bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxytocin receptor agonists enhance inhibitory synaptic transmission in the rat hippocampus by activating interneurons in stratum pyramidale
Authors: Zaninetti Marc , Raggenbass Mario 
Published: March 2003

AbstractOxytocin probably plays a role as a neurotransmitter/neuromodulator in the hippocampus of the rat. Oxytocin binding sites are present in the subiculum and CA1 region and oxytocin can excite a class of CA1 nonpyramidal neurons. In the present work we characterized the effect of oxytocin on hippocampal synaptic transmission. Whole‐cell recordings were obtained from pyramidal neurons, in conditions of nearly symmetrical chloride concentrations. The selective oxytocin receptor agonist, [Thr4,Gly7]‐oxytocin (TGOT), caused an increase in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) in virtually all neurons. These peptide‐enhanced IPSCs were blocked by bicuculline, but not by strychnine, and reversed near 0 mV, indicating that they were mediated by γ‐aminobutyric acid (GABA)A receptors. On average, TGOT caused a nearly threefold increase in the frequency and almost a doubling in the amplitude of spontaneous IPSCs. TGOT did not influence the frequency and the amplitude of miniature IPSCs or spontaneous excitatory postsynaptic currents (EPSCs), and had no effect on evoked IPSCs. The peptide did not affect the basic membrane properties of pyramidal neurons or their GABA sensitivity. Thus, TGOT facilitated inhibitory transmission by exerting an excitatory action on the soma and/or dendrites of GABAergic interneurons. Extracellular recordings were performed in interneurons located in various hippocampal strata. Their sensitivity to TGOT was compared to that of substance P (SP). Interneurons in stratum pyramidale were excited both by TGOT and by SP. By contrast, stratum radiatum interneurons responded to SP but not to TGOT. In stratum oriens, half of the interneurons responded to SP, but only a minority to TGOT. Thus, oxytocin‐responsive interneurons appear to be preferentially located in close vicinity of pyramidal neurons.
A role for protein kinase C in a form of metaplasticity that regulates the induction of long‐term potentiation at CA1 synapses of the adult rat hippocampus
Authors: Bortolotto Zuner A. , Collingridge Graham L. 
Published: March 2003

AbstractThe possibility that protein kinase C (PKC) is involved in the induction of N‐methyl‐ D‐aspartate (NMDA) receptor‐dependent long‐term potentiation (LTP) at CA1 synapses in the hippocampus has been the subject of considerable investigation. However, many of the conclusions have been drawn from the use of relatively nonspecific PKC inhibitors. In the present study we have examined the role of PKC in tetanus‐induced LTP of AMPA receptor‐mediated synaptic transmission in hippocampal slices obtained from adult rats. In particular, we have investigated the possible role of PKC in a molecular switch process that is triggered by the synaptic activation of metabotropic glutamate receptors and regulates the induction of LTP. We find that the three PKC inhibitors examined, chelerythrine, Ro‐31–8220 and Gö 6983, all block the setting of the molecular switch at concentrations consistent with inhibition of PKC. In contrast, these inhibitors are without affect on the induction of LTP, even when applied in very much higher concentrations. A PKA inhibitor, Rp‐cAMPS, had no effect on either process. We suggest that neither PKC nor PKA is required to induce LTP at this synapse. However, PKC is involved in the regulation of LTP induction, via the molecular switch process.
Distinct roles for GFRα1 and GFRα2 signalling in different cranial parasympathetic ganglia in vivo
Authors: Rossi Jari , Tomac Andreas , Saarma Mart , Airaksinen Matti S. 
Published: March 2003

AbstractNeurturin (NRTN), signalling via the GDNF family receptor α2 (GFRα2) and Ret tyrosine kinase, has recently been identified as an essential target‐derived factor for many parasympathetic neurons. NRTN is expressed in salivary and lacrimal glands, while GFRα2 and Ret are expressed in the corresponding submandibular, otic and sphenopalatine ganglia. Here, we have characterized in more detail the role of GDNF and NRTN signalling in the development of cranial parasympathetic neurons and their target innervation. Gfra1 mRNA was expressed at E12 but not in newborn cranial parasympathetic ganglia, while Gfra2 mRNA and protein were strongly expressed in newborn and adult cranial parasympathetic neurons and their projections, respectively. In newborn GFRα1‐ or Ret‐deficient mice, where many submandibular ganglion neurons were still present, the otic and sphenopalatine ganglia were completely missing. In contrast, in newborn GFRα2‐deficient mice, most neurons in all these ganglia were present. In these mice, the loss and atrophy of the submandibular and otic neurons were amplified postnatally, accompanied by complete loss of innervation in some target regions and preservation in others. Surprisingly, GFRα2‐deficient sphenopalatine neurons, whose targets were completely uninnervated, were not reduced in number and only slightly atrophied. Thus, GDNF signalling via GFRα1/Ret is essential in the early gangliogenesis of some, but not all, cranial parasympathetic neurons, whereas NRTN signalling through GFRα2/Ret is essential for the development and maintenance of parasympathetic target innervation. These results indicate that GDNF and NRTN have distinct functions in developing parasympathetic neurons, and suggest heterogeneity among and within different parasympathetic ganglia.
Anatomy and physiology of a neural mechanism defining depth order and contrast polarity at illusory contours
Authors: Heider B. , Meskenaite V. , Peterhans E. 
Published: March 2003

AbstractWe studied the anatomy and physiology of neurons in monkey visual cortex, which contribute to mechanisms segregating figure and ground at contours based on information provided by occlusion cues. First, we defined the location of neurons sensitive to occluding (illusory) contours. These neurons were found most frequently in the pale cytochrome oxidase stripes of area V2 but rarely in V1. In area V2, they were found in all laminae and with similar frequencies. The few neurons recorded in area V1 concentrated in the upper laminae. Second, we studied the properties and anatomical location of neurons sensitive to occlusion cues (dark and light line‐ends, corners). These neurons had end‐stopped receptive fields and were found with similar frequencies in both areas. In area V1, they concentrated in the upper laminae. In area V2, they were found in all laminae and cytochrome oxidase stripes. These neurons responded to short stimuli of optimal length (bars, edges) and to stimuli terminating in their receptive field (line‐ends, corners). Overall, about half of these neurons detected the direction of such terminations and about 60% were selective for certain types of termination. In summary, our results suggest that in monkey visual cortex, occlusion cues are represented in areas V1 and V2, whereas grouping mechanisms detecting occluding contours concentrate in area V2.
β3, a novel auxiliary subunit for the voltage‐gated sodium channel, is expressed preferentially in sensory neurons and is upregulated in the chronic constriction injury model of neuropathic pain
Authors: Shah B. S. , Stevens E. B. , Gonzalez M. I. , Bramwell S. , Pinnock R. D. , Lee K. , Dixon A. K. 
Published: March 2003

AbstractAdult dorsal root ganglia (DRG) have been shown to express a wide range of voltage‐gated sodium channel α‐subunits. However, of the auxiliary subunits, β1 is expressed preferentially in only large‐ and medium‐diameter neurons of the DRG while β2 is absent in all DRG cells. In view of this, we have compared the distribution of β1 in rat DRG and spinal cord with a novel, recently cloned β1‐like subunit, β3. In situ hybridization studies demonstrated high levels of β3 mRNA in small‐diameter c‐fibres, while β1 mRNA was virtually absent in these cell types but was expressed in 100% of large‐diameter neurons. In the spinal cord, β3 transcript was present specifically in layers I/II (substantia gelatinosa) and layer X, while β1 mRNA was expressed in all laminae throughout the grey matter. Since the pattern of β3 expression in DRG appears to correlate with the TTX‐resistant voltage‐gated sodium channel subunit PN3, we co‐expressed the two subunits in Xenopus oocytes. In this system, β3 caused a 5‐mV hyperpolarizing shift in the threshold of activation of PN3, and a threefold increase in the peak current amplitude when compared with PN3 expressed alone. On the basis of these results, we examined the expression of β‐subunits in the chronic constriction injury model of neuropathic pain. Results revealed a significant increase in β3 mRNA expression in small‐diameter sensory neurons of the ipsilateral DRG. These results show that β3 is the dominant auxiliary sodium channel subunit in small‐diameter neurons of the rat DRG and that it is significantly upregulated in a model of neuropathic pain.
Opioid tolerance induced by metamizol (dipyrone) microinjections into the periaqueductal grey of rats
Authors: Tortorici Víctor , Vanegas Horacio 
Published: March 2003

AbstractNon‐opioid analgesics have been shown to elicit antinociception by an action upon central nervous system structures, in addition to their well known action upon peripheral tissues. Microinjection of metamizol (dipyrone), a widely used nonopioid analgesic, into the periaqueductal grey matter (PAG) of rats activates pain‐modulating systems in the nucleus raphe magnus and inhibits spinal nociceptive neurons and the tail‐flick reflex. Since these effects involve an activation of endogenous opioidergic systems, the possibility that metamizol induces opioid tolerance was investigated. Microinjection of metamizol into the ventrolateral PAG in awake rats induced antinociception, as demonstrated in the heat‐elicited tail flick and hot plate tests. When microinjected into the ventrolateral PAG twice daily for 2 days, metamizol induced tolerance, i.e. a progressive loss of its antinociceptive effect. In contrast to rats repeatedly microinjected with saline, metamizol‐tolerant rats were also tolerant to morphine microinjection into the same PAG site, and displayed signs of opioid withdrawal upon systemic administration of naloxone. These and other results suggest that metamizol activates endogenous opioid systems and that nonopioid analgesics may, by an action upon the central nervous system, lead to opioid tolerance and the risk of opioid withdrawal.
Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat
Authors: Windels François , Bruet Nicolas , Poupard Annie , Urbain Nadia , Chouvet Guy , Feuerstein Claude , Savasta Marc 
Published: March 2003

AbstractHigh frequency stimulation (130 Hz) of the subthalamic nucleus has dramatic beneficial motor effects in severe parkinsonian patients. However, the mechanisms underlying these clinical results remain obscure. The objective of the present work was to study the neurochemical changes induced in rats by high frequency stimulation of the subthalamic nucleus by using intracerebral microdialysis within its target structures. Our results show that high frequency stimulation of the subthalamic nucleus induces a significant increase of extracellular glutamate levels in the ipsilateral globus pallidus and substantia nigra while GABA was augmented only in the substantia nigra. These data suggest that functional effects induced by high frequency stimulation of the subthalamic nucleus might imply distal mechanisms involving the synaptic relationships with the subthalamic efferences. They question the current view that the direct inhibition of the subthalamic neurons is induced by high frequency stimulation.
Reduced operant ethanol self‐administration and in vivo mesolimbic dopamine responses to ethanol inPKCε‐deficient mice
Authors: Olive M. Foster , Mehmert Kristin K. , Messing Robert O. , Hodge Clyde W. 
Published: March 2003

AbstractThere is increasing evidence that individual protein kinase C (PKC) isozymes mediate specific effects of ethanol on the nervous system. In addition, multiple lines of evidence suggest that the mesoaccumbens dopamine reward system is critically involved in the rewarding and reinforcing effects of ethanol. Yet little is known about the role of individual PKC isozymes in ethanol reinforcement processes or in regulation of mesolimbic systems. In this study, we report that mice lacking the epsilon isoform of PKC (PKCε) show reduced operant ethanol self‐administration and an absence of ethanol‐induced increase in extracellular dopamine levels in the nucleus accumbens. PKCε null mice exhibited a 53% decrease in alcohol‐reinforced operant responses under basal conditions, as well as following ethanol deprivation. Behavioural analysis revealed that while both genotypes had the same number of drinking bouts following deprivation, PKCε null mice demonstrated a 61% reduction in number of ethanol reinforcers per bout and a 57% reduction in ethanol‐reinforced response rate. In vivo microdialysis experiments showed that, in contrast to wild‐type mice, PKCε null mice exhibited no change in extracellular levels of dopamine in the nucleus accumbens following acute administration of ethanol (1 and 2 g/kg i.p.), while mesolimbic dopamine responses to cocaine (20 mg/kg i.p.) or high potassium (100 m m) in these mice were comparable with that of wild‐types. These data provide further evidence that increases in extracellular mesolimbic dopamine levels contribute to the reinforcing effects of ethanol, and indicate that pharmacological agents inhibiting PKCε may be useful in the treatment of alcohol dependence.
Influence of arm movements on saccades in humans
Authors: Lünenburger L. , Kutz D. F. , Hoffmann K. ‐P. 
Published: March 2003

AbstractWhen reaching for an object we usually look at it before we touch it with the hand. This often unconscious eye movement prior to the arm movement allows guiding of the final part of the hand trajectory by visual feedback. We examined the temporal and spatial coordination of this control system by psychophysical measurements of eye and arm movements of naive human subjects looking or looking and pointing as fast as possible to visual targets in physical and virtual‐reality setups. The reaction times of saccades to a step‐displaced target were reduced, and the number of corrective saccades decreased, when the subject had to produce a corresponding simultaneous hand movement to the same target. The saccadic reaction time was increased when saccade and hand movement went in opposite directions. In a double‐step task the reaction time for the second saccade was longer than for the first. Co‐use of the hand leads to an additional increase of saccadic reaction time. Taken together this study shows an improvement in initial saccades if they are accompanied by hand movements to the same target. This effect might ensure that the reach target is foveated early and accurately enough to support the visual feedback control of the hand near the target. Longer reaction times for the second saccade to double‐step displaced targets might reflect a saccadic refractory time intensified by simultaneous arm movements. These results are discussed in the light of recent findings from our laboratory on saccade‐ and reach‐related neurons in the superior colliculus of macaque monkeys.
Effects of eletriptan on the peptidergic innervation of the cerebral dura mater and trigeminal ganglion, and on the expression of c‐fos and c‐jun in the trigeminal complex of the rat in an experimental migraine model
Authors: Knyihár‐Csillik Elizabeth , Tajti János , Csillik Anita E. , Chadaide Zoltán , Mihály András , Vécsei László 
Published: March 2003

AbstractNociceptive axons and terminals in the supratentorial cerebral dura mater display an intense calcitonin gene‐related peptide (CGRP) immunoreactivity. In an experimental migraine model, it has been shown that electrical stimulation of the rat trigeminal ganglion induced an increase in the lengths of CGRP‐immunoreactive axons, increased size and number of pleomorphic axonal varicosities in the dura mater, and an increased number of c‐jun and c‐fos protein‐expressing nerve cells in the trigeminal complex. We demonstrate the effect of the highly specific and moderately lipophilic serotonin agonist eletriptan (Pfizer) which prevents the effects of electrical stimulation in the dura mater. Eletriptan also affected the caudal trigeminal complex; it markedly reduced the numbers of the oncoprotein‐expressing cells, mainly after stimulation and to some extent also in nonstimulated animals. Eletriptan also affected expression of CGRP in perikarya of trigeminal ganglion cells, insofar as the number of small nerve cells exhibiting a compact CGRP immunoreaction was decreased to one quarter of the original value. In all these respects, eletriptan acted in a similar way to sumatriptan, with the notable exception that eletriptan also blocked the stimulation‐induced effects in the nucleus caudalis trigemini and the upper cervical spinal cord (trigeminal complex), whereas sumatriptan did not. It is concluded that eletriptan, acting on perikarya and both the peripheral and the central axon terminals of primary sensory neurons, exerts its antimigraine effect by an agonist action on 5‐HT1B/1D receptors throughout the entire trigeminal system, probably by passing the blood–brain‐barrier because of its lipophilic character.
A model of gamma‐frequency network oscillations induced in the rat CA3 region by carbachol in vitro
Authors: Traub Roger D. , Bibbig Andrea , Fisahn André , LeBeau Fiona E. N. , Whittington Miles A. , Buhl Eberhard H. 
Published: March 2003

AbstractCarbachol (> 20 μm) and kainate (100 nm) induce, in the in vitro CA3 region, synchronized neuronal population oscillations at ≈ 40 Hz having distinctive features: (i) the oscillations persist for hours; (ii) interneurons in kainate fire at 5–20 Hz and their firing is tightly locked to field potential maxima (recorded in s. radiatum); (iii) in contrast, pyramidal cells, in both carbachol and kainate, fire at frequencies as low as 2 Hz, and their firing is less tightly locked to field potentials; (iv) the oscillations require GABAA receptors, AMPA receptors and gap junctions. Using a network of 3072 pyramidal cells and 384 interneurons (each multicompartmental and containing a segment of unmyelinated axon), we employed computer simulations to examine conditions under which network oscillations might occur with the experimentally determined properties. We found that such network oscillations could be generated, robustly, when gap junctions were located between pyramidal cell axons, as suggested to occur based on studies of spontaneous high‐frequency (> 100 Hz) network oscillations in the in vitro hippocampus. In the model, pyramidal cell somatic firing was not essential for the oscillations. Critical components of the model are (i) the plexus of pyramidal cell axons, randomly and sparsely interconnected by gap junctions; (ii) glutamate synapses onto interneurons; (iii) synaptic inhibition between interneurons and onto pyramidal cell axons and somata; (iv) a sufficiently high rate of spontaneous action potentials generated in pyramidal cell axons. This model explains the dependence of network oscillations on GABAA and AMPA receptors, as well as on gap junctions. Besides the existence of axon–axon gap junctions, the model predicts that many of the pyramidal cell action potentials, during sustained gamma oscillations, are initiated in axons.
Stimulation of the mesencephalic locomotor region elicits controlled swimming in semi‐intact lampreys
Authors: Sirota Mikhail G. , Di Prisco Gonzalo Viana , Dubuc Réjean 
Published: March 2003

AbstractThe role of the mesencephalic locomotor region (MLR) in initiating and controlling the power of swimming was studied in semi‐intact preparations of larval and adult sea lampreys. The brain and the rostral portion of the spinal cord were exposed in vitro, while the intact caudal two‐thirds of the body swam freely in the Ringer's‐containing chamber. Electrical microstimulation (2–10 Hz; 0.1–5.0 μA) within a small periventricular region in the caudal mesencephalon elicited well‐coordinated and controlled swimming that began within a few seconds after the onset of stimulation and lasted throughout the stimulation period. Swimming stopped several seconds after the end of stimulation. The power of swimming, expressed by the strength of the muscle contractions and the frequency and the amplitude of the lateral displacement of the body or tail, increased as the intensity or frequency of the stimulating current were increased. Micro‐injection of AMPA, an excitatory amino acid agonist, into the MLR also elicited active swimming. Electrical stimulation of the MLR elicited large EPSPs in reticulospinal neurons (RS) of the middle rhombencephalic reticular nucleus (MRRN), which also displayed rhythmic activity during swimming. The retrograde tracer cobalt‐lysine was injected into the MRRN and neurons (dia. 10–20 μm) were labelled in the MLR, indicating that this region projects to the rhombencephalic reticular formation. Taken together, the present results indicate that, as higher vertebrates, lampreys possess a specific mesencephalic region that controls locomotion, and the effects onto the spinal cord are relayed by brainstem RS neurons.
Light‐induced phase‐shifts in the circadian expression rhythm of mammalian Period genes in the mouse heart
Authors: Sakamoto Katsuhiko , Ishida Norio 
Published: March 2003

AbstractTo investigate the molecular mechanism that regulates circadian rhythms in mammalian peripheral tissues, we examined the phase shifts evoked by light exposure in the circadian mRNA expression rhythms of mammalian Period genes (mPer1, mPer2 and mPer3) and a clock‐controlled gene Dbp, in the mouse heart, by Northern blot analysis. The light pulse did not induce any acute mRNA expression of mPer in the heart, but the pulse gave rise to phase shifts in the circadian mRNA rhythms. On the first day after the exposure, only mPer1 mRNA showed a phase shift, whereas obvious phase shifts were not observed in the rhythms of mPer2, mPer3 and Dbp mRNAs. On the second day, phase shifts occurred to a similar extent in the mRNA rhythms of all four genes examined. The rhythm of mPer1 mRNA shifted fastest among those of the three mPers. Therefore mPer1 seems to play an important role in phase resetting of mammalian peripheral oscillators. Immediate responses to light pulses in mRNA expression of mPers may not be required for phase shifting of peripheral circadian oscillators. Our findings suggest that mammals require more than one day to have peripheral oscillators entrained to a new daily schedule.