bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced function of l‐AP4‐sensitive metabotropic glutamate receptors in human epileptic sclerotic hippocampus
Authors: Dietrich D. , Kral T. , Clusmann H. , Friedl M. , Schramm J. 
Published: March 2003

AbstractHuman temporal lobe epilepsy is characterized by strong synaptic reorganization that leads to abnormal recurrent excitatory synaptic connections among hippocampal neurons. In addition, electrophysiological studies show that synaptic activity of the main afferent input to the hippocampus, the perforant path, is prolonged and amplified by changes in postsynaptic glutamate receptors. The current view is that these morphological and physiological abnormalities contribute significantly to the hyperexcitability seen in the hippocampus of temporal lobe epilepsy. Recently, it was found that presynaptic inhibitory metabotropic glutamate receptors are an important negative feedback mechanism that controls synaptic release of glutamate in the hippocampus. In this study, we assessed the functionality of this feedback system by investigating the metabotropic glutamate receptor mediated depression of excitatory synaptic transmission in surgically removed hippocampi from patients with marked synaptic reorganization (Ammon's horn sclerosis group) and from patients without detectable reorganization (lesion group). We report here that this control of synaptic transmission is lost in hippocampi from the Ammon's horn sclerosis group whereas this control is preserved in hippocampi from the lesion group. The data presented here suggest that the loss of feedback inhibition mediated by metabotropic glutamate receptors could be a further, previously not recognized, mechanism in the pathophysiology of temporal lobe epilepsy.
Mobilization of intracellular calcium stores participates in the rise of [Ca2+]i and the toxic actions of the HIV coat protein GP120
Authors: Medina Igor , Ghose Sraboni , Ben‐Ari Yehezkel 
Published: March 2003

AbstractThe HIV envelope glycoprotein, GP120, increases intracellular Ca2+ concentration and induces degeneration of human and animal neurons in culture. Using patch‐clamp recordings and Ca2+ imaging techniques, we have now examined the contribution of intracellular stores of calcium in the effects of GP120. We report that in rat hippocampal neuronal cultures, GP120 induces a dramatic and persistent increase in [Ca2+]i which is prevented by drugs that either deplete (caffeine, carbachol, thapsigargin) or block (dantrolene) Ca2+ release from intracellular stores. In contrast, N‐methyl‐d‐aspartate (NMDA) receptors or voltage‐dependent calcium channels do not participate in these effects, as: (i) the increase in [Ca2+]i was not affected by NMDA receptor antagonists or calcium channel blockers; and (ii) and GP120 did not generate any current in whole‐cell recording. Dantrolene, a ryanodine stores inhibitor, also prevented neuronal death induced by GP120. Our results show that the GP120‐induced rise in [Ca2+]i originates from intracellular calcium stores, and suggest that intracellular stores of calcium may play a determinant role in the pathological actions of GP120.
Expression of TrkB and TrkC but not BDNF mRNA in neurochemically identified interneurons in rat visual cortex in vivo and in organotypic cultures
Authors: Gorba Thorsten , Wahle Petra 
Published: March 2003

AbstractThe mammalian visual cortex contains morphologically diverse populations of interneurons whose neurochemical properties are believed to be regulated by neurotrophic factors. This requires the expression of neurotrophin receptors. We have analysed whether brain‐derived neurotrophic factor (BDNF), its receptor trkB and the NT‐3 receptor trkC are expressed in interneurons of rat visual cortex in vivo, and in organotypic visual cortex cultures, paying particular attention to the subsets of neuropeptidergic neurons. In situ hybridization in combination with immunofluorescence for calcium‐binding proteins and neuropeptides revealed that BDNF is not expressed in interneurons in vivo or in vitro. For the neurotrophin receptors we found in vivo at postnatal day 70 (P70) that ≈ 80% of the parvalbumin‐immunoreactive (‐ir), but only 50% of the intensely calbindin‐ir, and only 20% of the calretinin‐ir neurons express trkB. Double labelling with neuropeptides revealed that ≈ 50% of the neuropeptide Y‐ir and ≈ 50% of the somatostatin‐ir neurons express trkB in a laminar‐specific way. Only 25% of the vasoactive intestinal polypeptide (VIP)‐ir neurons coexpress trkB. The coexpression of neuropeptide Y with trkB, but not with BDNF or trkC, was confirmed with a double in situ hybridization. In contrast, the percentages differed in the immature cortex; at P14 70% of the NPY‐ir neurons and 46% of the calretinin‐ir neurons revealed trkB expression, while the ratio for calbindin‐ir cells was fairly constant (59%). From the interneuron populations studied, only 12% of the parvalbumin‐ir neurons expressed trkC. A triple labelling revealed that some neurons coexpressed both trk mRNAs, while others had only trkC. The analysis of interneurons in organotypic cultures yielded very similar results. The results indicate that trkB ligands synthesized by pyramidal neurons influence neuropeptide or calcium‐binding protein expression in a paracrine or transsynaptic manner. However, in contrast to current belief, in the adult only about half of all interneurons appear responsive to trkB ligands. Although the proportion is higher in the immature cortex, not all of the interneurons appear neurotrophin‐receptive. With regard to the presence or absence of neurotrophin receptors, the molecular heterogeneity of GABAergic interneurons in the visual cortex is higher than currently assumed, and the responsiveness to neurotrophins changes with development in a cell type‐specific way.
Cleavage of the TrkA neurotrophin receptor by multiple metalloproteases generates signalling‐competent truncated forms
Authors: Díaz‐Rodríguez Elena , Cabrera Noemí , Esparís‐Ogando Azucena , Montero Juan Carlos , Pandiella Atanasio 
Published: March 2003

AbstractThe ectodomain of the neurotrophin receptor TrkA has been recovered as a soluble fragment from the culture media of cells by a process that involves endoproteolytic cleavage. This cleavage may be upregulated by several treatments, including NGF treatment or protein kinase C activation. In this report we have investigated the cellular site and proteolytic activities involved in TrkA cleavage, and the effects of ectodomain truncation on signalling. Cleavage occurs when the receptor is at, or near, the cell surface, and it can be prevented by agents that affect protein sorting. Cleavage generates several cell‐bound fragments, and their generation can be differentially blocked by inhibitors, documenting the involvement of multiple plasma membrane metalloendoproteases. The major cell‐bound receptor fragment (i) is tyrosine‐phosphorylated in vivo; (ii) does autophosphorylate in vitro; and (iii) is able to associate with intracellular signalling substrates. Artificial deletion of the TrkA ectodomain results in an active receptor that induced neurite outgrowth in pheochromocytoma cells. Cleavage by this natural cellular mechanism appears thus to serve not only as an outlet of receptor binding fragments, but also to generate signalling‐competent cell‐bound receptor fragments. In the nervous system this ligand‐independent receptor activation could play important roles in the development and survival of neurons.
Regional distribution of Y‐receptor subtype mRNAs in rat brain
Authors: Parker R. M. C. , Herzog H. 
Published: March 2003

AbstractMolecular cloning techniques have recently led to the identification of a growing number of neuropeptide Y‐receptor subtypes, suggesting possible subtype‐specific involvement in different physiological processes. Here we report the first study which determines and compares the mRNA expression of all four cloned functional Y‐receptor subtypes (Y1, Y2, Y4 and Y5) in consecutive sections of the rat brain on a cellular level, using a uniform in situ hybridization technique. Our results demonstrate that Y‐receptor subtype mRNA expression is widely distributed throughout the rat brain. Interestingly, coexpression of all four Y‐receptors, at different levels, is particularly evident within the limbic system, including the hypothalamus, hippocampus, amygdala, piriform and cingulate cortices and tegmental areas, all of which are heavily involved in behaviour, emotion and homeostatic regulation. Particularly interesting is the demonstration that Y5‐receptor mRNA expression always coincides with the presence of Y1‐receptor mRNA (although not vice versa), possibly due to the overlapping organization and transcriptional control of their genes. However, it is also clear that several brain nuclei display preferential expression of one or a selective combination of Y‐receptor subtype mRNAs. Furthermore, it is evident that there is regionalization of expression within certain loci which express all four receptor subtype mRNAs, particularly within the paraventricular and arcuate hypothalamic nuclei. Our results suggest that some of neuropeptide Y's (NPY) effects may be mediated through one particular subtype, whereas other physiological processes might require the coordinated action of different subtypes within the same or discrete areas.
Biophysical properties of scorpion α‐toxin‐sensitive background sodium channel contributing to the pacemaker activity in insect neurosecretory cells (DUM neurons)
Authors: Lapied B. , Stankiewicz M. , Grolleau F. , Rochat H. , Zlotkin E. , Pelhate M. 
Published: March 2003

AbstractA scorpion α‐toxin‐sensitive background sodium channel was characterized in short‐term cultured adult cockroach dorsal unpaired median (DUM) neurons using the cell‐attached patch‐clamp configuration. Under control conditions, spontaneous sodium currents were recorded at different steady‐state holding potentials, including the range of normal resting membrane potential. At −50 mV, the sodium current was observed as unclustered, single openings. For potentials more negative than −70 mV, investigated patches contained large unitary current steps appearing generally in bursts. These background channels were blocked by tetrodotoxin (TTX, 100 nm), and replacing sodium with TMA‐Cl led to a complete loss of channel activity. The current–voltage relationship has a slope conductance of 36 pS. At −50 mV, the mean open time constant was 0.22 ± 0.05 ms (n = 5). The curve of the open probability versus holding potentials was bell‐shaped, with its maximum (0.008 ± 0.004; n = 5) at –50 mV. LqhαIT (10–8m) altered the background channel activity in a time‐dependent manner. At −50 mV, the channel activity appeared in bursts. The linear current–voltage relationship of the LqhαIT‐modified sodium current determined for the first three well‐resolved open states gave three conductance levels: 34, 69 and 104 pS, and reversed at the same extrapolated reversal potential (+52 mV). LqhαIT increased the open probability but did not affect either the bell‐shaped voltage dependence or the open time constant. Mammal toxin AaHII induced very similar effects on background sodium channels but at a concentration 100 × higher than LqhαIT. At 10–7m, LqhαIT produced longer silence periods interrupted by bursts of increased channel activity. Whole‐cell experiments suggested that background sodium channels can provide the depolarizing drive for DUM neurons essential to maintain beating pacemaker activity, and revealed that 10–7 m LqhαIT transformed a beating pacemaker activity into a rhythmic bursting.
Modelling the mosaic organization of rod and cone photoreceptors with a minimal‐spacing rule
Authors: Galli‐Resta L. , Novelli E. , Kryger Z. , Jacobs G. H. , Reese B. E. 
Published: March 2003

AbstractThe mosaic of photoreceptors is regarded as a prime example of the precise control of cellular positioning in the vertebrate nervous system. This study was undertaken with the idea that understanding the intrinsic geometrical features of photoreceptor mosaics is a necessary step to unveil the biological mechanisms governing their formation. We show in the retina of the ground squirrel that the arrays of both the rods and S cones are non‐random, but that nothing more than a simple minimal‐spacing rule constraining receptor positioning is sufficient to account for the spatial organization of both mosaics. The size of this ‘exclusion zone’ is an intrinsic characteristic of each cell type, and it is simply the difference in the size of this domain that accounts for the regularity of the S cone array and the irregularity of the rod array at identical density. Consequently, regularity in receptor mosaics is produced by two independent biological events, one embodying the exclusion zone, and another specifying the local density of a given receptor type.
Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study
Authors: Abadie P. , Boulenger J. P. , Benali K. , Barré L. , Zarifian E. , Baron J. C. 
Published: March 2003

AbstractThe central benzodiazepine receptor (cBZr) has long been implicated in anxiety disorders on the basis of: (i) the well‐known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a possibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced, namely changes in the concentration or properties of the latter, and changes in the GABAA complex conformation, which contains the cBZr. Neither postmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure both the density and affinity of the cBZr in multiple brain regions in unmedicated patients and age‐ and sex‐matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr parameters and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 : 1; mean age: 39 years), prospectively recruited using DSM III‐R criteria, and 10 age‐ and gender‐matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of 11C‐flumazenil (at high and low specific radioactivity) and previously validated by us, we estimated the Bmax, Kd and bound : free (B/F) ratios in 11 neocortical areas and in the cerebellum. Before and after the PET session, anxiety scores from Spielberger's and Covi's scales were obtained. There was no statistically significant difference in Bmax, Kd or B/F‐values between the two groups for any region. Across the two groups, there were only a few marginally significant anxiety‐score–PET correlations, suggesting chance findings. This is the first fully quantitative study to report on the relationships between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across‐group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cerebellum in this sample. These findings, if confirmed by studies on larger samples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of anxiety.
The dopamine D2 receptor subfamily in rat retina: ultrastructural immunogold and in situhybridization studies
Authors: Derouiche Amin , Asan Esther 
Published: March 2003

AbstractDopamine, a major neurotransmitter in the vertebrate retina, is released from interplexiform cells and a restricted subset of amacrine cells. Dopamine effects vary between different retinal cell types, most likely due to differences in cell‐specific receptor subtype expression. Identification of cells expressing receptors of the D2‐subfamily (D2R, D3R, D4R) on a light microscopical level has rendered equivocal results, and no information is as yet available concerning the subcellular distribution of receptor protein. In the present study, D2R and D2/3R subtype‐specific antisera, and D2R‐, D3R‐ and D4R‐specific oligonucleotide probes were used for ultrastructural and in situ hybridization analyses of the receptor subtype distribution in the rat retina.Light and electron microscopy showed that in addition to the known localization of intense D2R‐immunoreactivity in all dopaminergic cells immunoreactive for tyrosine hydroxylase (TH), homogeneous, less intense D2R‐immunoreactivity was also seen throughout the inner plexiform layer (IPL). Ultrastructurally, many additional amacrine cell processes devoid of TH‐immunoreactivity at all levels of the inner plexiform layer were immunoreactive. D2R‐immunoreactivity was found mainly on intracellular vesicles, and immunoreactivity associated with the plasma membrane was always extrasynaptic. No D2R‐immunoreactivity was found in amacrine cell somata postsynaptic to the so‐called dopaminergic ‘ring endings’. Many D2R‐mRNA reactive cells were observed throughout the inner nuclear layer. Morphologically, labelled cells resemble amacrines and bipolars but not horizontal cells. Reactivity with splice variant‐specific oligonucleotide probes suggested that the D2LR variant is the predominant if not the only D2R isoform in the rat retina. D2R‐mRNA reactivity was not observed in other retinal layers, in particular not in photoreceptor inner segments, which displayed D4R‐mRNA reactivity. D3R‐mRNA reactivity was not detected.The results indicate that D2‐like responses are mediated through the D2R subtype, by an autoreceptor mechanism in dopaminergic cells, and by volume transmission in non‐dopaminergic cells of the inner retina. D2‐like responses in photoreceptors probably represent D4R activation.
Conditioned enhancement and suppression in the developing auditory midbrain
Authors: Thornton Sally K. , Semple Malcolm N. , Sanes Dan H. 
Published: March 2003

AbstractNeural responses in the adult central auditory system to binaural stimuli can be altered by preceding acoustic events, including auditory motion. To determine whether the juvenile auditory system also exhibits this feature, we have examined interaural level difference (ILD) processing in the developing gerbil. A long binaural stimulus was followed without interruption by modulation of the level difference (virtual acoustic motion), which in turn was followed smoothly by a new steady state ILD. Auditory responses of single neurons in the inferior colliculus (IC) were assessed for sensitivity to the final steady state ILD. The response of EI neurons (excited by contralateral stimulation and inhibited ipsilaterally) was examined at postnatal (P) days 17–18, P24–25, and in adult animals. In adult animals, a sudden reduction of the inhibitory stimulus level resulted in a long‐lasting (median = 4.3 s) enhanced discharge rate (conditioned enhancement). In P17–18 animals, conditioned enhancement only lasted for 1.2 s. When the inhibitory stimulus level was suddenly increased, adult neurons often displayed a conditioned suppression of discharge rate (median = 4.5 s), whereas P17–18 neurons remained suppressed for a much briefer period (median = 1.2 s). Moreover, the difference between conditioned responses and control discharge rates was three–four times greater in adult neurons compared to those recorded in P17–25 animals.Because conditioned responses are sensitive to the relative balance of contralateral excitation and ipsilateral inhibition, we examined the relationship between excitatory and inhibitory thresholds. In adult animals, excitatory thresholds were an average of 12 dB lower than inhibitory thresholds, while at P17–25 excitatory and inhibitory thresholds were roughly the same. These results indicate that computational properties of juvenile and adult IC neurons differ quantitatively, and this may reflect an imbalance between excitation and inhibition. The developmental differences described herein may limit the ability of young animals to locate a sound source with the latency and accuracy of an adult.
Rhombomere origin plays a role in the specificity of cranial motor axon projections in the chick
Authors: Warrilow Joanne , Guthrie Sarah 
Published: March 2003

AbstractGuidance of cranial motor axons to their targets conforms to a segmental plan in the chick embryo. Trigeminal motor neurons lie within rhombomeres 2 and 3 and project via an exit point in rhombomere 2 to innervate the first branchial arch. Facial motor neurons lie within rhombomeres 4 and 5 and grow out via an exit point in rhombomere 4 to innervate the second branchial arch. We have investigated the axial level‐specific matching of motor neurons and branchial arches using donor to host transplantation in avian embryos. Previous work has shown that rostrocaudal reversal of a single hindbrain segment (rhombomere 3) leads to misprojection of a contingent of trigeminal axons via the facial nerve exit point. Using the same experimental manipulation in chick embryos and quail–chick chimaeras, we have analysed the pathways of these aberrant projections. We have found that in the majority of embryos analysed from stage 19 to 31, trigeminal axons from the transplanted rhombomere projected towards second branchial arch muscles, in addition to their normal first arch muscle targets. However, from stage 32 to 36, aberrant projections to second arch‐derived muscles were detected only in a small minority of embryos. These experiments show that trigeminal motor neurons show a lack of specificity in their early projection into the periphery but that inappropriate projections may be later eliminated. This suggests that segmental mechanisms intrinsic to the hindbrain specify motor neurons with respect to their eventual innervation pattern.
Sprouting and regeneration after pyramidotomy and blockade of the myelin‐associated neurite growth inhibitors NI 35/250 in adult rats
Authors: Raineteau Olivier , Z'Graggen Werner J. , Thallmair Michaela , Schwab Martin E. 
Published: March 2003

AbstractAfter a selective unilateral lesion of the corticospinal tract (CST) at the level of the brainstem (pyramidotomy) and neutralization of the myelin associated neurite growth inhibitors NI‐35/250 with the monoclonal antibody (mAb) IN‐1, we had previously observed a strong behavioural recovery in parallel with an enhanced structural plasticity of the lesioned as well as the unlesioned CST. The present study focuses on the regenerative response of the cut CST axons at the lesion site in these adult rats. The results show a strong enhancement of regenerative sprouting of CST fibres by treatment with the mAb IN‐1. Successful elongation of these sprouts through the pyramidal decussation and into the cervical spinal cord was also dependent on the presence of this antibody. In the spinal cord, regenerating fibres were rarely found in the position of the former CST; most of the fibres were distributed seemingly randomly over the entire lateral extent of the spinal cord.