bluuebunny/crossref_metadata_2025 huggingface dataset:
Recovery of ChAT lmmunoreactivity in Axotomized Rat Cholinergic Septal Neurons Despite Reduced NGF Receptor Expression
Authors: Naumann T. , Straube A. , Frotscher M.
Published: April 2006

Previous studies have suggested that target‐derived nerve growth factor (NGF) is essential for the survival of cholinergic basal forebrain neurons. Thus, axotomy of septohippocampal neurons in adult rats resulting in the withdrawal of target‐derived NGF caused a dramatic loss of choline acetyltransferase (ChAT)‐immunoreactive neurons in the medial septum‐diagonal band complex. We have recently shown that this loss of immunolabelled neurons does not indicate cell death, since many septohippocampal cholinergic neurons recover their immunoreactivity for ChAT after a long survival time despite disconnection from target‐derived neurotrophins. One possibility would be that these surviving ChAT‐immunoreactive neurons have gained access to other, probably local, NGF sources. Here we provide evidence that the recovery of ChAT immunoreactivity after axotomy is not accompanied by a similar recovery of NGF receptor expression in these neurons. In situ hybridization for p75NTR mRNA and trkA mRNA 6 months after bilateral fimbria‐fornix transection revealed a substantial loss of labelled cells. In addition, there was a persisting loss of p75NTR‐immunoreactive and NGF‐immunoreactive medial septal neurons. Cholinergic neurons in controls did not express NGF mRNA, but were heavily immunostained for NGF protein due to receptor‐mediated uptake. These data suggest that at least some cholinergic septohippocampal neurons re‐express ChAT either independently of NGF or with a reduced need for NGF.
Modulation of Responses of Four Types of Feline Ascending Tract Neurons by Serotonin and Noradrenaline
Authors: Jankowska E. , Hammar I. , Djouhri L. , Hedén C. , Läckberg Z. Szabo , Yin X.‐K.
Published: April 2006

Modulation of responses of four types of ascending tract cells by noradrenaline and serotonin was compared in order to investigate how information forwarded by these cells may be gated by monoaminergic tract neurons. Spinocervical tract, postsynaptic dorsal column and dorsal spinocerebellar tract neurons located in Clarke's column and in the dorsal horn were identified by their axonal projections. Noradrenaline and serotonin were applied ionophoretically close to a selected neuron, and their effects were tested on extracellularly recorded responses of this neuron to electrical stimulation of low‐threshold skin afferents and group II muscle spindle afferents. The modulatory actions of noradrenaline and serotonin were estimated from changes in the number of responses evoked by 30 successive stimuli, the minimal latencies of these responses, and their firing frequency. All four populations of ascending tract neurons investigated were modulated by serotonin and noradrenaline, but not in the same way. The responses were most often depressed by noradrenaline and facilitated by serotonin, but in some types of neuron they were affected in the same direction. Transmission from low‐threshold skin and group II muscle afferents changed in the same direction in some types of neuron but in the opposite direction in other types. The results indicate that transfer of information from skin and group II muscle afferents to supraspinal centres may be gated by descending monoaminergic pathways in a highly differentiated manner, and is adjusted to the requirements of various behavioural situations.
Differential Regulation of mRNAs for GDNF and its Receptors Ret and GDNFRα After Sciatic Nerve Lesion in the Mouse
Authors: Naveilhan Philippe , ElShamy Wael M. , Ernfors Patrik
Published: April 2006

Glial cell line‐derived neurotrophic factor (GDNF), first characterized for its effect on dopamine uptake in central dopaminergic neurons, appears to be a powerful neurotrophic factor for motor neurons. GDNF has recently been shown to signal through a multisubunit receptor. This receptor is composed of a ligand‐binding subunit, called GDNF receptor α (GDNFRα), and a signalling tyrosine kinase subunit, Ret. To gain further insight into GDNF function, we investigated the expression of GDNF and its receptors after nerve lesion in adult mice. Analysis of expression in muscle, nerve and spinal cord by RNase protection assay and in situ hydridization revealed that, in adult non‐lesioned mice, GDNF mRNA was expressed in the nerve and GDNFRα mRNA in the nerve and the spinal cord, while the expression of Ret was restricted to spinal cord motor neurons. After a sciatic nerve crush a rapid increase in GDNF mRNA was observed in the distal part of the nerve and a delayed elevation in the muscle, while GDNFRα mRNA was up‐regulated in the distal part of the sciatic nerve but not in proximal nerve or spinal cord. The lesion also induced a rapid increase in Ret mRNA expression, but the increase was observed only in spinal cord motor neurons and in dorsal root ganglion neurons. A pattern of expression of GDNF and its receptors similar to that seen after lesion in the adult was detected during embryonic development. Administration of GDNF enhanced sciatic nerve regeneration measured by the nerve pinch test. Taken together, these results suggest that GDNF has an important role during regeneration after nerve damage in the adult.
Modulation of Sensory and Excitatory Amino Acid Responses by Nitric Oxide Donors and Glutathione in the Ventrobasal Thalamus of the Rat
Authors: Shaw P. J. , Salt T. E.
Published: April 2006

Nitric oxide has been identified as having a role in synaptic transmission in the central nervous system. In the ventrobasal complex of the thalamus (VB), the precursor of nitric oxide synthesis, L‐arginine, causes enhancement of excitatory amino acid responses and somatosensory transmission. In this study, the nitric oxide donors sodium nitroprusside, 3‐morpholinosydnonimine and S‐nitrosoglutathione were applied to VB relay neurons by iontophoresis and responses of single neurons were recorded extracellularly. Sodium nitroprusside caused selective inhibition of responses to NMDA, probably mediated by a by‐product, ferrocyanide, as described in previous studies. 3‐Morpholinosydnonimine and S‐nitrosoglutathione, however, caused potentiation of responses to sensory stimuli and to excitatory amino acids. In contrast, glutathione in both its reduced and oxidized forms reduced such responses, and this suggests that the potentiating effect of S‐nitrosoglutathione could be due to nitric oxide production. These results are consistent with the hypothesis that nitric oxide may have a local modulatory role in the thalamus. Data are presented which suggest that glutathione may have a negative modulatory influence on neurotransmission and excitatory amino acid responses in the ventrobasal thalamus.
Metabotropic Glutamate Receptors in the Rat Nucleus Accumbens
Authors: Manzoni Olivier , Michel Jean‐Marie , Bockaert Joél
Published: April 2006

The effects of glutamate metabotropic receptors (mGluRs) on excitatory transmission in the nucleus accumbens were investigated using electrophysiological techniques in rat nucleus accumbens slices. The broad‐spectrum mGluR agonist (1S,3R)‐1‐aminocyclopentyl‐1,3‐dicarboxylate, the mGluR group 2 selective agonists (S)‐4‐carboxy‐3‐hydroxyphenylglycine, (1S,3S)‐ACPD) and (2S,1′S,2′S)‐2‐(2′‐carboxycyclopropyl)glycine (L‐CCG1), and the mGluR group 3 specific agonist L‐2‐amino‐4‐phosphonobutyrate (L‐AP4) all reversibly inhibited evoked excitatory synaptic responses. The specific group 1 mGluR agonist (R,S)‐3,5‐dihydroxyphenylglycine [(R,S)‐DHPG] did not depress transmission. Dose‐response curves showed that the rank order of agonist potencies was: L‐CCGI > L‐AP4 > (1 S,3S)‐ACPD. Group 2 and 3 mGluRs inhibited transmission via a presynaptic mechanism, as they increased paired‐pulse facilitation, decreased the frequency of miniature excitatory postsynaptic currents and had no effect on their amplitude. The mGluRs did not inhibit transmitter release by reducing voltage‐dependent Ca2+ currents through N‐ or P‐type Ca2+ channels, as inhibition persisted in the presence of a‐conotoxin‐GVIA or Aga‐IVA. The depression induced by mGluRs was not affected by specific antagonists of dopamine D1, GABA‐B or adenosine A1 receptors, indicating direct effects. Finally, (13,s)‐DHPG specifically blocked the postsynaptic afterhyperpolarization current (Iahp). Our results represent the first direct demonstration of functional mGluRs in the nucleus accumbens of the rat.
Evidence that Blue‐on Cells are Part of the Third Geniculocortical Pathway in Primates
Authors: Martin Paul R. , White Andrew J. R. , Goodchild Ann K. , Wilder Heath D. , Sefton Ann E.
Published: April 2006

Colour vision in primates is mediated by cone opponent ganglion cells in the retina, whose axons project to the dorsal lateral geniculate nucleus in the visual thalamus. It has long been assumed that cone opponent ganglion cells project to the parvocellular layers of the geniculate. Here, we examine the role of a third subdivision of the geniculocortical pathway: the interlaminar or koniocellular geniculate relay cells. We made extracellular recordings in the dorsal lateral geniculate nucleus of the common marmoset Callithrix jacchus, a New World monkey in which the interlaminar cells are well segregated from the parvocellular layers. We found that one group of colour opponent cells, the blue‐on cells, was largely segregated to the interlaminar zone. This segregation was common to dichromatic (‘red‐green colour‐blind’) and trichromatic marmosets. The result calls into question the traditional notion that all colour information passes through the parvocellular division of the retino‐geniculo‐cortical pathway in primates.
Modulation of NCAM Polvsialvlation is Associated with Morphofunctional Modifkations in the Hypothalamo‐neurohypophysial System During Lactation
Authors: Nothias Fatiha , Vernier Philippe , von Boxberg Ysander , Mirman Simone , Vincent Jean‐Didier
Published: April 2006

Post‐transcriptional modification of the neural cell adhesion molecule (NCAM) by polysialic acid significantly decreases NCAM adhesiveness and more generally modifies cell‐cell interactions. Polysialic acid‐NCAM (PSA‐NCAM) is mainly expressed in the developing nervous system. In the adult, its expression is restricted to regions that retain morphological plasticity, such as the hypothalamo‐neurohypophysial system during lactation in rats. Since cell‐cell interactions and synaptic contacts in the hypothalamo‐neurohypophysial system are greatly increased during lactation, we examined whether PSA‐NCAM expression is modified during this period. lmmunohistochemistry and immunoblotting showed that, compared with virgin rats, PSA‐NCAM dramatically decreased during lactation in both the supraoptic nuclei and the neurohypophysis, and returned to its initial level only after weaning. This decrease was progressive and became significant only at the end of the first week of lactation. By contrast, modifications in the level of NCAM protein or changes in the splicing pattern of NCAM mRNAs could not be detected. The decline in polysialic acid on the NCAM molecule could strengthen membrane appositions, thereby stabilizing the newly established synapses and neurohaemal contacts in the hypothalamo‐neurohypophysial system that accompany the increased neuronal activity that occurs during lactation. We also studied the regulation of the phosphorylated microtubule‐associated protein‐1B (MAP1B‐P), whose distribution pattern largely overlaps with that of PSA‐NCAM in the adult brain. Expression of MAP1B‐P was greatly increased during lactation in the hypothalamic axons projecting into the neurohypophysis. Thus, the expression patterns of both PSA‐NCAM and MAP1B‐P may reflect the permanent structural plasticity characterizing the hypothalamo‐neurohypophysial system in the adult.
Interneuron‐specific Ca2+ Responses Linked to Metabotropic ‐and lonotropic Glutamate Receptors in Rat Hippocampal Slices
Authors: Carmant Lionel , Woodhall Gavin , Ouardouz Mohamed , Robitaille Richard , Lacaille Jean‐Claude
Published: April 2006

Glutamate‐mediated regulation of intracellular Ca2+ levels was examined in different populations of CA1 interneurons, using confocal microscopy and the Ca2+ indicator fluo 3‐AM in rat hippocampal slices. Interneurons in basal [stratum oriendalveus (OA)] and apical [strata radiatum and lacunosum‐moleculare (R/LM)] dendritic layers responded heterogeneously to glutamate. In control medium, OA interneurons responded mostly with oscillatory Ca2+ responses, which consisted of a large Ca2+ transient and successive smaller elevations. R/LM interneurons responded mostly with biphasic responses, characterized by an initial large transient and a secondary prolonged elevation. Other interneurons in both R/LM and OA responded with transient elevations in Ca2+ levels. lonotropic glutamate receptor antagonists (±)2‐amino‐5‐phosphonopentanoic acid and 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione reduced peak Ca2+ responses in OA and R/LM cells, and blocked biphasic responses in R/LM interneurons. The metabotropic glutamate receptor antagonist (RS)‐α‐methyl‐4‐carboxyphenylglycine reduced peak Ca2+ responses only in OA interneurons, and prevented oscillatory responses. In low Ca2+ medium, peak responses were reduced in R/LM but not in OA interneurons, and oscillatory responses were absent. Combination of ionotropic and metabotropic receptor antagonists blocked all glutamate‐evoked Ca2+ responses. Activation of different types of glutamate receptors may thus produce heterogeneous Ca2+ signals in subpopulations of CA1 interneurons. lonotropic receptors may generate biphasic responses in interneurons in apical dendritic layers, whereas combined activation of metabotropic and ionotropic receptors may trigger oscillatory responses in interneurons of basal dendritic layers. These heterogeneous Ca2+ responses indicate that glutamate‐mediated Ca2+ processes and second messenger systems differ in subpopulations of hippocampal interneurons and suggest possible postsynaptic functional specialization of interneurons.
Epidermal Growth Factor is a Motility Factor for Microglial Cells In Vitro: Evidence for EGF Receptor Expression
Authors: Nolte Christiané , Kirchhoff Frank , Kettenmann Helmut
Published: April 2006

Epidermal growth factor (EGF) and its receptor are present in the central nervous system and modulate a variety of neural functions. Here we show that microglial cells, the brain‐intrinsic macrophages, express the receptor for EGF and migrate in response to EGF. Transcripts encoding the EGF receptor could be detected in purified microglial cultures obtained from newborn mouse cortex. More specifically, cDNA fragments derived from EGF receptor mRNA could be amplified from 21% of electrophysiologically characterized microglial cells by the use of a single‐cell reverse transcription‐polymerase chain reaction method. Expression of the protein was confirmed on rat microglia by flow cytometty. EGF dose‐dependently stimulated chemotactic migration, as revealed with a microchemotaxis assay. The dose‐response curve peaked at 10 ng/ml EGF, reaching a 3‐fold increase in migration over the unstimulated control; migration was about half of that induced by complement 5a (10 nM), a previously described microglial chemoattractant. Chequerboard analysis showed that EGF‐induced motility was composed of both chemotaxis and chemokinesis. In contrast to its pronounced effect on cell motility, EGF (0.01–10 ng/ml) was not a mitotic signal for microglia, as shown by lack of bromodeoxyuridine incorporation. Acute and chronic pathological processes within the brain stimulate the synthesis and release of immunoregulators and growth factors (including EGF) that play a major role in the brain's response to injury. EGF may serve as a paracrine factor to direct microglial cells to the lesion site. Moreover, since EGF is secreted by activated microglia themselves in vivo, it may act as an autocrine modulator of microglial cell function.
Distinct Effects of Clostridial Toxins on Activity‐dependent Modulation of Autaptic Responses in Cultured Hippocampal Neurons
Authors: Owe‐Larsson Björn , Kristensson Krister , Hill Russell H. , Brodin Lennart
Published: April 2006

Clostridial neurotoxins proteolyse specific proteins implicated in synaptic vesicle exocytosis, but their actions on the release machinery in functional synapses is not well understood. Here we examine the effects of botulinum toxin A (BoNT/A) and tetanus toxin (TeTx) on autaptic transmission in cultured rat hippocampal neurons using whole‐cell voltage clamp recordings. The proportion of cells responding to stimulation with an excitatory postsynaptic current (EPSC) and the magnitude of the remaining responses decreased gradually with increasing concentration of either toxin. However, the activity‐dependent modulation (5 Hz repetitive stimulation) of EPSCs remaining after toxin inhibition differed markedly between the two toxins. The TeTx inhibition was associated with a persistent activity‐dependent depression similar to that in control cells. In contrast, the BoNT/A inhibition was accompanied by a reversal of the modulation into facilitation, resembling that induced by lowering of the calcium concentration. These results demonstrate a difference between BoNT/A and TeTx in their mode of inhibition of synaptic vesicle exocytosis, which suggests that they exert their preferential actions at distinct steps of the release process.
Changes in the Expression of the Extracellular Matrix Molecules Tenascin‐C and Tenascin‐R after 3–Acetylpyridine‐induced Lesion of the 01ivocerebe1lar System of the Adult Rat
Authors: Wintergerst Eva Sabine , Bartsch Udo , Batin Cesira , Schachner Melitta
Published: April 2006

In the central nervous system of rodents, the extracellular matrix glycoproteins tenascin‐C and tenascin‐R are expressed predominantly by astrocytes and oligodendrocytes respectively. Both molecules support neurite outgrowth from several neuronal cell types when presented as uniform substrates. When offered as a sharp boundary with a permissive substrate, however, both molecules prevent neurite elongation. On the basis of these observations it has been suggested that tenascin‐C and tenascin‐R may be relevant in determining the cellular response after injury in the adult rodent central nervous system. To investigate whether tenascin‐C and tenascin‐R may play important functional roles in the lesioned central nervous system, we have analysed their expression in the olivocerebellar system of the adult rat after 3–acetylpyridine‐induced degeneration of nerve cells in the inferior olivary nucleus. Tenascin‐C mRNA was not detectable at any time in the unlesioned or lesioned inferior olivary nucleus by in situ hybridization. In the cerebellar cortex, tenascin‐C mRNA in Golgi epithelial cells was down‐regulated 3 days after the lesion and returned to control values 80 days after the lesion. Tenascin‐R mRNA was expressed by distinct neural cell types in the unlesioned olivocerebellar system. After a lesion, the density of cells containing tenascin‐R transcripts increased significantly in the inferior olivary nucleus and in the white matter of the cerebellar cortex. Immunohistochemical and immunochemical investigations confirmed these observations at the protein level. Our data thus suggest differential functions of tenascin‐C and tenascin‐R in the injured central nervous system.
Increased Expression of trkB mRNA in Rat Caudate‐Putamen Following 6–OHDA Lesions of the Nigrostriatal Pathway
Authors: Numan S. , Seroogy K. B.
Published: April 2006

The tyrosine kinase receptors trkB and trkC are essential components of the high‐affinity receptors for members of the neurotrophin family, including brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3). Both neurotrophin receptor mRNAs are broadly distributed throughout the caudate‐putamen. In animal models of Parkinson's disease, loss of the ventral mesencephalic dopamine projection to the striatum has been shown to alter the expression of several striatal peptides, neurotransmitter‐synthesizing enzymes and receptors. To determine if expression of trkB and/or trkC striatal mRNAs is also regulated by the integrity of the dopaminergic afferents, adult rats were given unilateral injections of 6–hydroxydopamine (6–OHDA), selective catecholamine neurotoxin, or vehicle into the right ascending medial forebrain bundle. Following 2 week survival period, in situ hybridization with 35S‐labelled cRNA probes for the kinase‐specific, full‐length form of trkB mRNA and all forms of trkC mRNA was performed in striatal sections. A significant increase in the hybridization density for trkB mRNA was observed in the caudate‐putamen ipsilateral to the 6–OHDA injection, compared with the uninjected control side (P < 0.001). In contrast, no alteration in the hybridization density for trkC mRNA was observed in the striatum of 6–OHDA‐treated rats. No alterations in trkB or trkC mRNA levels were observed in the striata of vehicle‐treated animals. These data suggest that midbrain dopaminergic afferents regulate the expression of trkB mRNA in the caudate‐putamen. Alternatively, since dopaminergic neurons of the ventral mesencephalon express BDNF mRNA, the up‐regulation of striatal trkB mRNA may reflect compensatory response by striatal neurons due to loss of anterogradely and/or retrogradely derived trophic support from the ventral midbrain.
Development of Action Potential‐dependent and Independent Spontaneous GABAA Receptor‐mediated Currents in Granule Cells of Postnatal Rat Cerebellum
Authors: Wall Mark J. , Usowicz Maria M.
Published: April 2006

The postnatal development of spontaneous GABAergic transmission between cerebellar Golgi cells and granule cells was investigated with voltage‐clamp recording from rat cerebellar slices, in symmetrical Cl‐conditions. Between postnatal days 7 and 14 (P7–14), bicuculline‐and TTX (tetrodotoxin)‐sensitive spontaneous inhibitory postsynaptic currents (sIPSCs), occurred at high frequency in 56% of granule cells. Between P10 and P14, sIPSCs were superimposed on tonic current of‐12 ± 1.8 pA at ‐70 mV, that was accompanied by noise with variance of 17 ± 3 pA2. Both the current and noise were inhibited by bicuculline. TTX blocked the bicuculline‐sensitive current and noise by˜60%. Between P18 and P25, sIPSCs were less frequent; all cells showed tonic, bicuculline‐sensitive currents, but these were partially inhibited by TTX (˜35%). Between P40 and P53, slPSCs were rare; tonic, bicuculline‐sensitive currents and noise were greater in amplitude, with mean values of‐17 pA and 22 pA2 at‐70 mV, they were present in all cells but they were not inhibited by TTX. Glycine receptor channels that were expressed in immature, but not adult cells, did not mediate spontaneous currents. Our results indicate that spontaneous transmission onto cerebellar granule cells in immature animals consists primarily of action potential‐dependent, phasic release of vesicular GABA. This generates GABAA receptor‐mediated slPSCs. The effects of GABA transporter blockers suggest that it also produces the TTX‐sensitive current‐noise, as GABA spills out of synapses to activate extrasynaptic receptors or receptors in neighbouring synapses. In older animals, action potential‐independent release of transmitter is predominant and results in tonic activation of GABAA receptors. This does not appear to be spontaneous vesicular release of GABA. Neither does it appear to be reversed uptake of GABA, although further work is required to rule out these possibilities.
High Molecular Weight Protein of Human Central Nervous System Myelin Inhibits Neurite Outgrowth: an Effect which can be Neutralized by the Monoclonal Antibody IN‐1
Authors: Spillmann Adrian A. , Amberger Verena R. , Schwab Martin E.
Published: April 2006

Neurite outgrowth of PC12 cells in the presence of nerve growth factor and the spreading of 3T3 fibroblasts were inhibited by human myelin proteins from different areas of the central nervous system (CNS) in a dose‐dependent manner. Application of liposomes containing human CNS myelin proteins induced rapid collapse of PC12 growth cones. When 3T3 fibroblasts were plated on a human CNS myelin protein‐coated substrate the cells remained round, and spreading was inhibited. All these inhibitory effects could be neutralized by the monoclonal antibody IN‐1, which was raised against a 250 kDa neurite growth‐inhibiting protein (NI‐250) of rat CNS myelin. Comparison of the inhibitory properties of human and bovine CNS myelin on PC12 neurite outgrowth showed that human CNS myelin was slightly more inhibitory per unit of myelin protein. Analysis by sodium dodecyl sulphate‐polyacrylamide gel electrophoresis revealed that in human myelin, as in rat and bovine myelin, a high molecular weight protein is responsible for the inhibitory activities on neurite outgrowth and fibroblast spreading.
Organization of Glutamate Receptors at the Synapse
Authors: Ottersen Ole P. , Landsend Alf S.
Published: April 2006

Glutamate receptors can be divided in several groups with distinct functional properties. An additional level of complexity has emerged from recent high resolution immunogold analyses which have provided evidence for a differential targeting of glutamate receptors to specific subsynaptic membrane domains. Notably, different types of glutamate receptor may differ in their distance to the release site and in their spatial relation to glutamate transporters. These data imply that the subsynaptic expression of a given glutamate receptor may bias its response to a released quantum of transmitter and suggest that receptor targeting may be implicated in the modulation of glutamatergic neurotransmission.
Glutamate‐induced Release of the Nitric Oxide Precursor, Arginine, From Glial Cells
Authors: Grima Gilbert , Benz Beatrix , Do Kim Quang
Published: April 2006

Arginine, the nitric oxide precursor, is predominantly localized in glial cells, whereas the constitutive nitric oxide synthase is mainly found in neurons. Therefore, a transfer of arginine from glial cells to neurons is needed to replenish the neuronal precursor pool. This is further supported by the finding that arginine is released upon selective pathway stimulation both in vitro and in vivo. We investigated the mechanism underlying this glial‐neuronal interaction by analysing the effect of glutamate receptor agonists on the extracellular [3H]arginine level in cerebellar and cortical slices and in cultures of either cortical astroglial cells or neurons. We present data indicating that arginine is released from cerebellar and cortical slices and astroglial cell cultures upon activation of ionotropic non‐NMDA glutamate receptors. Glutamate had no effect on the extracellular [3H]arginine level in neuronal cultures. Moreover, the effect of glutamate in cerebellar slices was tetrodotoxin‐insensitive, and the calcium ionophore A23187 evoked the release of [3H]arginine from astroglial cell cultures. Thus, nitric oxide synthesis and nitric oxide transmission may be based on the glial‐neuronal transfer of arginine which is induced by activation of excitatory amino acid receptors on glial cells.
Spatially and Temporally Regulated Modification of the Receptor‐like Protein Tvrosine Phosphatase ζ/β isoforms with Keratan Sulphate in the Developing Chick Brain
Authors: Hamanaka Hiroki , Maeda Nobuaki , Noda Masaharu
Published: April 2006

Protein tyrosine phosphatase ζ (PTPζRPTPβ) is a proteoglycan‐type receptor‐like protein tyrosine phosphatase specifically expressed in the brain. In addition to the transmembrane form (PTPζ‐A), the extracellular splice variant (PTPζ‐S) occurs as a major soluble chondroitin sulphate proteoglycan in the brain. We prepared antibodies which specifically recognize PTPζ‐A and ‐S, and analysed the carbohydrate structures on the two PTPζ isoforms in the developing chick brain. lmmunoprecipitation experiments using these antibodies revealed that almost all of the keratan sulphate recognized by a monoclonal antibody (5D4) was exclusively bound to PTPζ‐A and PTPζ‐S. Addition of keratan sulphate to these proteoglycans markedly increased from embryonic day (E) 11, in contrast to the addition of LeX and HNK‐1 carbohydrates, which gradually increased during development in accordance with expression of the core proteins, suggesting that keratan sulphate modification plays some specific roles. Moreover, at the early embryonic stage keratan sulphate was observed only in several restricted regions, especially at boundary regions such as the roof plate of the tectum, the zona limitans intrathalamica in the diencephalon, and the mesencephalon‐metencephalon boundary. At the mesencephalon‐metencephalon boundary, keratan sulphate modification of PTPζ isoforms was specifically observed from E3 to E6 on a ring of cells encircling the neural tube and their radially oriented processes, which were identified as radial glial fibres. This expression pattern of keratan sulphate spatiotemporally corresponded well to the formation of the fovea isthmi, a groove separating the mesencephalon from the metencephalon. These results suggest that carbohydrates including keratan sulphate on PTPζ isoforms play important roles in brain development by modulating the cell‐cell and/or cell‐substrate interactions mediated by these molecules.
Polysialylated Neural Cell Adhesion is Involved in Target‐induced Morphological Differentiation of Arcuate Dopaminergic Neurons
Authors: Loudes Catherine , Rougon Geneviève , Kordon Claude , Faivre‐Bauman Annie
Published: April 2006

We have previously shown that the morphological and biochemical maturation of developing rat hypothalamic dopaminergic neurons is accelerated when they are cocultivated with pituitary intermediate lobe cells, one of their targets. Only two subsets of hypothalamic dopaminergic neurons (arcuate, A12, and periventricular, A14, nuclei) may project to the pars intermedia. In order to determine whether the two populations are equally responsive to coculture conditions, we microdissected the hypothalamus of 17‐day‐old rat fetuses in two fragments containing cell bodies from the A12 and from the A14 regions, prepared neuronal cultures from both portions and incubated them separately with intermediate lobe cells. The presence of intermediate lobe cells increased tyrosine hydroxylase levels in both dopaminergic neuron subsets, but morphological differentiation was accelerated in dopaminergic neurons originating in the arcuate nucleus only. We then investigated whether physical contact between developing arcuate neurons and their target cells was a prerequisite of the morphological effect by interposing a semipermeable membrane between cultivated neurons and intermediate lobe cells in transwell culture dishes. The morphological effect was no longer observed under transwell coculture conditions, pointing to the involvement of membrane‐bound molecules. Accordingly, the stimulating effect of coculture on arcuate dopaminergic neurons was completely abolished by the removal of polysialic acid on neural cell adhesion molecules by endoneuraminidase N treatment. Thus, maturation of A12 and A14 dopaminergic neurons exhibits differential susceptibility to intermediate lobe target cells, and polysialylated‐NCAM is required for the contact‐dependent effect.
Increased Expression of NGFI‐A mRNA in the Rat Striatum Following Burst Stimulation of the Medial Forebrain Bundle
Authors: Chergui Karima , Svenningsson Per , Nomikos George G. , Gonon François , Fredholm Bertil B. , Svennson Torgny H.
Published: April 2006

Using in situ hybridization, we examined the mRNA expression for several immediate early genes in dopamine‐innervated brain areas following electrical burst vs. regular stimulation of the medial forebrain bundle in anaesthetized rats. Two hours after 5 Hz burst stimulation, the expression of the nerve growth factor‐inducible clone A (NGFI‐A) mRNA was increased in the medial part of the striatum. This increase was prevented by pretreatment with the dopamine‐D1 receptor antagonist, SCH23390 (0.1 mg/kg i.p.). After 8 Hz burst stimulation, NGFI‐A mRNA expression was increased in the medial, central and lateral parts of the striatum. Induction occurred predominantly in cells expressing mRNAs for the dopamine‐D1 receptor, substance P and dopamine and CAMP‐regulated phosphoprotein (DARP‐32). Regular stimulation had no effect on NGFI‐A mRNA expression. The induction of NGFI‐A was related to the levels of dopamine released by burst or regular stimulation as demonstrated with in vivo amperometry. Two hours after stimulation, the expression of none of the other genes studied was altered. One hour after 8 Hz burst stimulation, the expression of NGFI‐A, NGFI‐B and jun‐B mRNAs was increased in the striatum and that of NGFI‐A, NGFI‐6, c‐fos, fos‐B and jun‐B mRNAs was variably increased in the nucleus accumbens and lateral septum. These results provide additional support for the physiological importance of burst firing activity in midbrain dopamine neurons for the activation of their target cells. They demonstrate a spatial and temporal specificity as regards the brain region, the gene activated, the receptor involved and the phenotype of the cells affected.
Csk and BatK Show Opposite Temporal Expression in the Rat CNS: Consistent with its Late Expression in Development, BatK Induces Differentiation of PC12 Cells
Authors: Kuo Sophia S. , Armanini Mark P. , Phillips Heidi S. , Caras Ingrid W.
Published: April 2006

BatK is a second member of the Csk family of regulatory kinases that phosphorylate a key inhibitory tyrosine on Src family kinases, leading to down‐regulation. To investigate the roles of BatK and Csk, both of which are expressed in the brain, we compared their temporal expression patterns during development of the central nervous system (CNS) in rats. BatK mRNA is undetectable at embryonic day 12 (E12), appears in the developing nervous system at approximately E15, and its expression progressively increases up to the time of birth, thereafter remaining high throughout the adult brain. In striking contrast, Csk is highly expressed throughout embryonic development and remains high in the CNS until birth. It is then dramatically down‐regulated in the adult brain except in the olfactory bulb. BatK and Csk thus exhibit complementary temporal expression patterns. Since BatK expression correlates with late‐stage development and terminal differentiation, we speculated that it might be involved in regulating neuronal differentiation. Using PC12 cells as a model system, we show that overexpression of BatK is sufficient to induce neurite outgrowth in the absence of nerve growth factor. Further, overexpression of BatK activates the mitogen‐activated protein kinase cascade. We propose a model suggesting that, despite overlapping in vifro activities, BatK and Csk regulate different targets in vivo and have different functions during and after neuronal development, BatK being the dominant regulator of Src kinases in the fully differentiated adult brain.
Histaminergic System in Co‐cultures of Hippocampus and Posterior Hypothalamus: A Morphological and Electrophysiological Study in the Rat
Authors: Diewald L. , Heimrich B. , Busselberg D. , Watanabe T. , Haas H. L.
Published: April 2006

Neurons of the tuberomammillary nucleus in the posterior hypothalamus diffusely project to most parts of the central nervous system, where their main transmitter, histamine, modulates the excitability of the target neurons. The development of a histaminergic hypothalamo‐hippocampal pathway and its function were studied in organotypic co‐cultures. lmmunocytochemistry for histidine decarboxylase, the specific synthesizing enzyme, stained clusters of neurons in the hypothalamic tuberomammillary area. lmmunolabelled varicose processes innervated the co‐cultured hippocampus and established a few synaptic contacts on dendrites. Cultured tuberomammillary neurons displayed their typical membrane properties and were spontaneously active. In hippocampal pyramidal cells of the CA3 region the long‐lasting afterhyperpolarization was reduced by histamine or impromidine and increased by the H2 antagonist cimetidine, but not by the H1 antagonist mepyramine. The membrane potential was depolarized in presence of an H2 agonist and hyperpolarized by an H2 antagonist. In single hippocampal cultures histamine antagonists did not affect afterhyperpolarization and membrane potential. Histaminergic neurons retain their main morphological and physiological characteristics in slice cultures and establish a functional connection with co‐cultured target cells.
The Pontine A5 Noradrenergic Cells which Project to the Spinal Cord Dorsal Horn are Reciprocally Connected with the Caudal Ventrolateral Medulla in the Rat
Authors: Tavares Lsaura , Lima Deolinda , Coimbra Antonio
Published: April 2006

A disynaptic pathway linking the caudal ventrolateral medulla (VLM) to the spinal cord via the A5 noradrenergic cell group of the pons has recently been described in the rat. In the present work, the projections of the A5 to the VLM and to the spinal dorsal horn were studied with double‐tracing techniques combined with immunostaining of the noradrenaline‐synthesizing enzyme dopamine‐β‐hydroxylase. Cholera toxin subunit B (CTb) injected into the VLM and fluoro‐gold injected into the spinal dorsal horn produced double retrograde labelling of A5 neurons immunoreactive for dopamine‐β‐hydroxylase, which received appositions of fibre varicosities labelled anterogradely with CTb injected into the VLM. After injecting CTb into the A5, retrogradely labelled neurons occurred in the VLM. These neurons were contacted by anterogradely labelled fibres from the A5 group. These observations indicate that the VLM cells acting upon the A5 spinally projecting neurons, which are likely to exert an α2‐adrenoreceptor‐mediated inhibition on the spinal cord, are targeted by collaterals of the A5 spinal cord‐bound axons. The A5‐VLM pathway may be the anatomical substrate of a negative feedback circuit whereby the modulatory action of the VLM on the spinal cord is self‐inhibited through activation of the A5.
The Oxytocin‐induced Inward Current in Vagal Neurons of the Rat is Mediated by G Protein Activation but not by an Increase in the lntracellular Calcium Concentration
Authors: Alberi Stefano , Dreifuss Jean Jacques , Raggenbass Mario
Published: April 2006

The neuropeptide oxytocin can depolarize parasympathetic preganglionic neurons in the dorsal motor nucleus of the vagus nerve of the rat by generating a sustained inward current, which is sodium‐dependent and tetrodotoxin‐insensitive. The second messenger activated by oxytocin receptor binding is, however, not yet known. In the present study, we attempted to characterize it by using the whole‐cell recording technique and brainstem slices. When loaded with GTP‐γ‐S, a non‐hydrolysable analogue of GTP, vagal neurons generated a persistent inward current in the absence of agonist and the oxytocin effect was suppressed, suggesting that the peptide‐evoked current was mediated by G‐protein activation. Loading vagal neurons with the calcium chelator 1,2–bis(2–aminophenoxy)ethane‐N,N,N′,N′,‐tetraacetic acid (BAPTA) suppressed a calcium‐dependent, slowly decaying potassium aftercurrent but did not affect the oxytocin response, suggesting that the latter was not mediated by an agonist‐induced increase in the intracellular calcium concentration. Protein kinase C (PKC) activation was probably not involved, since the peptide‐evoked current was not modified by loading neurons with the PKC inhibitor H7. Thus, the oxytocin‐evoked current in vagal neurons was probably not mediated by phospholipase C‐β (PLC‐β) activation. Loading neurons with 8–Br‐CAMP or with an adenylyl cyclase activator (forskolin) reduced the oxytocin‐evoked current by about half. SQ 22536, an adenylyl cyclase inhibitor, reduced this current by a similar amount. However, the peptide‐evoked current was unaffected by Rp‐CAMPS and Sp‐CAMPS, an inhibitor and an activator, respectively, of CAMP‐dependent protein kinase (PKA). We suggest that oxytocin activates two distinct signalling pathways in vagal neurons: one which is CAMP‐dependent, but PKA‐independent, and one, unidentified, which is PLC‐β‐and CAMP‐independent. Each pathway accounts for about half of the peptide effect and both appear to involve G‐protein activation.
NMDA Receptor Modulation by a Conditioned Medium Derived from Rat Cerebellar Granule Cells
Authors: Dus Laura , Canu Nadia , Zona Cristina , Ciotti Maria Teresa , Calissano Pietro
Published: April 2006

Our previous studies have shown that the response to the excitotoxic action of glutamate by cultured cerebellar granule cells depends upon the cell density or the volume of medium in which they have been grown: the higher the cell density or the lower the volume, the higher the response to glutamate. We have hypothesized that this variable response is due to the formation in culture of a glutamate‐sensitizing activity GSA more abundantly in conditioned medium derived from high‐density or low‐volume cultures than that present in low‐density or high volume cultures and capable of restoring sensitivity in previously resistant granule cells. In order to elucidate the mechanism of action of glutamate‐sensitizing activity, we measured the extent and function of NMDA receptors in low‐ and high‐volume cultures and assessed the effect of glutamate‐sensitizing activity on the same receptors. We found that under high‐volume conditions the extent of MK‐801 binding, the amount of NMDA receptor type 1, the currents evoked in whole cells after an NMDA pulse and the response of cultured cells to this ligand were markedly reduced compared with low‐volume cultures. Addition of glutamate‐sensitizing activity to high‐volume cultures increased their glutamate sensitivity, the NMDA‐evoked currents, the extent of MK‐801 binding and the amount of NMDA receptor type 1 protein present. The corresponding mRNA transcripts, on the contrary, were unchanged in high‐volume, low‐volume and high‐volume GSA‐treated cultures.
Developmental Changes in Neuronal Responsiveness to the CNS Myelin‐associated Neurite Growth Inhibitor N I‐35/250
Authors: Bandtlow Christine E. , Loschinger Jurgen
Published: April 2006

The extent of fibre regeneration in the adult injured vertebrate nervous system appears to be primarily determined by the local environment. Thus, the failure of axon regrowth in the central nervous system (CNS) is crucially influenced by the presence of the myelin‐associated neurite growth inhibitor Nl‐35/250 and possibly also by molecules such as the myelin‐associated glycoprotein and the proteoglycans. Developmental time course studies have shown that the capacity for regeneration declines sharply with the appearance of mature oligodendrocytes and myelin, which indicates a role of Nl‐35/250 in restricting CNS regeneration and plasticity. However, recent in vitro and in vivo studies showed that embryonic neurons are capable of extending fibres on and in adult CNS tissue apparently unaffected by myelinated areas. A possible explanation is that very immature neurons have yet to express the appropriate receptors and response mechanisms for factors that normally induce growth inhibition at a later stage of development. Here we report that embryonic rat dorsal root ganglion and chick retinal ganglion cells display different sensitivity to bovine Nl‐35/250 compared with mature neurons. In older neurons Nl‐35/250 could evoke long‐lasting collapse responses accompanied by a large increase in the intracellular calcium level, persisting for several minutes. In contrast, their embryonic counterparts collapsed only transiently when exposed to Nl‐35/250, and increases in intracellular calcium concentration were small and transient. Calcium influx induced experimentally by the calcium ionophore A23187 revealed that it was not the maximal size of the calcium increase but rather the duration of elevated calcium concentration that was the most important determinant for subsequent morphological alterations of the growth cone. Our data further suggest that developing neurons acquire their complete sensitivity for Nl‐35/250 around the time of myelination.
The Place of Language in a Scientific Psychology
Authors: Miller George A.
Published: April 2006

One of the psychologists’ great methodological difficulties is how they can make the events they wish to study publicly observable, countable, measurable. It is significant to note that the device most often used for conversion from private to public is language. Thus speech is a crucial problem for psychology. None of their other activities gives the same sort of insight into another person as does their language. Since people spend so many of their waking hours generating and responding to words, and since speech is such a typically human mode of adjustment, no general theory of psychology will be adequate if it does not take account of language.
Significance and Remembrance: The Role of Neuromodulatory Systems
Authors: McGaugh James L.
Published: April 2006

It is now well known that the retention of newly-acquired information can be modulated by drugs or hormones administered shortly following training. It is generally thought that such treatments influence retention by modifying processes underlying the storage of information. The fact that susceptibility to posttraining memory modulation is seen in many species, including bees, fish, birds, and mammals, argues that some common time-dependent memory storage processes have been conserved in evolution. Recent research findings have provided strong support for the view that such susceptibility to posttraining influences provides opportunity for modulation of memory storage by endogenous neurohormonal systems. In rats and mice, posttraining administration of hormones such as epinephrine that are normally released by training experiences enhances subsequent retention. Comparable effects are found with posttraining administration of opiate receptor antagonists such as naloxone. Findings of recent experiments indicate that these treatments affect memory by influencing the release of norepinephrine within the amygdaloid complex. The endogenous regulation of memory storage appears to involve interaction of neurohormones and transmitters in activating brain systems involved in memory storage.
Infants’ Perception of Phrase Structure in Music
Authors: Krumhansl Carol L. , Jusczyk Peter W.
Published: April 2006

A visual preference procedure was used to examine 6- and 41/2-monthold infants’ sensitivity to phrase structure in music. Sections of Mozart minuets were divided into segments that either did or did not correspond to the phrase structure of the music. Infants in both age groups listened significantly longer to the appropriately segmented versions. Their behavior accorded well with judgments of the same materials made by adults, suggesting that protracted musical experience may not be necessary to perceive phrase structure in music. Strong correlations were found between certain musical variables and the infants’ preferences for the musical passages, pointing to acoustic properties that may be important for defining musical phrases.
William James and Hypnosis: A Centennial Reflection
Authors: Kihlstrom John F. , McConkey Kevin M.
Published: April 2006

Like many other early psychologists, William James was fascinated by hypnosis and related phenomena. For James, hypnosis was both an experimental technique for creating divisions of consciousness, and a laboratory model of naturally occurring disorders of awareness. James’ treatment of consciousness in hypnosis presages contemporary interests in dissociation and implicit cognition, and underscores the role of the self in conscious mental life. At the same time, James recognized the complexity of hypnosis as an interpersonal process. In the end, James’ views suggest how a rapprochement between the cognitive and social approaches to hypnosis might be achieved.
Psycholegal Research on the Fourth Amendment
Authors: Kagehiro Dorothy K.
Published: April 2006

This article discusses the application of psychological theory and research on attributions, interpersonal relationships, and human territorial functioning to issues and assumptions in the law of searches and seizures, in particular, searches not based on a warrant, but on consent by the suspect or an appropriate third party, such as the suspect's spouse.