bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Basomedial and Basolateral Amygdaloid Nuclei Contribute to the Induction of Long‐term Potentiation in the Dentate Gyrus In Vivo
Authors: Ikegaya Yuji , Saito Hiroshi , Abe Kazuho 
Published: April 2006

AbstractRecent behavioural studies have provided evidence that the amygdala modulates hippocampal‐dependent memory. To test the possibility that the amygdala modulates hippocampal synaptic plasticity, we investigated the effects of surgical lesions of the amygdaloid nuclei on the induction of long‐term potentiation (LTP) in the dentate gyrus of anaesthetized rats. Previously we reported that LTP in the dentate gyrus was attenuated by lesion of the basolateral amygdala, but was not affected by lesion of the central amygdala. In the present study, dentate gyrus LTP was significantly attenuated by basomedial amygdala lesion but not by medial amygdala lesion. These results suggest that, among the amygdaloid nuclei, the basomedial and basolateral nuclei are involved in the modulation of hippocampal plasticity. The roles of the basomedial and basolateral amygdala were further supported by experiments examining the effects of electrical stimulation of these nuclei. High‐frequency stimulation of the basomedial amygdala alone did not induce dentate gyrus LTP, but when applied at the same time as tetanic stimulation of the perforant path increased the magnitude of the dentate gyrus LTP. Similarly, high‐frequency stimulation of the basolateral amygdala enhanced LTP induced by tetanic stimulation of the perforant path. Furthermore, facilitation of dentate gyrus LTP by basomedial or basolateral amygdala stimulation was observed even in rats lesioned in either amygdala, suggesting that neurons in the basomedial and basolateral amygdala can modulate dentate gyrus LTP independently. Activity‐dependent facilitation of hippocampal plasticity by the basomedial and basolateral amygdala may underlie memory processing associated with emotion.
The Glutamate Transport Inhibitor L‐trans‐pyrrolidine‐2,4‐dicarboxylate Indirectly Evokes NMDA Receptor Mediated Neurotoxicity in Rat Cortical Cultures
Authors: Blitzblau Rachel , Gupta Shalini , Djali Sina , Robinson Michael B. , Rosenberg Paul A. 
Published: April 2006

AbstractBecause of the well‐documented importance of glutamate uptake in protecting neurons against glutamate toxicity, we were interested in testing the effects of L‐trans‐pyrrolidine‐2,4‐ dicarboxylate (PDC) on rat cortical cultures. This compound is a substrate for glutamate transporters and is a potent glutamate transport inhibitor that does not interact significantly with glutamate receptors. Using a 30 min exposure, and assessing neuronal survival after 20‐24 h, PDC was neurotoxic in conventional astrocyte‐rich cortical cultures, with an EC50 in these cultures of 320 ± 157 μM. In astrocyte‐poor cultures, an EC50 for PDC of 50 ± 5 μM was determined. The neurotoxicity of PDC in both astrocyte‐rich and astrocyte‐poor cultures was blocked by the NMDA antagonist MK‐801, but not by the non‐NMDA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX). We tested the possibility that the neurotoxicity of PDC might be due to release of excitatory amino acids using several approaches. After pre‐loading cells with the non‐metabolizable analogue of glutamate, [3H]‐D‐aspartate, first we demonstrated that PDC caused significant efflux of [3H]‐D‐aspartate. This effect of PDC was dependent upon extracellular sodium. In contrast with glutamate neurotoxicity, PDC neurotoxicity was inhibited by removal of extracellular sodium. In the presence of 1 mM PDC, sodium caused neurotoxicity with an EC50 of 18 ± 7.6 mM. Tetrodotoxin had no effect on either PDC neurotoxicity or on PDC‐evoked [3H]‐D‐aspartate release. PDC‐evoked release of [3H]‐D‐aspartate was demonstrable in astrocyte cultures with no neurons present. PDC also evoked release of endogenous glutamate. Finally, the neurotoxicity of PDC was blocked by coincubation with glutamate‐pyruvate transaminase plus pyruvate to degrade extracellular glutamate. These results demonstrate the neurotoxicity of PDC, and suggest that the mechanism of this toxicity is the glutamate transporter‐dependent accumulation of glutamate in the extracellular space.
Plasticity of Metabolic Whisker Maps in Somatosensory Brainstem and Thalamus of Mice with Neonatal Lesions of Whisker Follicles
Authors: Melzer Peter , Smith Carolyn B. 
Published: April 2006

AbstractWe employed the autoradiographic deoxyglucose method to study metabolic whisker maps of the adult mouse somatosensory brainstem and thalamus after the neonatal removal of left whisker follicles C1, C2 and C3. Left whiskers B1–3 and D1–3 were deflected to metabolically activate the somatosensory pathway. Unoperated mice that were stimulated in the same fashion served as controls. Whisker stimulation resulted in an ipsilateral increase in metabolic activity in the three trigeminal brainstem structures in which the whiskers are represented topologically by segments of high cytochrome oxidase activity, i.e. subnucleus caudalis, subnucleus interpolaris and nucleus principalis. In the two subnuclei of mice with lesions and of controls, there was an increase in metabolic activity of the representations of the deflected whiskers, whereas the metabolic activity of representations A1–3 and E1–3 was low. Apart from these similarities, the metabolic activation of the representations originally representing whiskers C1–3 was remarkably greater in mice with lesions than in controls. This increase reached statistical significance in subnucleus caudalis and approached statistical significance in subnucleus interpolaris. In nucleus principalis the deprived territory was only partially activated and the degree of metabolic activation was less than in the subnuclei. In the thalamic ventrobasal complex of mice with lesions metabolic activity was unpatterned whereas two areas of metabolic activation were distinct in controls. Hence, the removal of whisker follicles in newborn mice resulted in the suppression of localized metabolic responses to whisker stimulation in the thalamus, whereas in the brainstem stimulus‐related activity was prominent and the deprived territory became responsive to the stimulation of whisker follicles adjacent to the lesion. Apparently, the modification of the whisker representation at the first synapse of the pathway induces a diminution of localized responsivity in the thalamus.
Neurotrophins and their Receptors in the Adult Hypo‐ and Hyperthyroid Rat after Kainic Acid Injection: an In Situ Hybridization Study
Authors: Calzà L. , Giardino L. , Ceccatelli S. , Hökfelt T. 
Published: April 2006

AbstractThyroid hormone plays a key role in trophic events during development of the central nervous system. In spite of neurological and psychiatric symptoms associated with adult hypothyroidism, the role of thyroid hormone in mature brain function is less clear. In this paper we investigated the effect of thyroid status on kainic acid‐induced up‐regulation of mRNAs for members of the nerve growth factor family and related receptors in adult male rats by means of in situ hybridization. We found that in hypothyroid rats there is a dramatic attenuation of the kainic acid‐induced up‐regulation of mRNA levels for nerve growth factor, brain‐derived neurotrophic factor and tyrosine kinase trkB in euthyroid rats. A trend to reduced c‐fos mRNA up‐regulation, which did not reach significance, was also found, whereas the increase in c‐jun mRNA after kainic acid was similar in eu‐, hypo‐ and hyperthyroid rats. These data indicate a severe impairment of the regulation of neurotrophin synthesis after excitotoxin administration in the hippocampus during adult hypothyroidism. Possible roles of thyroid hormone in molecular, biochemical and metabolic mechanisms of this defect are discussed.
Cholinergic Responses in Developing Outer Hair Cells of the Rat Cochlea
Authors: Dulon Didier , Lenoir Marc 
Published: April 2006

AbstractAcetylcholine‐evoked currents were investigated using the conventional whole‐cell patch‐clamp recording technique in developing outer hair cells (OHCs). The cells were isolated from the rat cochlea at different stages of postnatal development ranging from day 4 (P4) to P30. Acetylcholine‐evoked currents could be recorded at P6 and P8. At this developmental stage, the majority of OHCs displayed inward nicotinic‐like currents near the resting membrane potential. These cholinergic currents zeroed near 0 mV, as expected for a non‐selective cation current, and could be reversibly blocked by d‐tubocurarine. At P12 and adult stage, the cholinergic response of OHCs switched to an outward current reversing near EK and displaying a bell shape peaking between ‐40 and ‐30 mV. This change in polarity of the acetylcholine response during postnatal development might be explained by progressive functional coupling between acetylcholine ionotropic receptors permeable to Ca2+ and nearby Ca2+‐activated K+ channels at the synaptic pole of OHCs.
Evidence for Reactive Astrocytes in Rat Vestibular and Cochlear Nuclei Following Unilateral Inner Ear Lesion
Authors: de Waele C. , Torres A. Campos , Josset P. , Vidal P. P. 
Published: April 2006

AbstractWe investigated whether unilateral removal of the labyrinthine and cochlear receptors induces a macroglial reaction in rat vestibular and cochlear nuclei using vimentin and glial fibrillary acidic protein (GFAP) immunochemical markers. Antibody binding was visualized using the avidin‐biotin method and 3,3′‐diaminobenzidine as the peroxidase substrate. In addition, double‐labelling experiments were performed using specific secondary fluorescent antibodies. Potentially degenerating axon terminals were also studied using a silver impregnation method. In normal adult rats, vimentin was found only in ependymal cells, tanicytes around the fourth ventricle, endothelial cells in the blood vessels and Bergmann glia in the molecular layer of the cerebellum. In lesioned rats, all deafferented vestibular and ventral cochlear nuclei showed strong vimentin immunoreactivity. Furthermore, double‐labelling experiments demonstrated that these vimentin‐positive cells were also GFAP‐positive. The reaction became evident on the second day after the lesion, was intense for 3–8 days and then declined until day 21. No vimentin immunoreactivity could be detected at the level of the ipsilateral dorsal cochlear nucleus. Therefore, unilateral inner ear lesion induced an astroglial reaction within the deafferented vestibular and cochlear nuclei. The decrease in the resting discharge of the primary vestibular afferents and/or in the deafferented central vestibular neurons may induce the glial reaction in the vestibular complex, whereas both degeneration and silence of the cochlear nerve and central cochlear neurons are most probably responsible for the cochlear vimentin‐immunoreactive staining. The role of the reactive astrocytes in the vestibular compensation process remains to be determined.
The Competitive Transport Inhibitor L‐trans‐pyrrolidine‐2,4‐dicarboxylate Triggers Excitotoxicity in Rat Cortical Neuron‐Astrocyte Co‐cultures via Glutamate Release rather than Uptake Inhibition
Authors: Volterra Andrea , Bezzi Paola , Rizzini Barbara Lodi , Trotti Davide , Ullensvang Kyrre , Danbolt Niels C. , Racagni Giorgio 
Published: April 2006

AbstractWe studied the early and late effects of L‐trans‐pyrrolidine‐2,4‐dicarboxylate (PDC), a competitive inhibitor of glutamate uptake with low affinity for glutamate receptors, in co‐cultures of rat cortical neurons and glia expressing spontaneous excitatory amino acid (EAA) neurotransmission. At 100 or 200 μM, PDC induced different patterns of electrical changes: 100 μM prolonged tetrodotoxin‐sensitive excitation triggered by synaptic glutamate release; 200 μM produced sustained, tetrodotoxin‐insensitive and EAA‐mediated neuronal depolarization, overwhelming synaptic activity. At 200 μM, but not at 100 μM, PDC caused rapid elevation of the glutamate concentration ([Glu]0) in the culture medium, resulting in NMDA receptor‐mediated excitotoxic death of neurons 24 h later. The increase in [Glu]0 was largely insensitive to tetrodotoxin, independent of extracellular Ca2+, and present also in astrocyte‐pure cultures. By the use of glutamate transporters functionally reconstituted in liposomes, we showed directly that PDC activates carrier‐mediated release of glutamate via heteroexchange. Glutamate release and delayed neurotoxicity in our cultures were suppressed if PDC was applied in a Na+‐free medium containing Li+. However, replacement of Na+ with choline instead of Li+ did not result in an identical effect, suggesting that Li+ does not act simply as an external Na+ substitute. In conclusion, our data indicate that alteration of glutamate transport by PDC has excitotoxic consequences and that active release of glutamate rather than just uptake inhibition is responsible for the generation of neuronal injury.
The Influence of Nitric Oxide on Perigeniculate GABAergic Cell Activity in the Anaesthetized Cat
Authors: Rivadulla C. , Rodriguez R. , Martinez‐Conde S. , Acuña C. , Cudeiro J. 
Published: April 2006

AbstractWe have tested the effect of iontophoretic application of the nitric oxide synthase inhibitor l‐nitroarginine on the activity of a population of 53 perigeniculate (PGN) cells, recorded extracellularly in the anaesthetized paralysed cat. In all cells tested with visual stimulation during l‐nitroarginine application (n= 15), the visually elicited responses were markedly reduced, on average by 63 ± 15%, and there was a reduction in spontaneous activity too. This effect was blocked by co‐application of the substrate for nitric oxide synthase, l‐arginine, but not by the inactive d‐isoform, although application of l‐arginine alone was without effect. Pressure application of the nitric oxide donor S‐nitroso‐N‐acetylpenicillamine (SNAP) elevated both visual responses and spontaneous discharge, an effect also seen with a second nitric oxide donor, sodium nitroprusside (n= 12). The nitric oxide synthase inhibitor l‐nitroarginine was applied to a sub‐population of seven cells and it selectively decreased NMDA mediated excitation (reduction 80 % 14%) with little or no effect on the excitation mediated by α‐amino‐3‐hydroxy‐5‐5‐methyl‐4‐isoxazole‐propionic acid (AMPA) or quisqualate (effects not statistically significant), and it had no effect (n= 7) on excitation mediated by the metabotropic agonist (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (ACPD). Furthermore, application of SNAP also increased the magnitude of excitatory responses mediated by NMDA receptors. On a different population of seven cells, application of the new NO donor diethylamine‐nitric oxide (DEA‐NO) enhanced the actions Of NMDA without an effect on responses to AMPA. These effects are qualitatively and quantitatively similar to those we have previously described for X and Y type cells in the dorsal lateral geniculate nucleus (dLGN), despite the known opposite effects of acetylcholine (ACh) application in the dLGN and PGN (ACh is co‐localized with nitric oxide synthase at both sites). We propose that within the PGN nitric oxide acts to enhance transmission utilizing NMDA receptors selectively (thereby interacting with the globally inhibiting effect of ACh at this site) to enhance visual responses, reducing or removing the non‐specific inhibitory drive from PGN to dLGN seen in the spindling activity of slow‐wave sleep. These effects will act in concert with the facilitatory actions of both ACh and nitric oxide within the dLGN proper, and will thereby enhance the faithful transmission of visual information from retina to cortex.
Structural Analysis of the Murine Cell Adhesion Molecule L1 by Electron Microscopy and Computer‐assisted Modelling
Authors: Drescherl Bernd , Spies Eberhard , Schachner Melitta , Probstmeier Rainer 
Published: April 2006

AbstractIn the present study we have analysed the morphology of two fragments with apparent molecular weights of 180 and 140 kDa (L1‐180 and L1‐140) derived from the extracellular region of the murine neural cell adhesion molecule L1. The fragment L1‐180 consists of almost the entire extracellular part of the molecule, and is built up of six immunoglobulin‐like and five fibronectin type III‐like domains. Fragment L1‐140 lacks one‐half of the third, the fourth and the fifth fibronectin type III‐like domains. By electron microscopic analysis of rotary‐shadowed molecules, L1‐140 and L1‐180 revealed fibrillar structures 31‐43 nm long and 7‐12 nm wide with one pronounced globular terminal domain. As determined by complex formation with an L1 antibody, this terminal part of the molecule is formed by the fibronectin type III‐like domains. The individual structures showed variation and complexity, and four distinct aspects were identified. These different forms probably represent two‐dimensional projections of the same three‐dimensional helical structure. Computer‐assisted modelling of the L1 molecule, i.e. the protein backbone, showed no strong intramolecular interaction between the different fibronectin type III‐ or Ig‐like domains, suggesting that the formation of the globular part of the molecule is probably achieved by protein‐carbohydrate and/or carbohydrate‐carbohydrate rather than protein‐protein interactions. In addition, our model proposes that interactions occur within the interfaces between the different domains. The highly conserved amino acid residues in these regions point to the necessity of maintaining the orientation between the different domains.
Regulation of VIP and other Neuropeptides by c‐Jun in Sensory Neurons: Implications for the Neuropeptide Response to Axotomy
Authors: Mulderry Peter K. , Dobson Stephen P. 
Published: April 2006

AbstractPeripheral axotomy of adult rat sensory neurons causes induction of the transcription factor c‐Jun and increased expression of the neuropeptides vasoactive intestinal polypeptide (VIP), galanin and neuropeptide Y. To determine whether VIP induction is dependent on transcriptional regulation by c‐Jun, we exploited the fact that c‐Jun and VIP are also induced in cultured sensory neurons. We blocked c‐Jun synthesis by microinjecting antisense oligonucleotides and found that VIP expression, determined by quantitative immunofluorescence, was specifically reduced. Blockade of c‐Jun expression also resulted in reduced neuropeptide Y expression but left galanin, substance P and calcitonin gene‐related peptide unaffected. Since in vitro electrophoretic mobility shift assays showed that a nominal cyclic AMP responsive element (CRE) associated with the rat VIP gene could bind c‐Jun‐containing transcription factor complexes, we next investigated whether VIP expression in sensory neurons might depend on transcription factor binding to the CRE. When a DNA plasmid containing multiple copies of the CRE was injected into newly cultured sensory neurons to sequester transcription factors binding the endogenous CRE, there was a selective reduction in VIP expression. VIP induction in sensory neurons therefore probably results from transcriptional activation by c‐Jun acting in combination with other factor(s), possibly acting through the CRE. These results show that c‐Jun can regulate transcription of other genes affected by axotomy and imply that it could be a key regulator of the neuronal axotomy response.
Developmental Expression and Self‐regulation of Ca2+ Entry via AMPA/KA Receptors in the Embryonic Chick Retina
Authors: Allcorn Suzette , Catsicas Marina , Mobbs Peter 
Published: April 2006

AbstractExcessive activation of glutamate receptors in the late embryonic and adult retina leads to excitotoxic cell death through an increase in intracellular calcium concentration. Here we use the cobalt‐staining technique of Pruss et al. to investigate the developmental expression of Ca2+‐permeable α‐amino‐3–hydroxy‐5–methyl‐isoxazole‐4‐propionic acid/kainate (AMPNKA) receptors in the embryonic chick retina, and the effects of AMPNKA receptor activation on cell survival and AMPNKA receptor expression. Ca2+‐permeable AMPNKA receptors are present in the retina as early as embryonic day 6 (E6). While sustained activation of these receptors with KA led to massive cell death in explant and dissociated cultures of the chick retina late in development, continuous application of high doses of KA from early times was not excitotoxic. Cell survival in KA is correlated with both a reduction in cobalt staining and the KA‐evoked membrane current, and thus with a reduction in the Ca2+entry into cells via AMPNKA receptors. The effects of KA could be blocked by the non‐N‐methyl‐d‐aspartic acid (NMDA) receptor antagonist 6‐cyano‐7‐nitro‐quinoxaline‐2,3–dione (CNQX), but not by the NMDA receptor antagonist D‐2‐amino‐5‐phosphonovalerate (AP5) nor the L‐type Ca2+ channel blockers diltiazem and nifedipine. The action of AP5 was mimicked by exposure to glutamate but not by the metabotropic receptor agonist 1S,3R‐1–aminocyclopentane‐1,3–dicarboxylic acid. Thus exposure of retinal neurons to glutamate early in development may protect them from its excitotoxic actions later on.
Biphasic Response of Spinal GABAergic Neurons after a Lumbar Rhizotomy in the Adult Rat
Authors: Dumoulin Andréa , Alonso Gérard , Privat Alain , Feldblum Sophie 
Published: April 2006

AbstractThe expression of γ‐aminobutyric acid (GABA) and of the isoforms of the enzyme involved in its synthesis, glutamic acid decarboxylase (GAD), is modified in several rat brain structures in different injury models. The aim of the present work was to determine whether such plasticity of the GABAergic system also occurred in the deafferented adult rat spinal cord, a model where a major reorganization of neural circuits takes place. GABAergic expression following unilateral dorsal rhizotomy was studied by means of non‐radioactive in situ hybridization to detect GADs67 mRNA and by immunohistochemistry to detect GAD67 protein and GABA. Three days following rhizotomy the number of GAD67 mRNA‐expressing neurons was decreased in the superficial layers of the deafferented horn, while GABA immunostaining of axonal fibres located in this region was highly increased. Seven days after lesion, on the other hand, many GAD67 mRNA‐expressing neurons were bilaterally detected in deep dorsal and ventral layers, this expression being correlated with the increased detection of GADs67 immunostained somata and with the reduction of GABA immunostaining of axons. GABA immunostaining was frequently found to be associated with reactive astrocytes that exhibited intense immunostaining for glial fibrillary acidic protein (GFAP) but remained GADs67 negative. These results indicate that degeneration of afferent terminals induces a biphasic response of GABAergic spinal neurons located in the dorsal horn and show that many spinal neurons located in deeper regions re‐express GAD67, suggesting a possible participation of the local GABAergic system in the reorganization of disturbed spinal networks.