bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulphhydryl‐modifying Reagents Alter Ototoxin Block of Muscarinic Receptor‐linked Phosphoinositide Turnover in the Cochlea
Authors: Bartolami Sylvain , Planche Myriam , Pujol Rémy 
Published: April 2006

AbstractIn the 12‐day‐old rat cochlea, the synthesis of inositol phosphates (IPs) can be activated via M3 cholinoceptors. This stimulation is blocked by ototoxins (mercury, ethacrynate, cisplatin, neomycin), drugs with side effects that lead to damage of hair cells and strial cells. As these toxic effects can be reversed in vivo by thiol molecules, we investigated whether modifications of thiol compounds could be involved in ototoxin‐induced inhibition of the IP turnover in the cochlea. For this purpose, we assessed whether the sulphhydryl‐modifying reagents N‐ethylmaleimide and cadmium modify the carbachol‐stimulated formation of IPs in the 12‐day‐old rat cochlea. Both molecules inhibit the carbachol effect on a dose‐dependent way without altering the basal metabolism of IPs. As cadmium may block some calcium channels, the effect of verapamil, another calcium channel antagonist, was tested. Verapamil (1 –50 μM) does not alter carbachol‐evoked IP formation, suggesting that the inhibitory effect of cadmium is not due to a calcium influx block. Binding experiments with the muscarinic ligand quinuclidinyl benzylate (QNB) showed that the sulphhydryl‐modifying reagents do not displace QNB from binding sites. Combining ototoxins and reagents shows that N‐ethylmaleimide acts synergistically with all ototoxins but ethacrynate while cadmium does so only with mercury. Both N‐ethylmaleimide and cadmium have additive effects with ethacrynate. As a supplement, disulphide bond‐modifying agents do not alter the carbachol‐enhanced metabolism of IPs. These results suggest that molecules having thiol‐modifying properties inhibit the carbachol‐induced turnover of IPs without acting at the muscarinic sites. Since thiol modifiers and ethacrynate share similar features in both QNB binding and IP response it is hypothesized that they strike common targets, possibly G proteins.
Differential Regulation of Preprotachykinin‐A mRNA Expression in Striatum by Excitation of Hippocampal Neurons
Authors: Brené Stefan , Lindefors Nils , Herrera‐Marschitz Mario , Persson Håkan 
Published: April 2006

AbstractIn this report we have studied the influence of hippocampal neurons on neuropeptide mRNA expression in both dorsal and ventral striatum in the rat. Intrahippocampal unilateral kainic acid injections were performed in control animals and in animals with a unilateral 6‐hydroxydopamine‐induced dopamine deafferentation of the striatum. In situ hybridization combined with quantitative image analysis was used to study the expression of preprotachykinin A mRNA encoding the neuropeptides substance P and neurokinin A. The 6‐hydroxydopamine‐induced lesion caused a decrease of preprotachykinin A mRNA levels in the ipsilateral dorsal striatum and in both sides of the ventral striatum. In normal rats, the intrahippocampal kainic acid injection caused a twofold increase in preprotachykinin A mRNA in the limbic parts of the striatum, which are innervated by the hippocampus. No effect of the kainic acid injection was seen in the lateral parts of the dorsal striatum, a region which does not appear to be innvervated by the hippocampus. Animals with a 6‐hydroxydopamine lesion showed a similar kainic acid‐mediated increase in preprotachykinin A mRNA in parts of the ventral striatum. In the dopamine‐lesioned dorsal striatum and ventral striatum the decreased preprotachykinin A mRNA levels were normalized by the intrahippocampal kainic acid injection. These results show that kainic acid‐mediated excitation of hippocampal neurons causes a dopamine‐independent induction of preprotachykinin A mRNA expression in parts of the ventral striatum, and reverses the dopamine deafferentation‐induced decrease of preprotachykinin A mRNA in both dorsal and ventral striatum. Combined, our results suggest that hippocampal neurons can regulate preprotachykinin A mRNA expression in both the ventral and the dorsal striatum.
Functional Organization of Auditory Cortex in the Mongolian Gerbil (Meriones unguiculatus). I. Electrophysiological Mapping of Frequency Representation and Distinction of Fields
Authors: Thomas Hardy , Tillein Jochen , Heil Peter , Scheich Henning 
Published: April 2006

AbstractThe frequency representation within the auditory cortex of the anaesthetized Mongolian gerbil (Meriones unguiculatus) was studied using standard microelectrode (essentially multiunit) mapping techniques. A large tonotopically organized primary auditory field (AI) was identified. High best frequencies (BFs) were represented rostrally and low BFs caudally along roughly dorsoventrally oriented isofrequency contours. Additional tonotopic representations were found adjacent to AI. Rostral to AI was a smaller field with a complete tonotopic gradient reversed with respect to that in AI (mirror image representation) and was termed the anterior auditory field (AAF). BFs in the range from 0.1 to 43 kHz, apparently covering the hearing range of the Mongolian gerbil, were found in AI and AAF. Units in these two core fields responded to narrow frequency ranges with short latencies. Ventral to the common high‐frequency border to AAF and AI, a rapid transition to very low BFs suggested the presence of a ventral field (V). Caudal to AI two small tonotopically organized fields were identified, a dorsoposterior field (DP) and a ventroposterior field (VP). The VP showed a tonotopic organization mirror imaged to that of AI, i.e. low frequencies were represented rostrally near the caudal border of AI, and high frequencies caudally. The DP showed a concentric frequency organization with high BFs located in the centre. Units in DP and VP fired less strongly, with considerably longer latencies, and responded to a broader range of frequencies than units in AI and AAF. Dorsocaudal to AI a dorsal field (D) was identified, harbouring units that responded to very broad ranges of frequencies. A tonotopic organization of field D could not be discerned. In the border region of AI and D, low‐frequency responses were similar to those found in parts of AI and AAF, but without a clear‐cut tonotopic organization. This region was termed Aid. The two core fields AI and AAF appeared to be located within the koniocortex, while the remaining fields lay outside. Our data show that the organization of the gerbil auditory cortex is highly elaborate, with parcellation into fields as complex as in cat or primates.
Spatiotemporal Induction of Immediate Early Genes in the Rat Brain after Limbic Seizures: Effects of NMDA Receptor Antagonist MK‐801
Authors: Gass Peter , Herdegen Thomas , Bravo Rodrigo , Kiessling Marika 
Published: April 2006

Abstract Fos, jun and krox belong to multigene families coding for transcription factors. These cellular immediate early genes (IEGs) are thought to be involved in coupling neuronal excitation to changes of target gene expression. Immunocytochemistry with specific antisera was used to assess regional levels of six IEG‐encoded proteins (c‐Fos, Fos B, Krox‐24, c‐Jun, Jun B, Jun D) in the rat forebrain after kainic acid‐induced limbic seizures. The results demonstrate a complex spatial pattern of IEG induction and/or suppression in limbic and non‐limbic structures. The sequence of induction within hippocampal subpopulations was identical for all IEGs investigated, following the order dentate gyrus, CA1 and CA3, and irrespective of different temporal profiles for individual transcription factors. Since Fos and Jun proteins act via homo‐ and heterodimer complexes at specific DNA sites, our data imply that the postictal combinatorial changes of these dimers allow a sequential and differential regulation of target gene expression in specific forebrain regions. Pretreatment with the non‐competitive NMDA receptor antagonist MK‐801 did not affect kainate‐induced expression of IEGs in the limbic system, indicating that IEG induction in these regions is mediated by high‐affinity kainate and AMPA receptors rather than NMDA receptors. In contrast, MK‐801 abolished IEG induction in the somatosensory cortex and striatum, suggesting that IEG expression in non‐limbic neurons occurs transsynaptically and is mediated by NMDA receptors.
Propagation of Epileptiform Activity During Development of Amygdala Kindling in Rats: Linear and Non‐linear Association Between lpsi‐ and Contralateral Sites
Authors: Beldhuis Hans J. A. , Suzuki Takanori , Pijn Jan Pieter M. , Teisman Ard , da Silva Fernando H. Lopes , Bonus Béla 
Published: April 2006

AbstractThe relationship between ipsi‐ and contralateral epileptiform electroencephalographic (EEG) activity was investigated in rats that were kindled daily in the amygdala. Two types of relationship—linear and non‐linear associations—were studied and used to estimate time delays of EEG activity between homotopic amygdalar sites during consecutive tetanizations. The progressive development of epileptiform EEG and convulsive behaviour was accompanied by an increase in association. Maximal association values of the non‐linear function were significantly higher than linear association values. The gradual development of motor seizure severity was correlated with increased non‐linearity. Time delays between the two amygdalae were estimated comparably with the linear and non‐linear function: 30.0±3.3 and 24.6±1.7 ms (ipsilateral leading contralateral), respectively. However, in rats displaying exclusively bilaterally generalized motor convulsions, maximal values of both functions decreased but were still significantly higher than control values of phaserandomized EEG. Corresponding positive as well as negative interhemispheric time delays were recorded during the afterdischarge. These results demonstrated a strengthened association between the ipsi‐and contralateral amygdala during primary epileptogenesis induced by amygdala kindling. In contrast, development of a secondary focus in the contralateral homotopic region resulted in a weakened interhemispheric association. Secondary bilateral synchrony between the ipsi‐ and contralateral amygdala occurred during the evoked epileptiform EEG activity.
GABAA Receptor Function in the Early Period After Transient Forebrain Ischaemia in the Rat
Authors: Verheul H. B. , de Leeuw F.‐E. , Scholten G. , Tulleken C. A. F. , da Silva F. H. Lopes , Ghijsen W. E. J. M. 
Published: April 2006

AbstractThe purpose of this study was to evaluate the function of the GABAA receptor following transient forebrain ischaemia. The GABA‐stimulated chloride (36Cl−) uptake into synaptoneurosomes was determined as an indicator of GABAA receptor function. Synaptoneurosomes were isolated from control rats and rats in which the forebrain was made ischaemic by way of the two‐vessel occlusion model. Animals subjected to ischaemia were killed at the end of the ischaemic insult and at 30 min or 2 or 5 h of recirculation. The results showed a reduction of 75% in GABA‐mediated 36Cl− uptake in synaptoneurosomes isolated from animals shortly (<0.5 h) after the ischaemic episode (P < 0.01). After longer recirculation periods the GABA‐mediated 36Cl− uptake reached preischaemic control levels. To investigate whether alterations in 36Cl− uptake were related to the synaptoneurosomal metabolic status, the synaptoneurosomal ATP content was measured. The time course of the ATP recovery correlated with the recovery of the GABA‐mediated 36Cl− uptake (r= 0.7, P < 0.001). To investigate the importance of ATP in GABA‐mediated 36Cl−uptake more directly, synaptoneurosomes isolated from control rats were exposed to chemically induced ATP depletion with rotenone, an inhibitor of oxidative phosphorylation. This resulted in similar reductions in both ATP level and GABA‐stimulated 36Cl− uptake as observed after in vivo ischaemia. These findings indicate that GABAA receptor function is transiently impaired in the early postischaemic period in a way which is closely related to alterations in cellular energy metabolism. The relevance of these findings to the development of ischaemic cell death is discussed.
Interaction of the Amygdala with the Frontal Lobe in Reward Memory
Authors: Gaffan D. , Murray E. A. , Fabre‐Thorpe M. 
Published: April 2006

AbstractFive cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new two‐choice visual discriminations between coloured patterns displayed on a touch‐sensitive monitor screen; the feedback for correct choice was delivery of food. Normal learning in this task is known to be dependent on the amygdala. The monkeys received brain lesions which were designed to disconnect the amygdala from interaction with other brain structures thought to be involved in this memory task. All the monkeys received an amygdalectomy in one hemisphere and lesions in the other hemisphere of some of the projection targets of the amygdala, namely the ventral striatum, the mediodorsal thalamus and the ventromedial prefrontal cortex. The rate of learning new problems was assessed before and after each operation. Disconnection of the amygdala from the ventral striatum was without effect on learning rate. An earlier study had shown that disconnection of the amygdala from either the mediodorsal thalamus or the ventromedial prefrontal cortex produced only a mild impairment, significantly less severe than that produced by bilateral lesions of any of these three structures. The present results show, however, that disconnection of the amygdala from both the mediodorsal thalamus and the ventromedial prefrontal cortex in the same animal, by crossed unilateral lesions of the amygdala in one hemisphere and of both the mediodorsal thalamus and the ventromedial prefrontal cortex in the other hemisphere, produces an impairment as severe as that which follows bilateral lesions of any of these three structures. These results show that, in stimulus – reward associative memory, the role of the amygdala is entirely dependent on its interaction with the frontal lobe, either by direct projections or by indirect subcortical pathways including the mediodorsal nucleus of the thalamus; and that there are at least two partially independent pathways by which the amygdala can influence the frontal lobe.
Serotonin Differentially Modulates Responses Mediated by Specific Excitatory Amino Acid Receptors in the Rat Locus Coeruleus
Authors: Charléty P. J. , Chergui K. , Akaoka H. , Saunier C. F. , Buda M. , Aston‐Jones G. , Chouvet G. 
Published: April 2006

AbstractMicroiontophoretic application of selective agonists for the three major excitatory amino acid receptors, N‐methyl‐d‐aspartate (NMDA), quisqualate and kainate, increased the discharge rate of noradrenergic locus coeruleus (LC) neurons in vivo. NMDA activation was selectively attenuated by iontophoretic application of 2‐amino‐5‐phosphonopentanoate (AP5), an antagonist at NMDA receptors, whereas kainate‐ and quisqualate‐evoked responses were attenuated by both NMDA and non‐NMDA antagonists iontophoresis. NMDA‐ and quisqualate‐evoked responses were significantly decreased by co‐iontophoresis of serotonin (5‐HT). When the NMDA receptor‐mediated component of the response to kainate was blocked with AP5 iontophoresis, 5‐HT increased the response of LC neurons to kainate. These results revealed that 5‐HT differentially modulates the responsiveness of LC neurons to excitatory amino acids, depending on the receptor subtypes responsible for the neuronal activation.
Transection of Corticostriatal Afferents Reduces Amphetamine‐ and Apomorphine‐induced Striatal Fos Expression and Turning Behaviour in Unilaterally 6‐Hydroxydopamine‐lesioned Rats
Authors: Cenci M. A. , Björklund A. 
Published: April 2006

AbstractCorticofugal fibres from the prefrontal, prelimibic and anterior sensorimotor cortices were transected by a wide coronal knife‐cut through the forceps minor. The cut was performed on the dopamine‐depleted side of unilaterally 6‐hydroxydopamine‐lesioned rats, or on either the right or the left side of intact rats. Sham‐lesioned controls received a superficial cortical cut at the same level. Seven days after surgery, apomorphine (0.25 mg/kg s.c.) was administered to 6‐hydroxydopamine‐lesioned animals and D‐amphetamine (5 mg/kg i.p.) was administered to the non‐dopamine‐denervated ones. Two hours later, the animals were perfusion‐fixed for the immunohistochemical detection of the nuclear protein Fos. A computerized image analysis technique was used to quantify, bilaterally, striatal Fos expression in 11 areas of the striatum. The frontocortical transection reduced both apomorphine‐ and amphetamine‐induced Fos expression by 33 – 66% within the ipsilateral caudate‐putamen. The effect was observed throughout the rostral portion of the striatal complex, where the lesioned cortical fibres terminate most densely. A separate batch of unilaterally 6‐hydroxydopamine‐lesioned rats was used to test the effect of frontocortical transection on amphetamine‐and apomorphine‐induced turning behaviour. Two groups of rats, showing similar rates of contralateral turning (7 – 8 turns/min) in response to apomorphine (0.25 mg/kg s.c.), were subjected to either a complete frontocortical transection or a sham lesion on the dopamine‐denervated side. An additional two groups, showing comparable rates of ipsilateral turning (15 turns/min) in response to amphetamine (5 mg/kg i. p.), received similar lesions, but now on the side ipsilateral to the intact dopaminergic innervation. The frontocortical transection reduced both apomorphine‐ and amphetamine‐induced turning by, on average, 40%, while the sham lesion had no effect. The present findings suggest that the full expression of dopamine‐receptor‐induced Fos activation and turning behaviour depends on an intact glutamatergic corticostriatal input.
C‐fos mRNA is Spontaneously Induced in the Rat Brain During the Activity Period of the Circadian Cycle
Authors: Grassi‐Zucconi G. , Menegazzi M. , De Prati A. Carcereri , Bassetti A. , Montagnese P. , Mandile P. , Cosi C. , Bentivoglio M. 
Published: April 2006

AbstractThe basal expression of the proto‐oncogene c‐fos was studied by Northern blot analysis in different regions of the rat brain during 24 h. A striking spontaneous oscillation of c‐fos mRNA expression was detected in animals kept in basal conditions with a 12 h light/12 h dark cycle. In these animals c‐fos mRNA was just detectable during the rest hours (morning through afternoon), and was high during the activity hours (night). The periodicity of this oscillation persisted and became free‐running when the animals were exposed for 6 consecutive days to constant light or darkness. It was thus demonstrated that the fluctuation of c‐fos expression is circadian and is not created by the light‐dark cycle, but the latter exerts a synchronizing effect. The oscillation of c‐fos mRNA was modified by manipulations of the rest‐activity cycle. In particular, the fluctuation observed in basal conditions was inverted, keeping the animals awake during the rest hours (diurnal) and allowing them to sleep in the activity period (nocturnal). These data indicated a close relationship between the oscillation of c‐fos expression and the rest‐activity cycle. Finally, electroencephalographic (EEG) monitoring was performed under behavioural control for 3 h before the animals were killed. These experiments confirmed that, irrespective of the time of day, the EEG pattern typical of a state of sleep (including both slow waves and paradoxical sleep) was associated with low or undetectable c‐fos levels, whereas the protracted EEG desynchronization corresponding to wakefulness was associated with high c‐fos expression. Altogether these results indicate that c‐fos mRNA undergoes during the circadian cycle spontaneous oscillations related to the activation of genomic expression subserving the behavioural and electrical correlates of wakefulness. On the other hand, the behavioural and electrical correlates of sleep are associated with low c‐fos expression.
Long‐term Depression Requires Nitric Oxide and Guanosine 3′:5’Cyclic Monophosphate Production in Rat Cerebellar Purkinje Cells
Authors: Daniel H. , Hemart N. , Jaillard D. , Crepel F. 
Published: April 2006

AbstractIn patch‐clamped Purkinje cells, bath application of the nitric oxide synthase inhibitor NG‐methyl‐l‐arginine consistently prevents the induction of long‐term depression (LTD) of parallel fibre‐mediated excitatory postsynaptic potentials (EPSPs) induced by their pairing with calcium spikes. On the other hand, bath application of nitric oxide donors and of 8‐bromoguanosine 3′:5’cyclic monophosphate is able to reproduce an LTD‐like phenomenon. LTD of parallel fibre‐mediated EPSPs also occurs when nitric oxide donors or guanosine 3′:5’cyclic monophosphate are directly dialysed into Purkinje cells, and this effect partially occludes LTD induced by pairing protocols. These results show that nitric oxide does play a role in LTD induction, and demonstrate for the first time that its site of action is probably the soluble guanylate cyclase of Purkinje cells.
Distribution of Gephyrin Transcripts in the Adult and Developing Rat Brain
Authors: Kirsch J. , Malosio M.‐L. , Wolters I. , Betz H. 
Published: April 2006

AbstractThe peripheral membrane protein gephyrin copurifies with the inhibitory glycine receptor of mammalian spinal cord. It binds with high affinity to polymerized tubulin and has been implicated in the anchoring of the glycine receptor to cytoskeletal elements. Recently, cDNA cloning has identified variants of the gephyrin mRNA, which originate from alternative splicing of four exonic regions (cassettes 1 – 4). In this study, the expression patterns of gephyrin splice variants were determined in the adult and developing rat brain byin situhybridization with synthetic oligonucleotide probes. Gephyrin transcripts were detected throughout the brain and spinal cord, with mRNAs containing cassette 2 (C2 transcripts) being predominant in adult animals. C3 and C4 transcripts were seen in cerebellar granule cells and in the dentate gyrus, whereas a C1 probe did not produce detectable hybridization signals. During development, C2 and C3 mRNAs were found in most brain regions. Generally, the spatial and temporal distribution of gephyrin transcripts is similar to that of the glycine receptor β subunit mRNA reported previously.
Changes in DNA Synthesis Rate in the Schwann Cell Lineage In Vivo Are Correlated With the Precursor – Schwann Cell Transition and Myelination
Authors: Stewart Helen J. S. , Morgan Louise , Jessen Kristjan R. , Mirsky Rhona 
Published: April 2006

AbstractDuring the development of the rat sciatic nerve extensive proliferation of glial cells occurs, and there is a very substantial rearrangement of the cytoarchitecture as axons and Schwann cells assume relationships which lead to the formation of the myelinated and unmyelinated axons characteristic of adult nerve. The maturation of Schwann cells from Schwann cell precursors and the matching of Schwann cell numbers to axons is an important part of this process. We have therefore studied the proliferation of Schwann cell precursors and Schwann cells during the development of the rat sciatic nerve from embryonic day 14 to postnatal day 28 by combining bromodeoxyuridine injections of rats with double‐label immunohistochemical techniques. The results reveal that DNA synthesis occurs in both Schwann cell precursors and Schwann cells throughout early nerve development. The labelling index is already substantial at embryonic day 14, but from embryonic day 17, when essentially all the glial cells have converted from precursor to Schwann cell phenotype, it rises sharply, peaking between embryonic day 19 and 20 before declining precipitously in the early postnatal period. This rapid decline in DNA synthesis coincides with the appearance of the myelin protein Po, and in individual cells DNA synthesis is incompatible with the expression of Po protein. Non‐myelin‐forming Schwann cells, which mature later in development, continue to synthesize DNA until at least postnatal day 15, but by day 28 essentially all Schwann cells in the nerve are quiescent.