuron had a larger response in the cue phase. Therefore, most responses of basalis neurons in the choice phase could not be specific for the visual stimulus because similar responses did not occur when the same stimulus was presented in the cue phase. These results indicate that the frequent responses of basalis neurons in the choice phase are neither purely sensory nor motor in nature, but are highly dependent on the context of the stimulus or movement. The neuronal responses in the choice phase may reflect either transient increases in arousal or decision-making processes.
Different cellular types in mesopontine cholinergic nuclei related to ponto-geniculo-occipital waves
Authors: Steriade M , Pare D , Datta S , Oakson G , Curro Dossi R
Published: April 2018

The only mesopontine neurons previously described as involved in the transfer of ponto-geniculo-occipital (PGO) waves from the brain stem to the thalamus were termed PGO-on bursting cells. We have studied, in chronically implanted cats, neuronal activities in brain-stem peribrachial (PB) and laterodorsal tegmental (LDT) cholinergic nuclei in relation to PGO waves recorded from the lateral geniculate (LG) thalamic nucleus during rapid-eye-movement (REM) sleep. We constructed peri-PGO histograms of PB/LDT cells' discharges and analyzed the interspike interval distribution during the period of increased neuronal activity related to PGO waves. Six categories of PGO-related PB/LDT neurons with identified thalamic projections were found: 4 classes of PGO-on cells: PGO-off but REM-on cells: and post-PGO cells. The physiological characteristics of a given cell class were stable even during prolonged recordings. One of these cell classes (1) represents the previously described PGO-on bursting neurons, while the other five (2–6) are newly discovered neuronal types. (1) Some neurons (16% of PGO-related cells) discharged stereotyped low-frequency (120– 180 Hz) spike bursts preceding the negative peak of the LG-PGO waves by 20–40 msec. These neurons had low firing rates (0.5–3.5 Hz) during all states. (2) A distinct cell class (22% of PGO-related neurons) fired high-frequency spike bursts (greater than 500 Hz) about 20–40 msec prior to the thalamic PGO wave. These bursts were preceded by a period (150–200 msec) of discharge acceleration on a background of tonically increased activity during REM sleep. (3) PGO-on tonic neurons (20% of PGO-related neurons) discharged trains of repetitive single spikes preceding the thalamic PGO waves by 100–150 msec, but never fired high- frequency spike bursts. (4) Other PGO-on neurons (10% of PGO-related neurons) discharged single spikes preceding thalamic PGO waves by 15–30 msec. On the basis of parallel intracellular recordings in acutely prepared, reserpine-treated animals, we concluded that the PGO-on single spikes arise from conventional excitatory postsynaptic potentials and do not reflect tiny postinhibitory rebounds. (5) A peculiar cellular class, termed PGO-off elements (8% of PGO-related neurons), consisted of neurons with tonic, high discharge rates (greater than 30 Hz) during REM sleep. These neurons stopped firing 100– 200 msec before and during the thalamic PGO waves. (6) Finally, other neurons discharged spike bursts or tonic spike trains 100–300 msec after the initially negative peak of the thalamic PGO field potential (post-PGO elements, 23% of PGO-related neurons).(ABSTRACT TRUNCATED AT 400 WORDS)
Molecular cloning and sequencing of general odorant-binding proteins GOBP1 and GOBP2 from the tobacco hawk moth Manduca sexta: comparisons with other insect OBPs and their signal peptides
Authors: Vogt RG , Rybczynski R , Lerner MR
Published: April 2018

Odorant-binding proteins (OBPs) are small, water-soluble proteins uniquely expressed in olfactory tissue of insects and vertebrates. OBPs are present in the aqueous fluid surrounding olfactory sensory dendrites and are thought to aid in the capture and transport of hydrophobic odorants into and through this fluid. OBPs may represent the initial biochemical recognition step in olfaction, because they transport odorants to the receptor neurons. Insect OBPs are represented by multiple classes: pheromone-binding proteins (PBPs) and general odorant-binding proteins (GOBP1 and GOBP2). PBPs associate with pheromone-sensitive neurons, while GOBPs associate with general odorant- sensitive neurons. Analysis of N-terminal amino acid sequences of 14 insect OBPs isolated from six species indicated that the PBPs were variable and the GOBPs were highly conserved. However, inferred properties of these proteins were based only on partial sequence data. We now report the full-length sequences of a GOBP1 and GOBP2 from the moth Manduca sexta and compare these sequences with those of PBPs from three species, including M. sexta, Antheraea polyphemus, and A. pernyi. We also compare these with a GOBP2 of A. pernyi, previously identified only as a novel OBP. These comparisons fully support our N-terminal analysis. The signal peptide sequences of seven insect OBPs reveal conserved sequences within OBP classes, but not between OBP classes even within the same animal species. This suggests that multiple OBPs may be coexpressed in the same cell type, but differentially processed in a class-specific manner. Properties of the GOBPs suggest that general olfaction is broadly receptive at the periphery. Properties of the PBPs suggest that pheromone olfaction is discriminatory at the periphery, and that the initial biochemical steps in pheromone detection may play an active role in odor perception.
Cell-type-specific regulation of nerve growth factor (NGF) synthesis in non-neuronal cells: comparison of Schwann cells with other cell types
Authors: Matsuoka I , Meyer M , Thoenen H
Published: April 2018

We have previously shown that after peripheral nerve lesion the synthesis of NGF is induced in cells of the nerve sheath (Heumann et al., 1987a). Further analysis led to the identification of growth factors and intracellular mechanisms responsible for this induction in sciatic fibroblasts (Lindholm et al., 1988; Hengerer et al., 1990). The present work aimed at the elucidation of the regulation of NGF synthesis in Schwann cells. A variety of cytokines and peptide growth factors, including interleukin-1 (IL-1) and platelet-derived growth factor (PDGF), which are known to increase NGF-mRNA in fibroblasts and astrocytes, failed to do so in Schwann cell cultures. Forskolin (FK), an activator of adenylate cyclase, increased the level of NGF-mRNA eightfold within 3 hr of incubation. The effect of FK on NGF-mRNA was mimicked by analogs of cAMP but not by dideoxyforskolin, an FK derivative not activating adenylate cyclase. Application of norepinephrine and isoproterenol also augmented the NGF-mRNA content. Pretreatment of Schwann cells with N-[2-(methylamino)ethyl]-5- isoquinoline sulfonamide dihydrochloride (H-8), an inhibitor of cyclic- nucleotide-dependent protein kinases, decreased both basal and elevated levels of NGF-mRNA. Ionomycin, a Ca2+ ionophore, and phorbol 12- myristate 13-acetate (TPA), an activator of protein kinase C, potentiated the effect of FK in an H-8-sensitive manner. We show that the action of FK is independent of changes in mRNA stability and of protein synthesis. Thus, in cultured Schwann cells upregulation of NGF- mRNA expression seems to be mainly achieved by a cAMP-triggered transcriptional activation of the NGF gene. Another striking difference between various glial cell types was revealed by application of transforming growth factor beta-1 (TGF-beta 1), which is the strongest inducer of NGF-mRNA in cultured astrocytes (Lindholm et al., 1990). Schwann cells responded to TGF-beta 1 by decreasing basal as well as FK- induced NGF-mRNA levels. Together with previously published work, our results show that cell-type-specific mechanisms not only account for the different control of NGF expression in neurons as compared to glial cells, but also reveal a surprising specificity of regulatory mechanisms in different non-neuronal cell types, even those derived from the same tissue such as fibroblasts and Schwann cells of peripheral nerves.
Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine: possible cellular mechanisms of histaminergic control of arousal
Authors: McCormick DA , Williamson A
Published: April 2018

The thalamus is innervated by histaminergic fibers presumably arising from neurons in the tuberomammillary nucleus of the hypothalamus. The possible function of this histaminergic projection was addressed through investigation of the cellular actions of histamine on guinea pig and cat dorsal lateral geniculate (LGNd) relay neurons maintained as a slice in vitro. Local application of histamine to LGNd relay neurons resulted in a slow depolarization that was associated with a decrease in membrane conductance and was blocked by the H1-antagonists pyrilamine, triprolidine, or diphenhydramine. Current versus voltage relationships revealed that the slow depolarization was associated with an inward current that reversed near EK, indicating that it was due to a decrease in a potassium current. The slow depolarizing response to histamine was occluded by maximal activation of the slow depolarizing responses resulting from stimulation of alpha 1-adrenergic or muscarinic receptors, suggesting that they are all mediated by reduction in the same potassium current and/or alteration of a common second messenger. In the presence of H1-receptor antagonists, application of histamine resulted in a small depolarization that was associated with a marked increase in apparent membrane conductance. Voltage-clamp recordings revealed that this response was associated with enhancement of the hyperpolarization-activated cation current Ih. This response to histamine was blocked by local or bath application of the H2-antagonists cimetidine or tiotidine. The functional consequences of these actions of histamine were addressed with extracellular and intracellular recordings in guinea pig and cat LGNd relay neurons. Extracellular recordings in cat LGNd revealed the occurrence of highly regular 1-4 Hz rhythmic burst discharges. Application of histamine halted rhythmic bursting and replaced it with a prolonged period of single-spike activity. Intracellular recordings indicate that the histamine-induced switch in firing mode is due largely to the slow depolarizing response mediated by H1-receptors, but is also facilitated by the enhancement of Ih mediated by H2-receptors. These postsynaptic actions indicate that increased activity in the tuberomammillary histaminergic system may result in a switch of thalamic neuronal activity from rhythmic burst firing to single-spike activity and thereby promote the accurate transmission and processing of sensory information and cognition.
Network modulation of a slow intrinsic oscillation of cat thalamocortical neurons implicated in sleep delta waves: cortically induced synchronization and brainstem cholinergic suppression
Authors: Steriade M , Dossi RC , Nunez A
Published: April 2018

A slow (0.5–4 Hz) oscillation of thalamic neurons was recently described and attributed to the interplay of two intrinsic currents. In this study, we investigated the network modulation of this intrinsic thalamic oscillation within the frequency range of EEG sleep delta- waves. We performed intracellular and extracellular recordings of antidromically identified thalamocortical cells (n = 305) in sensory, motor, associational, and intralaminar nuclei of anesthetized cats. At the resting membrane potential, Vm (-60.3 +/- 0.4 mV, mean +/- SE), cortical stimulation induced spindle-like oscillations (7–14 Hz), whereas at Vm more negative than -65 mV the same stimuli triggered an oscillation within the EEG delta-frequency (0.5–4 Hz), consisting of low-threshold spikes (LTSs) followed by after hyperpolarizing potentials (AHPs). The LTS-AHP sequences outlasted cortical stimuli as a self-sustained rhythmicity at 1–2 Hz. Corticothalamic stimuli were able to transform subthreshold slow (0.5–4 Hz) oscillations, occurring spontaneously at Vm more negative than -65 mV, into rhythmic LTSs crowned by bursts of Na+ spikes that persisted for 10–20 sec after cessation of cortical volleys. Cortical volleys also revived a hyperpolarization-activated slow oscillation when it dampened after a few cycles. Auto- and crosscorrelograms of neuronal pairs revealed that unrelated cells became synchronized after a series of corticothalamic stimuli, with both neurons displaying rhythmic (1-2 Hz) bursts or spike trains. Since delta-thalamic oscillations, prevailing during late sleep stages, are triggered at more negative Vm than spindles characterizing the early sleep stage, we postulate a progressive hyperpolarization of thalamocortical neurons with the deepening of the behavioral state of EEG-synchronized sleep. In view of the evidence that cortical-elicited slow oscillations depend on synaptically induced hyperpolarization of thalamocortical cells, we propose that the potentiating influence of the corticothalamic input results from the engagement of two GABAergic thalamic cell classes, reticular and local-circuit neurons. The thalamocorticothalamic loop would transfer the spike bursts of thalamic oscillating cells to cortical targets, which in turn would reinforce the oscillation by direct pathways and/or indirect projections relayed by reticular and local-circuit thalamic cells. Stimulation of mesopontine cholinergic [peribrachial (PB) and laterodorsal tegmental (LDT)] nuclei in monoamine-depleted animals had an effect that was opposite to that exerted by corticothalamic volleys. PB/LDT stimulation reduced or suppressed the slow (1–4 Hz) oscillatory bursts of high- frequency spikes in thalamic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Role of the forebrain commissures in bihemispheric mnemonic integration in macaques
Authors: Lewine JD , Doty RW , Astur RS , Provencal SL
Published: April 2018

A serial probe recognition task was used to examine the interhemispheric exchange of visual data in macaques. Each block of trials began with the memorization of one to six visual target images. The monkeys then had to determine, in tests that followed immediately, whether probe images were or were not members of the learned target set. Previous work with both humans and macaques has shown that the time required for the evaluation of probes generally increases, while response accuracy decreases, as a function of the number of targets, the “memory load”. By testing animals with bisected optic chiasm, it was possible to direct visual information to only one hemisphere at a time, simply by occluding the opposite eye. In this fashion, the quality of intrahemispheric evaluations (in which a monocular probe was a match for a target previously viewed through the same eye) was compared with that of interhemispheric evaluations (in which a probe was a match for a target previously designated through the opposite eye). A key question was whether division of the target list between the hemispheres modified the relationships between reaction time, response accuracy, and memory load. Provided that either the anterior commissure or the splenium of the corpus callosum was intact, interhemispheric processing was only subtly less efficient than intrahemispheric processing. The ability to perform interhemispheric evaluations was selectively and completely disrupted if all forebrain commissural fibers were transected. In this latter split-brain condition, the time required for probe evaluations was, as expected, determined solely by the number of target items memorized by the probed hemisphere. Accuracy, however, was always a function of the total memory load, regardless of the distribution of targets between the hemispheres. This implies, first, that accuracy and latency do not reflect identical mnemonic factors, as frequently held, and second, that in mnemonic processing, the two hemispheres draw upon a unified, shared resource, probably allocated by the intact brainstem.
KT5926 selectively inhibits nerve growth factor-dependent neurite elongation
Authors: Teng KK , Greene LA
Published: April 2018

We have examined the effects of the protein kinase inhibitor KT5926 on NGF-promoted responses in PC12 and PC12-C41 cells (a subclone of the parental cell line). Our findings reveal that this compound specifically and reversibly prevents the NGF-induced outgrowth and regeneration of neurites. In addition, neurites of NGF-pretreated cells cease further elongation upon exposure to KT5926. However, preexisting neurite networks in the cultures remain intact in the presence of the drug. The inhibition of neuritic growth appears to occur at least in part at the level of growth cones since KT5926 also causes these structures to collapse and inhibits NGF-promoted reactivation of NGF- deprived growth cones. Although KT5926 is an analogue of K-252a, which blocks all responses to NGF, it does not affect other NGF-elicited cellular responses examined, including NGF-dependent priming of cells, gp140prototrk autophosphorylation, immediate-early gene induction, and phosphorylation of several known cytoskeletal proteins (MAP 1.2/1B, chartin MAPs, and beta-tubulin). However, phosphate incorporation into a cytoskeletally localized 58 kDa phosphoprotein, designated pp58, is selectively reduced in KT5926-treated cultures (+/- NGF). Although KT5926 is an in vitro inhibitor of myosin light chain kinase and calmodulin-dependent protein kinase II, inhibition of these two kinase activities by ML-9 and KN-62, respectively, applied alone or together, does not mimic the effects of KT5926 on neurite growth and on pp58 phosphorylation. Taken together, our findings suggest that KT5926, via a previously unidentified protein kinase inhibitory activity, differentially interferes with NGF-promoted growth cone function and consequently affects neuritic outgrowth. This compound should therefore be a useful tool for dissecting the mechanism of NGF actions and affords a means to identify phosphoproteins that play specific roles in neurite growth/elongation.
Presynaptic inhibition of primary afferent transmitter release by 5- hydroxytryptamine at a mechanosensory synapse in the vertebrate spinal cord
Authors: Sillar KT , Simmers AJ
Published: April 2018

The effects of the neuromodulatory monoamine 5-HT (serotonin) on a cutaneous mechanosensory (Rohon-Beard, R-B neuron) pathway in the spinal cord of postembryonic Xenopus laevis tadpoles have been examined. In paralyzed animals, exogenous 5-HT at 1–10 microM reversibly inhibits (within 1–2 min) the activation of fictive swimming in response to electrical stimulation of R-B free nerve endings in the skin. At threshold stimulus intensities for swimming under control conditions, intracellularly recorded EPSPs in contralateral motoneurons are completely abolished by 5-HT without any obvious change in neuronal conductance or membrane potential. However, increasing the stimulus voltage can activate swimming with enhanced motor burst discharge on each cycle (Sillar et al., 1992). This suggested that 5-HT inhibits the swim-initiating pathway rather than the motor rhythm-generating circuitry itself. Extracellular recordings from the central projections of R-B neurons indicated that the amine does not impair the generation of mechanoafferent impulses or their propagation into the spinal cord. However, 5-HT application blocks impulse activity in dorsolaterally positioned sensory interneurons (DLis) that are contacted by R-B neurons, suggesting that 5-HT acts at R-B to DLi synapses in the dorsal cord. By recording with microelectrodes from DLis, we find that skin stimulus-evoked EPSPs at this first-order synapse in the swim- initiating pathway are reversibly suppressed by 5-HT. No obvious change in DLi membrane potential or conductance could be detected during the inhibition, suggesting a presynaptic site of action for 5-HT. To investigate this suggestion further, the effects of 5-HT on the spontaneous release of R-B sensory transmitter (excitatory amino acid, EAA) were examined, again by recording postsynaptically from DLis. In quiescent preparations, DLis receive spontaneous glycinergic, GABAergic, and EAA receptor-mediated PSPs. The inhibitory potentials are abolished by strychnine and curare, respectively. The excitatory potentials that remain are not blocked by application of the calcium channel blocker cadmium chloride at 1 mM, but are suppressed by the EAA receptor antagonist kynurenic acid. They therefore resemble the TTX- resistant EPSPs described previously in Xenopus DLis (Sillar and Roberts, 1991), which are presumed to arise from the spontaneous liberation of EAA transmitter from R-B terminals. Bath application of 5- HT dramatically reduces the rate of occurrence of these spontaneous EPSPs consistent with a presynaptic locus for the inhibitory effects of 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)
Distinct populations of sensory neurons mediate the peristaltic reflex elicited by muscle stretch and mucosal stimulation
Authors: Grider JR , Jin JG
Published: April 2018

Recent studies suggest that muscle stretch and mucosal stimulation elicit intestinal peristalsis by activating distinct populations of sensory neurons that converge on the same population of enteric motor neurons. The present study sought to characterize the origin and projections of these sensory neurons. The reflex was elicited by applying muscle stretch and mucosal stroking to the central compartment of a three-compartment flat-sheet preparation of rat colon while ascending contraction and descending relaxation were measured in the orad and caudad compartments, respectively. Identical graded responses were elicited by muscle stretch and mucosal stimulation: atropine (1 microM) and the tachykinin antagonist spantide (10 microM) inhibited ascending contraction when added to the orad compartment only, while the vasoactive intestinal peptide antagonist VIP10–28 (10 microM) and the NO synthase inhibitor NG-nitro-L-arginine (100 microM) inhibited descending relaxation when added to the caudad compartment only. Addition of capsaicin (1 microM) to the central compartment for 30 min abolished ascending contraction and descending relaxation elicited by muscle stretch and mucosal stimulation. Recovery of response was complete when capsaicin was applied to the mucosa of the colon in situ and measurements made 1 d after, implying that at this low concentration capsaicin depleted sensory nerve terminals of their transmitter content.(ABSTRACT TRUNCATED AT 250 WORDS)
Power spectrum analysis of bursting cells in area MT in the behaving monkey
Authors: Bair W , Koch C , Newsome W , Britten K
Published: April 2018

It is widely held that visual cortical neurons encode information primarily in their mean firing rates. Some proposals, however, emphasize the information potentially available in the temporal structure of spike trains (Optican and Richmond, 1987; Bialek et al., 1991), in particular with respect to stimulus-related synchronized oscillations in the 30–70 Hz range (Eckhorn et al., 1988; Gray et al., 1989; Kreiter and Singer, 1992) as well as via bursting cells (Cattaneo et al., 1981a; Bonds, 1992). We investigate the temporal fine structure of spike trains recorded in extrastriate area MT of the trained macaque monkey, a region that plays a major role in processing motion information. The data were recorded while the monkey performed a near- threshold direction discrimination task so that both physiological and psychophysical data could be obtained on the same set of trials (Britten et al., 1992). We identify bursting cells and quantify their properties, in particular in relation to the behavior of the animal. We compute the power spectrum and the distribution of interspike intervals (ISIs) associated with individual spike trains from 212 cells, averaging these quantities across similar trials. (1) About 33% of the cells have a relatively flat power spectrum with a dip at low temporal frequencies. We analytically derive the power spectrum of a Poisson process with refractory period and show that it matches the observed spectrum of these cells. (2) About 62% of the cells have a peak in the 20–60 Hz frequency band. In about 10% of all cells, this peak is at least twice the height of its base. The presence of such a peak strongly correlates with a tendency of the cell to respond in bursts, that is, two to four spikes within 2–8 msec. For 93% of cells, the shape of the power spectrum did not change dramatically with stimulus conditions. (3) Both the ISI distribution and the power spectrum of the vast majority of bursting cells are compatible with the notion that these cells fire Poisson-distributed bursts, with a burst-related refractory period. Thus, for our stimulus conditions, no explicitly oscillating neuronal process is required to yield a peak in the power spectrum. (4) We found no statistically significant relationship between the peak in the power spectrum and psychophysical measures of the monkeys' performance on the direction discrimination task.(ABSTRACT TRUNCATED AT 400 WORDS)
Beta-adrenergic receptor-mediated regulation of extracellular adenosine in cerebral cortex in culture
Authors: Rosenberg PA , Knowles R , Knowles KP , Li Y
Published: April 2018

Adenosine is an important inhibitory neuromodulator in the CNS, yet the sources of extracellular adenosine have yet to be well characterized. In this study we show that beta-adrenergic stimulation of cortical cultures results in the extracellular accumulation of cAMP as well as adenosine, and that the extracellular adenosine derives from extracellular cAMP. The concentration dependence of isoproterenol in evoking cAMP secretion was determined by radioimmunoassay, and the EC50 for this effect was found to be approximately 100 nM. In order to investigate the effect of beta-adrenergic stimulation on the regulation of extracellular adenosine, the effect of isoproterenol in stimulating the extracellular accumulation of adenine-containing compounds was examined by HPLC. Isoproterenol stimulated cAMP secretion in both astrocyte cultures and astrocyte-rich mixed cultures of astrocytes and neurons. However, no extracellular cAMP was detectable in neuron- enriched astrocyte-poor cultures. Extracellular adenosine increased in response to isoproterenol in the astrocyte-rich mixed cultures, but not in the neuron-enriched astrocyte-poor cultures. After 30 min exposure to isoproterenol, the concentration of adenosine in the extracellular medium increased by 47% in 56 experiments in the mixed astrocyte-rich cultures. In order to establish whether the adenosine that accumulates in response to isoproterenol stimulation actually derives from extracellular cAMP, phosphodiesterase inhibitors were tested for their ability to block isoproterenol-stimulated adenosine accumulation. Isobutylmethylxanthine (IBMX; 100 microM), RO 20–1724 (180 microM), carbazeran (10 microM), dipyridamole (10 microM), and trifluoperazine (10 microM) had no inhibitory effect on the isoproterenol-stimulated accumulation of extracellular adenosine. However 100 microM IBMX plus 180 microM RO 20–1724 effectively blocked isoproterenol-stimulated adenosine accumulation and, as expected, increased extracellular cAMP. As a further test of the origin of isoproterenol-stimulated adenosine accumulation, we attempted to block this phenomenon by blocking cAMP secretion itself. For this purpose probenecid, a known inhibitor of cAMP secretion in many different cell types, was used. We found that probenecid at 1 mM blocked isoproterenol-stimulated adenosine accumulation. These studies suggest that one potentially important source of extracellular adenosine in the cerebral cortex is endogenous extracellular cAMP, secreted from astrocytes in response to beta- adrenergic receptor stimulation. Since the receptors of neuromodulators other than norepinephrine may also be coupled to adenylyl cyclase in the cerebral cortex, there may be several neuromodulatory systems that regulate extracellular adenosine levels by this mechanism.
bendless, a Drosophila gene affecting neuronal connectivity, encodes a ubiquitin-conjugating enzyme homolog
Authors: Oh CE , McMahon R , Benzer S , Tanouye MA
Published: April 2018

The Drosophila bendless (ben) gene was originally isolated as a mutation affecting the escape jump response. This behavioral defect was ascribed to a single lesion affecting the connectivity between the giant fiber and the tergotrochanter motor neuron. A closer examination of the ben phenotype suggests that ben activity is broader and affects a variety of other neurons including photoreceptor cells and their axons. Mosaic analysis indicates that the focus of ben activity is presynaptic. We have cloned the ben gene through a chromosomal walk and show that it is homologous to a class of ubiquitin-conjugating enzymes. The major role of ubiquitination in the protein degradative pathway suggests that ben regulates neural developmental processes such as growth cone guidance by targeting specific proteins for degradation.
Peripheral nerve injury induces Schwann cells to express two macrophage phenotypes: phagocytosis and the galactose-specific lectin MAC-2
Authors: Reichert F , Saada A , Rotshenker S
Published: April 2018

In N mice, peripheral nerve injury is followed by the normal rapid progression of Wallerian degeneration: Schwann cells proliferate and lose their myelin, which is phagocytized and metabolized by blood-borne macrophages. The role of Schwann cells in myelin phagocytosis is debated. Additionally, the molecular mechanisms underlying myelin phagocytosis by the two cell types are not well understood. To elucidate the role of Schwann cells as phagocytes we studied, electron microscopically, in vivo and in vitro degenerating, frozen, and neuroma nerve segments. The major cell types composing these tissues differed: Schwann and macrophages in in vivo degenerating; Schwann in in vitro degenerating; macrophages in frozen; Schwann, macrophages, and fibroblasts in neuroma nerve segments. Both macrophages and Schwann cells phagocytized myelin. We further studied, by immunocytochemistry and immunoblot analysis, the expression of molecules that are characteristically displayed by inflammatory and mature murine macrophages: MAC-1 (the C3b complement receptor), MAC-2 (a galactose- specific lectin), the Fc receptor, and the F4/80 antigen. All were detected in the macrophage-rich, in vivo degenerating, frozen, and neuroma nerve segments. Surprisingly, MAC-2 was also expressed in the macrophage-scarce, Schwann-rich, in vitro degenerating nerve. Immunocytochemistry and immunoblot analysis of isolated non-neuronal cells revealed that both macrophages and Schwann cells displayed MAC-2 on their surface and in their cytoplasm. Morphometry unveiled that galactose and lactose specifically inhibited myelin phagocytosis, as predicted if MAC-2 was mediating myelin phagocytosis by lectinophagocytosis (lectin-mediated phagocytosis). The role of MAC-2 in mediating myelin phagocytosis was further supported by two observations made in W mice that display very slow progression of Wallerian degeneration. First, the failure to degenerate in vivo was associated with deficient MAC-2 production. Second, degeneration that occurred in vitro was associated with MAC-2 production. Furthermore, a strong positive correlation between levels of MAC-2 expression and the extent of myelin destruction by phagocytosis was observed over a wide range of values.