bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibroblast Growth Factors Regulate Calcitonin Gene‐related Peptide mRNA Expression in Rat Motoneurons after Lesion and in Culture
Authors: Piehl Fredrik , Ru‐Rong Ji , Cullheim Staffan , Hökfelt Tomas , Lindholm Dan , Hughes Richard A. 
Published: April 2006

AbstractIn this study, we have investigated the effect of fibroblast growth factors (bFGF and FGF‐5) and brain derived neurotrophic factor (BDNF) on the expression of calcitonin gene‐related peptide (CGRP) in rat motoneurons in vivo and in vitro. Following sciatic nerve transection in adult rats, the levels of α‐CGRP and β‐CGRP mRNA were up‐ and down‐regulated respectively in axotomized motoneurons, revealed by in situ hybridization histochemistry. Local administration of 1 μg bFGF was able to entirely abolish the up‐regulation of α‐CGRP mRNA, and to further down‐regulate β‐CGRP. These effects, albeit less pronounced, were still evident with 0.2 μg bFGF. In contrast, bFGF did not attenuate the lesion‐induced decrease of choline acetyltransferase (ChAT) mRNA. Administration of BDNF did not significantly alter the expression of CGRP or ChAT mRNA in axotomized motoneurons. Both α‐ and β‐CGRP mRNAs could be detected by PCR in enriched motoneuron cultures prepared from rat embryos at embryonic day 14–15. Comparing the amplification of α‐ and β‐CGRP mRNAs with that of mRNA encoding glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) in parallel samples, we found that cultures treated with FGF‐5 had a lower ratio of α‐ and β‐CGRP mRNA to GAPDH mRNA, than did control or BDNF‐treated cultures. BDNF, on the other hand increased α‐CGRP and decreased β‐CGRP mRNA levels, though these effects were moderate compared with the effects of FGF‐5. The results obtained in this study suggest that members of the FGF family of growth factors influence the expression of CGRP in rat motoneurons, and that the increase of this neuropeptide induced by axotomy may, at least in part, be due to deprivation of these target‐derived factors.
All‐or‐none Excitatory Postsynaptic Potentials in the Rat Visual Cortex
Authors: Volgushev Maxim , Voronin Leon L. , Chistiakova Marina , Artola Alain , Singer Wolf 
Published: April 2006

AbstractIntracellular recordings were obtained from supragranular neurons in slices of the rat visual cortex. In ∼25% of the cells large (0.5–1.6 mV) excitatory postsynaptic potentials (EPSPs) of constant amplitude were observed after minimal, presumably single‐fibre stimulation. The amplitude variance of these large EPSPs was surprisingly small and within the range of the variance of the noise. These EPSPs could be reduced in amplitude by paired‐pulse and low‐frequency stimulation or by raising extracellular Mg2+ concentration. Reduced EPSPs could either continue to behave as all‐or‐none responses, or they could fluctuate between several amplitude levels. Conversely, responses where the amplitude fluctuated from trial to trial under control conditions could be converted into large all‐or‐none responses by paired‐pulse facilitation. This indicates that the large all‐or‐none EPSPs were composed of several subunits, probably reflecting the action of several different release sites. It is concluded that these release sites are either independent and operate with a probability close to 1 or, if operating with a lower probability, are coordinated by a mechanism which synchronizes release. Several observations suggest that release probabilities can switch from values close to 1 to 0 with repetitive stimulation or high Mg2+ concentration. Thus, a substantial fraction of single‐fibre inputs to supragranular cells possess synapses which operate with high synaptic efficiency and extremely low variance under control conditions but can undergo drastic changes in efficacy when release probabilities are interfered with. Such modifications of release probability could serve as an effective mechanism to regulate the gain of synaptic transmission.
TGF‐βs and cAMP Regulate GAP‐43 Expression in Schwann Cells and Reveal the Association of this Protein with the Trans‐Golgi Network
Authors: Stewart Helen J. S. , Curtis Rory , Jessen Kristjan R. , Mirsky Rhona 
Published: April 2006

AbstractWe have shown previously that growth‐associated protein 43 (GAP‐43) is expressed by rat Schwann cells and is restricted to non‐myelin‐forming Schwann cells in vivo. Here we examined the regulation of GAP‐43 using agents that are known to control Schwann cell differentiation in vitro. GAP‐43 protein and mRNA levels are decreased by forskolin and other agents that elevate intracellular cAMP (and promote expression of the myelinating Schwann cell phenotype). We also found that expression of GAP‐43 protein but not mRNA is down‐regulated by transforming growth factor betas (TGF‐βs). Moreover, TGF‐β treatment of Schwann cells results in cell clumping, process retraction and disappearance of GAP‐43 from the plasma membrane, revealing that GAP‐43 is associated with the Golgi apparatus. This association was confirmed by partial overlap of GAP‐43 with the trans‐Golgi network marker (23c) and the disruption of the Golgi with brefeldin A or monensin leading to altered GAP‐43 distribution. Golgi‐associated GAP‐43 appeared to have the same molecular weight as the plasma membrane‐associated GAP‐43. Thus these results show that GAP‐43 expression in Schwann cells is subject to regulation by both extracellular and intracellular signalling molecules and that Schwann cell GAP‐43 is often associated with the Golgi apparatus.
Stimulation of Ca2+‐Activated Non‐specific Cationic Channels by Phospholipase C‐linked Glutamate Receptors in Synaptoneurosomes?
Authors: Vignes Michel , Blanc Emmanuelle , Récasens Max 
Published: April 2006

AbstractThe regulation of intracellular Ca2+ concentration ([Ca2+]i) by glutamate metabotropic receptors (mGluR) was studied in 8‐day‐old rat forebrain synaptoneurosomes using spectrofluorimetric methods. Here we demonstrate that metabotropic glutamate agonists induce in rat brain synaptoneurosomes a Ca2+ influx largely dependent upon the presence of Ca2+ in the external medium. The pharmacological profile of this influx is strongly correlated with the pharmacological profile of the activation of phosphoinositide hydrolysis, i.e. quisqualic acid ∼ 1S,3R‐amino‐1‐dicarboxylate‐1,3 cyclopentane ≅ glutamate. This metabotropic glutamate receptor‐induced Ca2+ influx is insensitive to voltage‐dependent Ca2+ channel antagonists and occurs through a Mn2+ impermeant pathway. The study of the rapid kinetics shows that this influx is triggered after a 300 ms delay compared with that elicited by depolarizing agents and Ca2+ ionophore A23187. In order to assess further if mGluR stimulate this influx through the recruitment of inositol triphosphate (IP3)‐sensitive intracellular Ca2+ stores, we have tested the effect of thapsigargin on membrane potential and intracellular Ca2+ simultaneously. Thapsigargin induces a depolarization of the synaptoneurosomal membrane followed by a massive Ca2+ influx, occurring via a Mn2+ nonpermeant route. This depolarizing effect is sensitive to the presence of the intracellular Ca2+ chelator [1,2‐bis(2‐aminophenoxy)ethane‐N, N, N', N'‐tetraacetoxymethyl ester], and partially sensitive to extracellular Na+, but insensitive to the presence of extracellular Ca2+. Taken together, our data suggest that mGluR stimulate self‐maintained increases of [Ca2+]i in rat forebrain synaptoneurosomes via the activation of a multistep mechanism, sequenced in the following steps: (i) mGluR‐induced IP3 synthesis; (ii) IP3‐stimulated intracellular Ca2+ release; (iii) Ca2+‐activated non‐specific cation channel, leading to local depolarization and a Ca2+ influx; and (iv) activation of Ca2+‐sensitive phospholipase C.
Focal Adhesion Kinase in Rat Central Nervous System
Authors: Burgaya Ferran , Menegon Andrea , Menegoz Mathias , Valtorta Flavia , Girault Jean‐Antoine 
Published: April 2006

AbstractFocal adhesion kinase (pp125FAK, FAK) is a 125 kDa non‐receptor tyrosine kinase enriched in focal adhesions of various cell types, where it is thought to transduce signals triggered by contact with the extracellular matrix. We have studied the expression and localization of FAK in rat CNS. Immunoblotting, immunohistochemistry and in situ hybridization revealed the presence of FAK in all regions of the adult brain and demonstrated its enrichment in specific neuronal populations of the cerebral and cerebellar cortex, as well as in the hippocampus. During development, FAK protein levels were highest around birth in cerebral cortex and caudate putamen and decreased in the adult. In situ hybridization revealed enrichment of FAK mRNA in the ventricular germinative and external layers during the last period of embryonic growth. In primary cultures FAK immunoreactivity was localized in focal adhesions in astrocytes, whereas in developing neurons the highest levels were found in growth cones and perikarya. In the growth cone, FAK immunoreactivity colocalized with actin filaments. In mature neurons FAK appeared to be distributed in the whole cytoplasm, with no enrichment in any cellular compartment. Our results demonstrate the presence of high levels of FAK in rat CNS, maximal during development but persistent in the adult. Its enrichment in growth cones suggests that it may play a role in neurite outgrowth, as well as in plasticity in the adult.
G‐Protein Modulation of Glycine‐resistant NMDA Receptor Desensitization in Rat Cultured Hippocampal Neurons
Authors: TureCek Rostislav , Vyklicky Ladislav , Vlachova Viktorie , Vyklicky Ladislav 
Published: April 2006

AbstractActivation of N‐methyl‐D‐aspartate (NMDA) subtype glutamate receptors increases the excitability of most neurons within the CNS. A common feature of ionotropic glutamate receptors is their ability to undergo desensitization. In the present experiments we have examined the role of guanine nucleotide‐binding proteins(G‐proteins) in the regulation of NMDA receptor desensitization. Repeated NMDA receptor activation with 2 mM extracellular Ca2+ increased the degree of glycine‐resistant NMDA receptor desensitization of subsequent responses to NMDA recorded in the presence of 0.2 mM Ca2+. The recovery of glycine‐resistant NMDA receptor desensitization after repeated NMDA receptor activation in the presence of 2 mM Ca2+ was significantly reduced in neurons intracellularly dialysed with guanosine‐5'‐0‐(3‐thiotriphosphate), guanosine‐5'‐triphosphate or AIC13 and CsF, compounds known to activate G‐proteins. lntracellular dialysis with guanosine‐5'‐0(2thiodiphosphate), adenosine triphosphate, or adenosine‐5'‐G(3‐thiotriphosphate) was ineffective. The calcium permeability of NMDA receptor‐channels was not altered by intracellular dialysis with GTPyS. This suggests that modulation of NMDA receptor desensitization by G‐proteins represents a novel mechanism forregulation of glutamate‐gated ion channel activity.
Anti‐nociception Induced by Systemic or PAG‐microinjected Lysine‐acetylsalicylate in Rats. Effects on Tail‐flick Related Activity of Medullary Off‐ and On‐cells
Authors: Tortorici Victor , Vanegas Horacio 
Published: April 2006

AbstractPrevious experiments using metamizol have shown that this non‐steroidal anti‐inflammatory drug (NSAID) produces a central anti‐nociceptive effect probably through neural substrates that also support the analgesic effects of opiates, such as the periaqueductal grey matter (PAG) and the off‐ and on‐cells of the rostral ventromedial medulla (RVM). Off‐ and on‐cells have been postulated to respectively inhibit and facilitate nociceptive transmission, since the heat‐elicited tail flick reflex (TF) occurs only after off‐cells have decreased (pause), and on‐cells have increased (burst) their activity. The aim of the present study was to examine whether the effect of metamizol upon TF and off‐ and on‐cells responses could be generalized to other NSAIDs such as, in this case, lysine‐acetylsalicylate (LASA). Fifty‐nine off‐ and on‐cells of the RVM were recorded in lightly anaesthetized rats. Systemic administration (200 and 300 mg/kg) or PAG microinjection (30, 50 and 100 μg) of LASA caused retardation of the heat‐elicited off‐cell pause, on‐cell burst and the corresponding TF. Neuronal responses and TF retained their mutual time relationship but shifted simultaneously toward longer latencies. This anti‐nociceptive effect of LASA was dose‐dependent, present 5 min after administration and reached a maximum in 30 min for both administration methods. These data confirm that analgesics typically defined as peripherally‐acting, such as metamizol and LASA in this study, may also have an anti‐nociceptive effect by acting directly upon PAG, and suggest that this central effect involves the RVM off‐ and on‐cells.
Visual Learning for an Auditory Secondary Reinforcer by Macaques is Intact after Uncinate Fascicle Section: Indirect Evidence for the Involvement of the Corpus Striatum
Authors: Gaffan D. , Eacott M. J. 
Published: April 2006

AbstractThree cynomolgus monkeys (Macaca fascicularis) were trained preoperatively in visual discrimination learning for an auditory secondary reinforcer. Each new discrimination problem was solved on the basis of the secondary reinforcer, and primary reinforcement (food reward) was given only after a new problem had been solved. The animals learned 50 new problems in each daily session and it was therefore possible to assess accurately their average rate of learning new discrimination problems in this procedure. After the learning rate had stabilized preoperatively the animals were operated upon to transect the uncinate fascicle, the cortico‐cortical pathway from visual association cortex in the temporal lobe to prefrontal cortex. The animals' learning rate was unchanged after uncinate fascicle section. A previous experiment had shown that visual learning for an auditory secondary reinforcer is unaffected by disconnection of visual association cortex from the amygdala and the fornix. Taken together, this negative evidence points strongly to the conclusion that visual learning for an auditory secondary reinforcer depends upon interaction of temporal lobe visual association cortex with the corpus striatum, since other possibilities have been excluded.
Extracellular Activation of Unitary Excitatory Synapses Between Hippocampal CA3 and CA1 Pyramidal Cells
Authors: Raastad Morten 
Published: April 2006

AbstractThe possibility of regular activation of unitary excitatory synapses on hippocampal CA1 cells by electrical stimulation of Schaffer collaterals was explored in the rat. The amplitude of the excitatory postsynaptic currents (EPSCs) and failures in response to a range of stimulation intensities around the threshold for the smallest detectable EPSC were analysed. After an abrupt appearance of EPSCs in response to increasing stimulation strength, both EPSC amplitude and failure rate could reach a plateau where increasing stimulation intensity did not cause additional responses. This was interpreted as a regular activation of mainly a single axon. Statistical methods showed, however, that only 12 out of ∼50 experiments using threshold stimulation were without significant contamination from additional fibres. In this subset of experiments, upper limits for contamination from other fibres were estimated by using bootstrapping methods. More than 90% of the responses were probably due to faithful activation of a single axon, assuming that the density of axons connecting to one target cell is relatively homogeneous. This result makes the described method suitable for examining some aspects of the transmission between individual hippocampal cells.
Transmitter Release Associated with Long‐term Synaptic Depression in Rat Corticostriatal Slices
Authors: Calabresi Paolo , Fedele Emesto , Pisani Antonio , Fontana Giovanni , Mercuri Nicola B. , Bernardi Giorgio , Raiteri Maurizio 
Published: April 2006

AbstractUsing a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long‐term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high‐frequency stimulation (100 Hz, three trains, 3 s duration, 20 s intervals) used to induce LTD caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.
Retraction of Spinule‐type Neurites from Carp Retinal Horizontal Cell Dendrites during Dark Adaptation Involves the Activation of Ca2+/Calmodulin‐dependent Protein Kinase II
Authors: Weiler Reto , Schultz Konrad , Janssen‐Bienhold Ulrike 
Published: April 2006

AbstractThe formation of spinules at the terminal dendrites of retinal horizontal cells with the onset of light and their subsequent retraction during darkness is a remarkable example of synaptic plasticity where sensory experience modifies reversibly, and on a time scale of minutes the ultrastructure of synaptic connectivity. The signals and the subsequent intracellular cascades underlying the prominent morphological alterations are only partially understood. We show here that lowering the external calcium concentration did prevent dark‐ and AMPA‐induced retraction of spinules in an eyecup preparation. Furthermore, spinule retraction was prevented in vivo by the injection of calmidazolium, an inhibitor of calmodulin, into the eyeball, and also by the injection of KN‐62, an inhibitor of Ca2+/calmodulin‐dependent protein kinase II (CaMkll). We conclude that local Ca2+ influx through AMPA‐gated channels followed by activation of CaMkll is an important step for spinule retraction during dark adaptation. The phosphorylation patterns of phosphoproteins derived from purified horizontal cells was affected by the inhibitors of camodulin and CaMkll respectively. Some of the affected phosphoproteins appeared to be cytoskeleton‐associated proteins, including GAP‐43. Based on these observations, a putative scenario for the retraction of spinules is proposed.
Differential Formation of Topographic Maps in the Cerebral Cortex and Superior Colliculus of the Mouse by Temporally Correlated Tactile‐Tactile and Tactile‐Visual Inputs
Authors: Benedetti Fabrizio 
Published: April 2006

AbstractCoincident electrical activity of nerve fibres seems to play a fundamental role in the development of ordered connections in the CNS. To test this hypothesis on the formation of topographic maps we connected two cutaneous regions of the body of newborn mice by implanting an artificial bridge of pig hair. Through this procedure we produced the mechanical fusion of the ear with either the shoulder or the nose. In these conditions the ear not only was connected with shoulder or nose, but was also in relation with the nasal or the inferior portion of visual space. Therefore the probability of temporally correlated tactile‐tactile inputs (earshoulder or ear‐nose) as well as tactile‐visual inputs (ear‐inferior or ear‐nasal visual space) increased. By recording from the primary somatosensory cortex and superior colliculus, we found that the formation of topographic maps was based on different principles. The somatosensory cortex developed in terms of tactiletactile correlated inputs, showing somatosensory neurons with receptive fields extending through the fused parts of the body. Conversely, the superior colliculus processed tactile‐visual correlated inputs; we found somatosensory‐visual bimodal neurons with visual receptive fields extending into the portion of visual space where the artificial bridge was directed. These results suggest that the fusion of two body parts is represented in terms of cutaneous coordinates in the cortex and external world (visual) coordinates in the superior colliculus. Therefore the differential tactile‐tactile and tactile‐visual coincident activity seems to be correlated to the different meaning of information processing of these two brain regions.
Guidance of Thalamocortical Axons by Growth‐promoting Molecules in Developing Rat Cerebral Cortex
Authors: Hübener Mark , Götz Magdalena , Klostermann Stefan , Bolz Jürgen 
Published: April 2006

AbstractSubstrate‐bound guidance cues play an important role during the development of thalamocortical projections. We used time‐lapse video microscopy to study the growth behaviour of thalamic axons on different substrates. On embryonic cortical membranes and on a pure laminin substrate, thalamic fibres advanced relatively slowly (∼15 μm/h) and on average their growth cones retracted transiently every ∼5 h. In contrast, on membranes prepared from early postnatal cortex, thalamic fibres grew twice as fast and spontaneous growth cone collapse occurred ∼8 times less often. Experiments in which we used the sugar‐binding lectin peanut agglutinin or heat inactivation to change the membrane properties indicated that these differences are due to growth‐supporting molecules on postnatal cortical membranes. When offered a choice between embryonic and postnatal cortical membranes, thalamic axons preferred the postnatal membrane substrate. Time‐lapse imaging revealed that borders between these two substrates effectively guided thalamic fibres, and in most cases axons changed their direction without collapse of the growth cone. Our results suggest that thalamic axons can be guided by the spatial distribution of growth‐promoting molecules in the developing cortex.
The Relationship Between Glycine and Gephyrin in Synapses of the Rat Spinal Cord
Authors: Todd A. J. , Spike R. C. , Chong D. , Neilson M. 
Published: April 2006

AbstractIn order to examine the relationship between gephyrin (the peripheral membrane protein associated with glycine receptors) and glycinergic boutons, we have carried out a post‐embedding immunogold study of glycine‐like immunoreactivity on sections of rat lumbar spinal cord which had previously been reacted with monoclonal antibody to gephyrin. In all three areas examined (laminae I and II, lamina III and lamina IX) the majority of profiles which were presynaptic at gephyrin‐immunoreactive synapses were enriched with glycine‐like immunoreactivity. It was estimated that at least 83% of profiles presynaptic to gephyrin‐immunoreactive synapses in the superficial dorsal horn (laminae I and II) were glycine‐immunoreactive, while for lamina III and the ventral horn (lamina IX) the proportions were at least 91% and 98% respectively. This provides strong evidence that glycine is a transmitter at those synapses where gephyrin‐ and glycine‐like immunoreactivities are both present, but suggests that gephyrin may sometimes be expressed at non‐glycinergic synapses and indicates the need for caution in using gephyrin‐immunoreactivity as a marker for glycinergic synapses within the spinal cord. By reacting serial sections of dorsal horn with antisera to glycine and GABA, we have shown that many boutons in laminae I‐III of the dorsal horn show both types of immunoreactivity and are therefore likely to use both amino acids as inhibitory transmitters. Many of the boutons which were presynaptic at axoaxonic synapses in the ventral part of lamina II and in lamina III were glycine‐ and GABA‐immunoreactive and in many cases the postsynaptic element was the central axon of a type II synaptic glomerulus. Taken together with pharmacological evidence, this suggests that inhibitory intemeurons in the dorsal horn which use both GABA and glycine may be important in controlling the flow of information from hair follicle afferents to other spinal neurons.