bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional Distribution of the Anticonvulsant and Behavioural Effects of Bicuculline Injected into the Pontine Reticular Formation of Rats
Authors: Shehab Safa , Guadagno Joseph , Ferguson Karen , Redgrave Peter 
Published: April 2006

AbstractPrevious experimental work has established that activation of sites in the dorsal midbrain can suppress tonic hindlimb extension in the electroshock model of epilepsy. The most sensitive region for this effect is centred on the intercollicular area and is referred to as the dorsal midbrain anticonvulsant zone (DMAZ). Subsequent experiments have shown that the ipsilateral descending projection from this region to the ventrolateral pons is critically involved in mediating its tonic seizure‐suppressing properties. The purpose of the present investigation was to test whether direct anticonvulsant effects in the electroshock model could be obtained from selective manipulation of DMAZ target regions in the ventrolateral pons. Animals were prepared with chronically implanted guide cannulae through which microinjections could be made directly into the lateral pontine reticular formation. Animals received injections of saline or bicuculline (25–200 pmol) administered either bilaterally or unilaterally. The effects of these injections on the animals' behaviour were determined in an open arena, after which maximal electroshock (1s, 40 mA, 50 Hz AC) was administered via ear‐clip electrodes and the duration of tonic hindlimb extension was recorded. Bilateral injections of bicuculline (100 pmol) suppressed tonic seizures at a significantly higher proportion of sites centred on DMAZ target regions of the ventrolateral pons than surrounding areas. For injections centred on this region the suppressive effects of bicuculline were dose‐related in the range 25–100 pmol. Unilateral injections of bicuculline into the ventrolateral pons also effectively suppressed tonic seizures in the electroshock model. Within the ventral pons there was a significant association between the behavioural and anticonvulsant effects of bicuculline; injections suppressing tonic seizures were associated with the induction of fast continuous locomotor activity, These data confirm that the DMAZ recipient region of the ventrolateral pontine reticular formation is part of a circuit which can suppress the manifestation of tonic hindlimb extension in the electroshock model. Whether this property is related to the participation of this region in normal locomotion and posture remains to be determined.
Retinal Ganglion Cell Depletion Alters the Phenotypic Expression of GABA and GAD in the Rat Retina
Authors: Yamasaki Edna N. , da Costa Belmira L. S. Andrade , Barbosa Valéria D. , Hokoç Jan Nora 
Published: April 2006

AbstractWe have looked at the phenotypic expression of γ‐aminobutyric acid (GABA) and the two isoforms of its synthetic enzyme [glutamic acid decarboxylase (GAD)‐65 and ‐671 in adult rat retinas that had the superior colliculus, pretectum and optic tract lesioned unilaterally at birth. It has been shown previously that this type of manipulation induces retrograde degeneration of retinal ganglion cells presumably without affecting other intraretinal neurons. We present evidence that GABAergic amacrine cells are affected by such manipulation. The number of cells immunoreactive for GABA, GAD‐65 and GAD‐67 decreased in the inner nuclear layer. In the retinal ganglion cell layer, however, the number of GABA‐ and GAD‐65–labelled cells increased, while the number of GAD‐67–labelled cells did not change. Biochemical assay showed that overall GAD activity was not altered in retinas of lesioned animals. Our results support the notion that, while neonatal lesion reorganizes the expression of GABA and GAD in the retina, enzyme activity is maintained within normal levels.
Rolipram, a Selective Phosphodiesterase Type‐IV Inhibitor, Prevents Induction of Heat Shock Protein HSP‐70 and hsp‐70 mRNA in Rat Retrosplenial Cortex by the NMDA Receptor Antagonist DizociIpine
Authors: Hashimot Kenji , Tomitaka Shin‐ichiro , Bi Ying , Narita Natsuko , Minabe Yoshio , Lyo Masaomi 
Published: April 2006

AbstractThe non‐competitive NMDA receptor antagonists, such as (+)‐MK‐801 (dizocilpine), cause the expression of heat shock protein HSP‐70 and pathomorphological damage in the retrosplenial cortex of the rat brain. However, the precise mechanism(s) underlying the neurotoxicity of NMDA receptor antagonists is unknown. The present study was undertaken to examine the role of phosphodiesterase type IV in the expression of heat shock genes induced by dizocilpine. Heat shock protein HSP‐70, which is known as a sensitive marker of neuron injury, was induced in the retrosplenial cortex of the rat brain 24 h after a single administration of dizocilpine (1 mg/kg). Pretreatment with the specific phosphodiesterase type IV inhibitor rolipram (2.5, 5 or 10 mg/kg, 15 rnin before dizocilpine) attenuated the expression of HSP‐70 and hsp‐70 mRNA induced by dizocilpine (1 mg/kg) in a dose‐dependent manner. Furthermore, another phosphodiesterase type IV inhibitor, Ro 20–1724 (5 or 10 mg/kg, 15 min before dizocilpine), and a non‐selective phosphodiesterase inhibitor, 3–isobutyl‐1–methylxanthine (IBMX) (5 or 10 mg/kg, 15 min before dizocilpine), significantly attenuated the expression of HSP‐70 protein and hsp‐70 mRNA induced in the retrosplenial cortex by dizocilpine. However, the induction of the immediate early gene c‐fos and microglial activation in the retrosplenial cortex after administration of dizocilpine was not attenuated by pretreatment with rolipram (5 or 10 mg/kg, 15 min before dizocilpine). Moreover, histopathological study indicated that pretreatment with rolipram (5 or 10 mg/kg, 15 min before dizocilpine) did not prevent the formation of vacuoles caused by treatment with dizocilpine. The present findings suggest that phosphodiesterase type IV may play a significant role in the expression of HSP‐70 protein and hsp‐70 mRNA in the rat retrosplenial cortex after administration of dizocilpine, and that phosphodiesterase type IV may not play a role in the neurotoxicity of NMDA receptor antagonists such as dizocilpine.
Critical Period‐dependent Reduction of the Permissiveness of Cat Visual Cortex Tissue for Neuronal Adhesion and Neurite Growth
Authors: Schoop Veronika M. , Gardziella Stefan , Müller Christian M. 
Published: April 2006

AbstractDuring postnatal development, the visual cortex undergoes an experience‐dependent refinement of its circuitry. This process includes synapse formation, as well as synapse elimination. Both mechanisms appear to be restricted to a limited ‘critical period’ which lasts for ∼2 months in cats. We tested whether the termination of the critical period for cortical malleability is paralleled by changes in the growth permissiveness of the tissue. These changes may inhibit progressive reorganization of functional circuitries mediated by axon growth. Embryonic cortical neurons were cultured on unfixed cryostat sections of the visual cortex obtained from cats aged 2–50 weeks. After 2–3 days in vitro the distribution of viable cells and the percentage of neurite‐bearing cells were determined and analysed with respect to the developmental age and subdivisions of the underlying tissue substrate. It was shown that cell adhesion and neurite formation are correlated with the developmental age of the substrate tissue and the time period of myelination. While embryonic neurons adhered and survived on grey and white matter tissue from 2‐ and 4‐week‐old kittens, there was a significant reduction in cell adhesion on the myelinated white matter regions of the tissue sections of older animals. Quantitative analyses showed that neurite formation by cultured neurons also became successively impaired on grey and white matter areas of tissue substrates, corresponding to the time course of the critical period for cortical malleability. On grey matter tissue this effect was most pronounced between the second and sixth postnatal weeks. The effects were not antagonized by coating the substrate sections with the growth‐promoting molecule laminin. It is therefore proposed that neurite growth‐inhibiting factors, most probably associated with central nervous system myelin, are gradually expressed postnatally and may contribute to the termination of the critical period in the visual cortex of cats.
Effects of NMDA and AMPA Receptor Antagonists on Corticosterone Facilitation of Long‐term Memory in the Chick
Authors: Venero César , Sandi Carmen 
Published: April 2006

AbstractLong‐term memory formation for a weak passive avoidance task in day‐old chicks is facilitated by corticosterone administration. Since (i) glutamatergic systems, through different receptor types, play a key role in learning and memory processes, and (ii) glucocorticoids increase glutamate concentrations in learning‐related regions of the mammalian brain, we reasoned that glutamatergic activation might be a mechanism by which corticosterone facilitates the formation of an enduring memory. To assess this hypothesis, long‐term retention was evaluated in chicks trained on a weak passive avoidance task and intracerebrally injected with NMDA and a‐amino‐3‐hydroxyd‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonists (MK‐801 and 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione) with regard to training and corticosterone injection respectively. The results indicated that either of the antagonists prevented the facilitating effect of corticosterone when administered before the training trial, but failed to interfere with the steroid effect when injected before corticosterone administration in the post‐training period, suggesting that their early effectiveness was not related to corticosterone‐induced actions but to training‐triggered mechanisms. In addition, administration of the AMPA antagonist, 5.5 h after training, was also effective in impairing the long‐term memory‐potentiating effect of corticosterone. These results support the view that corticosterone facilitates the formation of an enduring memory in this learning model, through the modulation of late events during the consolidation period, including the activation of the AMPA receptor type.
Spatial Resolution and Contrast Sensitivity of Single Neurons in Area 19 of Split‐chiasm Cats: A Comparison With Primary Visual Cortex
Authors: Tardif Eric , Richer Louis , Bergeron André , Lepore Franco , Guillemot Jean‐Paul 
Published: April 2006

AbstractElectrophysiological recordings were carried out in the callosal recipient zone of area 19 in normal and split‐chiasm cats and, for comparison purposes, at the border of areas 17 and 18 of split‐chiasm cats. The influences of retinothalamic and callosal inputs on a single cortical neurons were thereby evaluated. Extracellular recordings of single cells were made in anaesthetized and paralysed cats in the zone representing the central visual field. Receptive field properties were assessed using sine wave gratings drifting in optimal directions. Results showed that in area 19 and areas 17/18 one‐third of the cells were binocularly driven after section of the optic chiasm. In area 19, the spatial resolution and contrast sensitivity of cells driven via the dominant eye were similar in the normal and split‐chiasm groups. In areas 17/18 and area 19 of split‐chiasm cats, binocular cells showed significant interocular matching of their receptive field properties (spatial resolution and contrast threshold), although small differences were observed. These small interocular differences were related to the cell's Ocular dominance rather than to the signal transmission route (thalamic or callosal).
Immunocytochemical Localization of a High‐affinity Glutamate‐Aspartate Transporter, GLAST, in the Rat and Guinea‐pig Cochlea
Authors: Furness David N. , Lehre Knut P. 
Published: April 2006

AbstractGlutamate transporters play an important role in the reuptake of glutamate after its release from glutamatergic synapses. Four such transporters have so far been cloned from the rat brain. One, the glutamate‐aspartate transporter GLAST, has been detected in the mammalian cochlea, in which the principal afferent synapse of the auditory nerve, between the inner hair cells and neurites of type I spiral ganglion neurons, has been suggested to be glutamatergic. The distribution of GLAST was therefore investigated to provide clues to the handling of glutamate in the cochlea. This was studied using light and electron microscopic immunocytochemistry in rats and guinea pigs with antibodies raised against synthetic peptides based on the sequence for GLAST. Significant immunoreactivity was found in the myelin sheath formed by satellite cells surrounding the type I spiral ganglion neurons, and along the plasma membranes of supporting cells around the inner hair cells; other cells in both locations were only weakly labelled, if at all. The absence of substantial numbers of synapses in the spiral ganglion suggests that GLAST is unlikely to be associated with the uptake of synaptic glutamate after release in this region. lmmunoreactivity associated with the inner hair cells is consistent with the utilization of glutamate at the afferent synapse.
Age‐dependent Variations in Potassium Sensitivity of A‐Currents in Rat Hippocampal Neurons
Authors: Klee Rolf , Eder Claudia , Ficker Eckhard , Heinemann Uwe 
Published: April 2006

AbstractHippocampal pyramidal neurons were either cultured from prenatal rats or acutely isolated from the brain of newborn and juvenile rats. The influence of lowering the concentration of the extracellular potassium concentration ([K+]0) on isolated fast transient outward K+ currents (IA) was studied in these neurons using the patch clamp technique in the whole cell configuration. With respect to the response of IA to lowering [K+]0, three types of cells were observed. The first subpopulation of neurons was characterized by a complete suppression of IA over the whole voltage range under potassium‐free solutions (type A neurons). A second proportion of cells showed an increase of IA at test pulses below ‐0 mV and a decrease of IA at voltages above ‐0 mV (type B neurons). In a third group of neurons, amplitudes of lA increased at all potentials tested during omission of potassium ions from the extracellular superfusate (type C neurons). Whereas type A and type B neurons were preferentially found in freshly plated cultures and newborn rats, the majority of type C cells was detected in long‐term cultures and in animals of older ages. Thus, hippocampal A‐currents lose their sensitivity to extracellular potassium ions during early ontogenesis.
Electrophysiological Evidence That Neurokinin A Acts Via NK‐1 Receptors in the Cat Dorsal Horn
Authors: Radhakrishnan V. , Henry J. L. 
Published: April 2006

AbstractThe aim of the present study was to investigate the effects of the non‐peptide NK‐2 receptor antagonist, SR 48968 on the responses of dorsal horn neurons to iontophoretic application of the endogenous NK‐2 receptor ligand, neurokinin A, and on synaptically elicited responses in chloralose‐anaesthetized cats. The effect of iontophoretic application of neurokinin A was tested on 51 dorsal horn neurons. Of these, 43 were wide dynamic range and the rest non‐nociceptive neurons. Neurokinin A induced a slow, prolonged excitation of 25 of the wide dynamic range neurons. All remaining neurons were unaffected. SR 48968 (50 pg to 1.0 mg/kg, i.v.) did not affect the on‐going basal activity (n= 8) or the slow excitation induced by neurokinin A in any of the nine wide dynamic range neurons tested. To eliminate the possibility that systemically administered SR 48968 may not be reaching central sites, SR 48968 was also applied iontophoretically (70–120 nA) to five neurons and tested against excitatory responses to iontophoretically applied neurokinin A. The on‐going activity of these cells were unaffected by SR 48968. The responses to neurokinin A were also unaffected suggesting that neurokinin A did not mediate its effects via NK‐2 receptors. SR 48968 also had no effect on the excitatory responses of seven neurons to iontophoretic application of the NK‐1 receptor agonist, substance P indicating that substance P actions are not mediated via NK‐2 receptors and that SR 48968 did not react with NK‐1 receptors. Responses of the neurons to non‐noxious (hair) stimulation (n = 10), noxious mechanical (n= 5) and noxious thermal (n= 8) stimulation of the receptive field were also unaffected by SR 48968, suggesting a lack of participation of NK‐2 receptors in these responses. However, responses of wide dynamic range neurons to neurokinin A were totally blocked by i.v. administration (0.5 mg/kg) of the NK‐1 receptor antagonists CP‐96,345 (n= 7) and CP‐99,994 (n= 5) but not by CP‐96,344 (n= 4), the inactive enantiomer of CP‐96,345. These data suggest that neurokinin A, like substance P may be acting via NK‐1, rather than NK‐2 receptors, to produce excitation of wide dynamic range neurons in the dorsal horn of the cat spinal cord.
Cerebellar Contribution to Spatial Event Processing: Right/Left Discrimination Abilities in Rats
Authors: Molinari Marco , Grammaldo Liliana G. , Petrosini Laura 
Published: April 2006

AbstractRecently, we demonstrated the involvement of cerebellar circuits in the procedural components of spatial information processing by testing hemicerebellectomized (HCbed) rats in classical spatial paradigms, such as the Morris Water Maze and the water T‐maze. Since procedural components are strongly present in these tests, an impairment also in processing more abstract spatial information, linked to ‘where an object is’ rather than to ‘how to find it’, could be hidden by the severe procedural deficits. On this basis, we investigated the influence of cerebellar lesions on spatial abilities strictly reducing procedural variables by employing an active avoidance task, first without and then with a request for righvleft discrimination. In the two‐way active avoidance task without spatial requests, controls and cerebellar operated rats developed active avoidance responses which were not statistically different, demonstrating that this kind of associative learning is not significantly affected by hemicerebellectomy (HCb). A second experimental group of cerebellar lesioned rats was tested in a modified version of this basic paradigm in which a rightheft discrimination request was added. This group displayed severe deficits, which even in the last testing sessions prevented them from performing comparably to the control animals. Reversal of the rewarded choice, even if it affected the performances of both controls and operated rats in the first inversion trials, elicited the lowest number of correct responses in HCbed rats throughout the entire spatial reversal learning, suggesting a severe deficit in the ability to change an initially learned behaviour. These results demonstrate that, beside having a marked impairment in facing procedural components of spatial processing, cerebellar lesioned rats are severely defective also in rightlleft discrimination tasks, suggesting a role of cerebellar networks also in the discriminative spatial information processing.
Expression and Coupling to Polyphosphoinositide Hydrolysis of Group I Metabotropic Glutamate Receptors in Early Postnatal and Adult Rat Brain
Authors: Casabona G. , Knopfel T. , Kuhn R. , Gasparini F. , Baumann P. , Sortino M. A. , Copani A. , Nicolettii F. 
Published: April 2006

AbstractWe investigated the expression and coupling to the phospholipase C signal transduction pathway of metabotropic glutamate receptor (mGluR) subtypes by Western blot analysis and agonist‐stimulated inositol monophosphate formation in several brain regions of postnatal day 9 (P9) and adult rats. In the cerebral cortex, hippocampus, corpus striatum, olfactory bulb, cerebellum and hypothalamus, the expression level of mGluR5 was greater at P9 than in adulthood. The mGluR5 signal was very low or absent in the adult cerebellum and hypothalamus. The expression of mGluR1a was slightly greater at P9 in the hypothalamus, hippocampus and olfactory bulb, whereas it substantially increased with age in the cerebellum, and did not change in the cerebral cortex and corpus striatum. mGluR1b and ‐1c were nearly undetectable by Western blot analysis. The expression level of mGluR5, but not that of mGluR1a, was significantly correlated with the extent of phosphoinositide hydrolysis stimulated by mGluR agonists in slices prepared from these brain regions. The mGluR antagonist cyclopropan[b]chromen‐1a‐carboxylic acid ethylester (CPCCOEt), potently antagonized responses mediated by mGluR1, but much less potently those mediated by mGluR5a in recombinant cells. CPCCOEt, at a concentration which efficently blocks mGluR1 responses, did not substantially affect the polyphosphoinositide response in hippocampal or cerebellar slices from newborn animals, and antagonized only a minor component of the polyphosphoinositide response in adult hippocampal slices. CPCCOEt, however, prevented the small stimulation of polyphosphoinositide hydrolysis by mGluR agonists in adult cerebellar slices. We conclude that (i) the efficient mGluR‐mediated polyphosphoinositide hydrolysis in 9‐day‐old rats is mediated by mGluR5; (ii) the increased expression of mGluR1 in the adult cerebellum does not substitute for the decline of mGluR5 expression in the ability to mediate polyphosphoinositide hydrolysis; and therefore (iii) mGluRla might couple less efficiently than mGluR5 to polyphosphoinositide hydrolysis.
Prevention of Kainic Acid‐induced Limbic Seizures and Fos Expression by the GABA‐A Receptor Agonist Muscimol
Authors: Zhang Xia , Le Gal La Salle Gildas , Ridoux Valerie , Yu Peter H. , Ju Gong 
Published: April 2006

AbstractFos oncoprotein expression has been shown to be a sensitive marker for sequential neuronal activation in response to a specific stimulus. The present study investigated the effect of the γ‐aminobutyric acid (GABA)‐A receptor agonist muscimol on kainic acid (KA)‐induced limbic seizures and Fos expression in the rat forebrain. One hour after KA injection, a substantial Fos expression was observed in the hippocampal dentate gyrus, whereas only a low level of Fos induction was seen in CA1–3 fields. Six hours post‐injection a prominent increase of Fos expression occurred in most forebrain structures, including the whole hippocampus. Following 0.5 mg/kg muscimol treatment a remarkable decrease of Fos expression occurred but only in the caudate putamen and core of the accumbens nucleus. Treatment with 1 mg/kg muscimol led to further significant decreases of Fos expression in CA1–3 pyramidal neurons and the disappearance of Fos induction in the cerebral cortex above the rhinal fissure, reticular thalamic nucleus, claustrum, fundus striati, ventral pallidum, septal nucleus, lateral habenular nucleus, and lateral amygdaloid nucleus. When 2 mg/kg muscimol was injected, animals exhibited ‘absence seizures’ instead of limbic seizures, and Fos expression in the hippocampus was effectively blocked. These results suggest that a reduction of GABAergic inhibition plays a crucial role not only in limbic seizure genesis in the dentate gyrus, but also in the seizure spread mechanism in many brain structures, among which the hippocampal CA1–3 fields are most markedly involved, less marked in the cerebral cortex and some other structures, and least marked in the caudate putamen and core of the accumbens nucleus.