bluuebunny/crossref_metadata_2025 huggingface dataset:
Viabilidade Técnica e Econômica da Implantação de uma Agroindústria de Extrato Vegetal
Authors: Lima Luciana Da Silva Corrêa , Da Luz Maria Laura Gomes Silva , Da Luz Carlos Alberto Silveira , Gadotti Gizele Ingrid , Maldaner Vanessa , Santos Júlia Bergmann , Bernardy Ruan
Published: April 2018

Estima-se que aproximadamente 15,2 milhões de brasileiros sejam vegetarianos, o que corresponde a 8% da população do país. Neste sentido, as bebidas de base vegetal surgem como alternativa de produto alimentício para vegetarianos e veganos, bem como para alérgicos à proteína do leite e intolerantes à lactose. Este trabalho teve o objetivo de analisar a viabilidade técnica e econômica de uma agroindústria que produza dois tipos de extrato vegetal: de noz-pecã e de amendoim. Nesse estudo, foi computado o mercado consumidor relativo à quantidade para dimensionar a agroindústria e foi realizado um teste de análise sensorial para orientar a formulação do extrato. A análise econômica do projeto mostrou que a proposta é viável, com retorno do capital investido em 4 ou 6 anos, para os cenários estudados.
GESTÃO FINANCEIRA: UMA ANÁLISE DE INVESTIMENTO/FINANCIAL MANAGEMENT: AN INVESTMENT ANALYSIS
Authors: Simas Neves Francine , Merlin Bervian Luciana , Chiarelli Cliverson , Alberton Anete , Vieira Marinho Sidnei
Published: April 2018

Neste caso para ensino, os protagonistas levantam um problema muito comum nas empresas, vivenciado diariamente por seus gestores, que é a identificação da necessidade de investimentos e a análise econômica – financeira do mesmo. O principal objetivo deste caso é evidenciar a importância dessa análise, sendo que os autores fundamentam teoricamente o sistema de amortização e os métodos de análise de investimento utilizados nos cálculos pertinentes as respostas das questões propostas.
CONFLITO TRABALHO-FAMÍLIA, POLÍTICAS DE APOIO À FAMÍLIA E GÊNERO: UM PANORAMA DO ATUAL CENÁRIO DE ESTUDOS/WORK-FAMILY CONFLICT, FAMILY AND GENDER SUPPORT POLICY: A PANORAMA OF THE CURRENT SCENARIO OF STUDIES
Authors: Silva Vilela Nágila Giovanna , Lourenço Mariane Lemos
Published: April 2018

A dificuldade em conciliar as demandas do trabalho e da família tem contribuído para que homens e mulheres regularmente enfrentem conflitos entre essas duas esferas. O conflito trabalho-família, decorrente da incompatibilidade de pressões de papéis profissionais e familiares vem sendo o cerne de diversos trabalhos, principalmente na literatura internacional. Visando reduzir os impactos negativos causados por tais conflitos, as organizações e os governos de vários países têm proposto políticas para auxiliar na harmonia entre trabalho e família. Diante disso, o objetivo desse trabalho é analisar como as políticas de apoio à família que visam reduzir o conflito trabalho-família se diferem entre países e de acordo com o gênero, tanto no que diz respeito à oferta, quanto à sua utilização. Para atingir esse propósito, foi feita uma pesquisa bibliográfica em periódicos de destaque (como Employee Relations, Equality, Diversity and Inclusion, Human Resource Management, Journal of Family Issues, Personnel Review, Revista de Administração Contemporânea, entre outros) com publicações sobre a temática nos últimos anos.  Foi possível verificar a importância do contexto social para a compreensão dessas políticas e como elas são percebidas pelos trabalhadores.
Invertebrate Synapsins: A Single Gene Codes for Several Isoforms inDrosophila
Authors: Klagges Bert R. E. , Heimbeck Gertrud , Godenschwege Tanja A. , Hofbauer Alois , Pflugfelder Gert O. , Reifegerste Rita , Reisch Dietmar , Schaupp Michael , Buchner Sigrid , Buchner Erich
Published: April 2018

Vertebrate synapsins constitute a family of synaptic proteins that participate in the regulation of neurotransmitter release. Information on the presence of synapsin homologs in invertebrates has been inconclusive. We have now cloned aDrosophilagene coding for at least two inferred proteins that both contain a region with 50% amino acid identity to the highly conserved vesicle- and actin-binding “C” domain of vertebrate synapsins. Within the C domain coding sequence, the positions of two introns have been conserved exactly from fly to human. The positions of three additional introns within this domain are similar. TheDrosophilasynapsin gene (Syn) is widely expressed in the nervous system of the fly. The gene products are detected in all or nearly all conventional synaptic terminals. A single amber (UAG) stop codon terminates the open reading frame (ORF1) of the most abundant transcript of theSyngene 140 amino acid codons downstream of the homology domain. Unexpectedly, the stop codon is followed by another 443 in-frame amino acid codons (ORF2). Using different antibodies directed against ORF1 or ORF2, we demonstrate that in the adult fly small and large synapsin isoforms are generated. The small isoforms are only recognized by antibodies against ORF1; the large isoforms bind both kinds of antibodies. We suggest that the large synapsin isoform inDrosophilamay be generated by UAG read-through. Implications of such an unconventional mechanism for the generation of protein diversity from a single gene are discussed.
Selective, Activity-Dependent Uptake of Histamine into an Arthropod Photoreceptor
Authors: Stuart Ann E. , Morgan Jennifer R. , Mekeel Harold E. , Kempter Elizabeth , Callaway Joseph C.
Published: April 2018

The synapses made by many arthropod photoreceptors are disinhibitory and use histamine as their transmitter. Because decreases and not increases in the cleft concentration of transmitter constitute the important event at these synapses, a transporter to clear the cleft of histamine would seem particularly crucial to signal transfer. We report here that3H-histamine is taken up selectively into barnacle photoreceptors by a Na+-dependent mechanism, presumably a transporter. Using light microscopic autoradiography, we observe heavy label over axons and presynaptic terminals of these neurons when they are stimulated during uptake. The radioactivity taken up was identified as3H-histamine by thin layer chromatography; no metabolites were detected, even after 5 hr. Radiolabeled 5-hydroxytryptamine and GABA are not taken up by the photoreceptor.3H-histamine uptake into photoreceptors is decreased markedly by an excess of unlabeled histamine and by chlorpromazine and phenoxybenzamine. Unexpectedly for uptake dependent on the Na+gradient, photoreceptor terminals label more intensely in the light (when depolarized) than in the dark (when hyperpolarized). Glia label more strongly than photoreceptors in dark-incubated preparations. The presence of presynaptic uptake strengthens the evidence that histamine is the neurotransmitter of arthropod photoreceptors and provides a mechanism by which this synapse could recycle transmitter, control its steady-state cleft concentration, and clear it from the cleft in response to decreases in its release from the photoreceptors.
Transgenic Expression of Embryonic MAP2 in Adult Mouse Brain: Implications for Neuronal Polarization
Authors: Marsden Kathryn M. , Doll Thierry , Ferralli Jacqueline , Botteri Florence , Matus Andrew
Published: April 2018

The major neuronal microtubule-associated protein MAP2 is selectively localized in dendrites, where its expression is under strong developmental regulation. To learn more about its potential effects on neuronal morphogenesis and its sorting within the neuronal cytoplasm, we have raised transgenic mice that express high levels of the embryonic form, MAP2c, in the adult brain. One transgenic line expressed higher levels of MAP2c than endogenous adult MAP2. This had no detectable effect on either the arrangement or morphology of neurons, suggesting that although MAP2c is necessary for neuronal morphogenesis it is not involved in its regulation. Like endogenous adult MAP2, transgenic MAP2c was present in dendrites but not axons, indicating that the signal responsible for its cytoplasmic sorting is contained within the 1.5 kb of its coding sequence.In situhybridization with specific probes showed that transgenic MAP2c mRNA was limited to cell bodies. Thus, the dendritic localization of MAP2c protein cannot be the result of previous transport of its mRNA but must depend on a signal associated with the protein itself. Furthermore, because the amino acid sequence of MAP2c is present in all forms of MAP2, this signal is also contained within adult high-MrMAP2 protein. This raises the possibility that, rather than the conventional scheme of mRNA sorting preceding protein localization, the transport of adult MAP2 mRNA into dendrites could depend on it being part of a translation complex in which the targeting signal is on the nascent protein.
Low-Frequency Stimulation Cancels the High-Frequency-Induced Long-Lasting Effects in the Rat Medial Vestibular Nuclei
Authors: Grassi S. , Pettorossi V. E. , Zampolini M.
Published: April 2018

In rat brainstem slices, we investigated the effects of low-frequency stimulation (LFS) of the primary vestibular afferents on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN). LFS induced long-term effects, the sign of which depended on whether the vestibular neurons were previously conditioned by HFS. In unconditioned slices, LFS evoked modifications of the responses that were similar to those observed after HFS but had a smaller extension. In fact, LFS caused long-lasting potentiation of the N1 wave in the MVN ventral portion (Vp) and long-lasting depression of the N2 wave in the MVN dorsal portion (Dp), whereas it provoked small and variable effects on the N1 wave. By contrast, when the synaptic transmission was already conditioned, LFS influenced the synaptic responses oppositely, reducing or annulling the HFS long-term effects. This phenomenon was specifically induced by LFS, because HFS was not able to cause it. The involvement of NMDA receptors in mediating the LFS long-term effects was supported by the fact that AP-5 prevented their induction. In addition, the annulment of HFS long-term effects by LFS was also demonstrated by the shift in the latency of the evoked unitary potentials after LFS. In conclusion, we suggest that the reduction of the previously induced conditioning could represent a cancellation mechanism, useful to quickly adapt the vestibular system to continuous different needs and to avoid saturation.
Actions of Endogenous Opioids on NMDA Receptor-Independent Long-Term Potentiation in Area CA3 of the Hippocampus
Authors: Williams Stephen H. , Johnston Daniel
Published: April 2018

The opioid peptides represent a major class of neurotransmitter in the vertebrate nervous system and are prevalent in the hippocampus. There is considerable interest in the physiological function of the opioids contained in the mossy fiber pathway. The release of opioids from mossy fibers shows a strong frequency dependence. Long-term potentiation (LTP) at this synapse, an NMDA receptor-independent form of LTP, also depends on high-frequency synaptic activity, and this has led to speculation that endogenous opioids may be a critical factor in LTP induction. Previous reports using extracellular recordings have provided evidence for and against a role for opioids in mossy fiber LTP. Using single-cell recording techniques, we have tested the hypothesis that endogenous opioids are required for mossy fiber LTP induction. We recorded from a defined population of synapses that had EPSCs with fast rise times, short latencies, and monophasic decays, consistent with a proximally terminating synapse. The opioid antagonist naloxone prevented mossy fiber LTP in the rat, but had no effect on the commissural/associational system, a nonopioid-containing pathway. The action of naloxone was not mediated through disinhibition because GABAAreceptors were pharmacologically blocked in these experiments. We also tested the hypothesis that variations in postsynaptic receptor subtype distribution between species might explain previous controversies regarding the role of endogenous opioids. In contrast to the rat, LTP of the mossy fiber field potential in guinea pig was not blocked by naloxone. Our data suggest that opioids may be the presynaptically released, frequency-dependent, associative factor for mossy fiber LTP induction.
Regenerative Proliferation in Organ Cultures of the Avian Cochlea: Identification of the Initial Progenitors and Determination of the Latency of the Proliferative Response
Authors: Warchol Mark E. , Corwin Jeffrey T.
Published: April 2018

Sensory hair cells in the cochleae of birds are regenerated after the death of preexisting hair cells caused by acoustic overstimulation or administration of ototoxic drugs. Regeneration involves renewed proliferation of cells in an epithelium that is otherwise mitotically quiescent. To determine the identity of the first cells that proliferate in response to the death of hair cells and to measure the latency of this proliferative response, we have studied hair-cell regeneration in organ culture. Cochleae from hatchling chicks were placed in culture, and hair cells were killed individually by a laser microbeam. The culture medium was then replaced with a medium that contained a labeled DNA precursor. The treated cochleae were incubated in the labeling media for different time periods before being fixed and processed for the visualization of proliferating cells. The first cells to initiate DNA replication in response to the death of hair cells were supporting cells within the cochlear sensory epithelium. All of the labeled supporting cells were located within 200 μm of the hair-cell lesions. These cells first entered S-phase ∼16 hr after the death of hair cells. The results indicate that supporting cells are the precursors of regenerated hair cells and suggest that regenerative proliferation of supporting cells is triggered by signals that act locally within the damaged epithelium.
Spatially Restricted Increase in Polysialic Acid Enhances Corticospinal Axon Branching Related to Target Recognition and Innervation
Authors: Daston Maryellen M. , Bastmeyer Martin , Rutishauser Urs , O’Leary Dennis D. M.
Published: April 2018

The polysialic acid (PSA) modification of the neural cell adhesion molecule (NCAM) has been shown to alter the responses of developing axons to their environment. We have studied the potential role of PSA in regulating the innervation of the spinal cord by corticospinal axons, which occurs by a delayed formation of collateral branches from the parent axons. Developmental changes in the distribution of PSA were examined immunohistochemically using light and electron microscopy. Whereas NCAM is distributed along the entire pathway of rat corticospinal axons as they grow from the cortex to the spinal cord, PSA-modified NCAM does not become evident until later. When PSA becomes evident, it is restricted to the distal segment of these axons from the caudal hindbrain through the spinal cord. The increase in PSA on corticospinal axons coincides with the time that they begin to form collateral branches in the spinal cord. This unique spatiotemporal distribution of PSA suggests its involvement in corticospinal axon branching. To test this hypothesis, PSA was selectively removed by anin vivoinjection of endoneuraminidase N. This treatment did not seem to interfere with the pathfinding of corticospinal axons; however, PSA removal delayed the onset of collateral branching by corticospinal axons within the spinal cord and later diminished the magnitude of branching. These findings indicate a role for PSA in the regulation of interstitial axon branching, a crucial step in the process of target recognition and innervation by corticospinal axons.
Multiple Channel Types Contribute to the Low-Voltage-Activated Calcium Current in Hippocampal CA3 Pyramidal Neurons
Authors: Avery Robert B. , Johnston Daniel
Published: April 2018

Hippocampal neurons exhibit low-voltage-activated (LVA) and high-voltage-activated (HVA) calcium currents. We characterized the LVA current by recording whole-cell Ca2+currents from acutely isolated rat hippocampal CA3 pyramidal neurons in 2 mmCa2+.

Long depolarizing steps to −50 mV revealed two components to the LVA current: transient and sustained. The transient phase had a fast decay time constant of 59 msec. The sustained phase persisted throughout the depolarization, even for steps lasting several seconds. The transient current was inhibited by the classic T-type channel antagonists Ni2+and amiloride. The anticonvulsant phenytoin preferentially blocked the sustained phase, but ethosuximide had no effect. Steady-state inactivation of the transient component was half-maximal at −80 mV.

Nimodipine, an L-type channel antagonist, partly inhibited the sustained current. BayK-8644, an L-type channel agonist, potentiated the sustained current. Calciseptine, another L-type channel antagonist, inhibited the sustained component. ω-Conotoxin-MVIIC, a nonselective toxin for HVA channels, had no effect on either of the LVA current components. ω-Grammotoxin-SIA, another nonselective toxin, partially inhibited the sustained component. The voltage dependence of activation of the nimodipine-sensitive current could be fit with a single Boltzmann, consistent with a homogenous population of L-type channels in CA3 neurons. Half-maximal activation of the nimodipine-sensitive current occurred at −30 mV, considerably more negative than the remaining HVA current.

These results suggest that in physiologic Ca2+more than one type of Ca2+channel contributes to the LVA current in CA3 neurons. The transient current is carried by T-type channels. The sustained current is carried, at least in part, by dihydropyridine-sensitive channels. Thus, the designation “low-voltage-activated” should not be limited to T-type channels. These findings challenge the traditional designation of L-type channels as exclusively HVA and reveal a possible role in subthreshold Ca2+signaling.
Induction of Hippocampal Long-Term Depression Requires Release of Ca2+from Separate Presynaptic and Postsynaptic Intracellular Stores
Authors: Reyes Magali , Stanton Patric K.
Published: April 2018

Studies have suggested that an increase in intracellular [Ca2+] is necessary for the induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission, and that release of Ca2+from intracellular storage pools can be necessary to induce LTP. We investigated whether release of Ca2+from intracellular stores also is required for the induction of LTD at Schaffer collateral–CA1 synapses in hippocampal slices. Both thapsigargin (1 μm) and cyclopiazonic acid (1 μm), compounds that deplete all intracellular Ca2+pools by blocking ATP-dependent Ca2+uptake into intracellular compartments, blocked the induction, but not maintenance, of LTD by low-frequency stimulation (LFS) (1 Hz/15 min) without affecting baseline synaptic transmission. Washout of the reversible inhibitor cyclopiazonic acid restored the ability to induce LTD. In contrast, thapsigargin did not blockdepotentiationof LTP by 1 Hz LFS, suggesting that LTP causes a reduction in the threshold [Ca2+] necessary for LTD. Selective depletion of the ryanodine receptor-gated Ca2+pool by bath application of ryanodine (10 μm) also blocked the induction of LTD, indicating a requirement for Ca2+-induced Ca2+release. Impalement of CA1 pyramidal neurons with microelectrodes containing thapsigargin (500 nmto 200 μm) prevented the induction of LTD at synapses on that neuron without blocking LTD in the rest of the slice. In contrast, similar filling of CA1 pyramidal neurons with ryanodine (2 μmto 5 mm) did not block the induction of LTD. From these data, we conclude that the induction of LTD requires release of Ca2+both from apresynapticryanodine-sensitive pool and frompostsynaptic(presumably IP3-gated) stores.
Specific Domains of β-Amyloid from Alzheimer Plaque Elicit Neuron Killing in Human Microglia
Authors: Giulian Dana , Haverkamp Lanny J. , Yu J. H. , Karshin William , Tom D. , Li Jun , Kirkpatrick Joel , Kuo Y.-M. , Roher A. E.
Published: April 2018

Alzheimer’s disease (AD) is found to have striking brain inflammation characterized by clusters of reactive microglia that surround senile plaques. A recent study has shown that microglia placed in contact with isolated plaque fragments release neurotoxins. To explore further this process of immunoactivation in AD, we fractionated plaque proteins and tested for the ability to stimulate microglia. Three plaque-derived fractions, each containing full-length native Aβ1-40 or Aβ1-42 peptides, elicited neurotoxin release from microglia. Screening of various synthetic peptides (Aβ1-16, Aβ1-28, Aβ12-28, Aβ25-35, Aβ17-43, Aβ1-40, and Aβ1-42) confirmed that microglia killed neurons only after exposure to nanomolar concentrations of human Aβ1-40 or human Aβ1-42, whereas the rodent Aβ1-40 (5Arg→Gly, 10Tyr→Phe, 13His→Arg) was not active. These findings suggested that specific portions of human Aβ were necessary for microglia–plaque interactions. When coupled to microspheres, N-terminal portions of human Aβ (Aβ1-16, Aβ1-28, Aβ12-28) provided anchoring sites for microglial adherence whereas C-terminal regions did not. Although itself not toxic, the 10–16 domain of human Aβ was necessary for both microglial binding and activation. Peptide blockade of microglia–plaque interactions that occur in AD might prevent the immune-driven injury to neurons.
Lipocalin-Type Prostaglandin D Synthase (β-Trace) Is Located in Pigment Epithelial Cells of Rat Retina and Accumulates within Interphotoreceptor Matrix
Authors: Beuckmann Carsten T. , Gordon William C. , Kanaoka Yoshihide , Eguchi Naomi , Marcheselli Victor L. , Gerashchenko Dimitry Y. , Urade Yoshihiro , Hayaishi Osamu , Bazan Nicolas G.
Published: April 2018

Glutathione-independent prostaglandin D synthase, identical to β-trace, (a major CSF protein), is localized in the CNS. This enzyme, lipocalin-type prostaglandin D synthase, is a member of the lipocalin family of secretory proteins that transport small lipophilic substances. This enzyme’s activity in adult rat retina was enriched sixfold in retinal pigment epithelium (RPE) and even more in interphotoreceptor matrix (IPM), all higher than brain. Western blots with anti-lipocalin-type prostaglandin D synthase showed three distinct immunoreactive bands. In the retinal cytosolic fraction, only one band was observed (Mr25,000); in IPM, the larger component occurred (Mr26,000). The RPE membrane-bound fraction showed two bands (Mr20,000 and 23,000), indicating synthesis, and the cytosolic fraction contained two bands (Mr23,000 and 26,000), indicating modification for release into IPM. At least two glycosylation sites occurred on the prostaglandin D synthase moiety, explaining the three immunoreactive bands in Western blots. Immunohistochemistry with polyclonal antibodies against this lipocalin-type enzyme showed intense localization in RPE, but less in photoreceptor outer and inner segments.In situhybridization showed mRNA specifically expressed in RPE. Thus, lipocalin-type prostaglandin D synthase is predominantly expressed in RPE and actively accumulated in IPM. This may demonstrate gene sharing because, while catalyzing prostaglandin D2synthesis, it may perform an additional, unrelated role in IPM. This enzyme is secreted from the RPE into IPM from which it is then taken up by photoreceptors. However, the nature of its ligand(s) is not known; they may be retinoids and/or docosahexanoic acid.
Rin, a Neuron-Specific and Calmodulin-Binding Small G-Protein, and Rit Define a Novel Subfamily of Ras Proteins
Authors: Lee Ching-Hsien J. , Della Neil G. , Chew Christina E. , Zack Donald J.
Published: April 2018

cDNAs encoding two novel 25 kDa Ras-like proteins, Rit and Rin, were isolated from mouse retina using a degenerate PCR-based cloning strategy. Using the expressed sequence tag database, human orthologs were also obtained and sequenced. The protein sequences of Rit and Rin, which are 64% identical, are more similar to each other than to any known Ras protein. Their closest homologs in the databases areMucor racemosusRas2 and Ras3, to which they show ∼48% identity. Rit and Rin both bind GTPin vitro. An unusual feature of their structure is that they lack a known recognition signal for C-terminal lipidation, a modification that is generally necessary for plasma membrane association among the Ras subfamily of proteins. Nonetheless, transiently expressed Rit and Rin are plasma membrane-localized. Both proteins contain a C-terminal cluster of basic amino acids, which could provide a mechanism for membrane association. Deletion analysis suggested that this region is important for Rit membrane binding but is not necessary for Rin. Rit, like most Ras-related proteins, is ubiquitously expressed. Rin, however, is unusual in that it is expressed only in neurons. In addition, Rin binds calmodulin through a C-terminal binding motif. These results suggest that Rit and Rin define a novel subfamily of Ras-related proteins, perhaps using a new mechanism of membrane association, and that Rin may be involved in calcium-mediated signaling within neurons.
Changes in the Regulatory Effects of Cell–Cell Interactions on Neuronal AChR Subunit Transcript Levels after Synapse Formation
Authors: Levey Marjory S. , Jacob Michele H.
Published: April 2018

Nicotinic acetylcholine receptors (AChRs) mediate excitatory synaptic transmission in the chick ciliary ganglion. AChR protein and mRNA levels are increased by both innervation and retrograde signals from target tissues during synapse formation. We now show that AChR α3, β4, and α5 subunit transcript levels stop increasing after synaptogenesis. Moreover, maintenance of these mRNA levels requires the continued presence of regulatory signals from both pre- and postganglionic tissues. Unilateral preganglionic denervation or postganglionic axotomy causes declines in α3, β4, and α5 transcript levels, ranging from twofold to 3.5-fold, relative to contralateral control neuron values in newly hatched chicks. The reductions are not merely an injury response; cβ4-tubulin mRNA levels are not affected by either axotomy or denervation. Further, similar decreases in AChR mRNA levels are observed after local application of colchicine to the postganglionic nerves, which blocks fast transport without disturbing axonal integrity. These results also demonstrate a developmental change in the regulatory effects of target tissues. Reductions in α5 mRNA levels caused by axotomy or colchicine treatment after peripheral synapse formation contrast with the lack of an effect on α5 when synapse formation with the target tissue is prevented. The ability of the target tissue to regulate α5 mRNA levels after synaptogenesis is interesting, because this subunit may be necessary for the formation of high-conductance AChRs. The specific regulatory effects of target tissues and inputs at different developmental stages demonstrate that neurons continually depend on signals from their pre- and postsynaptic tissues to accomplish mature levels of AChR subunit expression and optimal functioning of that neuronal circuit.
Functional Organization for Direction of Motion and Its Relationship to Orientation Maps in Cat Area 18
Authors: Shmuel Amir , Grinvald Amiram
Published: April 2018

The goal of this study was to explore the functional organization of direction of motion in cat area 18. Optical imaging was used to record the activity of populations of neurons. We found a patchy distribution of cortical regions exhibiting preference for one direction over the opposite direction of motion. The degree of clustering according to preference of direction was two to four times smaller than that observed for orientation. In general, direction preference changed smoothly along the cortical surface; however, discontinuities in the direction maps were observed. These discontinuities formed lines that separated pairs of patches with preference for opposite directions. The functional maps for direction and for orientation preference were closely related; typically, an iso-orientation patch was divided into regions that exhibited preference for opposite directions, orthogonal to the orientation. In addition, the lines of discontinuity within the direction map often connected points of singularity in the orientation map. Although the organization of both domains was related, the direction and the orientation selective responses were separable; whereas the selective response according to direction of motion was nearly independent of the length of bars used for visual stimulation, the selective response to orientation decreased significantly with decreasing length of the bars. Extensive single and multiunit electrical recordings, targeted to selected domains of the functional maps, confirmed the features revealed by optical imaging. We conclude that significant processing of direction of motion is performed early in the cat visual pathway.
Dynamics of Induction and Expression of Long-Term Synaptic Facilitation inAplysia
Authors: Mauelshagen Juliane , Parker Gretchen R. , Carew Thomas J.
Published: April 2018

Serotonin (5HT)-induced short-term facilitation and long-term facilitation (STF and LTF) of the monosynaptic connection between tail sensory neurons (SNs) and motor neurons (MNs) inAplysiahave been useful in delineating possible cellular mechanisms contributing to short-term and long-term memory. Previous work from our laboratory showed that LTF can be produced in the absence of STF, suggesting that these processes may be functionally independent. In the present study, we explored this hypothesis by examining the temporal relationship between STF and LTF. We recorded intracellularly from pairs of monosynaptically connected SNs and MNs in isolated pleural–pedal ganglia. In the first experimental series, we followed the time course of LTF across a 24 hr period after its induction by five applications of 10 μm5HT. STF completely decayed to baseline several hours before the expression of LTF. This biphasic expression profile of STF and LTF further supports the hypothesis that LTF is not a simple elaboration of STF. In the second experimental series, we monitored the immediate expression of facilitation during and after different numbers of 5HT applications. We identified a rapidly decaying STF (lasting 15–30 min) after one to four pulses of 50 μm5HT and a unique, prolonged intermediate-term facilitation (ITF; lasting up to 90 min) after five pulses of 50 μm5HT. These results raise the possibility that STF, ITF, and LTF may reflect components of different memory phases in the intact animal.
Role of Monkey Nucleus Reticularis Tegmenti Pontis in the Stabilization of Listing’s Plane
Authors: Van Opstal John , Hepp Klaus , Suzuki Yasuo , Henn Volker
Published: April 2018

An important problem in motor control is how the nervous system deals with redundant degrees of freedom. It has been well documented that voluntary eye movements are constrained to a plane by Listing’s law. Recent evidence has indicated that Listing’s law is implemented downstream from the motor superior colliculus (SC), but controversy exists whether this synergy results from a neural control mechanism or from passive mechanical properties of the oculomotor plant. To address this problem, we have investigated the role of the caudal nucleus reticularis tegmenti pontis (cNRTP), which is functionally positioned inbetween the SC and cerebellar vermis, in the three-dimensional (3-D) control of saccades. In three rhesus monkeys, 3-D eye movements were measured while recording from single units in the cNRTP. In contrast to the SC, movement fields of cNRTP cells were best described by 3-D eye displacement vectors. We also performed electrical microstimulation with the eyes starting from a large range of initial eye positions. Evoked movements were always ipsilaterally directed but were often endowed with a fixed torsional component in either the positive or the negative direction. In two monkeys, small amounts of muscimol were unilaterally injected into the cNRTP. The results of these experiments strongly suggest that the cNRTP contributes to the stabilization of Listing’s plane against torsional errors of the saccadic system. It is concluded, therefore, that the saccadic burst generator is 3-D, and that Listing’s law is at least partially implemented by a neural control strategy.
Contextual Modulation in Primary Visual Cortex
Authors: Zipser Karl , Lamme Victor A. F. , Schiller Peter H.
Published: April 2018

We studied extra-receptive field contextual modulation in area V1 of awake, behaving macaque monkeys. Contextual modulation was studied using texture displays in which texture covering the receptive field (RF) was the same in all trials, but the perceptual context of this texture could vary depending on the configuration of extra-RF texture elements. We found robust contextual modulation when disparity, color, luminance, and orientation cues variously defined a textured figure centered on the RF of V1 neurons. We found contextual modulation to have a spatial extent of ∼8 to 10° diameter parafoveally. Contextual modulation correlated with perceptual experience of both binocularly rivalrous texture displays and of displays with a simple example of surface occlusion. We found contextual modulation in V1 to have a characteristic latency of 80–100 msec after stimulus onset, potentially allowing feedback from extrastriate areas to underlie to this effect.
Metaphase Spindles Rotate in the Neuroepithelium of Rat Cerebral Cortex
Authors: Adams Richard J.
Published: April 2018

Time-lapse confocal microscopy has been used to image cells in mitosis at the apical surface of neuroepithelium from the rat cerebral cortex during the period of neurogenesis. Staining with vital chromatin dyes reveals that mitotic spindles that are aligned parallel to the surface of the tissue are highly motile, rotating within the plane of the epithelium throughout metaphase, and come to rest only as anaphase begins. Spindles may make several complete turns, parallel to the epithelium, but only rarely tumble into an orientation perpendicular to the epithelial sheet. Analysis shows that spindles do not rotate randomly; rather, they spend most of their time aligned parallel or antiparallel to the direction in which they will later enter anaphase and undergo cell division. This conclusion is strongly supported by statistical analyses of the data. Stereotyped movements of this kind show that the direction of division is determined early in mitosis. This suggests the existence of intracellular and perhaps intercellular signals that define the polarity of the cell both in the apico–basal direction and within the plane of the epithelium. Such mechanisms may be important for maintaining the structure of the epithelium and cell–cell communication during development and may also provide a mechanism for the precise distribution of cytoplasmic determinants that might influence the fate of the daughter cells at a time when neuronal fate is being determined.
TheDrosophila ergK+Channel Polypeptide Is Encoded by the Seizure Locus
Authors: Titus Steven A. , Warmke Jeffrey W. , Ganetzky Barry
Published: April 2018

Theeagfamily of K+channels contains three known subtypes:eag,elk, anderg. Genes representing the first two subtypes have been identified in flies and mammals, whereas the third subtype has been defined only by the human HERG gene, which encodes an inwardly rectifying channel that is mutated in some cardiac arrhythmias. To establish the predicted existence of aDrosophilagene in theergsubfamily and to learn more about the structure and biological function of channels within this subfamily, we undertook a search for theDrosophilacounterpart of HERG. Here we report the isolation and characterization of theDrosophila erggene. We show that it corresponds with the previously identified seizure (sei) locus, mutations of which cause a temperature-sensitive paralytic phenotype associated with hyperactivity in the flight motor pathway. These results yield new insights into the structure and evolution of theeagfamily of channels, provide a molecular explanation for theseimutant phenotype, and demonstrate the important physiological roles oferg-type channels from invertebrates to mammals.
Song- and Order-Selective Neurons in the Songbird Anterior Forebrain and their Emergence during Vocal Development
Authors: Doupe Allison J.
Published: April 2018

Auditory experience is critical for vocal learning in songbirds as in humans. Therefore, in a search for neural mechanisms for song learning and recognition, the auditory response properties of neurons in the anterior forebrain (AF) pathway of the songbird brain were investigated. This pathway plays an essential but poorly understood role during the period of song development when auditory feedback is most crucial.

Single-unit recordings demonstrated that both the lateral magnocellular nucleus of the anterior neostriatum (LMAN) and Area X (X) contain auditory neurons in adult male finches. These neurons are strongly selective for both spectral and temporal properties of song; they respond more robustly to the bird’s own song (BOS) than to songs of conspecific individuals, and they respond less well to the BOS if it is played in reverse. In addition, X neurons are more broadly responsive than LMAN neurons, suggesting that responses to song become progressively more refined along this pathway.

Both X and LMAN of young male finches early in the process of song learning (30–45 d old) also contain song-responsive auditory neurons, but these juvenile neurons lack the song and order selectivity present in adult birds. The spectral and temporal selectivity of the adult AF auditory neurons therefore arises during development in neurons that are initially broadly song-responsive. These neurons provide one of the clearest examples of experience-dependent acquisition of complex stimulus selectivity. Moreover, the auditory properties of the AF circuit suggest that one of its functions may be to mediate the auditory learning and feedback so essential to song development.
Morphological Alterations in the Peripheral and Central Nervous Systems of Mice Lacking Glial Cell Line-Derived Neurotrophic Factor (GDNF): Immunohistochemical Studies
Authors: Granholm Ann-Charlotte E. , Srivastava Nisha , Mott Justin L. , Henry Stephanie , Henry Michael , Westphal Heiner , Pichel Jose G. , Shen Liya , Hoffer Barry J.
Published: April 2018

Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-β superfamily of growth factors with neurotrophic activity on midbrain dopaminergic neurons and on developing and mature motoneurons of the brainstem and spinal cord. To investigate the extent of GDNF dependency of central and peripheral nervous structures during development, we have performed an immunohistochemical analysis of sections from the whole head including brain, peripheral ganglia, developing teeth and tongue, as well as intestines, in mutant mice lacking a part of the third exon that encodes the GDNF protein. As described previously, these null-mutated mice lack most of the enteric nerve plexus and are subject to agenesis or severe dysgenesis of the kidneys. In the present communication, we examined the development of vibrissae and incisor and molar teeth, as well as the innervation of these structures, and found no differences between null-mutated and control mice. A decrease in the immunohistochemical labeling intensity with tyrosine hydroxylase was observed in the superior cervical ganglion (SCG), as well as in the pontine nucleus locus coeruleus, and the sympathetic innervation of blood vessels and glands in the head was significantly decreased. None of the brain nuclei studied exhibited any significant decreases in the total number of neurons, but the packing density of neurons in the nucleus locus coeruleus was decreased. These data indicate that GDNF might be one neurotrophic factor that contributes to the development of central and peripheral noradrenergic neurons.
A Five Minute Experience in the Elevated Plus-Maze Alters the State of the Benzodiazepine Receptor in the Dorsal Raphe Nucleus
Authors: Gonzalez Luis E. , File Sandra E.
Published: April 2018

A single 5 min exposure to the elevated plus-maze test of anxiety renders animals insensitive to the anxiolytic effects of the benzodiazepines in this test. The purpose of the present experiments was to explore whether this phenomenon resulted from a change in the functional state of benzodiazepine receptors in the dorsal raphe nucleus. The benzodiazepine receptor agonist midazolam (0.5, 1, and 2 μg) and antagonist flumazenil (100 and 500 ng) were directly administered to the dorsal raphe nucleus in rats either naive to, or with one previous 5 min exposure of, the elevated plus-maze. In naive rats, midazolam produced significant anxiolytic effects at all doses, and flumazenil was silent. In plus-maze-experienced rats, midazolam no longer had anxiolytic effects in the plus-maze, but flumazenil did, indicating that the previous experience of the maze had changed the state of the benzodiazepine receptor. This changed receptor function generalized to the social interaction test. Thus, in naive animals tested in high light, midazolam (0.5, 1, and 2 μg) had significant anxiolytic effects and flumazenil (100 and 500 ng) was silent, whereas in plus-maze-experienced rats both midazolam (1 μg) and flumazenil (500 ng) had significant anxiolytic effects. Extensive analysis of locomotor activity in both tests showed that the changed responsivity to midazolam could not be explained by habituation, because on none of the measures used was there any difference in motor activity scores between plus-maze-naive and experienced rats.
Evoked Excitability Changes at the Terminals of Midlumbar Premotor Interneurons in the Cat Spinal Cord
Authors: Aggelopoulos N. C. , Chakrabarty S. , Edgley S. A.
Published: April 2018

We present evidence that the electrical excitability of the terminals of a group of spinal premotor interneurons can be increased after stimulation of sensory afferents. The interneurons were located in the midlumbar segments of the spinal cord and had projections to the lower lumbar motor nuclei. Thresholds for antidromic activation of a substantial number of interneurons were reduced after electrical stimulation of group II muscle afferents. Several observations suggest that the excitability changes are unlikely to have arisen from electrotonic spread of depolarization from the interneuron soma to its terminals or by environmental changes in the vicinity of the terminals related to neuronal activity. A particularly interesting possibility is that the excitability of the central terminals of the interneurons is increased because they are depolarized by a mechanism similar to that acting at the terminals of primary sensory afferents (primary afferent depolarization, PAD), which accompanies one type of presynaptic inhibition. This type of presynaptic action has been shown in premotor interneurons in the lamprey but not in the mammalian spinal cord. From our observations the organization of the systems generating excitability changes at the interneuron terminals seem in general to parallel the organization of the systems generating PAD at afferent terminals, raising the possibility that common principles might underlie the operation of this form of presynaptic control.
Frequency-Dependent Inactivation of Mammalian A-Type K+Channel KV1.4 Regulated by Ca2+/Calmodulin-Dependent Protein Kinase
Authors: Roeper Jochen , Lorra Christoph , Pongs Olaf
Published: April 2018

Ca2+/calmodulin dependent protein kinase (CaMKII) and protein phosphatase 2B (calcineurin) are key enzymes in the regulation of synaptic strength, controlling the phosphorylation status of pre- and postsynaptic target proteins. Here, we show that the inactivation gating of theShaker-related fast-inactivating KVchannel, Kv1.4 is controlled by CaMKII and the calcineurin/inhibitor-1 protein phosphatase cascade. CaMKII phosphorylation of an amino-terminal residue of KV1.4 leads to slowing of inactivation gating and accelerated recovery from N-type inactivated states. In contrast, dephosphorylation of this residue induces a fast inactivating mode of KV1.4 with time constants of inactivation 5 to 10 times faster compared with the CaMKII-phosphorylated form. Dephosphorylated KV1.4 channels also display slowed and partial recovery from inactivation with increased trapping of KV1.4 channels in long-absorbing C-type inactivated states. In consequence, dephosphorylated KV1.4 displays a markedly increased tendency to undergo cumulative inactivation during repetitive stimulation. The balance between phosphorylated and dephosphorylated KV1.4 channels is regulated by changes in intracellular Ca2+concentration rendering KV1.4 inactivation gating Ca2+-sensitive. The reciprocal CaMKII and calcineurin regulation of cumulative inactivation of presynaptic KV1.4 may provide a novel mechanism to regulate the critical frequency for presynaptic spike broadening and induction of synaptic plasticity.
Attention to One or Two Features in Left or Right Visual Field: A Positron Emission Tomography Study
Authors: Vandenberghe Rik , Duncan John , Dupont Patrick , Ward Robert , Poline Jean-Baptiste , Bormans Guy , Michiels Johan , Mortelmans Luc , Orban Guy A.
Published: April 2018

In human vision, two features of the same object can be identified concurrently without loss of accuracy. Performance declines, however, when the features belong to different objects in opposite visual fields. We hypothesized that different positron emission tomography activation patterns would reflect these behavioral results. We first delineated an attention network for single discriminations in left or right visual field and then compared this with the activation pattern when subjects divided attention over two features of a single object or over two objects in opposite hemifields. When subjects attended to a single feature, parietal, premotor, and anterior cingulate cortex were activated. These effects were strongest in the right hemisphere and were, remarkably, unaffected by the direction of attention. In contrast, direction of attention affected occipital and frontal activity: right occipital and left lateral frontal activity were higher with attention to the left, whereas right lateral frontal activity was higher with attention to the right. When subjects identified two features of the same object, parietal, premotor, and anterior cingulate activity was enhanced further, predominantly this time in the left hemisphere. Again, there was no direction sensitivity. Direction-sensitive activation of lateral frontal cortex also was increased. Finally, when subjects divided their attention over opposite hemifields, activity in the direction-sensitive occipital and frontal regions fell to a level midway between those seen during exclusively leftward or rightward attention. Thus, the behavioral efficiency with which we attend to multiple features of a single peripheral object is paralleled by enhanced activity in structures generally active during peripheral selective attention as well as in structures that depend on the specific direction of attention, most notably lateral frontal cortex. In addition, in the direction-sensitive regions, dividing attention over hemifields causes a compromise pattern between the extreme levels obtained during unilateral attention.