bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine inhibition of auditory nerve activity in the adult mammalian cochlea
Authors: Ruel Jérôme , Nouvian Régis , D'Aldin Christine Gervais , Pujol Rémy , Eybalin Michel , Puel Jean‐Luc 
Published: March 2003

AbstractEfferent feedback systems provide a means for modulating the input to the central nervous system. The lateral olivocochlear efferents modulate auditory nerve activity via synapses with afferent dendrites below sensory inner hair cells. We examined the effects of dopamine, one of the lateral olivocochlear neurotransmitters, by recording compound and single unit activity from the auditory nerve in adult guinea pigs. Intracochlear application of dopamine reduced the compound action potential (CAP) of the auditory nerve, increased the thresholds and decreased the spontaneous and driven discharge rates of the single unit fibres without changing their frequency‐tuning properties. Surprisingly, dopamine antagonists SCH‐23390 and eticlopride decreased CAP amplitude as did dopamine. In some units, both SCH‐23390 and eticlopride increased the basal activity of auditory nerve fibres leading to an improvement of threshold sensitivity and a decrease of the maximum driven discharge rates to sound. In other units, the increase in firing rate was immediately followed by a marked reduction to values below predrug rates. Because CAP reflects the summed activity of auditory nerve fibres discharging in synchrony, both the decrease in sound‐driven discharge rate and the postexcitatory reduction account for the reduction in CAP. Ultrastructural examination of the cochleas perfused with eticlopride showed that some of the afferent dendrites were swollen, suggesting that the marked reduction in firing rate may reflect early signs of excitotoxicity. Results suggest that dopamine may exert a tonic inhibition of the auditory nerve activity. Removal of this tonic inhibition results in the development of early signs of excitotoxicity.
Phosphorylation of voltage‐gated ion channels in rat olfactory receptor neurons
Authors: Wetzel Christian H. , Spehr Marc , Hatt Hanns 
Published: March 2003

AbstractIn olfactory receptor neurons (ORNs), ligand–odorant receptor interactions cause G protein‐mediated activation of adenylate cyclase and a subsequent increase in concentration of the intracellular messenger cAMP. Odorant‐evoked elevation in cAMP is thought to directly activate a cation‐selective cyclic nucleotide‐gated channel, which causes external Ca2+ influx, leading to membrane depolarization and the generation of action potentials. Our data show that in freshly dissociated rat ORNs, odorant‐induced elevation in cAMP also activates cAMP‐dependent protein kinase (PKA), which is then able to phosphorylate various protein targets in the olfactory signal transduction pathway, specifically voltage‐gated sodium and calcium channels. The presence of PKI (PKA inhibitor peptide) blocked the modulatory action of cAMP on voltage‐gated ion channels. By modulating the input/output properties of the sensory neurons, this mechanism could take part in the complex adaptation process in odorant perception. In addition, we found modulation of voltage‐gated sodium and calcium channel currents by 5‐hydroxytryptamine and the dopamine D1 receptor agonist SKF 38393. These findings suggest that in situ ORNs might also be a target for efferent modulation.
Potentially epileptogenic dysfunction of cortical NMDA‐ and GABA‐mediated neurotransmission in Otx1–/– mice
Authors: Sancini G. , Franceschetti S. , Lavazza T. , Panzica F. , Cipelletti B. , Frassoni C. , Spreafico R. , Acampora D. , Avanzini G. 
Published: March 2003

AbstractKnockout Otx1 mice present a microcephalic phenotype mainly due to reduced deep neocortical layers and spontaneous recurrent seizures. We investigated the excitable properties of layer V pyramidal neurons in neocortical slices prepared from Otx1–/– mice and age‐matched controls. The qualitative firing properties of the neurons of Otx1–/– mice were identical to those found in wild‐type controls, but the proportion of intrinsically bursting (IB) neurons was significantly smaller. This is in line with the lack of the Otx1 gene contribution to the generation and differentiation of neurons destined for the deep neocortical layers, in which IB neurons are located selectively in wild‐type rodents. The pyramidal neurons recorded in Otx1–/– mice responded to near‐threshold electrical stimulation of the underlying white matter, with aberrant polysynaptic excitatory potentials often leading to late action potential generation. When the strength of the stimulus was increased, the great majority of the Otx1–/– neurons (78%) responded with a prominent biphasic inhibitory postsynaptic potential that was significantly larger than that observed in the wild‐type mice, and was often followed by complex postinhibitory depolarizing events. Both late excitatory postsynaptic potentials and postinhibitory excitation were selectively suppressed by NMDA receptor antagonists, but not by AMPA antagonists. We conclude that the cortical abnormalities of Otx1–/– neocortex due to a selective loss of large projecting neurons lead to a complex rearrangement of local circuitry, which is characterized by an excess of N‐methyl‐d‐aspartate‐mediated polysynaptic excitation that is counteracted by GABA‐mediated inhibition in only a limited range of stimulus intensity. Prominent postsynaptic inhibitory potentials may also act as a further pro‐epileptogenic event by synchronizing abnormal excitatory potentials.
Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation
Authors: Gerlai R. , McNamara A. , Choi‐Lundberg D. L. , Armanini M. , Ross J. , Powell‐Braxton L. , Phillips H. S. 
Published: March 2003

AbstractExogenous glial cell line‐derived neurotrophic factor (GDNF) exhibits potent survival‐promoting effects on dopaminergic neurons of the nigrostriatal pathway that is implicated in Parkinson's disease and also protects neurons in forebrain ischemia of animal models. However, a role for endogenous GDNF in brain function has not been established. Although mice homozygous for a targeted deletion of the GDNF gene have been generated, these mice die within hours of birth because of deficits in kidney morphogenesis, and, thus, the effect of the absence of GDNF on brain function could not be studied. Herein, we sought to determine whether adult mice, heterozygous for a GDNF mutation on two different genetic backgrounds, demonstrate alterations in the nigrostriatal dopaminergic system or in cognitive function. While both neurochemical and behavioural measures suggested that reduction of GDNF gene expression in the mutant mice does not alter the nigrostriatal dopaminergic system, it led to a significant and selective impairment of performance in the spatial version of the Morris water maze. A standard panel of blood chemistry tests and basic pathological analyses did not reveal alterations in the mutants that could account for the observed performance deficit. These results suggest that endogenous GDNF may not be critical for the development and functioning of the nigrostriatal dopaminergic system but it plays an important role in cognitive abilities.
Fluctuation of extracellular hypocretin‐1 (orexin A) levels in the rat in relation to the light–dark cycle and sleep–wake activities
Authors: Yoshida Y. , Fujiki N. , Nakajima T. , Ripley B. , Matsumura H. , Yoneda H. , Mignot E. , Nishino S. 
Published: March 2003

AbstractHypocretins/orexins are neuropeptides implicated in sleep regulation and the sleep disorder narcolepsy. In order to examine how hypocretin activity fluctuates across 24 h with respect to the sleep–wake cycle, we measured changes in extracellular hypocretin‐1 levels in the lateral hypothalamus and medial thalamus of freely moving rats with simultaneous sleep recordings. Hypocretin levels exhibited a robust diurnal fluctuation; levels slowly increased during the dark period (active phase), and decreased during the light period (rest phase). Levels were not correlated with the amount of wake or sleep in each period. Although an acute 4‐h light‐shift did not alter hypocretin levels, 6‐h sleep deprivation significantly increased hypocretin release during the forced‐wake period. Hypocretin activity is, thus, likely to build up during wakefulness and decline with the occurrence of sleep. These findings, together with the fact that a difficulty in maintaining wakefulness during the daytime is one of the primary symptoms of hypocretin‐deficient narcolepsy, suggest that hypocretin activity may be critical in opposing sleep propensity during periods of prolonged wakefulness.
Auditory and vestibular defects in the circling (ci2) rat mutant
Authors: Kaiser Alexander , Fedrowitz Maren , Ebert Ulrich , Zimmermann Elke , Hedrich Hans‐Jürgen , Wedekind Dirk , Löscher Wolfgang 
Published: March 2003

AbstractThe circling rat is an autosomal recessive mutant (homozygous ci2/ci2) that displays lateralized circling behaviour, locomotor hyperactivity, ataxia and stereotypic head‐movement. These abnormal behaviours occur in phases or bursts either spontaneously or in response to stress. Heterozygous (ci2/+) littermates display normal spontaneous behaviours. We have previously found that ci2/ci2 rats of both genders have a lower tissue content of dopamine in the striatum ipsilateral to the preferred direction of rotation, indicating that the rats turn away from the brain hemisphere with higher striatal dopaminergic activity. In view of the similarities of the motor syndrome of the ci2/ci2 mutant rat to that of mouse deafness mutants, the present study evaluated the hearing ability of the circling rat mutant by recording brainstem auditory‐evoked potentials. To test for vestibular dysfunction, a swimming test was conducted. Histological methods were used to examine the cochlear and vestibular parts of the inner ear and the cochlear and vestibular brainstem nuclei for defects. The absence of auditory‐evoked potentials demonstrated a complete hearing loss in the adult ci2/ci2 mutant rat, whereas heterozygous littermates exhibited auditory‐evoked potentials with thresholds resembling those of other laboratory strains. Furthermore, the mutant rats were unable to swim. Histological analysis of the inner ear of adult mutants revealed virtually complete loss of the cochlear neuroepithelium, while no such hair cell degeneration was seen in the vestibular parts of the inner ear. However, part of the vestibular hair cells showed protrusions into the endolymphatic space, suggesting alterations in the cytoskeletal architecture. The histological findings in mutant circling rats strongly indicate that the hearing loss of the mutants is of the sensory neural type, the most prevalent type of hearing loss. In the cochlear nuclei of the brain stem of mutant rats, neurons exhibited an abnormal shape, reduced size and increased density compared to controls. In contrast, no abnormal neuronal morphology was seen in the vestibular nuclei, but a significantly reduced neuronal density was found in the medial vestibular nucleus. Abnormal vestibular function would be a likely explanation for the disturbed balance of mutant rats as exemplified by the ataxia and the inability to swim, whereas the previous data on these rats strongly indicate an involvement of the basal ganglia in the abnormal circling behaviour. The genetic defect in the mutant rats, thus, results in a clinical syndrome with features also seen in human genetic disorders with deafness and hyperkinesia, making the ci2/ci2 rat an excellent model for investigating both cochlear/vestibular dysfunction and hyperkinetic movement disorders.
Molecular cloning and dendritic localization of rat SH3P7
Authors: Yamazaki Hiroyuki , Takahashi Hideto , Aoki Takeo , Shirao Tomoaki 
Published: March 2003

AbstractSH3P7 was originally isolated by cloning SH3 domain ligand targets from a mouse embryo cDNA library. SH3P7 is an actin‐binding protein implicated in antigen reception, JNK1 signalling, and Rac activation. It contains a drebrin homology sequence in its N‐terminal region and a cortactin homology sequence (SH3 domain) in its C‐terminal region. Both drebrin and cortactin are actin‐binding proteins, and both have been suggested as possible regulators of the actin cytoskeleton in neurons. In the present study, we performed cDNA cloning of rat SH3P7, performed RT‐PCR analysis, generated polyclonal antibodies against the recombinant rat SH3P7 protein, and examined the distribution of SH3P7 in the rat brain using immunohistochemistry. Sequence analysis revealed that there were at least four isoforms of the SH3P7 protein: SH3P7r1–SH3P7r4. RT‐PCR analysis revealed that the predominant isoforms expressed in the brain were SH3P7r1 and SH3P7r3. The relative levels of isoform expression were similar among regions. Immunohistochemistry revealed that the most intense immunolabelling for SH3P7 was observed in the hippocampus and cerebellar cortex. Double‐labelling studies with anti‐SH3P7 antibody and other neuronal marker proteins revealed that SH3P7 was located primarily in dendrites, and in moderate amounts in cell bodies. Immunoreactivity was absent in the presynaptic terminals. In cultured astrocytes, SH3P7 was localized at protrusive structures of the cell periphery and in the cell body. We concluded that SH3P7 is ubiquitous in the rat brain, and occurs as several isoforms. Also, its dendritic localization suggests that SH3P7 is functionally linked to actin cytoskeleton organization in dendrites.
Distinct properties and differential β subunit regulation of two C‐terminal isoforms of the P/Q‐type Ca2+‐channel α1A subunit
Authors: Sandoz Guillaume , Bichet Delphine , Cornet Veronique , Mori Yasuo , Felix Ricardo , De Waard Michel 
Published: March 2003

AbstractTwo C‐terminal splice variants (BI‐1 and BI‐2, now termed Cav2.1a and Cav2.1b) of the neuronal voltage‐gated P/Q‐type Ca2+ channel α1A pore‐forming subunit have been cloned (Mori et al., 1991, Nature, 350, 398–402). BI‐1 and BI‐2 code for proteins of 2273 and 2424 amino acids, respectively, and differ only by their extreme carboxyl‐termini sequences. Here, we show that, in Xenopus oocytes, the two isoforms direct the expression of channels with different properties. Electrophysiological analysis showed that BI‐1 and BI‐2 have peak Ba2+ currents (IBa) at a potential of +30 and +20 mV, respectively. The different C‐terminal sequence (amino acids 2229–2273) of BI‐1 caused a shift in steady‐state inactivation by +10 mV and decreased the proportion of fast component of current inactivation twofold. Likewise, the biophysical changes in IBa caused by coexpression of the β4 auxiliary subunit were substantially different in BI‐1‐ and BI‐2‐containing channels in comparison to those induced by β3. Several of these differences in β regulation were abolished by deleting the carboxyl‐terminal splicing region. By creating a series of GST fusion proteins, we identified two locations in the C‐terminal (Leu2090–Gly2229 for BI‐1 and BI‐2, and Arg2230–Pro2424 for BI‐2 only) that determine the differential interaction of β4 with the distinct α1A isoforms. These interactions appear to favour the binding of β4 to the AID site, and also the plasma membrane expression of BI‐2. These results demonstrate that the final segment of the C‐terminal affects α1A channel gating, interaction and regulation with/by the β subunits. The data will have several implications for the understanding of the biophysical effects of many channelopathies in which the carboxyl‐termini of α1A and β4 are affected.
Taurine selectively modulates the secretory activity of vasopressin neurons in conscious rats
Authors: Engelmann Mario , Ludwig Mike , Singewald Nicolas , Ebner Karl , Sabatier Nancy , Lubec Gert , Landgraf Rainer , Wotjak Carsten T. 
Published: March 2003

AbstractPrevious experiments have shown that a 10‐min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic–neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 °C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6‐aminomethyl‐3‐methyl‐4H‐1,2,4‐benzothiadiazine‐1,1‐dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABAA receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states.
Subunit composition of strychnine‐sensitive glycine receptors expressed by adult rat basolateral amygdala neurons
Authors: McCool Brian A. , Farroni Jeffery S. 
Published: March 2003

AbstractIn neonatal rats, strychnine‐sensitive glycine receptors are widely expressed in the spinal cord, brainstem and forebrain. During development, these ‘neonatal’ receptors are replaced by an adult isoform, the expression of which becomes restricted primarily to brain stem and spinal cord. Unlike most forebrain regions, functional strychnine‐sensitive glycine receptors appear to persist within adult rat amygdala. However, the subunit composition of glycine receptors expressed by amygdala neurons and its relationship to the adult isoform in brain stem/spinal cord has not been defined precisely. In this report, we have utilized RT‐PCR and single‐cell RT‐PCR to demonstrate that the ‘neonatal’α2‐subunit mRNA persists in adult rat amygdala neurons and is the predominant α‐subunit. We further demonstrate that native amygdala glycine receptors are relatively insensitive to the receptor antagonist picrotoxin, suggesting that α2‐ and β‐subunits may be present together in the same multisubunit complex. We further demonstrate that α2‐ and β‐subunits cloned from adult rat amygdala can form functional channels when expressed in a heterologous system. Together, these studies highlight both the unique characteristics of strychnine‐sensitive glycine receptors in the adult rat amygdala as well as the possibility that α2/β channels may represent the adult forebrain isoform of the strychnine‐sensitive glycine receptor.
Chronic morphine exposure increases the phosphorylation of MAP kinases and the transcription factor CREB in dorsal root ganglion neurons: an in vitro and in vivo study
Authors: Ma Weiya , Zheng Wen‐Hua , Powell Kelly , Jhamandas Khem , Quirion Remi 
Published: March 2003

AbstractTolerance to opiates reduces their effectiveness in the treatment of severe pain. Although the mechanisms are unclear, overactivity of pro‐nociceptive systems has been proposed to contribute to this phenomenon. We have reported that the development of morphine tolerance significantly increased calcitonin‐gene‐related‐peptide‐like immunoreactivity (CGRP‐IR) in primary sensory afferents of the spinal dorsal horn, suggesting that changes in pain‐related neuropeptides in the dorsal root ganglion (DRG) neurons may be involved (Menard et al., 1996, J. Neurosci., 16, 2342–2351). Recently, we have shown that repeated morphine treatments induced increases in CGRP‐ and substance P (SP)‐IR in cultured DRG, mimicking the in vivo effects (Ma et al., 2000, Neuroscience, 99, 529–539). In this study, we investigated the intracellular signal transduction pathways possibly involved in morphine‐induced increases in CGRP‐ and SP‐IR in DRG neurons. Repeated morphine exposure (10–20 µm) for 6 days increased the number of neurons expressing phosphorylated (p) mitogen‐activated protein (MAP) kinases, including the extracellular signal‐regulated kinase (pERK), c‐jun N‐terminal kinase (pJNK) and P38 (pP38 MAPK). The number of neurons expressing phosphorylated cAMP responsive element binding protein (pCREB) was also markedly increased in morphine‐exposed cultured DRG neurons. pERK‐, pP38‐, pJNK‐ and pCREB‐IR were colocalized with CGRP‐IR in cultured DRG neurons. Naloxone effectively blocked these actions of morphine, whereas a selective MEK1 inhibitor, PD98059, inhibited the morphine‐induced increase in the phosphorylation of ERK and CREB, and the expression of CGRP and SP. Moreover, in morphine‐tolerant rats, the number of pCREB‐, CGRP‐ and SP‐IR neurons in the lumbar DRG was also significantly increased. These in vitro and in vivo data suggest that the phosphorylation of MAP kinases and CREB plays a role in the morphine‐induced increase in spinal CGRP and SP levels in primary sensory afferents, contributing to the development of tolerance to opioid‐induced analgesia.
Behavioural rhythm splitting in the CS mouse is related to clock gene expression outside the suprachiasmatic nucleus
Authors: Abe Hiroshi , Honma Sato , Namihira Masakazu , Masubuchi Satoru , Honma Ken‐ichi 
Published: March 2003

AbstractCS mice exhibit a spontaneous splitting in the circadian rhythm of locomotor activity under constant darkness, suggesting that they contain two weakly coupled oscillators in the circadian clock system regulating locomotor activity rhythm. In order to clarify whether the two oscillators are located in the suprachiasmatic nucleus (SCN), a site of the master circadian pacemaker in mammals, circadian rhythms in mRNA of mousePeriodgenes (mPer1,mPer2andmPer3) in the SCN and cerebral cortex were examined during rhythm splitting byin situhybridization. In the SCN,mPer1andmPer2showed a circadian rhythm with a single peak in both split and unsplit mice. The rhythms ofmPer1andmPer2were slightly phase delayed during rhythm splitting in reference to the activity onset, but the phase relationship between the two rhythms was not changed. In the cerebral cortex, the expression ofmPer1andmPer2underwent the bimodal fluctuation with peaks temporally corresponding to split activity components. The unsplit mice showed the circadian rhythms with a single peak. There was no difference in themPer3rhythms in either the SCN or the cerebral cortex between the split and unsplit mice. These results indicate that the circadian oscillations ofmPer1,mPer2andmPer3in the SCN are not related to the rhythm splitting of CS mice. The split rhythms of the CS mice are suggested to be caused by uncoupling of oscillators located outside the SCN from the SCN circadian pacemaker.