bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesencephalic Substrate of Reward: Axonal Connections
Authors: Boye Sandra M. , Rompré Pierre-Paul 
Published: April 2018

The behavioral version of the collision technique was used to study the existence of axonal linkage between reward-relevant sites in the ventral tegmental area (VTA) and posterior mesencephalon (PM) in six rats trained to self-administer trains of electrical brain stimulation. The combined use of fixed and moveable stimulation electrodes allowed us to carry out collision tests at a total of 46 different combinations of VTA-PM sites, and collision-like effects were observed at 24 of these. Stimulation of the VTA and the most caudal PM sites generally resulted in collision curves that were characterized by a single increase in paired-pulse effectiveness (E-values), whereas recovery in those collision curves obtained from stimulation of the VTA and more rostral PM sites was generally slower, and often characterized by a double rise. Despite little variability in interelectrode distances (1.0–3.8 mm), collision intervals varied widely, ranging from 1.5 to 7.3 msec. Recovery from refractoriness (initial 25%) was also estimated and ranged from 0.7 to 1.0 msec, resulting in conduction-time estimates of 0.7–6.3 msec. The lack of correspondence between interelectrode distances and conduction times suggests the presence of axonal branching. Results of this study constitute the first behavioral evidence of a reward-relevant axonal link between the VTA and the PM. In addition, the finding that in one animal the anterior electrode was located within the posterior portion of the lateral hypothalamus (LH) suggests that the reward-relevant axonal bundle linking the LH and VTA may extend as far back as the caudal regions of the PM.
Selective Effects of Nerve Growth Factor on Spatial Recent Memory as Assessed by a Delayed Nonmatching-to-Position Task in the Water Maze
Authors: Markowska Alicja L. , Price Donald , Koliatsos Vassilis E. 
Published: April 2018

Nerve growth factor (NGF) ameliorates age-related deficits in certain types of memory in rats. Although the effects of NGF on reference memory are well documented, the influence of NGF on recent memory is less well understood. The issue of recent memory is of primary importance in the design of therapies for cognitive disorders, because this type of memory is impaired in elderly humans and is severely affected early in the course of Alzheimer’s disease (AD). The present study was designed to evaluate the effects of NGF on recent memory in a task that used escape from water as the motivating stimulus and used the same design as forced-choice recognition tasks given to humans. Fischer-344 rats, 4 months old (4MO) or 23 months old (23MO), were pretested in a new spatial recent memory task designed for the Morris water maze, a delayed nonmatching-to-position task, and infused intraventricularly with recombinant human NGF or vehicle. After 2 weeks of NGF infusion, no substantial changes in behavior were observed in either age group. However, NGF treatment extended over 4 weeks improved considerably the choice accuracy of 23MO rats to a level similar to the performance of 4MO rats. These results, together with our previous work (Markowska et al., 1994), indicate that the effects of NGF on spatial recent memory are more intense than on spatial reference memory. NGF suppressed the body weight gain in 4MO rats but did not affect 23MO rats. In 23MO rats, NGF mildly counteracted age-related deficits in inhibitory avoidance, but did not have an effect in young rats.
A Novel Type of Programmed Neuronal Death in the Cervical Spinal Cord of the Chick Embryo
Authors: Yaginuma Hiroyuki , Tomita Misako , Takashita Noriko , McKay Sharen E. , Cardwell Chareba , Yin Qin-Wei , Oppenheim Ronald W. 
Published: April 2018

We examined the massive early cell death that occurs in the ventral horn of the cervical spinal cord of the chick embryo between embryonic days 4 and 5 (E4 and E5). Studies with immunohistochemistry,in situhybridization, and retrograde-tracing methods revealed that many dying cells express Islet proteins andLim-3mRNA (motoneuron markers) and send their axons to the somatic region of the embryo before cell death. Together, these data strongly suggest that the dying cells are somatic motoneurons. Cervical motoneurons die by apoptosis and can be rescued by treatment with cycloheximide and actinomycin D. Counts of motoneuron numbers between E3.5 and E10 revealed that, in addition to cell death between E4 and E5, motoneuron death also occurs between E6 and E10 in the cervical cord. Studies with [3H]thymidine autoradiography and morphological techniques revealed that in the early cell-death phase (E4–E5), genesis of motoneurons, axonal elongation, and innervation of muscles is still ongoing. However, studies with [3H]thymidine autoradiography also revealed that the cells dying between E4 and E5 become postmitotic before E3.5. Increased size of peripheral targets, treatment with neuromuscular blockade, and treatment with partially purified muscle or brain extracts and defined neurotrophic agents, such as NGF, BDNF, neurotrophin-3, CNTF, bFGF, PDGF, S100-β, activin, cholinergic differentiation factor/leukemia inhibitory factor, bone morphogenetic protein-2, IGF-I, interleukin-6, and TGF-β1, were all ineffective in rescuing motoneurons dying between E4 and E5. By contrast, motoneurons that undergo programmed cell death atlaterstages (E6–E10) in the cervical cord are target-dependent and respond to activity blockade and trophic factors. Experimental approaches revealed that early cell death also occurs in a notochord-induced ectopic supernumerary motoneuron column in the cervical cord. Transplantation of the cervical neural tube to other segmental regions failed to alter the early death of motoneurons, whereas transplantation of other segments to the cervical region failed toinduceearly motoneuron death. These results suggest that the mechanisms that regulate motoneuron death in the cervical spinal cord between E4 and E5 are independent of interactions with targets. Rather, this novel type of cell death seems to be determined by signals that either are cell-autonomous or are derived from other cellswithinthe cervical neural tube.
Modulation of a Neural Network by Physiological Levels of Oxygen in Lobster Stomatogastric Ganglion
Authors: Massabuau Jean-Charles , Meyrand Pierre 
Published: April 2018

Although a large body of literature has been devoted to the role of O2in the CNS, how neural networks function during long-term exposures to low but physiological O2partial pressure (Po2) has never been studied. We addressed this issue in crustaceans, where arterial blood Po2is set in the 1–3 kPa range, a level that is similar to the most frequently measured tissue Po2in the vertebrate CNS. We demonstrate that over its physiological range, O2can reversibly modify the activity of the pyloric network in the lobsterHomarus gammarus. This network is composed of 12 identified neurons that spontaneously generate a triphasic rhythmic motor outputin vitroas well asin vivo. When Po2decreased from 20 to 1 kPa, the pyloric cycle period increased by 30–40%, and the neuronal pattern was modified. These effects were all dose- and state-dependent. Specifically, we found that the single lateral pyloric (LP) neuron was responsible for the O2-mediated changes. At low Po2, the LP burst duration increased without change in its intraburst firing frequency. Because LP inhibits the pyloric pacemaker neurons, the increased LP burst duration delayed the onset of each rhythmic pacemaker burst, thereby reducing significantly the cycling frequency. When we deleted LP, the network was no longer O2-sensitive.In conclusion, we propose that (1) O2has specific neuromodulator-like actions in the CNS and that (2) the physiological role of this reduction of activity and energy expenditure could be a key adaptation for tolerating low but physiological Po2in sensitive neural networks.
Structure, Functional Expression, and Cerebral Localization of the Levocabastine-Sensitive Neurotensin/Neuromedin N Receptor from Mouse Brain
Authors: Mazella Jean , Botto Jean-Marie , Guillemare Eric , Coppola Thierry , Sarret Philippe , Vincent Jean-Pierre 
Published: April 2018

This work describes the cloning and expression of the levocabastine-sensitive neurotensin (NT) receptor from mouse brain. The receptor protein comprises 417 amino acids and bears the characteristics of G-protein-coupled receptors. This new NT receptor (NTR) type is 39% homologous to, but pharmacologically distinct from, the only other NTR cloned to date from the rat brain and the human HT29 cell line. When the receptor is expressed inXenopus laevisoocytes, the H1 antihistaminic drug levocabastine, like NT and neuromedin N, triggers an inward current. The pharmacological properties of this receptor correspond to those of the low-affinity, levocabastine-sensitive NT binding site described initially in membranes prepared from rat and mouse brain. It is expressed maximally in the cerebellum, hippocampus, piriform cortex, and neocortex of adult mouse brain.
Enhanced Fast Synaptic Transmission and a Delayed Depolarization Induced by Transient Potassium Current Blockade in Rat Hippocampal Slice as Studied by Optical Recording
Authors: Barish Michael E. , Ichikawa Michinori , Tominaga Takashi , Matsumoto Gen , Iijima Toshio 
Published: April 2018

In hippocampal neurons, a slowly inactivating aminopyridine-sensitive transient potassium current, D-current, influences the time course of action potential repolarization and therefore activity-dependent Ca2+entry. We used high-speed optical recording techniques to study the effects of selectively inhibiting D-current with 4-AP (40 μm) on transmission at the Schaffer collateral (CA3)-CA1 synapse in rat hippocampal slices stained with the voltage-sensitive dye RH-155. We observed that addition of 4-AP to the bathing solution resulted in (1) augmentation of a fast component of the optical signal corresponding to the postsynaptic EPSP and action potential, and (2) the appearance of a delayed depolarization of CA1 neurons and other adjacent cells. 4-AP appeared to alter the presynaptic action potential and the dynamics of synaptic transmission to both reduce the sensitivity of the postsynaptic EPSP and action potential to ω-toxin calcium channel blockers (ω-conotoxin GVIA and ω-agatoxin IVA) and the Ca2+-dependent potassium channel blocker charybdotoxin, and to increase sensitivity to the dihydropyridine nifedipine, the NMDA receptor blocker aminophosphonopentanoic acid, and the intracellular Ca2+release inhibitor thapsigargin. The delayed depolarization induced by 4-AP was inhibited in hyperosmotic extracellular solution, suggesting that enhanced transmitter release resulted in increased accumulation of K+in the extracellular space. Because 4-AP is a convulsant at concentrations similar to those used here, we suggest that the 4-AP-targeted channel(s) carrying D-current may contribute to the hyperexcitability associated with epilepsy.
Development of an Identified Spinal Commissural Interneuron Population in an Amniote: Neurons of the Avian Hofmann Nuclei
Authors: Eide Anne Lill , Glover Joel C. 
Published: April 2018

The commissural interneurons of the Hofmann nuclei (HN) of the avian spinal cord (The axonal projections of the Hofmann nuclei in the spinal cord of the late stage chicken embryo, Anat Embryol (Berl), A. L. Eide, 1996, Vol 193, pp 543–557) provide a unique opportunity to describe the development of an identified spinal commissural axon projection and its terminal collaterals in an amniote vertebrate. Here, we use the lipophilic tracer DiI to label these and other commissural projections anterogradely and retrogradely from the time the HN neurons are born. [3H]thymidine birthdating shows that the final mitoses of HN neurons occur at stages 21–24 [developmental day (d) 4]. By direct comparison, this follows the generation of motoneurons and of large, dorsally located commissural interneurons. The first HN neurons reach the ventrolateral margin of the spinal cord by d6 by a radial migration through the ventral horn. Radial migration occurs after the extension of HN axons across the midline. Thus, HN neurons are determined to be commissural interneurons before attaining their definitive locations. The HN neurons subsequently aggregate into segmentally iterated clusters at the ventrolateral margin of the spinal cord by d8. Also by d8 their longitudinal axons attain mature extent in the ventral funiculus of the contralateral side and begin to sprout collaterals. The collaterals are directed predominantly toward the medial aspect of the ventral horn at all stages, forming by d12 a dense thicket of terminals that thins out over several segments to each side of the HN of origin. The initial direction of collateral outgrowth is largely appropriate for the mature termination pattern of the HN. Terminal arbors, however, are less focused at early developmental stages than at later stages.
Cholinergic Stimulation of AP-1 and NFκB Transcription Factors Is Differentially Sensitive to Oxidative Stress in SH-SY5Y Neuroblastoma: Relationship to Phosphoinositide Hydrolysis
Authors: Li Xiaohua , Song Ling , Jope Richard S. 
Published: April 2018

Oxidative stress appears to contribute to neuronal dysfunction in a number of neurodegenerative conditions, notably including Alzheimer’s disease, in which cholinergic receptor-linked signal transduction activity is severely impaired. To test whether oxidative stress could contribute to deficits in cholinergic signaling, responses to carbachol were measured in human neuroblastoma SH-SY5Y cells exposed to H2O2. DNA binding activities of two transcription factors that are respondent to oxidative conditions, AP-1 and NFκB, were measured in nuclear extracts. H2O2and carbachol individually induced dose- and time-dependent increases in AP-1 and NFκB. In contrast, when given together, H2O2concentration dependently (30–300 μm) inhibited the increase after carbachol in AP-1. Carbachol’s stimulation of NFκB was not inhibited except with a high concentration (300 μm) of H2O2, which was associated with impaired activation of protein kinase C. Lower concentrations of H2O2(30–300 μm) inhibited carbachol-induced [3H]phosphoinositide hydrolysis, and this inhibition correlated (r = 0.95) with the inhibition of carbachol-induced AP-1. Activation of [3H]phosphoinositide hydrolysis by the calcium ionophore ionomycin was unaffected by H2O2, indicating that phospholipase C and phosphoinositides were impervious to this treatment. In contrast, activation with NaF of G-proteins coupled to phospholipase C was concentration dependently inhibited by H2O2, indicating impaired G-protein function. These effects of H2O2are similar to signaling impairments reported in Alzheimer’s disease brain, which involve deficits in receptor- and G-protein-stimulated phosphoinositide hydrolysis, but not phospholipase C activity. Thus, these findings indicate that oxidative stress may contribute to impaired phosphoinositide signaling in neurological disorders in which oxidative stress occurs, and that oxidative stress can differentially influence transcription factors activated by cholinergic stimulation.
Microtubule Assembly in Growing Dendrites
Authors: Wang Jun , Yu Wenqian , Baas Peter W. , Black Mark M. 
Published: April 2018

Dendritic microtubules (MTs) are nonuniform with respect to polarity orientation, with roughly equal proportions having a plus-end-distal or minus-end-distal orientation. In the present studies, we have microinjected biotin-labeled tubulin (Bt–tub) into cultured sympathetic neurons extending dendrites to explore the contribution of MT assembly to the elaboration and maintenance of the dendritic MT array. Within minutes of injecting Bt–tub, an enormous number of MTs were seen emanating from a point source in the cell body. Over time, this pattern changed such that by 120 min after injection, biotinylated MTs no longer emanated from a discrete site, but were distributed over a broad region that extended from the cell body into the dendrites. The observation that biotinylated MTs emanate from a point source in the soma at relatively short times after injection, but not at longer times, suggests that they undergo a redistribution subsequent to their initial nucleation rather than a simple radial expansion from the somal nucleation site. Bt–tub assembly also occurred in dendrites but, unlike in the cell body, assembly was dispersed throughout the dendrite rather than emanating from a discrete site. Immunoelectron microscopic analyses revealed that assembly in dendrites reflected the addition of Bt–tub onto the ends of both plus-end-distal and minus-end-distal MTs that existed in the cell at the time of injection. The time course of Bt–tub appearance in dendritic MTs suggested an average half-life of ∼76 min for these MTs. We discuss these observations in the context of a model for generating the MT array of dendrites that combines both MT transport and MT assembly.
Consequences of Trisomy 16 for Mouse Brain Development: Corticogenesis in a Model of Down Syndrome
Authors: Haydar Tarik F. , Blue Mary E. , Molliver Mark E. , Krueger Bruce K. , Yarowsky Paul J. 
Published: April 2018

We have studied abnormalities in the tangential and radial expansion of the cerebral cortex during fetal development in the trisomy 16 (Ts16) mouse, a model for human trisomy 21 (Down syndrome). Slowed tangential expansion of the neuroepithelium in Ts16 resulted in a reduction of final telencephalic size and is predicted to decrease the number of radial cortical units in the mature brain. In addition, radial growth of the Ts16 cortex was delayed at the time of peak cortical neurogenesis in normal mice, but by embryonic day 18 the cortex reached normal thickness. Because mouse chromosome 16 shares many genes with human chromosome 21, abnormalities in Ts16 brain development may parallel abnormalities in trisomy 21.
Neurotrophin Effects on Survival and Expression of Cholinergic Properties in Cultured Rat Septal Neurons under Normal and Stress Conditions
Authors: Nonner Doris , Barrett Ellen F. , Barrett John N. 
Published: April 2018

These studies tested the hypothesis that survival-promoting effects of neurotrophins on basal forebrain cholinergic neurons are enhanced under stress. Septal neurons from embryonic day 14–15 rats exposed for 10–14 d to neurotrophin [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4 (NT-4), each at 100 ng/ml] showed a two- to threefold increase in choline acetyltransferase (ChAT) activity, with little evidence of synergistic interactions. Neurotrophins produced no significant increase in the survival of total or acetylcholinesterase (AChE)-positive neurons at moderate plating density (1200–1600 cells/mm2). However, with very low plating densities (2–28 cells/mm2) BDNF, NT-3, and NT-4 (but not NGF) increased total neuronal survival, and BDNF increased survival of AChE-positive neurons.NGF and BDNF enhanced ChAT activity and survival of cholinergic neurons after a 24 hr hypoglycemic stress, even when added 1 hr after stress onset. All four tested neurotrophins increased total neuronal survival after hypoglycemic stress. These results suggest that neurotrophins are important for preservation of central cholinergic function under stress conditions, with different neurotrophins protecting against different stresses. The stress-associated survival-promoting effects of neurotrophins were not limited to the cholinergic subpopulation.
Cloning and Functional Expression of aDrosophilaMetabotropic Glutamate Receptor Expressed in the Embryonic CNS
Authors: Parmentier Marie-Laure , Pin Jean-Philippe , Bockaert Joël , Grau Yves 
Published: April 2018

The excitatory neurotransmitter glutamate plays important roles in the mammalian brain, ranging from synaptic plasticity to memory. To mediate these functions, glutamate activates two types of receptors: ligand-gated channels and metabotropic receptors coupled to G-proteins. Both families of glutamate receptors share no sequence homology and possess original structural features compared with other ligand-gated channels and G-protein-coupled receptors, respectively. Glutamate-gated receptor-channel subunits have already been characterized in invertebrates. Here we report the cloning and functional characterization of an invertebrate metabotropic glutamate receptor (DmGluRA) isolated fromDrosophila melanogaster. This receptor displays 45 and 43% amino acid sequence identity with its mammalian homologs mGluR3 and mGluR2, respectively. Moreover, its pharmacology and transduction mechanisms are surprisingly similar to those of mGluR2 and mGluR3. DmGluRA is expressed in the CNS of the late embryo. These results indicate that the original structural features of both glutamate receptor types are conserved from insects to mammals and suggest that the functions of these receptors have been highly conserved during evolution.
A SNARE Complex Containing Syntaxin 3 Is Present in Ribbon Synapses of the Retina
Authors: Morgans Catherine W. , Brandstätter Johann H. , Kellerman Joseph , Betz Heinrich , Wässle Heinz 
Published: April 2018

In contrast to conventional synapses, which release neurotransmitter transiently, ribbon synapses formed by photoreceptors and bipolar cells of the retina release neurotransmitter continuously and modulate the rate in response to light. Both modes of release are mediated by synaptic vesicles but probably differ in the regulation of docking and fusion of synaptic vesicles with the plasma membrane. We have found that syntaxin 1, an essential component of the core fusion complex in conventional synapses, is absent from ribbon synapses of the retina, raising the possibility that these synapses contain a different type of syntaxin or syntaxin-like protein. By immunoprecipitating syntaxin 1-depleted retina and brain extracts with a SNAP-25 antibody and microsequencing the precipitated proteins, syntaxin 3 was detected in retina complexed with SNAP-25, synaptobrevin, and complexin. Using an anti-syntaxin 3 antiserum, syntaxin 3 was demonstrated to be present at high levels in retina compared to brain. Immunofluorescent staining of rat retina sections confirmed that syntaxin 3 is expressed by photoreceptor and bipolar cells in the retina. Thus, in the retina, expression of syntaxin 3 is correlated with ribbon synapses and may play a role in the tonic release of neurotransmitter.
Characterization of Densin-180, a New Brain-Specific Synaptic Protein of theO-Sialoglycoprotein Family
Authors: Apperson Michelle L. , Moon Il Soo , Kennedy Mary B. 
Published: April 2018

We purified an abundant protein of apparent molecular mass 180 kDa from the postsynaptic density fraction of rat forebrain and obtained amino acid sequences of three tryptic peptides generated from the protein. The sequences were used to design a strategy for cloning the cDNA encoding the protein by polymerase chain reaction. The open reading frame of the cDNA encodes a novel protein of predicted molecular mass 167 kDa. We have named the protein densin-180. Antibodies raised against the predicted amino and carboxyl sequences of densin-180 recognize a 180 kDa band on immunoblots that is enriched in the postsynaptic density fraction. Immunocytochemical localization of densin-180 in dissociated hippocampal neuronal cultures shows that the protein is highly concentrated at synapses along dendrites. The message encoding densin-180 is brain specific and is more abundant in forebrain than in cerebellum. The sequence of densin-180 contains 17 leucine-rich repeats, a sialomucin domain, an apparent transmembrane domain, and a PDZ domain. This arrangement of domains is similar to that of several adhesion molecules, in particular GPIbα, which mediates binding of platelets to von Willebrand factor. We propose that densin-180 participates in specific adhesion between presynaptic and postsynaptic membranes at glutamatergic synapses.