bluuebunny/crossref_metadata_2025 huggingface dataset:
Extraskeletal mesenchymal chondrosarcoma of the kidney
Authors: KANEKO TAKUJI , SUZUKI YASUSHI , TAKATA RYO , TAKATA KOH , SAKUMA TSUTOMU , FUJIOKA TOMOAKI
Published: April 2006

Abstract  A 61‐year‐old woman was referred for evaluation of an incidental mass found on the right kidney. Abdominal ultrasonography and computed tomography showed a 3‐cm tumor with calcification and peripheral enhancement. Under the diagnosis of renal cell carcinoma, a transabdominal right radical nephrectomy was performed. The pathological diagnosis was extraskeletal mesenchymal chondrosarcoma of the kidney. No recurrence or metastasis occurred during a 6‐year follow up. Primary renal chondrosarcoma is extremely rare, this being only the fifth case reported in the English literature, and the patient's extended survival is attributed to the small size of the tumor, as well as early diagnosis and treatment.
Prostaglandin E2 Receptors in the Chicken Spinal Cord:
Authors: Pralong E. , Vesin M.‐F. , Droz B.
Published: April 2006

Prostaglandins (PGs) are neuroactive substances which act in the vicinity of their site of synthesis through receptors coupled to G‐proteins. Since large amounts of PGE2 can be synthesized by chicken spinal cord, binding sites for PGE2 were looked for in various cell fractions of spinal cord. In the 17 000 g pellet incubated with 0.3 nM [3H]PGE2, 70% of ligand was specifically bound. Two types of PGE2 binding site were characterized (i) high affinity, low capacity binding sites (KD1 1.34 nM, Bmax1 34.5 fmol/mg prot); (ii) low affinity, high capacity binding sites (KD2 2.23 μM, Bmax2 13.2 pmol/mg prot). The high affinity binding sites fulfil several requirements for being receptors to PGE2: (i) since the KD1 is increased in the presence of the GTP analogue, Gpp(NH)p, these binding sites would be regulated by a G‐protein; (ii) a desensitization was obtained by an excess of unlabelled PGE2 and reversed by Gpp(NH)p; (iii) the competition experiments between PGE2 and various prostanoids pointed to PGE2 receptors such as EP2 or EP3. The receptor characteristics of the low‐affinity binding sites were not investigated. Hence, our results support the presence of two types of PGE2 binding site in the chicken spinal cord; a high affinity site, which corresponds to a PGE2 receptor responding to nanomolar concentrations and a low affinity site sensitive to micromolar concentrations of PGE2.
Fibroblast Growth Factor Enhances Long‐term Potentiation in the Hippocampal Slice
Authors: Terlau Heinrich , Seifert Wilfried
Published: April 2006

Recently we reported that perfusion of hippocampal slices with epidermal growth factor (EGF) lead to enhancement of potentiated responses after tetanic stimulation. In the present study we report that basic fibroblast growth factor (FGF) can also lead to an enhancement of potentiated responses. FGF is a mitogen for several cell types and exhibits neurotrophic effects on neurons of the central nervous system (CNS). Rat hippocampal slices were perfused with FGF at a concentration of 10−9 M. During extra‐ and intracellular recordings in the CA1 ‐region, the addition of FGF to the perfusing medium produced no change in evoked responses if single pulse or paired pulse stimulation was used. Furthermore FGF had no influence on the resting membrane potential and input resistance. However, after tetanic stimulation, FGF‐treated slices showed an increase in the magnitude of potentiation compared to control slices. Taken together with the EGF data these results support the hypothesis that growth factors like FGF with neurotrophic potential on CNS‐neurons can influence synaptic efficacy. Furthermore these results show that factors which are able to modulate developmental plasticity and regenerative plasticity can also modulate synaptic plasticity.
Prechiasmatic Reordering of Fibre Diameter Classes in the Retinofugal Pathway of Ferrets
Authors: Baker G. E.
Published: April 2006

This study examines the distribution of fibre diameter classes at various sites along the retinofugal pathway of adult ferrets. Light microscopic observations were made on semi‐thin sections, and regional fibre diameter spectra were constructed from diameter measurements taken from electron micrographs of thin sections of the intraorbital optic nerve (2.5 mm from the optic disc), the intracranial optic nerve (1 mm rostral to the fusion of the nerves), and the optic tract (just caudal to the optic chiasm).

Whereas diameter types are relatively evenly distributed behind the eye in the postoptic nerve, they begin to segregate along its prechiasmatic course. Within this prechiasmatic region, coarse and fine calibre fibres are confined increasingly to more ventral locations in the nerve, leaving a dorsal band populated predominantly by intermediate calibre fibres. In conjunction with this redistribution of axon size classes, the fascicular arrangement of axons which is present distally, changes to a non‐fascicular organization. The prechiasmatic organization of fibre types approximates that found in the optic tract where the coarse and fine calibre fibres lie further ventrally towards the pial surface.

The prechiasmatic region can be viewed as a region of transition where the order of fibres in the nerve (retinotopic) starts to change to that present in the optic tract (chronotopic), resulting in the first‐born beta cell axons becoming segregated dorsally, and rostral to the coarse and fine calibre classes which segregate at further caudal locations. Further, since the sorting of fibres according to diameter appears before the fibres reach the optic chiasm, the segregation of diameter classes is not dependent on the chiasmatic sorting of fibres according to their crossed or uncrossed course.
Immunocytochemistry of cGMP in the Cerebellum of the Immature, Adult, and Aged Rat: the Involvement of Nitric Oxide. A Micropharmacological Study
Authors: de Vente J. , Bol J. G. J. M. , Berkelmans H. S. , Schipper J. , Steinbusch H. M. W.
Published: April 2006

In this study we describe the localization of formaldehyde‐fixed cGMP‐immunoreactivity (cGMP‐IR) in rat cerebellar tissue slices incubated in vitro. In the absence of phosphodiesterase inhibition, cGMP‐immunofluorescence was of low intensity in tissue slices prepared from immature cerebella. Addition of isobutylmethylxanthine (IBMX) to the incubation medium resulted in the appearance of cGMP‐IR in clusters of astrocytes in the internal granular layer. Addition of N‐methyl‐D‐aspartate (NMDA), kainic acid, atrial natriuretic factor (ANF), or sodium nitroprusside (SNP) gave an intense cGMP‐IR in Bergmann fibres, Bergmann cell bodies, and astrocytes in the internal granular layer. Astrocytes in the white matter showed cGMP‐IR after incubation of the slice in the presence of ANF or nitroprusside, but not after NMDA or kainic acid. In addition, after SNP stimulation of cGMP production, cGMP‐IR was found in fibres which were not positive for glial fibrillary acidic protein (GFAP). In the adult cerebellar slice, intense basal cGMP‐immunostaining was observed in Bergmann fibres, Bergmann cell bodies, and astrocytes in the granular layer. No cGMP‐IR was observed in Purkinje cells. Stimulation of the cGMP‐content in the glial structures by NMDA, ANF, or SNP, was suggested by the immunocytochemical results. However, when measured biochemically, only the effect of SNP was statistically significant, and immunocytochemistry showed that SNP clearly stimulated cGMP synthesis in neuronal cell structures. In the cerebellum of the aged rat a reduced cGMP‐IR was found compared to the adult, in the same structures which showed cGMP‐IR in the adult. Basal cGMP‐immunostaining was reduced in the presence of haemoglobin, methylene blue, by inhibiting nitric oxide synthesis with NG‐monomethyl‐L‐arginine (NGMAr), or by depletion of external Ca2+. Also the stimulatory effect of NMDA and of ANF (partly) on the cGMP‐IR was inhibited by these compounds. cGMP‐IR after stimulation of guanylate cyclase by SNP was reduced by the concomitant presence of haemoglobin or methylene blue, but not by NGMAr, or by omission of Ca2+. Our results point to an important role for cGMP in the functioning of glial tissue in the cerebellum and also suggest a role for nitric oxide as an intercellular mediator in the functioning of glutamate and ANF in the cerebellum.
Pharmacological and Biochemical Properties of Nicotinic Receptors from Chick Retina
Authors: Loring Ralph H. , Zigmond Richard E.
Published: April 2006

Previous work has established that functional nicotinic receptors in the chick retina are blocked by neuronal bungarotoxin (NBT), and that the binding of radio‐iodinated NBT to retinal homogenates is displaced by nicotinic ligands. In the present study, we examined the desensitizing effects of agonists on nicotinically‐mediated depolarizations recorded from chick retina. The concentrations of five agonists necessary to reduce the amplitude of these depolarizations by 50% were found to correlate closely with the concentrations of these same agonists previously found necessary to displace 50% of NBT binding. In addition, bromoacetylcholine (BAC), a selective affinity alkylating agent for the agonist binding site, irreversibly inactivated the functional responses of intact chick retina with an inhibiting concentration for 50% block (IC50) near 10‐6 M, the same concentration of BAC that displaced 50% of labelled NBT binding from alkylated retinal homogenates. These data suggest that NBT acts at the receptor agonist binding site. Furthermore, this binding site has a relatively low affinity for agonists, in the micromolar range, even in the desensitized state. Multiple subtypes of nicotinic receptors are known to exist in neuronal tissue, and receptors that bind agonists in the nanomolar range have been detergent‐solubilized and purified using monoclonal antibodies. Under similar conditions, detergent‐solubilization of chick retinal homogenates interfere with the interaction between NBT and the low‐affinity neuronal nicotinic receptors. These data suggest that the conditions used to purify high‐affinity neuronal nicotinic receptors may denature the subtype(s) of neuronal receptors recognized by NBT.
The Microtubular Pattern Changes at the Spinal Cord‐Root Junction and Reverts at the Root‐Peripheral Nerve Junction in Sensory and Motor Fibres of the Rat
Authors: López José Manuel A. , Alvarez Jaime
Published: April 2006

In the rat, we studied the microtubular content of central nervous system (CNS) axons (pyramidal tract, dorsal funiculus, and intracord domain of motor axons), of radicular axons (ventral and dorsal roots), and of peripheral axons (sural and lateral gastrocnemius nerves). The microtubular density had an inverse relationship with the size of the axon. Within the CNS, values ranged from over 120 microtubules/μm2 for axons smaller than 0.1 μm2 of the pyramidal tract and dorsal funiculus to 24 for 3‐μm motor axons (area, 7 μm2) in their spinal cord domain. Peripheral nerve and CNS axons of the same size had comparable microtubular densities. In contrast, the microtubular density of dorsal and ventral root axons was one half that of CNS or peripheral nerve axons of equal calibre. Considered along the axon, the microtubular density of motor and sensory fibres is high in the CNS domain, low in the root, and high again in the peripheral nerve domain. These observations are inconsistent with the notion that the cytoskeleton moves coherently away from the perikaryon. We conclude that the axonal microtubular content accords with the calibre of the fibre and with the anatomical region where it courses. We propose that axonal microtubules are regulated by local cues.
Accumulation of N‐CAM 180 at Contact Sites Between Neuroblastoma Cells and Latex Beads Coated with Extracellular Matrix Molecules
Authors: Pollerberg G. Elisabeth , Nolte Christiane , Schachner Melitta
Published: April 2006

Neuronal cells expressing neural cell adhesion molecule (N‐CAM) accumulate the largest N‐CAM component (N‐CAM 180) at cell — cell contact sites. To test whether this accumulation is induced by interactions at the surface membrane, latex beads coated with several purified adhesion molecules or extracellular matrix (ECM) components were co‐cultured with neuroblastoma cells. Beads coated with L1, N‐CAM, the L2/HNK‐1 carbohydrate epitope‐carrying molecules from adult mouse brain or laminin from Engelbreth‐Holm‐Swarm (EHS) sarcoma did not induce an accumulation of N‐CAM 180 or L1 at sites of contact suggesting that these molecules are not directly involved in N‐CAM 180 accumulation or that their mobility is required for this process. Beads coated with ECM components of the PF‐HR9 cell line induced accumulation of N‐CAM 180 at sites of contact with neuroblastoma cells. Accumulation was seen at cell bodies of undifferentiated and differentiated neuroblastoma cells, as well as on neurites and growth cones of differentiated neuroblastoma cells. Accumulation of the neural adhesion molecule L1 was also seen, but less prominently and reproducibly. These observations suggest that molecules of the ECM can directly or indirectly, e.g. via molecules linked to N‐CAM 180 on the cell surface, induce accumulation of N‐CAM 180.
Electrophysiology and Pharmacology of the Corticothalamic Input to Lateral Thalamic Nuclei: an Intracellular Study in the Cat
Authors: Deschênes Martin , Hu Bin
Published: April 2006

Though most experimental evidence indicates that the corticothalamic (CT) pathway would exert a direct excitatory action on thalamic relay neurons, the electrophysiological features of this excitation have never been clearly described. A methodological problem in previous electrophysiological studies was that direct corticofugal effects on relay cells could not be separated from those mediated by collateral activation of reticular thalamic neurons. In the present study, the reticular complex was lesioned by kainic acid and the CT response of relay neurons of the ventral lateral nucleus was recorded intracellularly in cats under pentobarbital or urethane anaesthesia.

Following reticular thalamic lesions, a prominent depolarization was triggered in thalamic relay cells by stimulation of the CT pathway. This depolarization strongly drove spike discharges, and its amplitude augmented when the stimulation rate exceeded 2 Hz. Tetanizing the CT input with short trains (100–200 Hz for 200–300 ms) produced a similar augmentation to test volleys for 15–30 s after the tetanos. The CT excitation and its frequency‐dependent augmentation were depressed by ketamine injection or by local application of N‐methyl‐D‐aspartate (NMDA) antagonists. The augmenting phenomenon appeared strictly homosynaptic. For instance, it did not appear during repetitive stimulation of the cerebellar input, nor did the CT input potentiate subthreshold synaptic potentials of cerebellar origin during a conditioning procedure. Conversely, the cerebellar excitation was depressed when it occurred during the CT depolarization.

It is concluded that the direct synaptic responses induced by CT fibres in relay neurons are mediated at least partly by the activation of NMDA receptors. Moreover, the marked non‐linear additivity of cerebellar and CT synaptic potentials raises questions concerning the presumed improvement of thalamic transmission of peripheral informations ensured by the CT input. Instead, both inputs could compete for control of the firing of thalamic neurons. The numerical importance of CT fibres and the strong augmenting mechanism operating at synaptic sites in the thalamus suggest that the role of the thalamus is not only to transfer peripheral informations toward the cortex, but also and mainly to feed back to the cortex a modified copy of its own neuronal constructs.
Complex Expression Patterns for Na+,K+ ‐ATPase Isoforms in Retina and Optic Nerve
Authors: McGrail Kevin M. , Sweadner Kathleen J.
Published: April 2006

Three genetically distinct isozymes of the catalytic subunit of the Na,K‐ATPase have been detected and have been designated α1, α2, and α3. To determine whether their expression is restricted to identifiable neurons and glia, specific monoclonal antibodies were used for immunofluorescent localization in the rat retina and optic nerve. The patterns of staining were markedly different, suggesting differences in cellular localization. Photoreceptor inner segments and optic nerve fibers expressed predominantly α3. Müller glia in the retina and astrocytes in the optic nerve expressed α1 and α2. Isolated, dissociated bipolar, horizontal, and Müller cells expressed different isozymes separately or in combination. The complexity of staining of neurons and their axons and dendrites suggested that Na,K‐ATPase isozyme expression is not stereotyped, but is tailored to the ion transport needs of individual cell types, and targeted to specified membrane domains.
Effect of Prior Dopamine Denervation on Survival and Fiber Outgrowth from Intrastriatal Fetal Mesencephalic Grafts
Authors: Doucet G. , Brundin P. , Descarries L. , Björklund A.
Published: April 2006

[3H]Dopamine (DA) uptake radioautography and tyrosine hydroxylase (TH) immunocytochemistry were used to assess quantitatively the effects of the presence or absence of host mesostriatal DA afferents on the survival and fiber outgrowth from fetal ventral mesencephalic DA neurons grafted into the neostriatum of adult recipient rats. Rats received bilateral intrastriatal transplants of fetal ventral mesencephalic tissue 1 month after a unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the right nigrostriatal bundle (denervated side). Five to six months later, some of the grafted rats received a second 6‐OHDA injection in the left nigrostriatal bundle (acutely denervated or ‘intact’side). After a further 7 days, slices of each hemisphere from the latter rats were incubated with [3H]DA and processed for film and high resolution radioautography. The density of the film radioautographs was measured with a computerized image analysis system and calibrated by silver grain cluster (i.e. DA terminal) counting over selected areas of the same sections in light microscope radioautographs. The brains of the remaining grafted rats were processed for TH immunoreactivity 6–12 months after graft surgery. Neither the size of the grafts, nor the number of surviving TH‐positive graft neurons showed any significant difference between the nondenervated and the denervated sides. However, the size of the TH‐positive cell bodies was significantly greater in the grafts on the denervated side. In the [3H]DA uptake radioautographs, considerable outgrowth of DA fibers was evident in the neostriatum on the ‘intact’side in spite of the presence of an intact host DA innervation until 7 days before sacrifice. The overall DA fiber outgrowth was nevertheless almost two‐fold greater on the denervated side, and extended deeper into the host neostriatum than on the ‘intact’side; only 7% of the total neostriatal area, on average, was at background level compared to 30% on the ‘intact’side, and the overall density of neostriatal DA innervation amounted to 36% of normal as compared to 20% on the ‘intact’side. The correlation between the overall density of graft‐derived DA innervation and the size of the grafts was linear on the ‘intact’side, but reached a plateau with relatively small grafts on the denervated side. However, the ventral striatum on both sides was very poorly innervated by these grafts. These findings demonstrate that the mature neostriatal tissue can support axonal growth and innervation from grafted fetal DA neurons even in the presence of a normal complement of endogenous DA fibers. Prior removal of the host striatal DA innervation does not influence the overall size of the grafts nor the number of surviving DA neurons, but induces an increase in the cell body size and fiber outgrowth of the grafted DA neurons.
7‐Chlorokynurenate Blocks NMDA Receptor‐Mediated Neurotoxicity in Murine Cortical Culture
Authors: Hartley D. M. , Monyer H. , Colamarino S. A. , Choi D. W.
Published: April 2006

We examined the neuroprotective actions of the glycine site N‐methyl‐D‐aspartate (NMDA) antagonist, 7‐chlorokynurenate, in murine neocortical cell cultures. Cultures exposed for 5 min to 100–500 μM NMDA in the absence of added glycine developed substantial neuronal degeneration over the next 24 h. The addition of 10 μM glycine did not increase submaximal NMDA‐induced neuronal injury, suggesting that endogenous glycine levels were sufficient to saturate its receptor sites on NMDA receptor complexes. Addition of 3–300 μM 7‐chlorokynurenate produced concentration‐dependent reduction in this neuronal damage with an IC50 of approximately 30 μM. Some injury reduction was seen even if the drug was added after completion of the NMDA exposure. The protective effect of 100 μM 7‐chlorokynurenate could be overcome by adding 10–1000 μM glycine (glycine median effective concentration (EC50) approximately 100 μM) or 1 mM D‐serine. As predicted by its ability to block NMDA receptor‐mediated injury, 10–300 μM 7‐chlorokynurenate also produced concentration‐dependent reduction in the neuronal loss induced by 50–60 min exposure to combined glucose and oxygen deprivation. These data support the suggestion that pharmacologic interference with the binding of glycine to the NMDA receptor complex represents a potentially effective approach to blocking NMDA receptor‐induced neurotoxicity in ischemia.
Targets and Quantitative Distribution of GABAergic Synapses in the Visual Cortex of the Cat
Authors: Beaulieu C. , Somogyi P.
Published: April 2006

The morphology and postsynaptic targets of GABA‐containing boutons were determined in the striate cortex of cat, using a postembedding immunocytochemical technique at the electron microscopic level. Two types of terminals, both making symmetrical synaptic contacts, were GABA‐positive. The first type (95% of all GABA‐positive boutons) contained small pleomorphic vesicles, the second type (5%) contained larger ovoid vesicles. Furthermore, 99% of all cortical boutons containing pleomorphic vesicles were GABA positive, and all boutons with pleomorphic vesicles made symmetrical synaptic contacts. These results together with previously published stereological data (Beaulieu and Colonnier, 1985, 1987) were used to estimate the density of GABA‐containing synapses, which is about 48 million/mm3 in the striate cortex. The postsynaptic targets of GABA positive boutons were also identified and the distribution was calculated to be as follows: 58% dendritic shafts, 26.4% dendritic spines, 13.1% somata and 2.5% axon initial segments. A total of 11% of the postsynaptic targets were GABA immunoreactive and therefore originated from GABAergic neurons. The results demonstrate that the majority of GABAergic synapses exert their action on the membrane of dendrites and spines rather than on the somata and axons of neurons.
Horizontal Interactions in Cat Striate Cortex: I. Anatomical Substrate and Postnatal Development
Authors: Luhmann H. J. , Singer W. , Martinez‐Millán L.
Published: April 2006

The system of tangential connections was studied in area 17 of normally reared (NR), binocularly deprived (BD) and dark‐reared (DR) kittens and adult cats. Connections were labelled antero‐ and retrogradely by intracortical micro‐injections of several fluorescent markers and horseradish peroxidase conjugated with wheat‐germ agglutinin (WGA‐HRP). In 5‐day‐old kittens tangential connections consist of homogeneously distributed fibres extending maximally over 2.7 mm. Around postnatal day (pnd) ten these connections start to express the patchy pattern characteristic of the adult. Retrogradely stained somata and anterogradely labelled terminals become organized in individual 300 to 350 μm wide clusters with a centre‐to‐centre spacing of about 500 μm. During the first three postnatal weeks the horizontal connections increase their span to up to 10.5 mm and the spacing between individual patches increases to about 700 μm. Over the following 4 weeks these projections become reduced in length and number. In adult NR cats, tangential connections span a distance of up to 3 mm and form a lattice of 200–500 μm wide clusters, which have an average centre‐to‐centre spacing of 1050 μm. Tangential connections originate and terminate in all cortical laminae except layer I and they are organized in register. The distances spanned are largest in supragranular, intermediate in infragranular and shortest in granular layers. In BD and DR cats older than 10 weeks, the length of intracortical tangential fibres becomes reduced to the same extent as in NR animals, but individual clusters are less numerous. The authors conclude that the lattice‐like structure of lateral connections evolves independently of visual experience, and that the selectivity of interactions results from pruning of initially exuberant connections. It is suggested that this pruning process is dependent on activity and influenced by visual experience.
Horizontal Interactions in Cat Striate Cortex: II. A Current Source‐Density Analysis
Authors: Luhmann H. J. , Greuel J. M. , Singer W.
Published: April 2006

The current source‐density (CSD) analysis was used to investigate the organization of tangential synaptic connections in primary visual cortex of normally reared (NR) kittens and of NR, binocularly deprived (BD) and dark‐reared (DR) adult cats. Laminar profiles of field potentials, elicited by intracortical microstimulation were measured at various distances from the stimulating electrodes. To exclude contamination by axon collaterals of antidromically stimulated thalamo‐cortical fibres, these were destroyed by injecting the cytotoxin N‐methyl‐D‐aspartate (NMDA) into the lateral geniculate nucleus 13–27 days before recording. The CSD profiles revealed distinct layer‐specific patterns of lateral spread of activity. Invariably, the most prominent, long‐lasting and far reaching responses were recorded in supragranular layers. Responses in layer IV were brief and confined to the vicinity of the stimulation site. Responses in infragranular layers spread as far as those in supragranular layers, but were of smaller amplitude. Latency considerations, the results of double shock stimulation, and the effects of translaminar cuts, suggest that these responses were monosynaptic and mediated by intracortical pathways with a conduction velocity of 0.3–5 m/s. The spatial spread of these responses changed substantially with age but was not influenced by visual deprivation. In NR adults, supra‐ and infragranular responses were recordable up to 2.5 mm from the stimulation site and layer IV responses up to 1 mm from the stimulation site. In kittens, the former responses spread up to 5 mm and the latter up to 2 mm from the site of stimulation. The amplitude of the responses decreased with distance from the stimulation site. This decrease was not always monotonic suggesting inhomogeneities in the tangential projections. The laminar distribution of current sinks and sources indicates that the pathways mediating tangential interactions form excitatory synapses on apical dendrites of pyramidal cells. It is concluded that the spatial spread of tangential excitatory interactions decreases with age, but that neither the laminar pattern nor the age‐dependent reduction in the strength of tangential interactions are influenced by visual deprivation.
Cross‐desensitization Reveals Pharmacological Specificity of Excitatory Amino Acid Receptors in Isolated Hippocampal Neurons
Authors: Kiskin N. I. , Krishtal O. A. , Tsyndrenko A. Ya.
Published: April 2006

Ionic currents elicited by excitatory amino acids were studied, using the concentration clamp method, in enzymatically isolated rat hippocampal neurons. Cross‐desensitization between the responses to various agonists was applied to separate the activity of two types of receptors, N‐methyl‐D‐aspartate (NMDA) and non‐NMDA. NMDA receptors were selectively activated by NMDA, L‐ and D‐aspartate, D‐glutamate and quinolinate. Kainate and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate appeared to be selective, and quisqualate relatively less selective non‐NMDA agonists, acting on the same receptor type. L‐Glutamate, L‐ and D‐homocysteate activated both receptor types. It is supposed that two receptor sites, activation site and densensitization site, control the action of agonists at the non‐NMDA receptor. When examined in the cross‐desensitization experiments, NMDA and non‐NMDA receptors appear to be represented by the two homogeneous and independent receptor populations operating different ionic channels.
Distribution of Tyrosine Hydroxylase mRNA in the Rat Central Nervous System Visualized by Alkaline Phosphatase in situ Hybridization Histochemistry
Authors: Kiyama H. , Emson P. C. , Ruth J.
Published: April 2006

The expression of tyrosine hydroxylase mRNA in the rat brain was examined using a novel alkaline phosphatase labelled antisense oligodeoxynucleotide probe. The alkaline phosphatase labelled probe revealed the presence of tyrosine hydroxylase mRNA in all the major cell groups and cell bodies previously described as containing catecholamine fluorescence or known to contain tyrosine hydroxylase immunoreactivity. Using standardized development protocols qualitative comparisons between the amount of mRNA signal in different adrenergic, noradrenergic or dopaminergic cell groups could be made. These studies showed that of the three known catecholaminergic cell types the level of tyrosine hydroxylase mRNA signal was high in the noradrenergic and dopaminergic cells, but much lower in the adrenergic cell groups. The sensitivity of this nonradioactive method of in situ hybridization is excellent and has considerable potential for studies of coexistence or coexpression of two mRNA signals for the localization of mRNA signals at the electron—microscope level.
Modulation of VIP‐Stimulated cAMP Formation by Excitatory Amino Acids in Mouse Cerebral Cortex
Authors: Schaad N. C. , Schorderet M. , Magistretti P. J.
Published: April 2006

We have investigated the modulatory action of excitatory amino acids (EAA) on vasoactive intestinal polypeptide (VIP)‐stimulated cAMP formation in mouse cerebral cortical slices. Glutamate and aspartate potentiate in a concentration‐dependent manner the effect of VIP. In order to characterize the type of receptor involved, we have used three prototypical EAA receptor agonists, that is, kainate, N‐methyl‐D‐aspartate (NMDA) and quisqualate. Kainate mimicked the effect of glutamate, NMDA was inactive and quisqualate displayed an inhibitory action. Furthermore, ibotenate also potentiated the effect of VIP on cAMP formation, while L‐homocysteate exhibited an inhibitory action. Ibotenate was 4‐fold more potent and 2.5 times more effective than glutamate. However, the effects of kainate and ibotenate were not additive, suggesting the activation of a common receptor. Thus, based on this metabotropic action, EAA can be categorized into the following classes: (i) those that potentiate the effect of VIP, such as glutamate, aspartate, kainate and ibotenate; (ii) those that inhibit the effect of VIP, such as L‐homocysteate and quisqualate; and (iii) those that are ineffective, such as NMDA and D‐homocysteate. The effects of glutamate or ibotenate on VIP‐stimulated cAMP formation were completely inhibited by L‐phosphoserine and only partially by kynurenate. In a low chloride medium, or in the presence of 8‐(N,N‐diethylamino) octyl‐3,4,5‐trimethoxybenzoate‐hydrochloride (TMB‐8), an inhibitor of calcium release from internal stores, EAA did not potentiate the effect of VIP, thus stressing the importance of these ions for the transduction of the glutamatergic signal. Our results indicate the existence of marked interactions between EAA and VIP on cAMP formation; the pharmacology of these interactions is, however, clearly distinct from the classical pharmacology of EAA which is mainly based on electrophysiological and binding studies.
Distribution of Galanin mRNA Containing Cells and Galanin Receptor Binding Sites in Human and Rat Hypothalamus
Authors: Bonnefond C. , Palacios J. M. , Probst A. , Mengod G.
Published: April 2006

The distribution of cells containing galanin mRNA and that of galanin receptor binding sites were investigated using in situ hybridization histochemistry and receptor autoradiography in male rat hypothalamus and in postmortem hypothalamic tissues from control human brains. Oligonucleotide probes labelled with 32P were used for hybridization experiments. The specificity of the hybridization signal was ascertained using several probes, competition assays and Northern blot analysis. High levels of hybridization were found in the paraventricular, supraoptic and arcuate nuclei of rat and human hypothalamus. Human intermediate nuclei and scattered cells of the posterior perifornical nucleus also contained galanin mRNA. Galanin mRNA was also found in the dorsomedial nucleus of the rat. The distribution of galanin receptor sites was investigated by receptor autoradiography using 125I‐labelled porcine galanin. The specificity of the binding was assessed by competition with different neuropeptides. While galanin blocked the binding at nanomolar concentrations, the other neuropeptides examined were ineffective at 10‐7 M concentrations. The highest densities of galanin binding sites were seen in the preoptic area, ventromedial and lateral nuclei, of rat and human hypothalamus. In contrast, very low densities of binding sites were observed in the paraventricular, supraoptic and arcuate nuclei. Our results show that the distribution of neurons expressing galanin is complementary to that of galanin receptors in the rat and human hypothalamus. This suggests that receptors for galanin are not located on the cell bodies of galaninergic neurons, but are probably presynaptic on or postsynaptic to the processes of these cells.
Differential Actions of Endogenous and Iontophoretic Dopamine in Rat Striatum
Authors: Williams Graham V. , Millar Julian
Published: April 2006

We have voltammetrically monitored dopamine release in the rat striatum evoked either by stimulation of the median forebrain bundle or by iontophoresis. Neuronal spike activity was recorded with the same microelectrode alternately with voltammetric scans. Low levels of stimulation‐evoked dopamine (< 1 μM) excited all striatal units tested. However, this effect could be converted into an inhibition at higher levels of release. In contrast to the results with neuronally released dopamine, excitation was never seen when dopamine was applied by iontophoresis. Inhibition was, however, observed at high concentrations (> 1–5 μM) of exogenous dopamine. These data show that endogenous dopamine at low levels may be predominantly an excitatory transmitter in the striatum, but exogenous (iontophoretic) dopamine does not have the same effect on striatal unit activity as the endogenous material.
Efferent Pattern of Fictive Locomotion in the Cat Forelimb: with Special Reference to Radial Motor Nuclei
Authors: Gödderz W. , Illert M. , Yamaguchi T.
Published: April 2006

In immobilized decerebrate cats fictive locomotion was evoked by midbrain stimulation to analyse the efferent pattern to elbow and to distal forelimb muscles innervated by the deep radial nerve. The locomotor activity was assessed by recording nerve discharges and motoneuronal membrane potential changes. The elbow flexor and extensor motoneurons showed a reciprocal activity; the membranes were correspondingly depolarized and hyperpolarized. In the motor nuclei to the wrist and digit extensors the active phases changed systematically according to the radio‐ulnar order of the muscles: the extensor carpi radialis (ECR) was flexor‐coupled, the ulnaris (ECU) extensor‐coupled, the digitorum communis (EDC), the lateralis (EDL) and the indicis proprius (EIP) displayed intermediate patterns. Intracellular recordings from these motoneurons revealed in all motor nuclei, except ECR, a double depolarization. The first occurred early and the second later in the flexor phase; a hyperpolarization was interposed. The second depolarization mainly determined the active phase. According to the radio‐ulnar order of the muscles the onset and termination of the second depolarization were delayed. This was presumably due to the interposed hyperpolarization, which progressively increased in amplitude. The ECR exhibited a single depolarization, into which the double depolarization apparently merged. The other radial motor nuclei, supinator (Sup) and Abductor pollicis longus (APL) displayed complex patterns. Sup showed tonic discharges, flexor‐type discharges or discharges extending both into the flexor and extensor phase, APL showed discharges similar to either EIP or Sup. Membrane potential changes were small in APL and Sup. Thus, the central locomotor network generates differentiated efferent activities in the distal forelimb muscles, the radio‐ulnar order of the muscles being important for the generated pattern.
The Maturation of the Superior Collicular Map of Auditory Space in the Guinea Pig is Disrupted by Developmental Auditory Deprivation
Authors: Withington‐Wray D. J. , Binns K. E. , Dhanjal S. S. , Brickley S. G. , Keating M. J.
Published: April 2006

Guinea pigs, reared from birth in an environment of omnidirectional white noise, fail to develop a map of auditory space in the deeper layers of the superior colliculus. Collicular responses from such noise‐reared animals reveal large auditory spatial receptive fields. The representation of auditory space in the colliculus shows no topographic order. Exposing developing animals to the noise environment only for restricted time periods showed that animals reared normally up to 26 days after birth (DAB) and then placed in the noise chamber could not construct spatial maps, whereas animals reared normally to 30 DAB and then placed in the noise chamber until the terminal mapping experiment could construct topographically organized spatial maps with local receptive fields. Limiting the noise exposure to the period between 26 and 30 DAB was sufficient to prevent spatial map formation. The failure to form a map of auditory space did not reflect environmental damage to the cochlea or the functional organization of the primary auditory pathway. The response thresholds of cochlear microphonics and of auditory responses in both the inferior and superior colliculus were normal in noise‐reared animals. Similarly normal were the tonotopic organization and frequency tuning characteristics of inferior collicular neurons. The rearing environment thus appears to exert a selective effect upon the maturation of the superior collicular map of auditory space. We attribute this effect to the masking, by the omnidirectional broad‐band noise, of discrete localized auditory stimuli. Cues deriving from these latter stimuli would appear to be necessary for the elaboration of the map of auditory space. This auditory experience operates during a 4 day crucial developmental period from 26 to 30 DAB. This is the same developmental time window as that during which visual experience is required for the construction of the map.
Lateral Mobility of the Cell Adhesion Molecule L1 Within the Surface Membrane of Morphologically Undifferentiated and Differentiated Neuroblastoma Cells
Authors: Pollerberg G. Elisabeth , Davoust Jean , Schachner Melitta
Published: April 2006

Lateral mobility and localization in the surface membrane of the adhesion molecule L1 was studied in morphologically undifferentiated and differentiated neuroblastoma cells to gain insight into its possible association with the different molecular forms of N‐CAM. In undifferentiated cells, the fraction of mobile L1 molecules is high and similar to that of N‐CAM 140. Upon long‐term morphological differentiation, the fraction of mobile L1 molecules is reduced by a factor of three and is similar to that of N‐CAM 180, the predominant molecular form of N‐CAM in differentiated neuroblastoma cells. Comparable to N‐CAM 180, L1 is also preferentially accumulated at contact sites between these cells as seen by indirect immunofluorescence. These observations raise the question of whether at least part of the L1 molecules may be directly or indirectly (e.g. via N‐CAM 180) linked to the cytoskeleton, thus stabilizing cell contacts between differentiated cells.
Heterogeneity in the Dorsal Subiculum of the Rat. Distinct Neuronal Zones Project to Different Cortical and Subcortical Targets
Authors: Witter Menno P. , Ostendorf Robert H. , Groenewegen Henk J.
Published: April 2006

The aim of the present study was to relate the distribution of efferents of the dorsal subiculum to their origin along the proximo‐distal axis of the subiculum. The distribution of subicular projections was studied in detail by means of the sensitive anterograde tracer Phaseolus vulgaris‐leucoagglutinin (PHA‐L), and the precise origin of these projections analysed with retrogradely transported fluorescent tracers, using double‐ and triple‐labelling protocols. Injections of PHA‐L in the proximal part of the dorsal subiculum, i.e. that part which borders field CA1, result in labelling of the infralimbic, entorhinal and perirhinal cortices, the nucleus accumbens and the lateral septa) region, the interanteromedial nucleus of the thalamus, the core of the nucleus gelatinosus, and the mammillary nuclei, in particular in the rostral parts of the medial nucleus. In contrast, injections in the distal part of the dorsal subiculum, i.e. that part which borders the presubiculum, give rise to labelling in the retrosplenial and postrhinal cortices, the presubiculum, the anterior thalamic complex, the shell of the nucleus gelatinosus, and the mammillary nuclei, preferentially in the caudal part of the medial nucleus. The results of injections of different retrograde tracers, simultaneously placed in two or three targets of the subicular efferents, confirm the results of the anterograde tracing experiments. Moreover, they clearly demonstrate that the population of subicular neurons which, for example, projects to the nucleus accumbens and the interanteromedial nucleus of the thalamus is almost completely segregated from the population that projects to the retrosplenial cortex and the anterior complex of the thalamus. Thus within the dorsal subiculum, populations of neurons can be differentiated so that each population projects to a unique set of target structures. These cell populations are differentially positioned along the proximo‐distal axis. In view of additional evidence indicating that some of the major afferents to the subiculum are organized along the same axis, we suggest that the heterogeneity of the dorsal subiculum along the proximo‐distal axis reflects a general organizational characteristic of this hippocampal field.
Climbing Fibre Responses in Olivo‐cerebellar Slice Cultures. I. Microelectrode Recordings from Purkinje Cells
Authors: Knöpfel T. , Audinat E. , Gähwiler B. H.
Published: April 2006

Cerebellar slices prepared from newborn rats were co‐cultured with slices derived from the inferior olive of 4‐day‐old rats. After several weeks in vitro olivary fibres projecting into the cerebellar tissue could be assessed by anterograde labelling with the fluorescent dye 1,1‐dioctadecyl‐3,3,3,3′‐tetramethylindocarbocyanine perchlorate (Dil). Following electrical field stimulation of the olivary tissue, all‐or‐nothing complex spikes were generated in Purkinje cells, which closely resembled climbing fibre responses as seen in situ. These responses were completely and reversibly abolished by 6‐cyano‐7‐nitroquinoxaline‐2‐3‐dione (CNQX, 5 μM), an antagonist of non‐N‐methyl‐D‐aspartate excitatory amino acid receptors. Wash in of smaller concentrations of CNQX (0.5–2 μM) resulted in a graded dose‐dependent depression of the climbing fibre‐induced postsynaptic potentials and in a consecutive failure of distinct active components of the complex spikes. With climbing fibre synaptic transmission blocked by CNQX, complex spike‐like potentials could, however, still be evoked by intrasomatic injection of depolarizing current pulses. Increasing the concentration of Mg2+ in the bathing solution from 0.5 to up to 8 mM depressed regenerative complex‐spike components. Olivary stimulation elicited only monophasic postsynaptic potentials in Purkinje cells under these conditions. These observations indicate that voltage‐gated conductances which are substantially involved in the generation of the complex spike, are gated by the climbing fibre synaptic depolarization rather than directly by the climbing fibre transmitter.
Relation Between Putative Transmitter Phenotypes and Connectivity of Subplate Neurons During Cerebral Cortical Development
Authors: Antonini A. , Shatz C. J.
Published: April 2006

During development, the earliest generated neurons of the mammalian telencephalon reside in a region of the white matter, the subplate, just beneath the cortical plate. Neurons in the subplate are only transiently present in the telencephalon: shortly after birth in the cat the majority have disappeared. During their brief life, however, subplate neurons mature; they extend long‐distance and local projections, and express immunoreactivity for GABA and several neuropeptides. In the present study we examined the relation between possible transmitter phenotypes of subplate neurons and their connectivity. To do so, we used a double‐label technique in which immunohistochemistry for neuropeptide Y (NPY), somatostatin (SRIF) or calbindin (CaBP) was combined with retrograde tracing. Experiments were performed in neonatal cats and in ferret kits at equivalent postconceptional ages, times when subplate neurons are numerous. Subplate neurons immunoreactive for neuropeptides and CaBP could be double‐labelled by an injection of retrograde tracer either into the cortical plate or the white matter, indicating that this particular subset of subplate neurons can make local circuit projections. In contrast, peptide or CaBP immunoreactive subplate neurons could never be retrogradely labelled from a tracer injection into the thalamus. Taken together, these observations indicate that subplate neurons immunoreactive for NPY, SRIF and CaBP are likely to be interneurons exclusively. On the other hand, subplate neurons with long‐distance projections to the thalamus or the contralateral hemisphere could be labelled by the retrograde transport of D‐[3H]aspartate, suggesting that at least some projection subplate neurons might use an excitatory amino acid as a neurotransmitter. These results indicate that there is a defined relationship between the putative transmitter phenotypes of subplate neurons and their patterns of projection. Interneurons of the subplate express peptidergic properties while projection neurons to the thalamus may use an excitatory amino acid. Thus, these basic organizational features of the transient subplate are reminiscent of those found in the adult cortical layers.
Acetorphan, an Enkephalinase Inhibitor, Modulates Dopaminergic Transmission in Rat Olfactory Tubercle, but not in the Nucleus Accumbens and Striatum
Authors: Dourmap Nathalie , Michael‐Titus Adina , Costentin Jean
Published: April 2006

The present study focused on the effects of acetorphan, a parenterally active enkephalinase inhibitor, on dopaminergic transmission in rat olfactory tubercle, nucleus accumbens and striatum. Acetorphan was administered i.v. (10 mg/kg) 15 min before measurement of the in vivo specific binding of [3H]N‐propyl‐norapomorphine ([3H]NPA) or measurement of the levels of dopamine (DA) and its metabolites 3‐methoxytyramine‐homovanillic acid (3MT‐HVA) in the three areas. Acetorphan decreased the in vivo specific binding of [3H]NPA in the olfactory tubercle, this effect being antagonized by naloxone 1.5 mg/kg s.c. DA release in this brain structure was also significantly increased by acetorphan 10 mg/kg, as indicated by the 3MT:DA and HVA:DA ratios. Neither the specific binding of [3H]NPA nor DA metabolism and release were modified by the inhibitor in the striatum and the nucleus accumbens. The stimulant effect of acetorphan was significantly decreased in rats in which a bilateral lesion of dopaminergic endings in the olfactory tubercle had been produced by 6‐hydroxydopamine (6‐OHDA). These results suggest that dopaminergic transmissions in the olfactory tubercle are particularly sensitive to the modulation exerted by endogenous enkephalins, this modulation being at least partly involved in the increased locomotion induced by the enkephalinase inhibitor.