bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Doses of the Glycine/NMDA Receptor Antagonist R‐(+)‐HA‐966 but not d‐Cycloserine Induce Paroxysmal Activity in Limbic Brain Regions of Kindled Rats
Authors: Wlaź Piotr , Ebert Ulrich , Löscher Wolfgang 
Published: April 2006

Abstract(+)‐HA‐966 [R‐(+)‐3‐amino‐1‐hydroxypyrrolid‐2‐one], a functional antagonist at the glycine modulatory site on the W‐methyl‐D‐aspartate (NMDA) receptor/ion channel complex, was evaluated in amygdala‐kindled rats, a model of epilepsy recently shown to exhibit enhanced susceptibility to the adverse effects of competitive and non‐competitive NMDA receptor antagonists. Since (+)‐HA‐966 displays weak partial agonistic effects at the glycine site (−10% efficacy of glycine), D‐cycloserine, a glycine ligand with much higher intrinsic activity, was evaluated in kindled rats for comparison. Following drug administration, electrographic activity was recorded from the basolateral amygdala (i.e. the focal site) as well as the ipsilateral piriform cortex, ventral hippocampus and nucleus accumbens. In addition to the evaluation of original recordings, power spectrum analysis was used to delineate drug effects. (+)‐HA‐966 (20–40 mg/kg i.p.) induced marked alterations in electrographic recordings, including increases in amplitude and isolated spiking, i.e. signs of paroxysmal activity. The severity or duration of fully kindled seizures was not changed by (+)‐HA‐966, but the drug dramatically increased the duration of immobilization and limbic seizure activity following a kindled motor seizure. In contrast to (+)‐HA‐966, D‐cycloserine did not induce any electrographic changes, even when administered in much higher doses than (+)‐HA‐966. The changes in electrographic recordings seen after administration of (+)‐HA‐966 in kindled rats were almost absent in non‐kindled rats, indicating that kindling had increased the sensitivity to the paroxysmal effects of the glycine/NMDA receptor ligand. The data indicate that functional glycine/NMDA antagonists with low intrinsic efficacy may bear the risk of proconvulsant activity.
Differential Effects of Serotonin and Raphe Grafts in the Hippocampus and Hypothalamus: A Combined Behavioural and Anatomical Study in the Rat
Authors: Richter‐Levin G. , Acsády L. , Freund T. F. , Segal M. 
Published: April 2006

AbstractCombined with a partial cholinergic deficiency, serotonergic lesions induce severe spatial learning deficits. Serotonergic lesions, however, have additional effects, such as reduced body weight and disruption of thermoregulation, which may be the cause of the observed learning deficits. Restoration of the serotonergic innervation of the hippocampus by raphe grafts reduces these learning deficits. The effects of the grafts may result from a direct support of spatial learning but may also be an indirect result of preventing some of the other effects of serotonergic lesions. In the present study we used raphe grafts to examine the selectivity and specificity of the effects of serotonergic lesions in the rat, and used the behavioural effects as an indication of successful transplantation in order to examine the fine details of such grafts. Raphe grafts in the hippocampus did not prevent the effects of the lesions on body weight, thermoregulation and exploratory behaviour but did minimize the effects of the lesions on spatial learning. In contrast, raphe grafts in the hypothalamus reduced the effects of the lesions on thermoregulation but failed to support learning. The grafted fibres showed termination specificity with the interneurons, which is typical of the serotonergic innervation of the normal hippocampus. The results indicate that the serotonergic innervation of the hippocampus functions locally to support spatial learning. This role of serotonin is independent of its involvement in modulation of body weight, thermoregulation or exploratory behaviour. The results confirm that the modes of serotonergic action in the hippocampus include the selective innervation of specific interneuron subpopulations.
HIV‐1 Envelope Protein gp120 Potentiates NMDA‐evoked Noradrenaline Release by a Direct Action at Rat Hippocampal and Cortical Noradrenergic Nerve Endings
Authors: Pittaluga A. , Raiteri M. 
Published: April 2006

AbstractExposure of rat or human neocortical or hippocampal tissue to glutamate receptor agonists elicits a Ca2+‐dependent, exocytotic‐like release of previously accumulated [3H]noradrenaline through activation of both N‐methyl‐d‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors colocalized on the noradrenergic axon terminals. Here we show that the NMDA (100 μM)‐evoked release of [3H]noradrenaline from superfused thin layers of isolated rat hippocampal or cortical nerve endings was potentiated when the human immunodeficiency virus type 1 coat protein gp120 was added to the superfusion medium concomitantly with NMDA. The effect of gp120 (10 pM to 3 nM) on the 100 μM NMDA‐evoked release of [3H]noradrenaline was concentration‐dependent; the maximal effect (‐140% potentiation) was reached at 100 pM of gp120. The protein was inactive on its own. The [3H]noradrenaline release evoked by NMDA (100 μM) + gp120 (100 μM) was prevented by classical NMDA receptor antagonists, as well as by 10 μM memantine. Neither the release evoked by NMDA nor that elicited by NMDA + gp120 was sensitive to the nitric oxide synthase inhibitor NG ‐nitro‐l‐arginine, suggesting no involvement of nitric oxide. The [3H]noradrenaline release elicited by 100 nM AMPA was unaffected by gp120. The protein potentiated the release evoked by 100 nM glutamate; the effect of 100 pM gp120 was quantitatively identical to that of 1 μM glycine, with no apparent additivity between gp120 and glycine. The antagonism by 1 μM 7‐chloro‐kynurenic acid of the NMDA‐induced [3H]noradrenaline release was reversed by glycine or gp120. The data are compatible with gp120 acting directly as a powerful positive allosteric modulator at a neuronal NMDA receptor.
Differential Expression of Synaptophysin and Synaptoporin During Pre‐ and Postnatal Development of the Rat Hippocampal Network
Authors: Grabs D. , Bergmann M. , Schuster Th. , Fox P. A. , Brich M. , Gratzl M. 
Published: April 2006

AbstractThe closely related synaptic vesicle membrane proteins synaptophysin and synaptoporin are abundant in the hippocampal formation of the adult rat. But the prenatal hippocampal formation contains only synaptophysin, which is first detected at embryonic day 17 (E17) in perikarya and axons of the pyramidal neurons. At E21 synaptophysin immunoreactivity extends into the apical dendrites of these cells and in newly formed terminals contacting these dendrites. The transient presence of synaptophysin in axons and dendrites suggests a functional involvement of synaptophysin in fibre outgrowth of developing pyramidal neurons. Synaptoporin expression parallels the formation of dentate granule cell synaptic contacts with pyramidal neurons: the amount of hippocampal synaptoporin, determined in immunoblots and by synaptoporin immunostaining of developing mossy fibre terminals, increases during the first postnatal week. Moreover, in the adult, synaptoporin is found exclusively in the mossy fibre terminals present in the hilar region of the dentate gyrus and the regio inferior of the cornu ammonis. In contrast, synaptophysin is present in all synaptic fields of the hippocampal formation, including the mossy fibre terminals, where it colocalizes with synaptoporin in the same boutons. Our data indicate that granule neuron terminals differ from all other terminals of the hippocampal formation by the presence of both synaptoporin and synaptophysin. This difference, observed in the earliest synaptic contacts in the postnatal hippocampus and persisting into adult life, suggests distinct functions of synaptoporin in these nerve terminals.
Role of Dopamine in the Plasticity of Glutamic Acid Decarboxylase Messenger RNA in the Rat Frontal Cortex and the Nucleus Accumbens
Authors: Rétaux Sylvie , Trovero Fabrice , Besson Marie‐Jo 
Published: April 2006

AbstractThe modulatory role of dopamine (DA) on the expression of mRNA encoding the large isoform of glutamic acid decarboxylase (GAD67), the biosynthesis enzyme of gamma aminobutyric acid (GABA), was examined in GABA neurons of two structures innervated by DA neurons originating from the ventral tegmental area (VTA): the medial frontal cortex (MFC) and the nucleus accumbens (NAcc). A bilateral electrolytic lesion of VTA was performed in rats to produce a DA denervation of both the MFC and NAcc. The efficacy of VTA lesions was verified by measurement of locomotor activity and by immunohistochemical detection of tyrosine hydroxylase in the mesencephalon. GAD67 mRNA was detected by in situ hybridization histochemistry using a 35S‐labelled cDNA probe. Densitometric analysis of GAD67 mRNA hybridization signals revealed in VTA‐lesioned rats a significant decrease (‐24%) in GAD67 mRNA levels in the prelimbic area of the MFC and no significant effect in the anterior cingulate area or the frontoparietal cortex. Single cell analyses by computer‐assisted grain counting showed that the decrease in GAD67 mRNA levels in prelimbic MFC was due to a change in GAD67 mRNA expression in a subpopulation of GABA interneurons located in the deep cortical layers (V‐VI). By contrast, in the NAcc of VTA‐lesioned rats, GAD67 mRNA levels were significantly increased in the anterior part and in the core but were unchanged in the shell part. These results suggest that in two target structures of VTA DA neurons, GAD67 mRNA expression is, in normal conditions, under a tonic stimulatory and a tonic inhibitory DA control in the MFC and the NAcc respectively. A schematic diagram is proposed for functional interactions between these structures.
Activity‐dependent Regulation of N‐Methyl‐d‐aspartate Receptor Subunit Expression in Rat Cerebellar Granule Cells
Authors: Audinat Etienne , Lambolez Bertrand , Rossier Jean , Crépel Francis 
Published: April 2006

AbstractThe glutamate receptor channels of the N‐methyl‐d‐aspartate (NMDA) subtype are composed of different subunits named NR1 and NR2A‐D. These subunits can combine in different oligomers with diverging properties and their expression is developmentally regulated. We have used rat cerebellar slice cultures to test the involvement of bioelectrical activity and synaptic transmission in the changes in NR2A‐C expression observed in developing granule cells. A correlation between the functional properties of the NMDA receptors and expression of the NR2A‐C mRNAs was obtained in single granule cells by coupling patch‐clamp recording and reverse transcription followed by polymerase chain reaction. Granule cells grown under standard culture conditions expressed mainly NR2A mRNA when examined after 15–40 days in vitro. Consistent with this observation, their responses to NMDA were only weakly reduced by 3 μM ifenprodil, a non‐competitive antagonist which discriminates between NR2A and NR2B subunits in expression systems. In cerebellar cultures chronically exposed to tetrodotoxin to eliminate spontaneous electrical activity, granule cells maintained a predominant expression of NR2B subunits and their responses to NMDA were largely inhibited by 3 μM ifenprodil. These results provide evidence that the expression of the NR2A and B subunits is regulated through an activity‐dependent mechanism leading to the formation of NMDA receptors with different pharmacological properties. Finally, the NR2C subunit, abundantly expressed in vivo by adult granule cells, was only rarely detected in slice cultures, even when excitatory synapses were formed between granule cells and fibres originating from co‐cultured brainstem explants. These data suggest that the induction of NR2C expression observed in vivo requires an additional factor(s) that remains to be identified.
Insulin and Insulin‐like Growth Factor System Components Gene Expression in the Chicken Retina From Early Neurogenesis Until Late Development and Their Effect on Neuroepithelial Cells
Authors: de La Rosa Enrique J. , Bondy Carolyn A. , Hernández‐Sánchez Catalina , Wu Xin , Zhou Jian , López‐Carranza Ana , Scavo Louis M. , Pablo Flora de 
Published: April 2006

AbstractTo better understand the role of insulin‐related growth factors in neural development, we have characterized by in situ hybridization in chicken embryonic retina the patterns of gene expression for insulin, insulin‐like growth factor I (IGF‐I), their respective receptors and the IGF binding protein 5 (IGFBP5) from early stages (E6) until late stages (E18)‐an analysis not performed yet in any species. In addition, we studied the effect of insulin and IGF‐I on cultured neuroepithelial cells. Insulin receptor mRNA and IGF‐I receptor mRNA were both present and showed a similar, widespread pattern throughout retina development. Insulin mRNA could be detected only by reverse transcription coupled to polymerase chain reaction. IGF‐I mRNA was concentrated in the ciliary processes and extraocular muscles early in development (embryonic day 6; E6) and in maturing retinal ganglion cells subsequently (E9–15). IGFBP5 mRNA was preferentially localized in the more differentiated central retinal zone and was maximally concentrated in the inner nuclear and ganglion cell layers at E9. These findings suggest a near constitutive expression of insulin receptor and IGF‐I receptor genes, while IGF‐I and IGFBP5 showed a highly focal spatiotemporal regulation of gene expression. Insulin and IGF‐I, already at 10−8 M, increased the proportion of PM1‐positive neuroepithelial cells found in E5 retinal cultures without affecting significantly the total number of proliferating cells. Together, these data support the finding that, during early neurogenesis in chicken retina, insulin and IGF‐I have a specific paracrine/autocrine action. This action, as well as possible effects elicited subsequently, may be dictated by restricted local synthesis of the ligands and limited access to the factors contained in the vitreous humour. In the case of IGF's role, local IGFBPs expression can contribute to the fine modulation.
Processing and Analysis of Form, Colour and Binocular Disparity in the Human Brain: Functional Anatomy by Positron Emission Tomography
Authors: Gulyás Balázs , Roland Per E. 
Published: April 2006

AbstractWith the purpose of mapping those anatomical structures participating in the processing and analysis of form, colour and disparity information, we have measured, with positron emission tomography and [15O]butanol, regional cerebral blood flow (rCBF) as an indicator of regional cerebral metabolic activity in 13 right‐handed male volunteers during visual discrimination of colour, form and disparity information. The brain images were anatomically standardized using a computerized brain atlas and statistically significant changes were localized by cluster analysis. The changes in rCBF between specific activation and reference states were measured and the volumes of changes were determined, as were the loci and volumes of areas commonly activated by two or three different tasks. Each of the tasks activated over a dozen distinct and separate fields in the cortex–in the occipital, parietal, temporal and frontal lobes as well as the cerebellum. A number of overlapping fields were commonly activated in two tasks (four in the form and colour tasks, five in the form and disparity tasks, and eleven in the colour and disparity tasks), and two field overlaps were present in all three tasks (in the right superior frontal and left lingual gyri). These findings indicate that, in a visual discrimination task, the processing and analysis of single visual submodalities take place in a number of cortical fields in the human brain. As the same visual submodality is processed and analysed by numerous fields and the same field may participate in the processing of different submodalities, a divergence‐convergence pattern of information processing is present in the human brain. This observation supports a hypothesis based on earlier studies in primates, namely that information processing in the visual system requires the concerted activation of a relatively large number of fields of functional networks in the brain.
Deficient Sensorimotor Gating After 6‐Hydroxydopamine Lesion of the Rat medial Prefrontal Cortex is Reversed by Haloperidol
Authors: Koch Michael , Bubser Michael 
Published: April 2006

AbstractThe present study sought to test the hypothesis that dopamine in the prefrontal cortex exerts an inhibitory influence on subcortical dopamine systems and that depletion of prefrontal dopamine may affect behaviour via an increase in dopamine release in the basal ganglia. We used prepulse inhibition of the acoustic startle response, i.e. the inhibition of the acoustic startle response by a preceding non‐startling stimulus, as the behavioural test, because this phenomenon of sensorimotor gating is modified in opposite directions by dopamine in the prefrontal cortex and in the basal ganglia. Rats were tested for prepulse inhibition before and after injections of the neurotoxin 6‐hydroxydopamine into the medial prefrontal cortex. We attempted to differentiate the contributions of prefrontal dopamine and noradrenaline by pretreating the animals with desipramine (6‐OHDADMI rats) or bupropion (6‐OHDABUP rats), selective inhibitors of noradrenaline and dopamine reuptake respectively. 6‐Hydroxydopamine lesion reduced prefrontal dopamine by 90% and noradrenaline by 80% in 6‐OHDADMI rats, while prefrontal dopamine was reduced by 54% and noradrenaline by 95% in 6‐OHDABUP rats. The ability of an acoustic prepulse (75 dB, 10 kHz) to inhibit the response to a startle pulse (100 dB noise burst) was maintained in sham‐lesioned rats and in 6‐OHDABUP rats. However, there was a marked reduction of prepulse inhibition (by 26%) in the 6‐OHDADMI rats. Systemic administration of the dopamine antagonist haloperidol (0.05 mg/kg), which did not affect prepulse inhibition in sham‐lesioned and in 6‐OHDABUP rats, antagonized the lesion‐induced deficit in prepulse inhibition in 6‐OHDADMI rats. These results suggest that prefrontal dopamine is involved in prepulse inhibition of the acoustic startle response. The haloperidol‐induced antagonism of the deficit in prepulse inhibition observed in 6‐OHDADMI rats is compatible with the view that prefrontal dopamine depletion led to overactivity of subcortical dopamine systems involved in prepulse inhibition, i.e. in the nucleus accumbens and/or anteromedial striatum. The significance of prefrontal noradrenaline depletion, which may have partially counteracted the effects of dopamine depletion on prepulse inhibition, is also discussed. Since prepulse inhibition is impaired in schizophrenics, the present findings lend support to the theory of prefrontal dopamine hypofunction in the aetiology of schizophrenia.
Development of the Pathway From the Reticular and Perireticular Nuclei to the Thalamus in Ferrets: A Dil Study
Authors: Mitrofanis John 
Published: April 2006

AbstractThis study examines the connections of the thalamic reticular and perireticular cell groups in developing ferrets. Small crystals of Dil (1,1′‐dioctadecyl‐3, 3, 3′, 3′‐tetramethylindocarbocyanine perchlorate) were implanted into either the dorsal thalamus or the cerebral cortex of aldehyde‐fixed prenatal and postnatal ferret brains. A small implant of Dil into the presumptive lateral geniculate nucleus during early prenatal development [between embryonic day 23 (E23) and E25] reveals many retrogradely labelled cells in the reticular nucleus. At E40, just before birth, the number of cells retrogradely labelled in the reticular nucleus has become reduced compared to earlier prenatal implants, whether from small or large implants of Dil into the lateral geniculate nucleus. By postnatal day 7, an adult‐like pattern of retrograde labelling is seen in the reticular nucleus; at this age, a small implant of Dil limited to the lateral geniculate nucleus retrogradely labels a discrete group of cells located in the caudal regions of the reticular nucleus. In the internal capsule, adjacent to the reticular nucleus, there are two distinct groups of neurons. One group, called the large‐celled perireticular zone (LPR), enters the internal capsule very early in development (from E25; Mitrofanis, J., Eur. J. Neurosci., 6, 253–263, 1994) and is not labelled from the lateral geniculate nucleus at any developmental stage. Small implants of Dil into presumptive visual and somatosensory cortices shows that the LPR lies in a distinct region of the primordial internal capsule. Corticothalamic and thalamocortical axons turn sharply in the region of the LPR, whilst corticospinal and corticobulbar axons pass straight through the LPR on towards their more caudal targets. Later, after both sets of axons have reached their targets, the LPR is not seen in the internal capsule. The other group of cells in the internal capsule, called the small‐celled perireticular zone (SPR), forms a distinct band of cells lying midway between the reticular nucleus and the globus pallidus. These cells enter the internal capsule much later in development, at about E40. Unlike the cells in the LPR, cells in the SPR are retrogradely labelled after an implant of Dil into the lateral geniculate nucleus, and there are many which remain in the adult (Clemence, A. E. and Mitrofanis, J., J. Comp. Neurol., 322, 167–181, 1992).
Distribution of Somatostatin Receptors 1, 2 and 3 mRNA in Rat Brain and Pituitary
Authors: Señarís R. M. , Humphrey P. P. A. , Emson P. C. 
Published: April 2006

AbstractIn this study sequence‐specific antisense oligonucleotide probes have been used to investigate the distribution of the mRNAs coding for the somatostatin receptor subtypes termed somatostatin receptor 1, somatostatin receptor 2 and somatostatin receptor 3 in the rat brain and pituitary using in situ hybridization techniques. The three receptor subtype mRNAs were found to be widely distributed in the brain with different patterns of expression, but with some overlap. Somatostatin receptor 1 mRNA was particularly concentrated in the cerebral and piriform cortex, magnocellular preoptic nucleus, hypothalamus, amygdala, hippocampus, and several nuclei of the brainstem. Somatostatin receptor 3 mRNA was very abundant in the cerebellum and pituitary (in contrast to somatostatin receptor 1), but it was also found in hippocampus, amygdala, hypothalamus and in motor nuclei of the brainstem. Somatostatin receptor 2 mRNA levels were very low relative to the other two mRNAs evaluated. Receptor 2 mRNA was observed in the anterior pituitary, and in the brain it was found in the medial habenular nucleus, claustrum, endopiriform nucleus, hippocampus, some amygdala nuclei, cerebral cortex and hypothalamus. None of the three somatostatin receptor mRNAs studied here was found in the caudate nucleus. Northern analysis revealed distinct sizes of mRNAs for each subtype, and displacement experiments showed that each probe sequence was subtype‐specific.