bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutamate‐induced Co2+uptake in rat auditory brainstem neurons reveals developmental changes in Ca2+permeability of glutamate receptors
Authors: Caicedo Alejandro , Kungel Martin , Pujol Rémy , Friauf Eckhard 
Published: March 2003

AbstractCa2+influx through glutamate receptors (GluRs) is thought to play a crucial part in developmental processes and neuronal plasticity. Here we have examined the spatiotemporal distribution of Ca2+‐permeable GluRs in auditory brainstem neurons of the rat from birth to adulthood, using the cobalt‐staining technique of Pruss and collaborators. In slices of young adult rats, 1 mmglutamate evoked intense cobalt uptake in subsets of neurons in the ventral cochlear nuclei, the medial nucleus of the trapezoid body, the lateral and the medial superior olive, and the lateral lemniscal nuclei. Neurones in the central nucleus of the inferior colliculus, and thalamic auditory nuclei appear to express few, if any, Ca2+‐permeable GluRs. Thus, in adults, Ca2+‐permeable GluRs are present in neurons of almost all main relay stations of the auditory brainstem. During development, cobalt‐stained cells first appeared at about hearing onset (at postnatal day 12 [P12]). At P16, staining levels were highest and the pattern of distribution was already adult‐like. The staining intensity slightly declined during the fourth postnatal week. In contrast, Ca2+‐permeable receptors were detected in the external cortex of the inferior colliculus as early as P4. Our results show that auditory neurons, characterized by a high temporal precision in neuronal activity, display Ca2+‐permeable GluRs. Because Ca2+permeability appears at about the onset of hearing and is highest during the following 2 weeks, Ca2+influx through GluRs is likely to be implicated in remodelling processes occurring during this ontogenetic period.
Different patterns of induction of FGF‐2, FGF‐1 and BDNF mRNAs during kindling epileptogenesis in the rat
Authors: Simonato Michele , Molteni Raffaella , Bregola Gianni , Muzzolini Anna , Piffanelli Maddalena , Beani Lorenzo , Racagni Giorgio , Riva Marco 
Published: March 2003

AbstractNeurotrophic factors (NTF) play important roles in the developing and in the adult brain. NTF involvement in neuronal plasticity is suggested by the modulation of NTF expression patterns in different physiological and pathological situations and by the effects they produce in the adult brain (e.g. axonal sprouting induction and neuroprotection). We used the RNAase protection assay to investigate the expression patterns of some NTFs during amygdala kindling, an animal model of epilepsy in which ‘pathological’ neuronal plasticity appears to occur. After a single kindling stimulation, fibroblast growth factor‐2 (FGF‐2) mRNA levels were increased in the hippocampus, the cortex and the hypothalamus, whereas they were not significantly altered in the thalamus and the striatum. A single stimulation did not alter fibroblast growth factor‐1 (FGF‐1) and brain‐derived neurotrophic factor (BDNF) gene expression. Fully kindled animals, left unstimulated for a week, did not exhibit any alteration in the mRNA levels for any of the NTFs examined. However, in contrast with the effect of a single stimulation, amygdala stimulation of kindled animals (evoking a generalized tonic‐clonic seizure) produced a great increase in hippocampal and cortical BDNF mRNA levels, but FGF‐1 mRNA levels were not altered, and FGF‐2 mRNA levels were significantly increased only in the cortex. These results suggest that different NTFs can be recruited at different stages of kindling epileptogenesis and, accordingly, may play different parts in the adaptive changes taking place in this experimental paradigm.
Electrophysiological evidence that noradrenergic neurons of the rat locus coeruleus are tonically inhibited by GABA during sleep
Authors: Gervasoni D. , Darracq L. , Fort P. , Soulière F. , Chouvet G. , Luppi P‐H. 
Published: March 2003

AbstractIt is well known that noradrenergic locus coeruleus (LC) neurons decrease their activity during slow wave sleep (SWS) and are virtually quiescent during paradoxical sleep (PS). It has been proposed that a GABAergic input could be directly responsible for this sleep‐dependent neuronal inactivation. To test this hypothesis, we used a new method combining polygraphic recordings, microiontophoresis and single‐unit extracellular recordings in unanaesthetized head‐restrained rats. We found that iontophoretic application of bicuculline, a specific GABAA‐receptor antagonist, during PS and SWS restore a tonic firing in the LC noradrenergic neurons. We further observed that the application of bicuculline during wakefulness (W) induced an increase of the discharge rate. Of particular importance for the interpretation of these results, using the microdialysis technique, Nitz and Siegel (Neuroscience 1997; 78: 795) recently found an increase of the GABA release in the cat LC during SWS and PS as compared with waking values. Based on these and our results, we therefore propose that during W, the LC cells are under a GABAergic inhibitory tone which progressively increases at the entrance and during SWS and PS and is responsible for the inactivation of these neurons during these states.
Potassium depolarization of mammalian vestibular sensory cells increases [Ca2+]i through voltage‐sensitive calcium channels
Authors: Boyer C. , Lehouelleur J. , Sans A. 
Published: March 2003

AbstractThe existence of voltage‐sensitive Ca2+ channels in type I vestibular hair cells of mammals has not been conclusively proven. Furthermore, Ca2+ channels present in type II vestibular hair cells of mammals have not been pharmacologically identified. Fura‐2 fluorescence was used to estimate, in both cell types, intracellular Ca2+ concentration ([Ca2+]i) variations induced by K+ depolarization and modified by specific Ca2+ channel agonists and antagonists. At rest, [Ca2+]i was 90 ± 20 nm in both cell types. Microperifusion of high‐K+ solution (50 mm) for 1 s increased [Ca2+]i to 290 ± 50 nm in type I (n = 20) and to 440 ± 50 nm in type II cells (n = 10). In Ca2+‐free medium, K+ did not alter [Ca2+]i. The specific L‐type Ca2+ channel agonist, Bay K, and antagonist, nitrendipine, modified in a dose‐dependent manner the K+‐induced [Ca2+]i increase in both cell types with maximum effect at 2 μm and 400 nm, respectively. Ni2+, a T‐type Ca2+ channel blocker, reduced K+‐evoked Ca2+ responses in a dose‐dependent manner. For elevated Ni2+ concentrations, the response was differently affected by Ni2+ alone, or combined to nitrendipine (500 nm). In optimal conditions, nitrendipine and Ni2+ strongly depressed by 95% the [Ca2+]i increases. By contrast, neither ω‐agatoxin IVA (1 μm), a specific P‐ and Q‐type blocker, nor ω‐conotoxin GVIA (1 μm), a specific N‐type blocker, affected K+‐evoked Ca2+i responses. These results provide the first direct evidence that L‐ and probably T‐type channels control the K+‐induced Ca2+ influx in both types of sensory cells.
Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice
Authors: Watase Kei , Hashimoto Kouichi , Kano Masanobu , Yamada Keiko , Watanabe Masahiko , Inoue Yoshiro , Okuyama Shigeru , Sakagawa Takashi , Ogawa Shin‐ichi , Kawashima Naoya , Hori Seiji , Takimoto Misato , Wada Keiji , Tanaka Kohichi 
Published: March 2003

AbstractTo study the function of GLAST, a glutamate transporter highly expressed in the cerebellar Bergmann astrocytes, the mouse GLAST gene was inactivated. GLAST‐deficient mice developed normally and could manage simple coordinated tasks, such as staying on a stationary or a slowly rotating rod, but failed more challenging task such as staying on a quickly rotating rod. Electrophysiological examination revealed that Purkinje cells in the mutant mice remained to be multiply innervated by climbing fibres even at the adult stage. We also found that oedema volumes in the mutant mice increased significantly after cerebellar injury. These results indicate that GLAST plays active roles both in the cerebellar climbing fibre synapse formation and in preventing excitotoxic cerebellar damage after acute brain injury.
Regulation of cell‐type specific expression of lacZ by the 5′‐flanking region of mouse GAD67 gene in the central nervous system of transgenic mice
Authors: Katarova Zoya , Mugnaini Enrico , Sekerková Gabriela , Mann Jeffrey R. , Aszódi Attila , Bösze Zsuzsanna , Greenspan Ralph , Szabó Gábor 
Published: March 2003

AbstractThe transcriptional regulation of the murine gene encoding the 67‐kDa form of glutamic acid decarboxylase (GAD67) was studied by β‐galactosidase histochemistry in transgenic mice carrying fusion genes between progressively longer portions of the 5′‐upstream regulatory region of GAD67 and E. coli lacZ. No expression was detected in brains of mice carrying 1.3 kb of upstream sequences including a housekeeping and two conventional promoters, and two negative regulatory elements with homology to known silencers. In mice carrying the same portion of the promoter region plus the first intron, lacZ expression in the adult central nervous system was found in few, exclusively neuronal sites. The number of correctly stained GABAergic centres increased dramatically with increasing the length of the 5′‐upstream region included in the construct which suggests that multiple putative spatial enhancers are located in this region. Their action is influenced by epigenetic mechanisms that may be due to site‐of‐integration and transgene copy‐number effects. Additional cis‐acting elements are needed to obtain fully correct expression in all GABAergic neurons of the adult central nervous system.
Different cell surface areas of polarized radial glia having opposite effects on axonal outgrowth
Authors: Stier Heike , Schlosshauer Burkhard 
Published: March 2003

AbstractDuring neuronal development neurites are likely to be specifically guided to their targets. Within the chicken retina, ganglion cell axons are extended exclusively into the optic fibre layer, but not into the outer retina. We investigated, whether radial glial cells having endfeet at the optic fibre layer and somata in the outer retina, might be involved in neurite guidance. In order to analyse distinct cell surface areas, endfeet and somata of these glial cells were purified. Glial endfeet were isolated from flat mounted retina by a specific detachment procedure. Glial somata were purified by negative selection using a monoclonal antibody/complement mediated cytolysis of all non‐glial cells. Retinal tissue strips were explanted either onto pure glial endfeet or onto glial somata. As revealed by scanning and fluorescence microscopy, essentially no ganglion cell axons were evident on glial somata, whereas axonal outgrowth was abundant on glial endfeet. However, when glial somata were heat treated and employed thereafter as the substratum, axon extension was significantly increased. Time‐lapse video recording studies indicated that purified cell membranes of glial somata but not of endfeet induced collapse of growth cones. Collapsing activity was destroyed by heat treatment of glial membranes. The collapsing activity of retinal glia was found to be specific for retinal ganglion cell neurites, because growth cones from dorsal root ganglia remained unaffected. Employing four different kinase inhibitors revealed that the investigated protein kinase types were unlikely to be involved in the collapse reaction. The data show for the first time that radial glial cells are functionally polarized having permissive endfeet and inhibitory somata with regard to outgrowing axons. This finding underscores the pivotal role of radial glia in structuring developing nervous systems.
The perforant path projection from the medial entorhinal cortex layer III to the subiculum in the rat combined hippocampal–entorhinal cortex slice
Authors: Behr J. , Gloveli T. , Heinemann U. 
Published: March 2003

AbstractIntracellular recordings were performed to examine the perforant path projection from layer III of the entorhinal cortex to the subiculum in rat combined hippocampal–entorhinal cortex slices. Electrical stimulation in the medial entorhinal cortex layer III caused short latency combined excitatory and inhibitory synaptic responses in subicular cells.In the presence of the GABAA antagonist bicuculline and the GABAB antagonist CGP‐55845 A inhibition was blocked and isolated AMPA‐ or NMDA receptor‐mediated EPSPs could be elicited. After application of the non‐NMDA antagonist NBQX and the NMDA antagonist APV excitatory responses were completely blocked indicating a glutamatergic input from the neurons of the medial entorhinal cortex layer III. By stimulation from a close (< 0.2 mm) position in the presence of NBQX and APV and either CGP‐55845 A or bicuculline we could record monosynaptic fast GABAA or slow GABAB receptor‐mediated IPSPs, respectively.We compared synaptic responses in subicular cells induced by stimulation in the medial entorhinal cortex layer III with responses elicited by stimulation of afferent fibres in the alveus. The EPSPs of subicular cells induced by stimulation of alvear fibres could be significantly augmented by simultaneous activation of perforant path fibres originating in the medial entorhinal cortex layer III, while delayed activation of alvear fibres after stimulation of the perforant path resulted in a weak inhibition of the alveus evoked EPSPs.Thus, the perforant path projection activates monosynaptic excitation of subicular neurons. Therefore the entorhinal cortex does not only function as an important input structure of the hippocampal formation but is also able to modulate the hippocampal output via the entorhinal–subicular circuit.
The neural processing of 3‐D visual information: evidence from eye movements
Authors: Miles F.A. 
Published: March 2003

AbstractPrimates have several reflexes that generate eye movements to compensate for bodily movements that would otherwise disturb their gaze and undermine their ability to process visual information. Two vestibulo‐ocular reflexes compensate selectively for rotational and translational disturbances of the head, and each has visual backups that operate as negative feedback tracking mechanisms to deal with any residual disturbances of gaze. Of particular interest here are three recently discovered visual tracking mechanisms that specifically address translational disturbances and operate in machine‐like fashion with ultra‐short latencies (< 60 ms in monkeys, < 85 ms in humans). These visual reflexes deal with motions in all three dimensions and operate as automatic servos, using preattentive parallel processing to provide signals that initiate eye movements before the observer is even aware that there has been a disturbance. This processing is accomplished by visual filters each tuned to a different feature of the binocular images located in the immediate vicinity of the plane of fixation. Two of the reflexes use binocular stereo cues and the third is tuned to particular patterns of optic flow associated with the observer's forward motion. Some stereoanomalous subjects show tracking deficits that can be attributed to a lack of just one subtype of cortical cell encoding motion in one particular direction in a narrow depth plane centred on fixation. Despite their rapid, reflex nature, all three mechanisms rely on cortical processing and evidence from monkeys supports the hypothesis that all are mediated by the medial superior temporal (MST) area of cortex. Remarkably, MST seems to represent the first stage in cortical motion processing at which the visual error signals driving each of the three reflexes are fully elaborated at the level of individual cells.
Stimuli which entrain the circadian clock of the neonatal Syrian hamster in vivo regulate the phosphorylation of the transcription factor CREB in the suprachiasmatic nucleus in vitro
Authors: McNulty S. , Schurov I.L. , Sloper P.J. , Hastings M.H. 
Published: March 2003

AbstractPhotic resetting of the adult mammalian circadian clock in vivo is associated with phosphorylation of the Ser133 residue of the calcium/cyclic AMP response‐element binding‐protein (CREB) in the retinorecipient region of the suprachiasmatic nucleus (SCN). Western blotting and immunocytochemistry were used to investigate whether agonists known to reset the clock of neonatal hamsters in vivo are also able to influence the phosphorylation of CREB in the suprachiasmatic hypothalamus in vitro. Antisera raised against synthetic CREB peptide sequences were used to differentiate between total CREB and the Ser133 phosphorylated form of CREB (pCREB). Western blot analysis of proteins isolated from suprachiasmatic tissue of 1‐day‐old Syrian hamsters revealed bands at ≈ 45 kDa corresponding to total CREB and pCREB. Treatment of the tissue with a mixture of glutamatergic agonists [N‐methyl‐d‐aspartate (NMDA), amino‐methyl proprionic acid (AMPA) and kainate, all at 1 μm], or native glutamate (1 μm) had no effect on the total CREB signal, but increased the pCREB signal, indicative of agonist‐stimulated phosphorylation of CREB on Ser133. A similar effect was seen following treatment of the suprachiasmatic blocks with either dopamine (1 μm) or forskolin (1 μm). Simultaneous treatment with melatonin (1 μm) significantly attenuated stimulation by forskolin. The effect of the agonists on nuclear pCREB‐immunoreactivity (‐ir) was investigated in primary cultures which contained a mixture of cell types characteristic of the suprachiasmatic nuclei in vivo. Basal expression of nuclear total CREB‐ir was high, whereas expression of pCREB‐ir was low. Treatment with glutamate (1 μm) or dopamine (1 μm) had no effect on total CREB‐ir, but increased pCREB‐ir in ≈ 50 and 30% of cells, respectively, whereas forskolin (1 μm) increased pCREB‐ir in almost all cells (> 90%). The effects of all three agonists were rapid (< 15 min), and dose and time dependent. Melatonin reversed the effects of forskolin in mixed cultures, but not in pure astrocyte cultures. Dual‐immunocytochemistry (ICC) revealed that glutamate (1 μm) increased nuclear pCREB‐ir in cells immunoreactive for microtubule‐associated protein II (MAP II‐ir), but not other cells, indicating an effect predominantly on neurons. This occurred equally in γ‐amino butyric acid (GABA)‐ir and non‐GABA‐ir neurons. Dopamine (1 μm) was more selective, increasing pCREB‐ir only in GABA‐ir neurons, whereas forskolin increased pCREB‐ir in all cells. The specific stimulation of pCREB‐ir in GABA‐ir neurons by dopamine was reversed by melatonin, but melatonin had no effect on the increase in pCREB‐ir induced in GABA‐ir neurons by glutamate. These results demonstrate that agonists known to entrain the circadian clock in vivo modulate phosphorylation of CREB in GABA‐ir neurons derived from the neonatal suprachiasmatic nuclei.
Functional heterogeneity of periglomerular cells in the rat olfactory bulb
Authors: Puopolo Michelino , Belluzzi Ottorino 
Published: March 2003

AbstractThe periglomerular cells of the rat olfactory bulb, a virtually unknown population of interneurons, have been studied applying the whole‐cell patch‐clamp technique to thin slices. A prominent result, obtained under current‐clamp conditions, is that these cells appear to be functionally heterogeneous, and show distinct excitability profiles. Voltage‐clamp analysis allows the identification of the ionic basis of these differences and suggests a division into at least two classes, based on the characteristics of the K+ conductances. The first group displays two K+ conductances (delayed rectifier, gKV, and fast transient, gA) of similar amplitude, and under current‐clamp conditions shows the usual outward rectifying behaviour at depolarized potentials. The second group has a large gA, and a small or absent gKV. Consequently, following sustained depolarizations under current‐clamp conditions leading to inactivation of gA, these neurons do not show any sign of outward rectification and behave as ohmic elements, as normally observed only at hyperpolarized potentials. The transition ion zinc (10–300 μm) affects gA but not gKV. The inactivation process (steady‐state curve and rate constant) is strongly altered by Zn2+, the activation process less so; open‐channel conductance is not affected. The Zn2+ effect is unlikely to be due to surface charge screening or to a mechanism involving channel block. In view of the substantial presence of zinc ions in the olfactory nerve terminals, its actions on the A‐current could be of some relevance for physiological function.
Lesion‐induced transneuronal plasticity of the cholinergic innervation in the adult rat entorhinal cortex
Authors: De Lacalle Sonsoles , Kulkarni Sunita , Wiley Ronald G. 
Published: March 2003

AbstractThe present experiments were designed to determine the effect that lesions of the basal forebrain cholinergic system exert on cholinergic interneurons within the entorhinal cortex (EC) in the rat. Unilateral infusion of 192 IgG‐saporin into the nucleus of the horizontal diagonal band of Broca (HDB) decreased the number of ipsilateral choline acetyltransferase immunoreactive (ChAT‐ir) neurons by 54%. Two–four weeks after the lesion, the ipsilateral EC exhibited a moderate but significant loss of ChAT‐ir fibres and interneurons. Adjacent sections revealed a parallel loss of vasoactive intestinal polypeptide (VIP) immunoreactivity. Cell counts in the cingulate cortex were unaffected, suggesting that this effect was indeed specific to the main target area for HDB neurons. Ibotenic acid lesions also induced a significant 36% decrease in the number of cholinergic neurons in the ipsilateral HDB, and disappearance of ChAT terminals in the EC, whereas the number of ChAT‐ir neurons in the EC was unchanged. Since ibotenic acid affects all cells and not only cholinergic ones, our results suggest that the specific degeneration of cholinergic neurons in the HDB after 192 IgG‐saporin treatment could be inducing transsynaptic effects on their targets. Injections of 192 IgG‐saporin directly into the EC also lesioned the cholinergic projection from the HDB, but had no effect on the intrinsic population.Eight weeks after immunolesion, the number of interneurons immunoreactive for ChAT and VIP in the EC had returned to normal values, and persisted for as long as 6 months after the lesion. By contrast, ChAT‐ir neurons in the HDB were permanently lost.Our results suggest that the transient down‐regulation of the cholinergic phenotype in entorhinal cortex interneurons could be a manifestation of activity‐dependent plasticity, and that the loss of cholinergic innervation from the basal forebrain could be responsible for these effects through an imbalance of inputs. We hypothesize that the recovery of the phenotypic expression of entorhinal interneurons could be due to a recovery in their innervation, perhaps from sprouting axons in the same fields, belonging to surviving cholinergic neurons in the basal forebrain.