bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different phosphatase‐dependent mechanisms mediate long‐term depression and depotentiation of long‐term potentiation in mouse hippocampal CA1 area
Authors: Jouvenceau Anne , Billard Jean‐Marie , Haditsch Ursula , Mansuy Isabelle M. , Dutar Patrick 
Published: September 2003

AbstractTwo types of synaptic depression have been described in the hippocampus, long‐term depression and depotentiation of long‐term potentiation known to recruit the serine/threonine protein phosphatases PP1, PP2A and PP2B (calcineurin). The contribution of each of these protein phosphatases is controversial. To examine the role of the Ca2+/calmodulin‐dependent protein phosphatase calcineurin in long‐term depression and depotentiation, we analysed the effect of genetically inhibiting calcineurin reversibly in the hippocampus, using the doxycycline‐dependent rtTA system in transgenic mice. We show that reducing calcineurin activity has no effect on long‐term depression but reversibly affects depotentiation. Consistently, the calcineurin inhibitor FK‐506 reproduces the depotentiation impairment observed in the mutant mice but does not affect long‐term depression in control animals. In contrast, the PP1/PP2A inhibitor okadaic acid fully blocks both long‐term depression and depotentiation. These data demonstrate that the nature of signalling cascades induced by synaptic activity depends on the initial synaptic state. While depression of potentiated synaptic responses requires activation of PP1/PP2A and/or calcineurin, depression of basal synaptic responses depends only on PP1/PP2A activation.
Kinase‐dependent loss of Na+ channel slow‐inactivation in rat CA1 hippocampal pyramidal cell dendrites after brief exposure to convulsants
Authors: Loftis Jordan L. , King Diana D. , Colbert Costa M. 
Published: September 2003

AbstractNa+ channels in the dendrites of rat CA1 pyramidal neurons display a profound activity‐dependent inactivation, termed slow inactivation, that limits excitability in the dendrites even at low physiological rates of firing. The magnitude of this slow inactivation is powerfully modulated by a protein kinase C‐dependent process. Because activation of kinases is a rapid and common feature of a number of seizure models, we hypothesized that a loss of slow inactivation of Na+ channels might exacerbate other changes in excitability. Thus, we observed the effects of a brief (5 min) chemical convulsant treatment on Na+ currents and action potentials in hippocampal slices. We found that slow inactivation decreased significantly and remained decreased for at least 30 min after return to control conditions. Pretreatment with either chelerythrine, a protein kinase C inhibitor, or U0126, a mitogen‐activated protein kinase/extracellular signal regulated kinase kinase (MEK) inhibitor, blocked this reduction of slow inactivation. These results demonstrate that a brief period of hyperexcitability leads to a rapid, protein kinase‐dependent loss of slow inactivation of Na+ channels that would contribute to and perhaps prolong the hyperexcitable state.
Lesions of mediodorsal thalamus and anterior thalamic nuclei produce dissociable effects on instrumental conditioning in rats
Authors: Corbit Laura H. , Muir Janice L. , Balleine Bernard W. 
Published: September 2003

AbstractTwo experiments examined the effects of bilateral excitotoxic lesions of either the mediodorsal (MD) or anterior (ANT) thalamic nuclei on instrumental acquisition and performance, sensitivity to changes in the value of the instrumental outcome, and sensitivity to changes in the instrumental contingency. Rats were food deprived and trained to press two levers, each earning a unique food outcome (pellets or sucrose). All rats acquired the instrumental response although ANT lesions appear slightly to increase and MD lesions slightly to suppress instrumental performance. After training, specific satiety‐induced devaluation of one of the two instrumental outcomes produced a selective reduction in responding on the lever that in training had earned the now devalued outcome but only in the SHAM and ANT groups. In contrast, MD animals failed to show evidence of a selective devaluation effect when tested in extinction. Additionally, SHAM and ANT animals selectively decreased responding when one action‐outcome contingency was degraded, whereas MD animals reduced responding nonselectively on the two levers. Subsequent tests established that an inability to discriminate between either the two actions or the two outcomes cannot account for the lack of selective responding observed in the MD animals. Together these data suggest that MD lesions produce a profound deficit in the ability of rats to utilize specific action–outcome associations and appear to render rats relatively insensitive to the causal consequences of their instrumental actions. In contrast, far from producing a deficit, ANT lesioned rats were as sensitive to the effects of these behavioural manipulations as the sham lesioned controls.
Activation of retinoic acid signalling after sciatic nerve injury: up‐regulation of cellular retinoid binding proteins
Authors: Zhelyaznik Nina , Schrage Kirsten , McCaffery Peter , Mey Jörg 
Published: September 2003

AbstractIn mammalian peripheral nerves a crush lesion causes interactions between injured neurons, Schwann cells and haematogenous macrophages that can lead to successful axonal regeneration. We suggest that the transcriptional activator retinoic acid (RA), takes part in gene regulation after peripheral nerve injury and that RA signalling is activated via the cellular retinoic acid binding protein (CRABP)‐II and cellular retinol binding protein (CRBP)‐I. With RT‐PCR and immunoblotting all necessary components of the RA signalling pathway were detected in the sciatic nerve of adult rats. These are retinoic acid receptors, retinoid X receptors, the retinoic acid synthesizing enzymes RALDH‐1, RALDH‐2, and RALDH‐3, in addition, the cellular retinoid binding proteins CRBP‐I, CRABP‐I and CRABP‐II. Enzyme activity of RALDH‐2 was detectable in the nerve, and using a transgenic reporter mouse we found local activation of RA responsive elements in the regenerating nerve. Sciatic nerve crush as well as transection resulted in a more than 10‐fold up‐regulation of CRBP‐I, which is thought to facilitate the synthesis of RA. Both kinds of injury also caused a 15‐fold increase in transcript and protein concentration of CRABP‐II, a possible mediator of RA transfer to its nuclear receptors.
Distinct receptors and different transduction mechanisms for ATP and adenosine at the frog motor nerve endings
Authors: Sokolova E. , Grishin S. , Shakirzyanova A. , Talantova M. , Giniatullin R. 
Published: September 2003

AbstractCorelease of ATP with ACh from motor endings suggests a physiological role for ATP in synaptic transmission. We previously showed that, on skeletal muscle, ATP directly inhibited ACh release via presynaptic P2 receptors. The receptor identification (P2X or P2Y) and its transduction mechanism remained, however, unknown. In the present study using the voltage‐clamp technique we analyzed the properties of presynaptic ATP receptors and subsequent effector mechanisms. ATP or adenosine presynaptically depressed multiquantal end‐plate currents, with longer latency for ATP action. ATPγS, agonist at P2X receptors, or Bz‐ATP, agonist at P2X7 receptors, were ineffective. The action of ATP was prevented by suramin and unchanged by PPADS or TNP‐ATP, antagonists of P2X receptors, or RB‐2, a blocker of certain P2Y receptors. The depressant action of ATP was reproduced by UTP, metabotropic P2Y receptor agonist. Pertussis toxin (PTX), antagonist of Gi/o‐proteins, and inhibitors of phosphatidylcholine specific PLC (D609) and PKC (staurosporine or chelerythrine) prevented the effect of ATP while blockers of PLA2 (OBAA) and COX (aspirin or indomethacin) attenuated it. Inhibitors of phosphatidylinositide‐specific PLC (U73122), guanylylcyclase (ODQ), PKA (Rp‐cAMPS) or PLD (1‐butanol) did not affect the action of ATP. No inhibitor of second messengers (except PTX) changed the action of adenosine. Our data indicate, for motor nerve endings, the existence of inhibitory P2Y receptors coupled to multiple intracellular cascades including phosphatidylinositide‐specific PLC/PKC/PLA2/COX. This divergent presynaptic P2 signalling (unlike the single effector mechanism for P1 receptors) could provide feedback inhibition of transmitter release and perhaps be involved in presynaptic plasticity.
Interleukin‐1β enhances non‐rapid eye movement sleep when microinjected into the dorsal raphe nucleus and inhibits serotonergic neuronsin vitro
Authors: Manfridi Alfredo , Brambilla Dario , Bianchi Susanna , Mariotti Maurizio , Opp Mark R. , Imeri Luca 
Published: September 2003

AbstractInterleukin‐1 (IL‐1) and IL‐1 receptors are constitutively expressed in normal brain. IL‐1 increases non‐rapid eye movements (NREM) sleep in several animal species, an effect mediated in part by interactions with the serotonergic system. The site(s) in brain at which interactions between IL‐1 and the serotonergic system increase NREM sleep remain to be identified. The dorsal raphe (DRN) is the origin of the major ascending serotonergic pathways to the forebrain, and it contains IL‐1 receptors. This study examined the hypothesis that IL‐1 increases NREM sleep by acting at the level of the DRN. IL‐1β (0.25 and 0.5 ng) was microinjected into the DRN of freely behaving rats and subsequent effects on sleep–wake activity were determined. IL‐1β 0.5 ng increased NREM sleep during the first 2 h post‐injection from 33.5 ± 3.7% after vehicle microinjection to 42.9 ± 3.0% of recording time. To determine the effects of IL‐1β on electrophysiological properties of DRN serotonergic neurons, intracellular recordings were performed in a guinea‐pig brain stem slice preparation. In 26 of 32 physiologically and pharmacologically identified serotonergic neurons, IL‐1β superfusion (25 ng/mL) decreased spontaneous firing rates by 50%, from 1.6 ± 0.2 Hz (before IL‐1β superfusion) to 0.8 ± 0.2 Hz. This effect was reversible upon washout. These results show that IL‐1β increases NREM sleep when administered directly into the DRN. Serotonin enhances wakefulness and these novel data also suggest that IL‐1β‐induced enhancement of NREM sleep could be due in part to the inhibition of DRN serotonergic neurons.
c‐Fos and peptide immunoreactivities in the central extended amygdala of morphine‐dependent rats after naloxone‐precipitated withdrawal
Authors: Veinante Pierre , Stoeckel Marie‐Elisabeth , Lasbennes François , Freund‐Mercier Marie‐José 
Published: September 2003

AbstractThe central extended amygdala, a forebrain macrostructure, may represent a common substrate for acute drug reward and the dysphoric effects of drug withdrawal. To test its involvement during opiate withdrawal, we studied the distribution of c‐Fos immunoreactive neurons, in relation to their neuropeptide content, in brain sections from morphine‐dependent or naive rats, killed 90 min after naloxone or saline intraperitoneal injection. Naloxone treatment in naive rats induced a slight increase in c‐Fos immunoreactivity in the central amygdaloid nucleus, the lateral bed nucleus of the stria terminalis and the interstitial nucleus of the posterior limb of the anterior commissure. In morphine‐dependent rats, naloxone injection significantly increased the number of c‐Fos‐positive neurons in these structures as well as in the majority of the other central extended amygdala components. Double immunocytochemistry was used to determine the neurochemical nature of c‐Fos‐positive neurons in the central extended amygdala. Corticotropin‐releasing factor‐ and methionine‐enkephakin‐immunoreactive neurons displayed c‐Fos immunoreactivity in naive rats after naloxone injection, whereas only enkephalinergic neurons were found to be c‐Fos positive in morphine‐dependent rats after naloxone injection. The possible involvement of the corticotropin‐releasing factor system during withdrawal is discussed. These results suggest that the whole central extended amygdala is activated during opiate withdrawal, with a lateral to medial decreasing gradient, and emphasize the role of peptidergic systems in this morphofunctional continuum.
Tissue inhibitor of metalloproteinases‐3 and matrix metalloproteinase‐3 regulate neuronal sensitivity to doxorubicin‐induced apoptosis
Authors: Wetzel M. , Rosenberg G. A. , Cunningham L. A. 
Published: September 2003

AbstractMetalloproteinase activity at the cell surface influences cellular sensitivity to extrinsic death vs. survival signals in a variety of cell types, through proteolytic shedding of cell surface signalling molecules. Tissue inhibitor of metalloproteinases‐3 (TIMP‐3) is a unique natural metalloproteinase inhibitor that plays a pro‐apoptotic role through its ability to inhibit metalloproteinases that proteolytically cleave death receptors and their ligands from the cell surface. To study the convergence of metalloproteinase activity and death receptor signalling in neurons, we established an in vitro model of neuronal apoptosis utilizing the chemotherapeutic drug, doxorubicin (Dox). Primary cultures established from embryonic rat cerebral cortices displayed robust and selective neuronal apoptosis in response to Dox, an effect that was dependent on the activation of the death receptor, Fas. We demonstrate that both TIMP‐3 and matrix metalloproteinase‐3 (MMP‐3) are constitutively expressed by primary cortical neurons in culture, and selectively modulated Fas‐mediated neuronal apoptosis induced by Dox. Metalloproteinase inhibition by TIMP‐3 was found to be necessary for Dox‐induced neuronal death, whereas addition of active MMP‐3 markedly attenuated apoptosis and diminished Fas–Fas ligand interaction at the cell surface. These observations implicate a physiological role for the balance of TIMP‐3 and MMP‐3 activity at the neuronal surface in regulating death receptor sensitivity. The convergence of metalloproteinase activity and death receptor signalling at the cell surface may influence neuronal cell death vs. survival decisions.
Compensatory dendritic growth of CA1 pyramidal cells following growth impairment in the neonatal period
Authors: Groc Laurent , Petanjek Zdravko , Gustafsson Bengt , Ben‐Ari Yehezkel , Khazipov Roustem , Hanse Eric 
Published: September 2003

AbstractIn the neonatal rat, inhibition of hippocampal neural activity in vivo by tetanus toxin results in a severe growth impairment of the basal dendrites of CA1 pyramidal cells. Here we tested whether this early growth impairment results in a permanent reduction of the basal dendritic tree or whether recovery processes are recruited later in development when synaptic activity has fully recovered. Quantitative analysis of dendritic parameters and spine density from reconstructed CA1 pyramidal cells showed that young adult CA1 pyramidal (postnatal day 31–34) cells that were exposed to activity deprivation in the neonatal period were almost indistinguishable from control cells of the same age. These results suggest that the early hippocampal activity controls the growth rate but is not necessary for the generation of an adult normal basal dendritic tree.
Plasma membrane and vesicular glutamate transporter mRNAs/proteins in hypothalamic neurons that regulate body weight
Authors: Collin Maria , Bäckberg Matilda , Ovesjö Marie‐Louise , Fisone Gilberto , Edwards Robert H. , Fujiyama Fumino , Meister Björn 
Published: September 2003

AbstractAfter synaptic release, glutamate is taken up by the nerve terminal via a plasma membrane‐associated protein termed excitatory amino acid transporter 3 (EAAT3). Following entry into the nerve terminal, glutamate is pumped into synaptic vesicles by a vesicular transport system. Three different vesicular glutamate transporter proteins (VGLUT1‐3) representing unique markers for glutamatergic neurons were recently characterized. The presence of EAAT3, glutaminase and VGLUT1‐3 was examined in mouse, rat and rabbit species at mRNA and protein levels in hypothalamic neurons which are involved in the regulation of body weight using in situ hybridization and immunohistochemistry. EAAT3 and glutaminase mRNAs were demonstrated in all parts of the arcuate nucleus in the dorsomedial and ventromedial hypothalamic nuclei and lateral hypothalamic area. VGLUT1 mRNA was present in the magnocellular lateral hypothalamic nucleus. VGLUT2 mRNA was demonstrated in a subpopulation of neurons in the arcuate nucleus and in the ventromedial and dorsomedial hypothalamic nuclei and lateral hypothalamic area. Few VGLUT3 mRNA expressing neurons were scattered throughout the medial and lateral hypothalamus. EAAT3‐like immunoreactivity (‐li) was demonstrated in glutamate, neuropeptide Y (NPY), agouti‐related peptide (AGRP), pro‐opiomelanocortin (POMC), cocaine and amphetamine‐regulated transcript (CART), melanin‐concentrating hormone and orexin‐immunoreactive (‐ir) neurons. VGLUT2‐li could only be demonstrated in POMC‐ and CART‐ir neurons of the ventrolateral arcuate nucleus. The results show that key neurons involved in regulation of energy balance are glutamatergic and/or densely innervated by glutamatergic nerve terminals. Whereas orexigenic NYP/AGRP neurons situated in the ventromedial part of the arcuate nucleus are mainly GABAergic, it is shown that several anorexigenic POMC/CART neurons of the ventromedial arcuate nucleus are most likely glutamatergic.
Gene expression of AMPA‐type glutamate receptor subunits in rod‐type ON bipolar cells of rat retina
Authors: Kamphuis Willem , Dijk Frederike , O'Brien Brendan J. 
Published: September 2003

AbstractThe retinal rod bipolar cell type is involved in the sign‐inverting depolarizing ON‐type response to light. This response is mediated by the metabotropic glutamate receptor type 6 (mGluR6) expressed on the rod bipolar dendrites. In a previous immunocytochemical study, an unexpected colocalization was reported [W. Kamphuis et al. (2003) J. Comp. Neurol., 455, 172–186] of mGluR6 with the ionotropic AMPA‐type glutamate receptor subunit GluR2 in rod bipolar cells of rat retina. The aim of the present study was to investigate whether expression of both genes could be found at the single‐cell level. Two approaches were followed. (i) Retinal cells were isolated by enzymatic and mechanical treatment. Single cells with a bipolar morphology were harvested, subjected to multiplex PCR with protein kinase C (PKC)‐, mGluR6‐ and GluR1–4‐specific primers, followed by a real‐time quantitative PCR assay. Of 23 studied cells, 74% expressed PKC and 87% expressed mGluR6. Using the presence of both transcripts as the criterion for a rod bipolar cell signature (n = 15), 73% of these cells expressed GluR2, with a minor contribution of GluR1 (20%), GluR3 (7%), and GluR4 (20%). Quantification of the transcript levels demonstrated that mGluR6 and GluR2 genes are expressed at similar levels in rod ON‐type bipolar cells. (ii) Rod bipolar cells were identified in retinal sections by immunolabelling with a protein kinase C antibody and isolated using laser pressure catapulting (LPC). Quantitative PCR was employed to assess gene expression levels of reference genes, PKCα, mGluR6 and the GluR subunits. However, in samples from PKCα‐immunopositive somata no significant enrichment of PKCα transcript levels was observed when compared with control samples from immunonegative somata. We conclude that this approach lacks sufficient spatial specificity. In conclusion, the results show coexpression of mGluR6 and GluR2 in rod bipolar cells; this is in good agreement with the results of previous immunocytochemical studies. The functional implications of AMPA‐type glutamate receptors for ON‐type rod bipolar‐mediated signal transduction remains to be elucidated.
Morphometrical analysis of dendritic arborization in axotomized retinal ganglion cells
Authors: Germain Francisco , Fernández Eduardo , De La Villa Pedro 
Published: September 2003

AbstractIt has been reported that section of the optic nerve in mammals causes death in >90% of the retinal ganglion cells (RGCs). The cells which survive the section experience an irreparable loss of many of their dendritic segments and a rapid retraction of the dendritic tree. However, some growth cones and abnormal processes have been also reported. Our aim was to make a quantitative study of the morphological changes found in rabbit RGCs after optic nerve section. The morphometrical analysis of the RGCs which survived the axotomy showed an increase in the diameter of the soma and a significant increase in the area of the dendritic field; also, the length of the dendritic segments was significantly longer in axotomized RGCs than in control cells. Terminal dendritic segments (T) and preterminal segments (PT) were both measured in control and axotomized cells; the length ratio of T : PT segments was significantly greater in the axotomized cells than in the controls. We conclude that RGCs which survived the axotomy experienced a significant growth of their terminal dendritic branches.
Bicarbonate‐dependent depolarizing potentials in pyramidal cells and interneurons during epileptiform activity
Authors: Perez Velazquez Jose L. 
Published: September 2003

AbstractExperimental and theoretical evidence indicates that GABAergic neurotransmission is fundamental for the synchronization of neuronal activity. In particular, the role of GABA in epileptiform activity has received increased attention due to, among others, the fact that the GABA‐mediated potentials can be depolarizing, and hence excitatory, in some circumstances. Evidence is presented here that bicarbonate efflux via GABAA receptors in interneurons and pyramidal cells of the CA1 hippocampal area contribute to depolarizing GABAA‐mediated potentials in an in vitro nonpharmacological seizure‐like model of status epilepticus. Seizure‐like and interictal activity was evoked in rat horizontal hippocampal slices using a superfusing solution with low magnesium concentration (0.5–0.9 mm). Whole‐cell recordings from stratum oriens–alveus interneurons and CA1 pyramidal cells revealed that, during epileptiform activity, some GABAA‐mediated potentials were depolarizing, and were suppressed by the carbonic anhydrase inhibitor ethoxyzolamide as well as by the GABAA‐receptor antagonist bicuculline. These observations indicate that the depolarizing potentials observed during epileptiform activity reflect both glutamatergic and GABAA‐receptor‐mediated activity, and adds further support for the important role of GABAergic interneurons in promoting long‐range synchronization.