bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter
Authors: Jaber Mohamed , Dumartin Brigitte , Sagné Corinne , Haycock John W. , Roubert Christine , Giros Bruno , Bloch Bertrand , Caron Marc G. 
Published: March 2003

AbstractMice lacking the dopamine transporter (DAT) display biochemical and behavioural dopaminergic hyperactivity despite dramatic alteration in dopamine homeostasis. In order to determine the anatomical and functional integrity of the dopaminergic system, we examined the expression of tyrosine hydroxylase (TH), the rate‐limiting enzyme of dopamine synthesis as well as DOPA decarboxylase and vesicular monoamine transporter. TH‐positive neurons in the substantia nigra were only slightly decreased (–27.6 ± 4.5%), which can not account for the dramatic decreases in the levels of TH and dopamine that we previously observed in the striatum. TH mRNA levels were decreased by 25% in the ventral midbrain with no modification in the ratio of TH mRNA levels per cell. However, TH protein levels were decreased by 90% in the striatum and 35% in the ventral midbrain. In the striatum, many dopaminergic projections had no detectable TH, while few projections maintained regular labelling as demonstrated using electron microscopy. DOPA decarboxylase levels were not modified and vesicular transporter levels were decreased by only 28.7% which suggests that the loss of TH labelling in the striatum is not due to loss of TH projections. Interestingly, we also observed sporadic TH‐positive cell bodies using immunohistochemistry and in situ hybridization in the striatum of homozygote mice, and to some extent that of wild‐type animals, which raises interesting possibilities as to their potential contribution to the dopamine hyperactivity and volume transmission previously reported in these animals. In conjunction with our previous findings, these results highlight the complex regulatory mechanisms controlling TH expression at the level of mRNA, protein, activity and distribution. The paradoxical hyperdopaminergia in the DAT KO mice despite a marked decrease in TH and dopamine levels suggests a parallel to Parkinson's disease implying that blockade of DAT may be beneficial in this condition.
Development of L‐type calcium channels and a nifedipine‐sensitive motor activity in the postnatal mouse spinal cord
Authors: Jiang Z. , Rempel J. , Li J. , Sawchuk M. A. , Carlin K. P. , Brownstone R. M. 
Published: March 2003

AbstractIntrinsic membrane properties are important in the regulation of motoneuronal output during such behaviours as locomotion. A conductance through L‐type calcium channels has been implicated as an essential component in the transduction of motoneuronal input to output during locomotion. Given the developmental changes in calcium currents occurring postnatally in some neurons, and the increasing interest in the study of spinal locomotor output in neonatal preparations, experiments were conducted to investigate the postnatal development of L‐type calcium channels in mouse motoneurons. This was assessed both physiologically, using a chemically induced rhythmic motor output, and anatomically, using immunohistochemical methods. The electrophysiological data were obtained during rhythmic bursting produced by application of N‐methyl‐d‐aspartate (NMDA) and strychnine to the isolated spinal cord at various postnatal ages. The L‐type calcium channel blocker nifedipine has no effect on this ventral root bursting in postnatal day (P) P2–P5 animals, but reversibly reduced the amplitude and/or burst duration of this activity in animals greater than P7. The immunohistochemical evidence demonstrates a dramatic change in the cellular profile of both the α1C and α1D subunits of L‐type calcium channels during postnatal development; the labelling of both subunits increases with age, approximating the adult pattern by P18. These results demonstrate that in the spinal cord, the L‐type calcium channel profile develops both physiologically and anatomically in the early postnatal period. This development parallels the development of the mature functional behaviours of weight bearing and walking, and may be necessary for the production of complex motor behaviour in the mature mammal.
Induction of presynaptic differentiation in cultured neurons by extracellular matrix components
Authors: Son Young‐Jin , Patton Bruce L. , Sanes Joshua R. 
Published: March 2003

AbstractMotoneurons reinnervating skeletal muscles form nerve terminals at sites of contact with a specialized basal lamina. To analyse the molecules and mechanisms that underly these responses, we introduce two systems in which basal lamina‐derived components induce presynaptic differentiation of cultured neurons from chick ciliary ganglia in the absence of a postsynaptic cell. In one, ciliary neurites that contact substrates coated with a recombinant laminin β2 fragment form varicosities that are rich in synaptic vesicle proteins, depleted of neurofilaments, and capable of depolarization‐dependent exocytosis and endocytosis. Thus, a single molecule can trigger a complex, coordinated program of presynaptic differentiation. In a second system, neurites growing on cryostat sections of adult kidney form vesicle‐rich, neurofilament‐poor arbors on glomeruli. Glomerular basal lamina, like synaptic basal lamina, is rich in laminin β2 and collagen (α3–5) IV. However, glomeruli from mutant mice lacking these proteins were capable of inducing differentiation, suggesting the glomerulus as a source of novel presynaptic organizing molecules.
Axotomy results in major changes in BDNF expression by dorsal root ganglion cells: BDNF expression in large trkB and trkC cells, in pericellular baskets, and in projections to deep dorsal horn and dorsal column nuclei
Authors: Michael G. J. , Averill S. , Shortland P. J. , Yan Q. , Priestley J. V. 
Published: March 2003

AbstractBrain derived neurotrophic factor (BDNF) is normally expressed by a small number of predominantly trkA‐expressing dorsal root ganglion cells. Using immunocytochemistry and in situ hybridization, we have examined the effect of sciatic nerve section on the expression of BDNF in the adult rat. Following axotomy there was a long lasting (4‐week) increase in BDNF mRNA and protein in large‐diameter, trkB‐ and trkC‐expressing dorsal root ganglion cells. By 2 days postaxotomy, expression of BDNF mRNA had increased from 2% of trkB cells to 50%, and from 18% of trkC cells to 56%. In contrast, BDNF expression in most trkA cells was unchanged, although was increased in the small population of medium‐ and large‐sized trkA cells. Following axotomy, BDNF‐immunoreactive terminals appeared in the central axonal projections of large‐diameter cells, including the deep dorsal horn and gracile nucleus. Neuropeptide Y was also upregulated following axotomy and was coexpressed with BDNF in the cell bodies and central terminals of the large cells. Ultrastructural analysis in lamina IV of the spinal cord revealed that BDNF terminals in these central projections establish synaptic contacts. Immunoreactivity at 4 weeks was also observed in pericellular baskets that contained calcitonin gene‐related peptide (CGRP) and surrounded trkA‐ and trkB‐expressing cells in L4 and L5 lumbar ganglia. These baskets are likely to arise from local, highly immunoreactive, BDNF/CGRP/trkA‐expressing cells. Our results identify several novel targets for BDNF and imply that it acts locally in both autocrine and paracrine modes, as well as centrally in a synaptic mode, to modulate the response of somatosensory pathways in nerve injury.
Maturation of kainate‐induced epileptiform activities in interconnected intact neonatal limbic structures in vitro
Authors: Khalilov Ilgam , Dzhala Volodymyr , Medina Igor , Leinekugel Xavier , Melyan Zara , Lamsa Karri , Khazipov Roustem , Ben‐Ari Yehezkel 
Published: March 2003

AbstractIn vivo studies suggest that ontogenesis of limbic seizures is determined by the development of the limbic circuit. We have now used the newly‐developed in vitro intact interconnected neonatal rat limbic structures preparation to determine the developmental profile of kainate‐induced epileptiform activity in the hippocampus and its propagation to other limbic structures. We report gradual alterations in the effects of kainate during the first postnatal week on an almost daily basis; from no epileptiform activity at birth, through interictal seizures around postnatal day (P) 2 and ictal seizures by the end of the first week. The developmental profile of kainate‐induced hippocampal seizures is paralleled by the expression of postsynaptic kainate receptor‐mediated currents in CA3 pyramidal cells. Intralimbic propagation of the hippocampal seizures is also age‐dependent: whereas seizures readily propagate to the septum and to the contralateral hippocampus via the commissures on P2, propagation to the entorhinal cortex only takes place from P4 onwards. Finally, repeated brief applications of kainate to the hippocampus induce recurrent spontaneous glutamatergic ictal and interictal discharges which persist for several hours after the kainate is washed away and which replace the physiological pattern of network activity. Paroxysmal activities are thus generated by kainate in the hippocampus at an early developmental stage and are initially restricted to this structure. Before the end of the first week of postnatal life, kainate generates the epileptiform activities that may perturb activity‐dependent mechanisms that modulate neuronal development. Although at this stage neurons are relatively resistant to the pathological effects of kainate, the epileptiform activities that it generates will perturb activity‐dependent mechanisms that modulate neuronal development.
Chemical LTD in the CA1 field of the hippocampus from young and mature rats
Authors: Kamal Amer , Ramakers Geert M. J. , Urban Ivan J. A. , De Graan Pierre N. E. , Gispen Willem Hendrik 
Published: March 2003

AbstractWithin the hippocampal formation, two forms of long‐lasting synaptic plasticity, long‐term potentiation (LTP) and long‐term depression (LTD), can be induced which require the activation of NMDA receptors. Interestingly, it has been shown that both LTP and LTD are reduced in adult animals. Recently, a new chemical protocol has been described which elicits LTD in the CA1 field of the hippocampus. Application of 20 μm NMDA for 3 min results in a stable and long‐lasting decrease in the evoked synaptic responses. We used this protocol to induce LTD in hippocampal slices from young and adult rats and show that this form of LTD is AP5‐sensitive and can be blocked by the protein phosphatase inhibitor cyclosporin A in slices from adult animals. In contrast to electrical LTD (induced by prolonged low frequency stimulation), the extent of chemical LTD was not different between the young and adult rats. These findings indicate that the intracellular signal transduction cascades involved in long‐lasting synaptic depression are still intact in adult animals.
Correlations between neural discharges are related to receptive field properties in cat primary auditory cortex
Authors: Brosch Michael , Schreiner Christoph E. 
Published: March 2003

AbstractThe functional role of correlated neural activity in auditory cortex for the processing of sounds was explored by investigating whether and how cross‐correlation parameters are related to receptive field similarities of neurons. Multi‐unit activity was recorded simultaneously from several sites of isofrequency domains in primary auditory cortex. At each site various receptive field properties were determined. From the discharges of pairs of clusters, normalized cross‐correlation histograms (CCH) were calculated for extended periods of spontaneous activity and for periods with noise‐burst stimulation. In both conditions, most CCHs exhibited a symmetrical positivity near the origin of the CCH, a few to several tens of milliseconds wide. Cross‐correlation histograms were characterized with two parameters: the correlation strength, which was estimated from the peak correlation, and the correlation width, i.e. the time period of correlated firing, which was measured as the width of the positivity at half height. It was found that correlation strength increased and correlation width narrowed with increasing similarity of the receptive fields of two clusters. These relationships were observed both in the acoustically‐driven and spontaneous conditions. Specifically, correlation strength was most strongly associated with similarity in binaural interaction and in temporal response properties such as response onset, response offset and the temporal pattern of the response. Correlation width was predominantly associated with similarity in characteristic frequency, bandwidth and intensity threshold. Results suggest that correlated activity, reflecting potential mechanisms involved in the neural computation in auditory cortex, provides a means to evaluate the properties of the functional organization of auditory cortex. Systematic relationships were found between correlation properties and the receptive field‐based organization of cortical processing, suggesting that similar general mechanisms are utilized in many parts of the sensory cortex. In particular, the magnitude and/or the time period of synchronized firing of neurons is increased if the receptive field properties of the involved neurons are similar.
Disruption of the substance P receptor (neurokinin‐1) gene does not prevent upregulation of preprotachykinin‐A mRNA in the spinal cord of mice following peripheral inflammation
Authors: Palmer James A. , De Felipe Carmen , O'Brien John A. , Hunt Stephen P. 
Published: March 2003

AbstractThe neuropeptide substance P is thought to play an important role in nociception, although the function of the peptide remains controversial. Following peripheral inflammation there is a pronounced upregulation of substance P expression both in sensory neurons and in postsynaptic neurons within the spinal cord. We have examined the levels of expression of mRNA encoding substance P and dynorphin following the development of inflammatory hyperalgesia in mice in which the substance P receptor gene, also known as the neurokinin‐1 receptor gene, has been disrupted by homologous recombination. We show that inflammatory hyperalgesia following injection of complete Freund's adjuvant develops normally in animals that lack the neurokinin‐1 receptor and that expression of mRNAs encoding substance P and the neuropeptide dynorphin are upregulated regardless of the genotype of the mouse. This suggests that substance P activity is not required for the development and maintenance of inflammatory hyperalgesia and that the upregulation of substance P expression is mediated by neurotransmitters other than substance P.
Modulation of bistratified cell IPSPs and basket cell IPSPs by pentobarbitone sodium, diazepam and Zn2+: dual recordings in slices of adult rat hippocampus
Authors: Pawelzik Hannelore , Bannister A. Peter , Deuchars Jim , Ilia Maria , Thomson Alex M. 
Published: March 2003

AbstractSimultaneous intracellular recordings from presynaptic Stratum pyramidale interneurons and postsynaptic pyramidal cells in adult rat hippocampal slices were performed to investigate the strength of the modulation of single‐axon inhibitory postsynaptic potentials (IPSPs) by the GABAA receptor modulators pentobarbitone, diazepam and zinc. The processing of biocytin‐filled interneurons for light microscopy revealed that these single‐axon IPSPs were generated by basket cells (n = 33), bistratified cells (n = 18) and axo‐axonic cells (n = 2). The IPSPs generated by these three groups of interneurons had amplitudes and widths at half amplitude with similar ranges, but when bistratified cell IPSPs were compared with basket cell IPSPs with similar half widths their rise times were slower. Pentobarbitone sodium (250 μm) powerfully enhanced 13 tested IPSPs generated by all three cell types. Amplitudes were enhanced by 82 ± 56%, 10–90% rise times by 150 ± 101% and the widths at half amplitude by 71 ± 29%. Diazepam (1–2 μm) also increased all IPSPs tested, although the changes were more moderate in basket cell IPSPs (amplitudes increased by 19 ± 11%, n = 8) than in bistratified cell IPSPs (amplitudes increased by 66 ± 48%, n = 5). Basket cell IPSP 10–90% rise times and widths at half amplitude were not significantly increased. Bistratified cell IPSP 10–90% rise times were increased by 44 ± 24% and the widths at half amplitude by 32 ± 35%. The one tested IPSP generated by an axo‐axonic cell was also diazepam‐sensitive. Zinc, 250 μm, decreased four out of 10 IPSPs generated by basket cells and four out of five IPSPs generated by bistratified cells. The one tested axo‐axonic cell IPSP was zinc‐insensitive. These data suggest that IPSPs generated in CA1 pyramidal cells by basket and bistratified cells display different pharmacologies and may be mediated by different receptors or receptor combinations.
CAMs and FGF cause a local submembrane calcium signal promoting axon outgrowth without a rise in bulk calcium concentration
Authors: Archer Fabienne R. , Doherty Patrick , Collins Dominic , Bolsover Stephen R. 
Published: March 2003

AbstractBinding of basic fibroblast growth factor (bFGF) and cell adhesion molecules to the nerve cell membrane promotes axon outgrowth. This response can be blocked by antagonists of voltage‐gated calcium channels, yet no change of cytosolic calcium concentration in the growth cone can be detected upon binding of the growth factor bFGF or the cell adhesion molecule L1. Using barium as a charge carrier, we show that bFGF and L1 open a calcium influx pathway in growth cones of rat sensory neurons without changing the membrane voltage. L1 does not activate influx in cells expressing a dominant negative mutant of the fibroblast growth factor receptor (FGFR) tyrosine kinase. FGFR‐activated influx is blocked by specific antagonists of L‐ and N‐type voltage‐gated calcium channels and by an inhibitor of diacylglycerol lipase. We propose that both L1 and bFGF act via the FGFR to generate polyunsaturated fatty acids which in turn cause calcium channels to flicker open and shut. Short‐lived domains of raised calcium at the cytosolic mouth of open channels activate axon outgrowth without raising bulk cytosolic calcium concentration. In confirmation of this model, the rapidly‐acting calcium buffer BAPTA is significantly more effective at blocking FGF‐induced axon outgrowth when compared with the slower buffer EGTA. Generation of short‐lived calcium domains may provide a crucial mechanism for axon guidance during development and for promoting regeneration of damaged axons.
Immunocytochemical characterization of catecholaminergic neurons in the rat striatum following dopamine‐depleting lesions
Authors: Meredith G. E. , Farrell T. , Kellaghan P. , Tan Yun , Zahm D. S. , Totterdell S. 
Published: March 2003

AbstractIt is possible either permanently or transiently to deplete the rat striatum of dopamine. Following such depletions, striatal neurons immunoreactive for tyrosine hydroxylase (TH), aromaticl‐amino acid decarboxylase (AADC) or dopamine appear. The presence of dopamine‐producing neurons in the striatum has relevance for the treatment of Parkinson's disease, but whether these catecholaminergic phenotypes all produce dopamine is unclear. In the present study we establish that after unilateral 6‐hydroxydopamine lesions or methamphetamine administration, striatal TH‐immunoreactive neurons differ in size, morphology and location from those that are immunopositive for AADC or dopamine. The TH‐positive cells which were localized either to ventral parts of the striatum or to the central and dorsal areas of the caudate‐putamen generally have the morphological features of projection neurons, whereas those containing AADC or dopamine were confined to subcallosal positions in the dorsal medial quadrant of the caudate‐putamen and resemble small, local‐circuit neurons. The fact that AADC‐immunoreactive neurons overlap in size, morphology and location with the cells that produce dopamine suggests strongly that this population is dopaminergic. However, the simultaneous appearance of neurons that contain the TH enzyme but clearly do not make dopamine raises questions about the functional role of these cells and the cellular mechanisms responsible for their induction following striatal dopamine loss.
Voltage‐independent autocrine modulation of L‐type channels mediated by ATP, opioids and catecholamines in rat chromaffin cells
Authors: Hernández‐Guijo J. M. , Carabelli V. , Gandía L. , García A. G. , Carbone E. 
Published: March 2003

AbstractThe inhibition of L‐type channels induced by either bath application of ATP, opioids and catecholamines or by endogenously released neurotransmitters was investigated in rat chromaffin cells with whole‐cell recordings (5 mm Ba2+). In both cases, the L‐type current, isolated pharmacologically using ω‐toxin peptides and potentiated by Bay K 8644, was inhibited by ∼ 50% with nearly no changes to the activation–inactivation kinetics. Inhibition was voltage independent at a wide range of potentials (–20 to +50 mV) and insensitive to depolarizing prepulses (+100 mV, 50 ms). Onset and offset of the inhibition were fast (time constants: τon ∼ 0.9 s, τoff ∼ 3.6 s), indicating a rapid mechanism of channel modulation. Whether induced exogenously or from the released granules content in conditions of stopped cell superfusion, the neurotransmitter action was reversible and largely prevented by either intracellular GDP‐β‐S, cell treatment with pertussis toxin or simultaneous application of P2y,2x δ/μ‐opioidergic and α/β‐adrenergic antagonists. This suggests the existence of converging modulatory pathways by which autoreceptors‐activated G‐proteins reduce the activity of L‐type channels through fast interactions. The autocrine inhibition of L‐type currents, which was absent in superfused isolated cells, was effective on cell clusters, suggesting that L‐type channels may be potently inhibited by cell exocytosis under physiological conditions resembling the intact adrenal glands.
Acute desensitization of nociceptin/orphanin FQ inhibition of voltage‐gated calcium channels in freshly dissociated hippocampal neurons
Authors: Pu Lu , Bao Guo‐Bin , Ma Lan , Pei Gang 
Published: March 2003

AbstractNociceptin/orphanin FQ (N/OFQ), an endogenous ligand for opioid receptor‐like receptor, has been shown to inhibit high‐voltage‐gated calcium channels (VGCCs) in acutely dissociated rat hippocampal pyramidal cells [Knoflach, F., Reinscheid, R.K., Civelli, O. & Kemp, J.A. (1996), J. Neurosci., 16, 6657]. In this study, it was further demonstrated that N/OFQ inhibition of calcium channel current was blocked by its specific antagonist PGN, [Phe1‐ψ(CH2‐NH)‐Gly2]nociceptin (1‐13)‐NH2, and the EC50 of the N/OFQ inhibition was ∼ 10 nm, indicating that this effect was really mediated via the opioid receptor‐like receptor. The N/OFQ inhibition of the calcium channel current was significantly reduced, as the maximal inhibition decreased from 36 to 23%, by 1‐min pretreatment of freshly dissociated hippocampal neurons with the same peptide. The inhibition completely recovered from this acute desensitization in less than 20 min. The N/OFQ inhibition was also greatly attenuated by pretreatment of the neurons with the GABAB (γ‐aminobutyric acid) agonist baclofen while the baclofen inhibition of the calcium channel current was significantly reduced by N/OFQ pretreatment, revealing the agonist‐induced desensitization was heterologous in nature. This desensitization was blocked by pretreating the neurons with the sodium channel blocker, tetrodotoxin (TTX), or by removing the extracellular calcium, which indicates the necessity of membrane depolarization and extracellular calcium influx in the process. Furthermore, pretreatment of the neurons with the protein kinase C (PKC) activator, phorbol 12‐myristate 13‐acetate (PMA), attenuated the N/OFQ inhibition of the calcium channel current whereas the cAMP‐dependent kinase A activator, forskolin, showed no effect, suggesting the probable involvement of PKC in the N/OFQ‐induced desensitization.