bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide is required for expression of LTP that is induced by stimulation phase‐locked with theta rhythm
Authors: Hölscher Christian 
Published: March 2003

AbstractLong‐term potentiation (LTP) can be induced by giving only one burst (five stimuli at 200 Hz) on the positive phase of sensory‐induced theta rhythm in awake or anaesthetized rats, a stimulation protocol that mimics naturally occurring neuronal activity. Nitric oxide has been discussed as an important neuronal messenger in the induction of LTP. However, experiments testing inhibitors of nitric oxide synthase (NOS) in vitro produced contradictory results. The non‐specific NOS inhibitor Nitro‐l‐arginine (L‐NARG) impaired LTP induced by high‐frequency stimulation (HFS) [from 155 ± 7% to 122 ± 8%), but completely blocked theta‐dependent LTP induction (161 ± 8% to 102 ± 5%). NOS inhibitors, e.g. 7‐nitro indazole (7‐NI) or 1‐(2‐trifluoromethylphenyl) imidazole (TRIM) that are more selective for neuronal NOS and affect blood pressure less also impaired HFS‐induced LTP (186 ± 11% to 135 ± 9% for TRIM) but completely blocked theta‐dependent LTP (154 ± 7 to 91 ± 8). l‐Arginine reversed the effects of the NOS inhibitors tested. Therefore, NO appears to be a modulator that is important for synaptic plasticity in this more physiological stimulation technique in vivo. NO is not released in slice preparations in sufficient quantities or at the right timing. Instead, the unphysiologically strong HFS protocol appears to induce an NO‐independent type of LTP in some cases.
Zn2+ entry produces oxidative neuronal necrosis in cortical cell cultures
Authors: Kim Eun Young , Koh Jae Young , Kim Yang Hee , Sohn Seonghyang , Joe Eunhye , Gwag Byoung Joo 
Published: March 2003

AbstractEvidence has accumulated that Zn2+ plays a central role in neurodegenerative processes following brain injuries including ischaemia or epilepsy. In the present study, we examined patterns and possible mechanisms of Zn2+ neurotoxicity. Inclusion of 30–300 μm Zn2+ for 30 min caused neuronal necrosis apparent by cell body and mitochondrial swelling in cortical cell cultures. This Zn2+ neurotoxicity was not attenuated by antiapoptosis agents, inhibitors of protein synthesis or caspase. Blockade of glutamate receptors or nitric oxide synthase showed no beneficial effect against Zn2+ neurotoxicity. Interestingly, antioxidants, trolox or SKF38393, attenuated Zn2+‐induced neuronal necrosis. Pretreatment with insulin or brain‐derived neurotrophic factor increased the Zn2+‐induced free radical injury. Kainate or AMPA facilitated Zn2+ entry and potentiated Zn2+ neurotoxicity in a way sensitive to trolox. Reactive oxygen species and lipid peroxidation were generated in the early phase of Zn2+ neurotoxicity. These findings indicate that entry and accumulation of Zn2+ result in generation of toxic free radicals and then cause necrotic neuronal degeneration under certain pathological conditions in the brain.
Rapid desensitization converts prolonged glutamate release into a transient EPSC at ribbon synapses between retinal bipolar and amacrine cells
Authors: Maguire Greg 
Published: March 2003

AbstractThe mechanisms underlying the conversion of prolonged glutamate release from ribbon synapses in bipolar cells to sustained and transient excitatory postsynaptic responses in identified retinal amacrine cells were studied in tiger salamander (Ambystoma tigrinum) retina. A retina slice preparation with whole cell patch recording techniques under voltage‐ and current‐clamp conditions was used to assay the electrical properties of bipolar and amacrine cells. Amacrine cells were categorized into two basic forms: (i) transient amacrine cells that respond to a step of light with a burst of spikes only at the transitions of the step; and (ii) sustained amacrine cells that respond with continuous spiking during the entire light step. The two cell types each had a characteristic morphology: transient amacrine cells possessed wide dendritic fields (χ = 375 μm), while sustained cells had much more narrowly confined dendritic fields (χ = 85 μm). Whole cell voltage‐gated currents of the transient and sustained cell types were not significantly different. Both cell types had spikes that were sensitive to tetradotoxin (TTX, 0.3 μm) with voltage deflections of up to 100 mV. Light‐evoked excitatory synaptic currents relaxed rapidly in transient neurons (τ1/2 = 100 ms) and more slowly in sustained neurons (τ1/2 = 1.2 s). EPSCs in both cells reversed near 0 mV. Rapid application of glutamate or kainate elicited rapidly desensitizing ionic currents (τ1/2 = 85 ms) followed by a slowly desensitizing component. Cyclothiazide, a drug that eliminates rapid desensitization, lengthened the time course of the glutamate gated current from τ1/2 = 85 ms to about 3 s, and the relaxation kinetics of the glutamatergic EPSC from τ1/2 = 85 ms to about 1.0 s. These data suggest that a key determinant in forming transient versus sustained responses in amacrine cells of vertebrate retina is the differences in their excitatory, glutamatergic synaptic inputs, and that rapid desensitization of glutamate receptors plays a role in converting the presynaptic signal associated with sustained glutamate release into a postsynaptic, transient signal at the ribbon synapse.
Synaptic and intrinsic mechanisms shape synchronous oscillations in hippocampal neurons in culture
Authors: Bacci Alberto , Verderio Claudia , Pravettoni Elena , Matteoli Michela 
Published: March 2003

AbstractWe have detected spontaneous, synchronous calcium oscillations, associated with variations in membrane potential, in hippocampal neurons maintained in primary culture. The oscillatory activity is synaptically driven, as it is blocked by tetrodotoxin, by the glutamate receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and by toxins inhibiting neurotransmitter release from presynaptic nerve endings. Neuronal oscillations do not require for their expression the presence of a polyneuronal network and are not primarily influenced by the γ‐aminobutyric acid (GABAA) receptor antagonist picrotoxin, suggesting that they entirely rely on glutamatergic neurotransmission. Synaptic and intrinsic conductances shape the synchronized oscillations in hippocampal neurons. The concomitant activation of N‐methyl‐d‐aspartate (NMDA) receptors and voltage‐activated L‐type calcium channels allows calcium entering from the extracellular medium and sustaining the long depolarization, which shapes every single calcium wave.
Stimulation of phospholipase C by the cloned μ, δ and κ opioid receptors via chimeric Gαq mutants
Authors: Joshi Sushma , Lee Jonathan W. M. , Wong Yung H. 
Published: March 2003

AbstractOpioid receptors (μ, δ and κ) are known to regulate diverse physiological functions and yet, at the molecular level, they are coupled to a seemingly identical set of G proteins. A recent study has discerned subtle differences between the opioid receptors in their ability to activate the pertussis toxin‐insensitive G16. Differences in microarchitecture might be magnified when these receptors are provided with ‘non‐native’ partners. Here, we examined whether the opioid receptors can interact productively with a set of chimeric Gαq subunits which are known to link many Gi‐coupled receptors to phosphoinositide‐specific phospholipase C (PI‐PLC). The qi5, qo5 and qz5 chimeras have the last five residues of Gαq replaced by those of Gαi, Gαo and Gαz, respectively. Except for μ‐receptor and qo5, each pair of opioid receptor and Gαq chimera allowed opioid agonists to stimulate PI‐PLC in transfected COS‐7 cells. The Gαq chimera‐mediated responses were ligand selective, agonist dose dependent and saturable. The most robust responses were obtained with κ‐receptor and qi5 or qz5, whereas the coupling of δ‐ and μ‐receptors to Gαq chimeras produced much weaker responses. Among the Gαq chimeras, qo5 was less efficiently coupled to the opioid receptors. As revealed by radioligand binding assays and immunoblot analysis, differences in the efficiency of coupling were not due to variations in the expression of receptors and Gαq chimeras. Differences in the magnitude of PI‐PLC responses are thus likely to represent structural incompatibility between opioid receptors and Gαq chimeras, suggesting that each opioid receptor possesses unique structural surfaces for the binding of G proteins.
Xenopus muscle‐specific kinase: molecular cloning and prominent expression in neural tissues during early embryonic development
Authors: Fu Amy K. Y. , Smith Frances D. , Zhou Hong , Chu Apple H. , Tsim Karl W. K. , Peng Benjamin H. , Ip Nancy Y. 
Published: March 2003

AbstractA muscle‐specific receptor tyrosine kinase, designated MuSK, mediates agrin‐induced aggregation of acetylcholine receptors at the vertebrate neuromuscular junction. cDNAs encoding Xenopus MuSK were isolated from embryonic cDNA libraries. The full‐length MuSK cDNA encodes for a polypeptide of 948 amino acids and possesses the features unique to mammalian MuSK, including four Ig‐like domains, C6 box, transmembrane region and an intracellular tyrosine kinase domain. Interestingly, Xenopus MuSK also contains a kringle domain similar to that previously reported for Torpedo MuSK. The overall amino acid sequence identity of Xenopus MuSK with mammalian MuSK is ≈ 65%. Northern blot analysis demonstrated the presence of three MuSK transcripts (≈ 1 kb, ≈ 3 kb and ≈ 7 kb) which were differentially expressed during development. The expression of the ≈ 7 kb MuSK transcript remained as the predominant species in adult tissues, e.g. skeletal muscle, spleen and lung. Immunocytochemical analysis with a MuSK‐specific antibody revealed that Xenopus MuSK was colocalized with AChRs at neuromuscular junctions as well as in spontaneous acetylcholine receptor hot spots of cultured muscle cells. In situ hybridization revealed prominent expression of MuSK transcripts in neural tissues and myotomal muscle during the period of neurulation and synaptogenesis. The MuSK transcript detected at abundant levels in the central nervous system (CNS) was localized to the brain, spinal cord and eye vesicles during early embryonic development. In addition, the MuSK protein in the developing eye was found to be prominently expressed during embryonic stages of 32 and 35. These findings raise an intriguing possibility that, in addition to the known function in the formation of the neuromuscular junctions, MuSK may be involved in neural development.
Role of retinoids in the CNS: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid
Authors: Zetterström Rolf H. , Lindqvist Eva , De Urquiza Alexander Mata , Tomac Andreas , Eriksson Ulf , Perlmann Thomas , Olson Lars 
Published: March 2003

AbstractRetinoic acid (RA), a retinoid metabolite, acts as a gene regulator via ligand‐activated transcription factors, known as retinoic acid receptors (RARs) and retinoid X receptors (RXRs), both existing in three different subtypes, α, β and γ. In the intracellular regulation of retinoids, four binding proteins have been implicated: cellular retinol binding protein (CRBP) types I and II and cellular retinoic acid binding protein (CRABP) types I and II. We have used in situ hybridization to localize mRNA species encoding CRBP‐ and CRABP I and II as well as all the different nuclear receptors in the developing and adult rat and mouse central nervous system (CNS), an assay to investigate the possible presence of RA, and immunohistochemistry to also analyse CRBP I‐ and CRABP Iimmunoreactivity (IR). RXRβ is found in most areas while RARα and ‐β and RXRα and ‐γ show much more restricted patterns of expression. RARα is found in cortex and hippocampus and RARβ and RXRγ are both highly expressed in the dopamine‐innervated areas caudate/putamen, nucleus accumbens and olfactory tubercle. RARγ could not be detected in any part of the CNS. Using an in vitro reporter assay, we found high levels of RA in the developing striatum. The caudate/putamen of the developing brain showed strong CRBP I‐IR in a compartmentalized manner, while at the same time containing many evenly distributed CRABP I‐IR neurons. The CRBP I‐ and CRABP I‐IR patterns were closely paralleled by the presence of the corresponding transcripts. The specific expression pattern of retinoid‐binding proteins and nuclear retinoid receptors as well as the presence of RA in striatum suggests that retinoids are important in many brain structures and emphasizes a role for retinoids in gene regulatory events in postnatal and adult striatum.
Substance P release in the dorsal horn assessed by receptor internalization: NMDA receptors counteract a tonic inhibition by GABAB receptors
Authors: Marvizón Juan Carlos G. , Grady Eileen F. , Stefani Enrico , Bunnett Nigel W. , Mayer Emeran A. 
Published: March 2003

AbstractInhibitory amino acids have antinociceptive actions in the spinal cord that may involve inhibition of neurotransmitter release from primary afferents. Rat spinal cord slices with dorsal roots were used to study the effect of GABA and glycine on substance P release, assessed by the internalization of neurokinin 1 receptors. After electrical stimulation of the dorsal root at 100 Hz, about half of neurokinin 1 receptor‐immunoreactive neurons in laminae I–IIo showed internalization. This internalization was inhibited by GABA (100 μm) and the GABAB agonist R‐baclofen (10 μm), but not by the GABAA agonist muscimol (20 μm) or glycine (100 μm). The GABAB antagonist 2‐hydroxysaclofen (100 μm) reversed the inhibitory effect of GABA, but not the GABAA antagonist bicuculline (100 μm). These findings demonstrate that GABAB receptors, but not GABAA or glycine receptors, inhibit substance P release induced by dorsal root stimulation. In contrast, R‐baclofen did not inhibit the internalization produced by NMDA (100 μm), indicating that the stimulatory effect of NMDA receptors on substance P release is able to surmount the inhibitory effect of GABAB receptors. In the presence of the GABAB antagonist 2‐hydroxysaclofen (100 μm), but not in its absence, stimulation of the dorsal root at 1 or 10 Hz was able to elicit internalization, which was not inhibited by the NMDA receptor antagonist AP‐5 (50 μm) or the channel blocker MK‐801 (10 μm). Therefore, inhibition of substance P release by GABAB receptors is tonic, and in its absence SP release no longer requires NMDA receptor activation.
Sustained activation of hippocampal pyramidal cells by ‘space clamping’ in a running wheel
Authors: Czurkó András , Hirase Hajime , Csicsvari Jozsef , Buzsáki György 
Published: March 2003

AbstractIn contrast to sensory cortical areas of the brain, the relevant physiological inputs to the hippocampus, leading to selective activation of pyramidal cells, are largely unknown. Pyramidal cells are thought to be phasically activated by spatial cues and a variety of sensory and motor stimuli. Here, we used a behavioural ‘space clamp’ method, which involved the confinement of the actively running animal in a defined position in space (running wheel) and kept sensory inputs constant. Twelve percent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel. Cell firing was specific to the direction of running and disappeared after rotating the recording apparatus. The discharge frequency of pyramidal cells and interneurons was sustained as long as the rat ran continuously in the wheel. Furthermore, the discharge frequency of pyramidal cells and interneurons increased with increasing running velocity, even though the frequency of hippocampal theta waves remained constant. The discharge frequency of some ‘wheel‐related’ pyramidal cells could increase more than 10‐fold between 10 and 100 cm/s, whereas the firing rate of ‘non‐wheel’ cells remained constantly low. We hypothesize that: (i) a necessary condition for place‐specific discharge of hippocampal pyramidal cells is the presence of theta oscillation; and (ii) relevant stimuli can tonically and selectively activate hippocampal pyramidal cells as long as theta activity is present.
Intrathecal galanin alleviates allodynia‐like behaviour in rats after partial peripheral nerve injury
Authors: Hao Jing‐Xia , Shi Tie‐Jun , Xu Isabella S. , Kaupilla Timo , Xu Xiao‐Jun , Hökfelt Tomas , Bartfai Tamas , Wiesenfeld‐Hallin Zsuzsanna 
Published: March 2003

AbstractWe have previously suggested that the neuropeptides galanin and galanin message‐associated peptide (GMAP) may have an inhibitory role in spinal nociception. The present study examined the effects of intrathecal (i.t.) administration of these two peptides on allodynia‐like behaviours in response to mechanical and cold stimulation in rats after photochemically induced ischaemic peripheral nerve injury. I.t. galanin significantly alleviated the mechanical‐ and cold‐allodynia‐like behaviours in nerve injured rats, and was not associated with motor impairment or sedation. I.t. GMAP relieved mechanical allodynia much less than galanin. I.t. M‐35, a high‐affinity galanin receptor antagonist, did not significantly alter the response of the rats to mechanical or cold stimulation. At 1 or 2 weeks postinjury, around 15% of dorsal root ganglion (DRG) neuron profiles showed galanin‐like immunoreactivity. These profiles were mostly small sized. Although the number of galanin positive cells was thus increased in the DRG in the present model, the increase was substantially less than after complete sciatic nerve section, as previously shown. The present results showed that spinal administration of galanin inhibited some abnormal pain‐like behaviours in rats after partial peripheral nerve injury. These results further support an inhibitory function for galanin in nociception. However, endogenous galanin may not play a significant role in suppressing nociceptive input after partial ischaemic peripheral nerve injury, as the upregulation of galanin is moderate.
The effects of lesions to the anterior thalamic nuclei on object–place associations in rats
Authors: Sziklas V. , Petrides M. 
Published: March 2003

AbstractRats with lesions of the anterior nuclei of the thalamus were trained postoperatively on two spatial conditional associative learning tasks. In the first task, the rats were required to choose one or the other of two objects depending on the location in which they were found. In the second task, the animals learned to turn left or right depending on which one of two visual cues was presented. A third experiment examined the effects of damage to the anterior thalamic nuclei on the eight‐arm radial maze, a spatial working memory task. Damage of the anterior thalamic nuclei impaired performance on the radial maze task and the conditional task requiring associations between objects and their location. By contrast, rats with anterior thalamic lesions were able to acquire, at a rate comparable with that of operated control animals, the conditional task requiring associations between objects and body turns. These findings suggest that lesions to the anterior thalamic nuclei result in a general impairment in learning about allocentric spatial information without disrupting the learning of egocentric spatial information.
Redefining the functional organization of working memory processes within human lateral prefrontal cortex
Authors: Owen Adrian M. , Herrod Nicholas J. , Menon David K. , Clark John C. , Downey Steve P. M. J. , Carpenter T. Adrian , Minhas Pawanjit S. , Turkheimer Federico E. , Williams Emma J. , Robbins Trevor W. , Sahakian Barbara J. , Petrides Michael , Pickard John D. 
Published: March 2003

AbstractIt is widely held that the frontal cortex plays a critical part in certain aspects of spatial and non‐spatial working memory. One unresolved issue is whether there are functionally distinct subdivisions of the lateral frontal cortex that subserve different aspects of working memory. The present study used positron emission tomography (PET) to demonstrate that working memory processes within the human mid‐dorsolateral and mid‐ventrolateral frontal regions are organized according to the type of processing required rather than according to the nature (i.e. spatial or non‐spatial), of the information being processed, as has been widely assumed. Two spatial working memory tasks were used which varied in the extent to which they required different executive processes. During a ‘spatial span’ task that required the subject to hold a sequence of five previously remembered locations in working memory a significant change in blood‐flow was observed in the right mid‐ventrolateral frontal cortex, but not in the anatomically and cytoarchitectonically distinct mid‐dorsolateral frontal‐lobe region. By contrast, during a ‘2‐back’ task that required the subject to continually update and manipulate an ongoing sequence of locations within working memory, significant blood flow increases were observed in both mid‐ventrolateral and mid‐dorsolateral frontal regions. When the two working memory tasks were compared directly, the one that emphasized manipulation of information within working memory yielded significantly greater activity in the right mid‐dorsolateral frontal cortex only. This dissociation provides unambiguous evidence that the mid‐dorsolateral and mid‐ventrolateral frontal cortical areas make distinct functional contributions to spatial working memory and corresponds with a fractionation of working memory processes in psychological terms.
Excitatory synaptic transmission and its modulation by PKC is unchanged in the hippocampus of GAP‐43‐ deficient mice
Authors: Capogna Marco , Fankhauser Christoph , Gagliardini Valeria , Gähwiler Beat H. , Thompson Scott M. 
Published: March 2003

AbstractWe compared excitatory synaptic transmission between hippocampal pyramidal cells in dissociated hippocampal cell cultures and in area CA3 of hippocampal slice cultures derived from wild‐type mice and mice with a genetic deletion of the presynaptic growth associated protein GAP‐43. The basal frequency and amplitude of action potential‐dependent and ‐independent spontaneous excitatory postsynaptic currents were similar in both groups. The probability that any two CA3 pyramidal cells in wild‐type or GAP‐43 knockout (–/–) slice cultures were synaptically connected was assessed with paired recordings and was not different. Furthermore, unitary synaptic responses were similar in the two genotypes. Bath application of phorbol 12,13‐diacetate (0.6–3 μm) elicited a comparable increase in the frequency of miniature excitatory synaptic currents in wild‐type and GAP‐43 (–/–) cultures. This effect was blocked by the protein kinase C inhibitor, bisindolylmaleimide I (1.2 μm). Finally, 3 μm phorbol 12,13‐diacetate potentiated the amplitude of unitary synaptic currents to a comparable extent in wild‐type and GAP‐43 (–/–) slice cultures. We conclude that GAP‐43 is not required for normal excitatory synaptic transmission or the potentiation of presynaptic glutamate release mediated by activation of protein kinase C in the hippocampus.