bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term consequences of early postnatal seizures on hippocampal learning and plasticity
Authors: Lynch Michael , Sayin Ümit , Bownds Jonathan , Janumpalli Sridevi , Sutula Thomas 
Published: March 2003

AbstractNeural activity influences the patterning of synaptic connections and functional organization of developing sensory and motor systems, but the long‐term consequences of intense neural activity such as seizures in the developing hippocampus are not adequately understood. To evaluate the possibility that abnormal neural activity during early development may have long‐term functional effects in hippocampal circuitry that plays a role in learning, memory and epilepsy, functional properties of hippocampal circuitry were assessed in adult rats that had experienced seizures induced by kainic acid on specific days during early postnatal development. Although previous studies have suggested that the immature hippocampus is relatively resistant to seizure‐induced alterations compared with adults, independent behavioural and physiological experiments demonstrated that seizures evoked by kainic acid during early postnatal development induced a long‐term loss of hippocampal plasticity manifesting as reduced capacity for long‐term potentiation, reduced susceptibility to kindling, and impaired spatial learning, which was associated with enhanced paired‐pulse inhibition in the dentate gyrus. The enhancement of inhibition and loss of plasticity were maximal when the seizures occurred on the first day of life, but were also observed when seizures were induced as late as postnatal day 14, which delimited a period of postnatal susceptibility in the developing rat hippocampus when disruption of normal neural activity by seizures produced consistent effects on a hippocampal‐dependent behaviour and several forms of hippocampal plasticity implicated in learning, memory and the development of epilepsy in adulthood.
Pituitary adenylate cyclase‐activating polypeptide promotes the survival of basal forebrain cholinergic neurons in vitro and in vivo: comparison with effects of nerve growth factor
Authors: Takei Nobuyuki , Torres Eduardo , Yuhara Aki , Jongsma Helen , Otto Christiane , Korhonen Laura , Abiru Yasuhiro , Skoglösa Ylva , Schütz Günther , Hatanaka Hiroshi , Sofroniew Michael V. , Lindholm Dan 
Published: March 2003

AbstractPituitary adenylate cyclase‐activating polypeptide (PACAP) is a member of the vasointestinal polypeptide gene family for which neurotrophic activity has been postulated. PACAP mRNA is expressed in the developing and adult hippocampus, which is the principal target region of septal cholinergic neurons. We therefore studied the effects of PACAP on septal cholinergic neurons. In primary cultures from septum of embryonic and postnatal rats, PACAP increased the number of neurons immunohistochemically stained for the low‐affinity nerve growth factor (NGF) receptor p75 and for the enzyme choline acetyltransferase (ChAT). PACAP also caused a corresponding increase in ChAT activity. In comparison, NGF had a greater effect than PACAP on the number of p75‐ and ChAT‐positive neurons in these cultures. In vivo, following fimbria fornix transection, the number of immunohistochemically stained septal cholinergic neurons fell significantly to 18% in rats given continuous intracerebroventricular infusion of vehicle, whereas in rats given NGF the number of these neurons did not differ significantly from unoperated controls. In PACAP‐treated rats the number was 48% of unoperated values, which represented a significant increase compared with vehicle‐treated rats and a significant decrease compared with NGF‐treated rats or unoperated controls. Double‐staining experiments revealed that most ChAT‐positive neurons in rat medial septum also express PACAP receptor 1. Together the results show that PACAP promotes the survival of septal cholinergic neurons in vitro, and after injury in vivo, suggesting that PACAP acts as a neurotrophic factor influencing the development and maintenance of these neurons.
Deafferentation‐induced apoptosis of neurons in thalamic somatosensory nuclei of the newborn rat: critical period and rescue from cell death by peripherally applied neurotrophins
Authors: Baldi Alfonso , Calia Eustachio , Ciampini Alessandro , Riccio Massimo , Vetuschi Antonella , Persico Antonio M. , Keller Flavio 
Published: March 2003

AbstractThis study shows that unilateral transection of the infraorbital nerve (ION) in newborn (P0) rats induces apoptosis in the contralateral ventrobasal thalamic (VB) complex, as evidenced by terminal transferase‐mediated deoxyuridine triphosphate‐biotin nick end labelling (TUNEL) and electron miscroscopy. Double‐labelling experiments using retrograde transport of labelled microspheres injected into the barrel cortex, followed by TUNEL staining, show that TUNEL‐positive cells are thalamocortical neurons. The number of TUNEL‐positive cells had begun to increase by 24 h postlesion, increased further 48 h after nerve section, and decreased to control levels after 120 h. Lesion‐induced apoptosis in the VB complex is less pronounced if ION section is performed at P4, and disappears if the lesion is performed at P7. This time course closely matches the critical period of lesion‐induced plasticity in the barrel cortex. Nerve growth factor (NGF) or brain‐derived neurotrophic factor (BDNF), applied on the ION stump alone or in combination, are able to partially rescue thalamic neurons from apoptosis. Total cell counts in the VB complex of P7 animals that underwent ION section at P0 confirm the rescuing effect of BDNF and NGF. Blockade of axonal transport in the ION mimics the effect of ION section. These data suggest that survival‐promoting signals from the periphery, maybe neurotrophins, are required for the survival of higher‐order neurons in the somatosensory system during the period of fine‐tuning of neuronal connections. We also propose that anterograde transneuronal degeneration in the neonatal rat trigeminal system may represent a new animal model for studying the pathways of programmed cell death in vivo.
Differential effect of oestradiol and astroglia‐conditioned media on the growth of hypothalamic neurons from male and female rat brains
Authors: Cambiasso M. J. , Colombo J. A. , Carrer H. F. 
Published: March 2003

AbstractTo determine whether soluble products from different CNS regions differ in their ability to support oestrogen‐stimulated neurite growth, hypothalamic neurons from sexually segregated embryos were cultured with astroglia‐conditioned medium (CM) derived from cortex, striatum and mesencephalon, with or without 17‐β‐oestradiol 100 n m added to the medium. After 48 h in vitro, neurite outgrowth was quantified by morphometric analysis. Astroglia‐CM from mesencephalon (a target for the axons of hypothalamic neurons) induced the greatest axogenic response in males and in this case only a neuritogenic effect could be demonstrated for oestradiol. On the other hand, astroglia‐CM from regions that do not receive projections from ventromedial hypothalamus inhibited axon growth. A sexual difference in the response of hypothalamic neurons to astroglia‐CM and oestradiol was found; growth of neurons from female foetuses was increased by astroglia‐CM from mesencephalon, but no neuritogenic effect could be demonstrated for oestradiol in these cultures. Blot immunobinding demonstrated the presence of receptors for neurotrophic factors in cultures of hypothalamic neurons; Western blot analysis of these cultures demonstrated that oestradiol increased the concentration of trkB and IGF‐I Rβ, whereas trkA was not detected and the concentration of trkC was not modified. These results support the hypothesis that target regions produce some factor(s) that stimulate the growth of axons from projecting neurons and further indicate that in the case of males this effect is modulated by oestradiol, perhaps mediated through the upregulation of trkB and IGF‐I receptors.
Species‐specific modulation of pattern‐generating circuits
Authors: Meyrand Pierre , Faumont Serge , Simmers John , Christie Andrew E. , Nusbaum Michael P. 
Published: March 2003

AbstractPhylogenetic comparison can reveal general principles governing the organization and neuromodulation of neural networks. Suitable models for such an approach are the pyloric and gastric motor networks of the crustacean stomatogastric ganglion (STG). These networks, which have been well studied in several species, are extensively modulated by projection neurons originating in higher‐order ganglia. Several of these have been identified in different decapod species, including the paired modulatory proctolin neuron (MPN) in the crab Cancer borealis [Nusbaum & Marder (1989) J. Neurosci., 9,1501–1599; Nusbaum & Marder (1989), J. Neurosci., 9, 1600–1607] and the apparently equivalent neuron pair, called GABA (γ‐aminobutyric acid) neurons 1 and 2 (GN1/2), in the lobster Homarus gammarus [Cournil et al. (1990) J. Neurocytol., 19, 478–493]. The morphologies of MPN and GN1/2 are similar, and both exhibit GABA‐immunolabelling. However, unlike MPN, GN1/2 does not contain the peptide transmitter proctolin. Instead, GN1/2, but not MPN, is immunoreactive for the neuropeptides related to cholecystokinin (CCK) and FLRFamide. Nonetheless, GN1/2 excitation of the lobster pyloric rhythm is similar to the proctolin‐mediated excitation of the crab pyloric rhythm by MPN. In contrast, GN1/2 and MPN both use GABA but produce opposite effects on the gastric mill rhythm. While MPN stimulation produces a GABA‐mediated suppression of the gastric rhythm [Blitz & Nusbaum (1999) J. Neurosci., 19, 6774–6783], GN1/2 activates or enhances gastric rhythmicity. These results highlight the care needed when generalizing neuronal organization and function across related species. Here we show that the ‘same’ neuron in different species does not contain the same neurotransmitter complement, nor does it exert all of the same effects on its postsynaptic targets. Conversely, a different transmitter phenotype is not necessarily associated with a qualitative change in the way that a modulatory neuron influences target network activity.
Elevation of intradendritic sodium concentration mediated by synaptic activation of metabotropic glutamate receptors in cerebellar Purkinje cells
Authors: Knöpfel T. , Anchisi D. , Alojado M. E. , Tempia F. , Strata P. 
Published: March 2003

AbstractCerebellar Purkinje cells express both ionotropic glutamate receptors and metabotropic glutamate receptors. Brief tetanic stimulation of parallel fibers in rat and mouse cerebellar slices evokes a slow excitatory postsynaptic current in Purkinje cells that is mediated by the mGluR1 subtype of metabotropic glutamate receptors. The effector system underlying this mGluR1 EPSC has not yet been identified. In the present study, we recorded the mGluR1 EPSC using the whole‐cell patch‐clamp technique in combination with microfluorometric recordings of the intracellular sodium concentration ([Na+]i) by means of the fluorescent sodium indicator SBFI. The mGluR1 EPSC was induced by local parallel fibre stimulation in the presence of the ionotropic glutamate receptor antagonists NBQX and D‐APV and the GABAA receptor antagonists bicuculline or picrotoxin. The mGluR1 EPSC was associated with an increase in [Na+]i that was restricted to a specific portion of the dendritic tree. The mGluR1 EPSC as well as the increase in [Na+]i were inhibited by the mGluR antagonist S‐MCPG. In the presence of NBQX, D‐APV, pictrotoxin and TTX, bath application of the selective mGluR agonist 3,5‐DHPG induced an elevation in [Na+]i which extended over the whole dendritic field of the Purkinje cell. This finding demonstrates that the mGluR1‐mediated postsynaptic current leads to a significant influx of sodium into the dendritic cytoplasm of Purkinje cells and thereby provides a novel intracellular signalling mechanism that might be involved in mGluR1‐dependent synaptic plasticity at this synapse.
Time‐dependent enhancement of inhibitory avoidance retention and MAPK activation by post‐training infusion of nerve growth factor into CA1 region of hippocampus of adult rats
Authors: Walz Roger , Lenz Guido , Roesler Rafael , Vianna Mônica M. R. , Martins Vilma , Brentani Ricardo , Rodnight Richard , Izquierdo Ivan 
Published: March 2003

AbstractSeveral studies have demonstrated that chronic intracerebroventricular nerve growth factor (NGF) infusion has a beneficial effect on cognitive performance of lesioned as well as old and developing animals. Here we investigate: (i) the effect of post‐training infusion of NGF into the CA1 region of hippocampus on inhibitory avoidance (IA) retention in rats; (ii) the extension of the effect, in time and space, of NGF infusion into CA1 on the activity of mitogen‐activated protein kinase (MAPK, syn: ERK1/2, p42/p44 MAPK). NGF was bilaterally injected into the CA1 regions of the dorsal hippocampus (0.05, 0.5 or 5.0 ng diluted in 0.5 μL of saline per side) at 0, 120 or 360 min after IA training in rats. Retention testing was carried out 24 h after training. The injection of 5.0 and 0.5, but not 0.05, ng per side of NGF at 0 and 120 min after IA training enhanced IA retention. The highest dose used was ineffective when injected 360 min after training. The infusion of 0.5 μL of NGF (5.0 ng) induced a significant enhancement of MAPK activity in hippocampal microslices; this enhancement was restricted to a volume with 0.8 mm radius at 30 min after injection. The MAPK activation was still seen 180 min after NGF infusion, although this value showed only a tendency. In conclusion, localized infusion of NGF into the CA1 region enhanced MAPK activity, restricted in time and space, and enhanced IA retention in a time‐ and dose‐dependent manner.
Multimeric CREB‐binding sites in the promoter regions of a family of G‐protein‐coupled receptors related to the vertebrate galanin and nociceptin/orphanin‐FQ receptor families
Authors: Saunders Susan E. , Burke Julian F. , Benjamin Paul R. 
Published: March 2003

AbstractFour related genes encoding a family of G‐protein‐coupled receptors (GPCRs) have been isolated from the mollusc Lymnaea stagnalis. The coding regions of this family of receptors share 97–99% sequence similarity at both the protein and nucleotide level, and they also share high sequence identity with vertebrate galanin and orphanin‐FQ/nociceptin GPCR families. Analysis of the promoter regions reveals shared domains, some of which encode highly conserved repeating units. One 27‐bp repeating unit, which encodes a c‐AMP response element (CRE) and binds CREB protein, is repeated 14 times in one promoter. In situ hybridization showed expression of these receptors in identified neurons of several behaviourly important networks including those involved in feeding and ion and water regulation. These Lymnaea receptors are likely to represent members of a novel family of invertebrate neuropeptide receptors extensively regulated in response to intracellular signalling cascades.
A blocker‐resistant, fast‐decaying, intermediate‐threshold calcium current in palaeocortical pyramidal neurons
Authors: Magistretti Jacopo , Brevi Sara , De Curtis Marco 
Published: March 2003

AbstractThe whole‐cell patch‐clamp technique was used to record Ca2+ currents in acutely dissociated neurons from layer II of guinea‐pig piriform cortex (PC). Ba2+ (5 mm) was used as charge carrier. In a subpopulation of layer II cells (≈ 22%) total Ba2+ currents (IBas) displayed a high degree (> 70%) of inactivation after 300 ms of steady depolarization. The application of L‐, N‐ and P/Q‐type Ca2+‐channel blockers to these high‐decay IBas left their fast inactivating component largely unaffected. The inactivation phase of the blocker‐resistant, fast‐decaying IBa thus isolated had a bi‐exponential time course, with a fast time constant of ≈ 20 ms and a slower time constant of ≈ 100 ms at voltage levels positive to −10 mV. The voltage dependence of activation of the blocker‐resistant, fast‐decaying IBa was shifted by ≈ 7–9 mV in the negative direction in comparison with those of other pharmacologically and/or kinetically different high‐voltage‐activated Ca2+ currents. We named this blocker‐resistant, fast‐decaying, intermediate‐threshold current IRfi. The amplitude of IRfi decreased only slightly (by ≈ 9%) when extracellular Ca2+ was substituted for Ba2+, in contrast with that of slowly decaying, high‐voltage‐activated currents, which was reduced by ≈ 41% on average. Moreover, IRfi was substantially inhibited by low concentrations of Ni2+ (50 μm). We conclude that IRfi, because of its fast inactivation kinetics, intermediate threshold of activation and resistance to organic blockers, represents a definite, identifiable Ca2+ current different from classical high‐voltage‐activated currents and clearly distinguishable from classical IT. The striking similarity found between IRfi and Ca2+ currents resulting from heterologous expression of α1E‐type channel subunits is discussed.
Altered expression and functions of serotonin 5‐HT1A and 5‐HT1B receptors in knock‐out mice lacking the 5‐HT transporter
Authors: Fabre V. , Beaufour C. , Evrard A. , Rioux A. , Hanoun N. , Lesch K. P. , Murphy D. L. , Lanfumey L. , Hamon M. , Martres M. ‐P. 
Published: March 2003

AbstractBy taking up serotonin (5‐hydroxytryptamine, 5‐HT) released in the extracellular space, the 5‐HT transporter (5‐HTT) regulates central 5‐HT neurotransmission. Possible adaptive changes in 5‐HT neurotransmission in knock‐out mice that do not express the 5‐HT transporter were investigated with special focus on 5‐HT1A and 5‐HT1B receptors. Specific labelling with radioligands and antibodies, and competitive RT‐PCR, showed that 5‐HT1A receptor protein and mRNA levels were significantly decreased in the dorsal raphe nucleus (DRN), increased in the hippocampus and unchanged in other forebrain areas of 5‐HTT–/– vs. 5‐HTT+/+ mice. Such regional differences also concerned 5‐HT1B receptors because a decrease in their density was found in the substantia nigra (−30%) but not the globus pallidus of mutant mice. Intermediate changes were noted in 5‐HTT+/– mice compared with 5‐HTT+/+ and 5‐HTT–/– animals. Quantification of [35S]GTP‐γ‐S binding evoked by potent 5‐HT1 receptor agonists confirmed such changes as a decrease in this parameter was noted in the DRN (−66%) and the substantia nigra (−30%) but not other brain areas in 5‐HTT–/– vs. 5‐HTT+/+ mice. As expected from actions mediated by functional 5‐HT1A and 5‐HT1B autoreceptors, a decrease in brain 5‐HT turnover rate after i.p. administration of ipsapirone (a 5‐HT1A agonist), and an increased 5‐HT outflow in the substantia nigra upon local application of GR 127935 (a 5‐HT1B/1D antagonist) were observed in 5‐HTT+/+ mice. Such effects were not detected in 5‐HTT–/– mice, further confirming the occurrence of marked alterations of 5‐HT1A and 5‐HT1B autoreceptors in these animals.
Subthalamic neuron activity related to tremor and movement in Parkinson's disease
Authors: Magariños‐Ascone Carlos M. , Figueiras‐Mendez Roberto , Riva‐Meana Concepción , Córdoba‐Fernández Andrés 
Published: March 2003

AbstractSingle cell activity recorded in the subthalamic nucleus (STN) of Parkinson's patients and the effect of tremor, passive and voluntary movement upon the same cells are described. Three types of cells were distinguished by the pattern of discharge: tonic, phasic and rhythmic. They all demonstrated high mean firing rates (65, 59 and 69 Hz, respectively). Simultaneous recordings of muscle activity and tremor helped in defining cell activity. The implantation of the definitive stimulating electrode in the patients was based on the number of STN cells related to tremor, active and passive movements (mean = 68%) along the track chosen. Cells were related to tremor (n = 21; 11%), modified the discharge with differences in the amplitude of tremor (n = 4), and changed the rate and pattern when tremor stopped spontaneously or artificially (n = 6). Movement‐related cells (n = 97; 51%) showed a cyclic activity correlated with phases of the movement, or modified the firing rate along the performance of the movement. Tremor and movement‐related cells (n = 11; 6%) revealed an interesting sensory‐motor integrative function.
Enhanced seizures and hippocampal neurodegeneration following kainic acid‐induced seizures in metallothionein‐I + II‐deficient mice
Authors: Carrasco Javier , Penkowa Milena , Hadberg Hanne , Molinero Amalia , Hidalgo Juan 
Published: March 2003

AbstractMetallothioneins (MTs) are major zinc binding proteins in the CNS that could be involved in the control of zinc metabolism as well as in protection against oxidative stress. Mice lacking MT‐I and MT‐II (MT‐I + II deficient) because of targeted gene inactivation were injected with kainic acid (KA), a potent convulsive agent, to examine the neurobiological importance of these MT isoforms. At 35 mg/kg KA, MT‐I + II deficient male mice showed a higher number of convulsions and a longer convulsion time than control mice. Three days later, KA‐injected mice showed gliosis and neuronal injury in the hippocampus. MT‐I + II deficiency decreased both astrogliosis and microgliosis and potentiated neuronal injury and apoptosis as shown by terminal deoxynucleotidyl transferase‐mediated in situ end labelling (TUNEL), detection of single stranded DNA (ssDNA) and by increased interleukin‐1β‐converting enzyme (ICE) and caspase‐3 levels. Histochemically reactive zinc in the hippocampus was increased by KA to a greater extent in MT‐I + II‐deficient compared with control mice. KA‐induced seizures also caused increased oxidative stress, as suggested by the malondialdehyde (MDA) and protein tyrosine nitration (NITT) levels and by the expression of MT‐I + II, nuclear factor‐κB (NF‐κB), and Cu/Zn‐superoxide dismutase (Cu/Zn‐SOD). MT‐I + II deficiency potentiated the oxidative stress caused by KA. Both KA and MT‐I + II deficiency significantly affected the expression of MT‐III, granulocyte‐macrophage colony stimulating factor (GM‐CSF) and its receptor (GM‐CSFr). The present results indicate MT‐I + II as important for neuron survival during KA‐induced seizures, and suggest that both impaired zinc regulation and compromised antioxidant activity contribute to the observed neuropathology of the MT‐I + II‐deficient mice.