bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Characterization and Modulation of Feedback Inhibitory Circuits in Area CA3 of Rat Hippocampal Slice Cultures
Authors: Fortunato Christian , Debanne Dominique , Scanziani Massimo , Gähwiler Beat H. , Thompson Scott M. 
Published: April 2006

AbstractFeedback inhibitory circuits were characterized electrophysiologically in the CA3 region of organotypic rat hippocampal cultures. Pyramidal cells were impaled with sharp microelectrodes and brief depolarizing current pulses were injected intracellularly to elicit single action potentials. An inhibitory postsynaptic potential (I PSP) was observed at fixed latency after the action potential in 27% of impaled cells (n= 131). These IPSPs were fully blocked by bicuculline, indicating that they were mediated solely by γ‐aminobutyric acid type A (GABAA) receptors. They were also blocked by 6‐cyano‐7‐nitro‐quinoxaline‐2, 3‐dione but not d‐2‐amino‐5‐ phosphonovalerate, indicating that non‐N‐methyl‐d‐asparttate receptors were necessary and sufficient for activating interposed GABAergic interneurons. Adenosine (0.1‐5 μM) increased the percentage of action potentials that were not followed by IPSPs by reducing the probability of glutamatergic activation of the interneurons. In 18 of 21 experiments adenosine also decreased the mean amplitude of successfully elicited IPSPs, indicating that more than one interneuron participated in the feedback inhibition of those pyramidal cells. In three experiments the non‐failure IPSP amplitude was not affected by adenosine, suggesting that only one interneuron participated. Repetitive stimulation at 2‐4 Hz decreased the amplitude of non‐failure feedback IPSPs and usually increased the number of failures of transmission. These effects were transient and insensitive to the GABAB antagonist CGP 35 348. We conclude that both the excitation of interneurons and the release of GABA from interneurons are modulated by repetitive stimulation.
Characterization of a Barium‐sensitive Outward Current following Glutamate Application on Rat Midbrain Dopaminergic Cells
Authors: Mercuri Nicola B. , Bonci Antonello , Calabresi Paolo , Bernardi Giorgio 
Published: April 2006

AbstractUsing intracellular electrophysiological recordings in dopaminergic (principal) neurons of the rat mesencephalon maintained in vitro, we studied a postexcitatory amino acid response (PEAAR). Under current‐clamp mode, bath application of glutamate produced a depolarization that was followed by a hyperpolarization when the perfusion of the excitatory amino acid was discontinued. Under single‐microelectrode voltage‐clamp mode, an outward current followed the glutamate‐induced inward current. The PEAAR was associated with an increase in membrane conductance and reversed polarity at about ‐85 mV (2.5 mM extracellular K+). The null potential for the PEAAR was independent of the intracellular loading of chloride ions and was shifted towards less negative values (˜23 mV) by increasing extracellular K+ from 2.5 to 8.5 mM. The PEAAR was present in neurons treated with tetraethylammonium (5–10 mM), apamin (1 μM) or glibenclamide (1–300 μM). However, it was strongly depressed or blocked by extracellular barium (300 μM to 1 mM), by low‐calcium (0.5 mM) plus cadmium (100 μM) or magnesium (10 mM), and by low‐sodium solutions. An outward response was also generated after an inward current induced by the perfusion of the specific agonists for the ionotropic excitatory amino acid receptors NMDA, a‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole (AMPA) and kainate. The PEAAR was not affected by tetrodotoxin (1 μM), saclofen (100–300 μM), bicuculline (30 μM), sulpiride (1 μM) or strychnine (1 μM). In addition, the inhibition of the ATP‐dependent Na+‐K+ pump by ouabain and strophanthidin (1–10 μM) prolonged the glutamate‐induced membrane depolarization/inward current while the subsequent PEAAR was reduced or not observed. Our data indicate that the PEAAR mainly results from the activation of a barium‐sensitive potassium current. This response might limit the excitatory and eventually neurotoxic effects of glutamate.
Contrast‐dependent Dissociation of Visual Recognition and Detection Fields
Authors: Strasburger Hans , Rentschler Ingo 
Published: April 2006

AbstractSeeing an object‘as something’is different from simply seeing it (see Watanabe, S., 1985, Pattern Recognition: Human and Mechanical, John Wiley). This distinction between recognition and detection often goes unnoticed in physiology and clinical practice, where visual performance is characterized in terms of acuity, visual field and contrast sensitivity. The corresponding functions of stimulus detection are consistent with the neural projection properties from the retina to the striate cortex, i.e. the‘cortical magnification theory’. Yet recognition performance for characters (Strasburger, H. et al., 1994, Eur. J. Neurosci., 6, 1583‐1588) and grey‐level patterns (Jüttner, M. and Reutschler, I., 1996, Vision Res., 36, 1007–1022) does not fit into this scheme. Here we show that this discrepancy results in the dissociation of visual recognition and detection fields, which is dramatic at low pattern contrast. Form proper can be appreciated exclusively within the much narrower field of recognition, the window of visual intelligence. Its function is, at low contrast, probably mediated by the magnocellular pathway and at all contrasts is determined by the processing characteristics of higher stages of the ventral visual pathway.
Recombinant Human Adenovirus with Rat MIP‐2 Gene Insertion Causes Prolonged PMN Recruitment to the Murine Brain
Authors: Bell M. D. , Taub D. D. , Kunkel S. J. , Strieter R. M. , Foley R. , Gauldie J. , Perry V. H. 
Published: April 2006

AbstractSingle injections of recombinant cytokines/chemokines into tissue have provided insights into their possible roles during the inflammatory response. Adenoviral technology may allow us to mimic the in vivo situation more closely, with protein generated in a continuous but transient fashion. Replication‐deficient human type 5 adenovirus containing a rat macrophage inflammatory protein‐2 (MIP‐2) gene insertion and cytomegalovirus promoter was injected into the mouse brain to investigate the inflammatory response to continuous overproduction of MIP‐2. Adenovirus with a LacZ gene insertion expressing β‐galactosidase was used as a control. At doses of 104 to 107 plaque‐forming units, a minimal inflammatory response was detected to the LacZ virus, with leukocyte recruitment that was restricted to the injection site. A dose of 107 plaque‐forming units of both the LacZ and the MIP‐2 vector produced extensive transgene product expression that persisted for at least 7 days. Astrocytes, recognized by their morphology, were the predominant cell type expressing MIP‐2 and β‐galactosidase. A dose of 107 plaque‐forming units of MIP‐2 vector caused dramatic polymorphonuclear leukocyte (PMN) recruitment to the brain parenchyma after 2 days. PMN recruitment was still observed after 4 and 7 days, but had become more localized to the injection site and was associated with numerous foam‐like macrophages. At both 2 and 7 days the blood‐brain barrier was breached in the region of leukocyte recruitment. Despite the extent of leukocyte recruitment there were no overt signs of neuronal degeneration or demyelination. Our findings demonstrate that continuous production of MIP‐2 in the CNS results in persistent PMN recruitment to the brain parenchyma with no evidence of tachyphylaxis. The lack of PMN recruitment to the brain parenchyma following CNS injury may be a result of deficient production of PMN chemoattractants.
Involvement of p53 in DNA Strand Break‐induced Apoptosis in Postmitotic CNS Neurons
Authors: Enokido Yasushi , Araki Toshiyuki , Tanaka Kiyoji , Aizawa Shinichi , Hatanaka Hiroshi 
Published: April 2006

AbstractThe tumour suppressor p53 gene serves as a critical regulator of the cell cycle and of apoptosis following the exposure of normal cells to DNA damage. To examine the role of p53 in postmitotic CNS neurons, we cultured cerebellar neurons from normal wild‐type mice and mutant p53‐null mice under various conditions inducing neuronal death. When cerebellar neurons from 15‐ to 16‐day postnatal wild‐type mice were treated with ionizing radiation or DNA‐damaging agents, massive neuron death occurred after 24‐72 h. In contrast, neurons from p53+ mice evidently resisted γ‐irradiation and some DNA‐damaging agents, such as etoposide and bleomycin. On the other hand, low‐K+ medium‐induced apoptosis of cerebellar neurons was not affected by p53 status. Neither cell cycle progression nor DNA synthesis occurred during cell death induced by γ‐irradiation and low‐K+ medium, as well as in normal cultures of p53+/+ and p53‐/‐ neurons. These results suggest that p53 is required for the apoptotic death of postmitotic cerebellar neurons induced by DNA strand breaks.
Effect of Feedback from Peripheral Movements on Neuron Activity in the Aplysia Abdominal Ganglion
Authors: Höpp H. P. , Falk C. X. , Cohen L. B. , Wu J. Y. , Cohen A. I. 
Published: April 2006

AbstractWe have made reasonably comprehensive measurements of action potential activity in the Aplysia californica abdominal ganglion to determine the amount of feedback the central nervous system (CNS) receives from a movement which it initiates. Voltage‐sensitive dye measurements of action potential activity of cells in the ganglion were made during the gill‐withdrawal reflex elicited by siphon stimulation. We compared recordings in two situations which differed dramatically in the amount the gill moved. In the control sea water, the gill withdrawal was normal; in low‐Ca2+, high‐Mg2+ sea water, the gill movement was blocked. Both the timing and the number of spikes of the individual neurons were similar in the two situations. Histograms of the summed spike activity versus time and histograms of the number of active neurons versus time in the two conditions were also similar. Finally, two numerical measures of trial‐to‐trial differences, a paired t‐test and a measure we named fractional similarity, did not indicate larger differences between two trials in the different sea waters than two trials in the same sea water. Feedback from sensory neurons activated by the gill movement itself does not make a large contribution to the spike activity in the abdominal ganglion. Apparently the Aplysia CNS issues the command for the withdrawal and does not make adjustments for the magnitude of the actual withdrawal. It may not even receive the information necessary for such adjustments to be made. A second motivation for these experiments was to test whether removing the feedback might simplify the neuronal activity that occurs during the gill‐withdrawal reflex. This did not occur.
Morphological and Biochemical Changes in Neurons: Apoptosis versus Mitosis
Authors: Philpott Karen L. , McCarthy Mary Jane , Becker David , Gatchalian Christine , Rubin Lee L. 
Published: April 2006

AbstractApoptosis and mitosis are often thought to share certain morphological similarities and therefore to be regulated by similar sets of enzymes. In this study, the Golgi apparatus and nuclear lamina were examined in PC12 cells and rat superior cervical ganglion neurons undergoing apoptosis in response to withdrawal of nerve growth factor or addition of staurosporine. We found that the Golgi apparatus disperses during apoptosis, without obvious degradation, in a manner similar to that occurring in mitosis. In contrast, the nuclear lamina did not become completely solubilized during apoptosis, as occurs in mitosis, but remained as a distinct structure around the nucleus, although some degradation of nuclear lamins was seen. To assess the integrity of the nuclear envelope, fluorescent probes were introduced into the cytoplasm of live and dying cells. High molecular weight tracers were still excluded from the nuclei of apoptotic cells, demonstrating the continued existence of a functional nuclear barrier. These data suggest, therefore, that cell death is unlikely to occur simply as a result of inappropriate activation of cell cycle enzymes.
Activity‐dependent Decay of Early LTP Revealed by Dual EPSP Recording in Hippocampal Slices from Young Rats
Authors: Xiao Min‐Yi , Niu Yin‐Ping , Wigström Holger 
Published: April 2006

AbstractThe early maintenance of long‐term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12‐ to 18‐day‐old rats in a low‐magnesium solution (0.1 mM). The α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) and N‐methyl‐D‐aspartate (NMDA) receptor‐mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(‐)‐2‐amino‐5‐phosphonopentanoic acid (50μM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 μM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity‐dependent and NMDA‐dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long‐term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one.
Inhibition of N‐type Calcium Channels: The Only Mechanism by which Presynaptic α2‐Autoreceptors Control Sympathetic Transmitter Release
Authors: Boehm Stefan , Huck Sigismund 
Published: April 2006

Abstractα2‐Adrenoceptors are known to inhibit voltage‐dependent Ca2+ channels located at neuronal cell bodies; the present study investigated whether this or alternative mechanisms, possibly downstream of Ca2+ entry, underlie the presynaptic α2‐adrenergic modulation of transmitter release from chick sympathetic neurons. Using chick sympathetic neurons, overflow of previously incorporated [3H]noradrenaline was elicited in the presence of extracellular Ca2+ by electrical pulses, 25 mM K+ or 10μM nicotine, or by adding Ca2+ to otherwise Ca2+‐free medium when cells had been made permeable by the calcium ionophore A23187 or by α‐latrotoxin. Pretreatment of neurons with the N‐type Ca2+ channel blocker ω‐conotoxin GVIA and application of the α2‐adrenergic agonist UK 14304 reduced the overflow elicited by electrical pulses, K+ or nicotine, but not the overflow caused by Ca2+ after permeabilization with α‐latrotoxin or A23187. In contrast, the L‐type Ca2+ channel blocker nitrendipine reduced the overflow due to K+ and nicotine, but not the overflow following electrical stimulation or α‐latrotoxin‐ and A23187‐permeabilization. The inhibition of electrically evoked overflow by UK 14304 persisted in the presence of nitrendipine and the L‐type Ca2+ channel agonist BayK 8644, which per se enhanced overflow. In ω‐conotoxin GVIA‐treated cultures, electrically evoked overflow was also enhanced by BayK 8644 and almost reached the value obtained in untreated neurons. However, UK 14304 lost its effect under these conditions. Whole‐cell recordings of voltage‐activated Ca2+ currents corroborated these results: UK 14304 inhibited Ca2+ currents by 33%, nitrendipine caused a 7% reduction, and BayK 8644 increased the currents by 30%. Moreover, the dihydropyridines failed to abolish the inhibition by UK 14304, but pretreatment with ω‐conotoxin GVIA, which reduced mean amplitude from 0.95 to 0.23 nA, entirely prevented α2‐adrenergic effects. Our results indicate that the α2‐autoreceptor‐mediated modulation of noradrenaline release from chick sympathetic neurons relies exclusively on the inhibition of ω‐conotoxin GVIA‐sensitive N‐type Ca2+ channels. Mechanisms downstream of these channels and voltage‐sensitive Ca2+ channels other than N‐type appear not to be important.
Transient Brain Ischaemia Provokes Ca2+, PIP2 and Calpain Responses Prior to Delayed Neuronal Death in Monkeys
Authors: Yamashima Tetsumori , Saido Takaomi C. , Takita Masatoshi , Miyazawa Atsuo , Yamano Jun , Miyakawa Atsuo , Nishijyo Hisashi , Yamashita Junkoh , Kawashima Seiichi , Ono Taketoshi , Yoshioka Tohru 
Published: April 2006

AbstractTo clarify the mechanism of postischaemic delayed cornu Ammonis (CA)‐1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5‐bisphosphate (PIP2) and Ca2+ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia‐hypoglycaemia of hippocampal acute slices. The CA‐1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA‐1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated μ‐calpain demonstrated μ‐calpain activation specifically in the CA‐1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA‐1 neurons by immunohistochemistry. CA‐1 neurons on day 1 showed sustained activation of μ‐calpain, and increased immunostaining for inactivated and activated forms of μ‐ and m‐calpains and for PIP2. Activated μ‐calpain and PIP2 were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia‐hypoglycaemia in vitro provoked intense Ca2+ mobilization with increased PIP2 immunostaining specifically in CA‐1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca2+ and PIP2 breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA‐1 neuronal death.
Localization and Axotomy‐induced Regulation of the Peptide Secretoneurin in the Rat Superior Cervical Ganglion
Authors: Klimaschewski Lars , Kroesen Stephan , Eder Ursula , Leitner Bernd , Fischer‐Colbrie Reiner 
Published: April 2006

AbstractThis study demonstrates the localization and regulation of a novel neuropeptide of 33 amino acids, secretoneurin (SN), in the rat superior cervical ganglion. Gel filtration chromatography of ganglion proteins followed by a specific radioimmunoassay revealed that SN is the predominant cleavage product of secretogranin II, a member of the chromogranin/secretogranin protein family, in adult ganglia. SN was detected within the majority of nerve endings surrounding postganglionic neurons that were identified by the presence of synaptophysin and, in part, colocalized leu‐encephalin. Applying immuno‐electronmicroscopy, SN was localized to large dense core vesicles of neuronal and small intensely fluorescent (SIF) cells. In situ hybridization revealed the presence of secretogranin II mRNA in postganglionic neurons and, to a lesser extent, in SIF cells. One week after transection of the postganglionic branches SN levels were not significantly altered; however, a decrease of secretogranin II mRNA was observed in postganglionic neurons but not in SIF cells. After decentralization of the ganglion, SN‐immunoreactive nerve terminals disappeared and intraganglionic SN levels were reduced by 70%, indicating the preganglionic origin of SN‐positive nerve fibres and varicosities. Secretogranin II mRNA was slightly reduced under this condition. Combined axotomy and decentralization further diminished intraganglionic secretogranin II mRNA, although peptide levels increased significantly above control values under these conditions. Double‐labelling immunofluorescence with antibodies against the somatodendritic marker microtubule‐associated protein 2 (MAP2) revealed that the increase in SN immunoreactivity was due to an accumulation of SN in axonal processes of postganglionic neurons. SN immunoreactivity was also detected in dissociated neonatal superior cervical ganglion cultures and increased significantly upon treatment with nerve growth factor, the survival and differentiation factor of sympathetic neurons during perinatal development. Co‐culture with non‐neuronal cells or addition of leukaemia inhibitory factor, a cytokine known to stimulate synthesis of various peptides after nerve transection, did not influence SN immunoreactivity. Therefore, since no fixed relationship between SN and any of the known neuropeptides or neurotransmitters expressed in sympathetic neurons was observed, the expression of this novel peptide appears to be independently regulated.
Activation of Multi‐modal Cortical Areas Underlies Short‐term Memory
Authors: Klingberg Torkel , Kawashima Ryuta , Roland Per E. 
Published: April 2006

AbstractWe wanted to examine whether there are cortical fields active in short‐term retention of sensory information, independent of the sensory modality. To control for selective attention, response selection and motor output, the cortical activity during short‐term memory (STM) tasks was compared with that during detection (DT) tasks. Using positron emission tomography and [15O]‐butanol as a tracer, we measured the regional cerebral blood flow in ten subjects during three STM tasks in which the subjects had to keep in mind: (i) the pitch of tones; (ii) frequencies of a vibrating stylus; and (iii) luminance levels of a monochrome light. Another group of ten subjects undertook three tasks in which subjects detected changes in similar stimuli. Six cortical fields were significantly more activated during STM than during DT. These fields were activated irrespective of sensory modality, and were located in the left inferior frontal gyrus, right superior frontal gyrus, right inferior parietal cortex, anterior cingulate, left frontal operculum and right ventromedial prefrontal cortex. Since the DT tasks and the STM tasks differed only with respect to the STM component, we conclude that the neuronal activity specifically related to retention of the stimuli during the delays was located in these six multi‐modal cortical areas. Since no differences were observed in the sensory‐specific association cortices, the results indicate further that the activity in the sensory‐specific association cortices due to selective attention is not different from the activity underlying short‐term retention of sensory information.