bluuebunny/crossref_metadata_2025_split huggingface dataset:
Release of Serotonin in the Rat Locus Coeruleus: Effects of Cardiovascular, Stressful and Noxious Stimuli
Authors: Singewald Nicolas , Kaehler Stefan , Hemeida Ramadan , Philippu Athineos 
Published: April 2006

AbstractTo investigate the function of serotonergic neurons within the locus coeruleus, this brain nucleus of conscious, freely moving rats was superfused with artificial cerebrospinal fluid through a push‐pull cannula and the extracellular concentration of serotonin was determined in the superfusate. Serotonin release was increased by depolarization with veratridine (5 μM) or 80 mM K+, while superfusion with tetrodotoxin (1 μM) or systemic administration of 8–hydroxy‐2–(di‐n‐propylamino)tetralin substantially diminished the release rate of serotonin in the locus coeruleus. The pressor response to intravenous infusion of noradrenaline (4 μg/kg/min) was associated with a pronounced increase in the release rate of serotonin. Superfusion of the locus coeruleus with tetrodotoxin (1 μM) abolished the increase in serotonin release evoked by the pressor response. A fall of blood pressure produced by intravenous administration of nitroprusside (150 μg/kg/min) or chlorisondamine (3 mg/kg) diminished the release rate of serotonin. Immobilization, noise (95 dB) or tail pinch increased the release of serotonin in the locus coeruleus and slightly elevated blood pressure. Chlorisondamine abolished the rise in blood pressure elicited by tail pinch without influencing the increased serotonin release. Tail pinch‐induced serotonin release was abolished by superfusion with tetrodotoxin. The findings demonstrate that neuronal serotonin release in the locus coeruleus responds to cardiovascular and sensory stimuli, suggesting a function of serotonergic neurons in central blood pressure regulation, as well as in the modulation of locus coeruleus activity by stress and noxious stimuli.
Electrophysiological Effects of Temporary Deafferentation on Two Characterized Cell Types in the Nucleus Gracilis of the Rat
Authors: Panetsos Fivos , Nuñez Angel , Avendaño Carlos 
Published: April 2006

AbstractSingle‐ and multiunit recordings were made in the nucleus gracilis of anaesthetized rats in order to study the characteristics of the responses to natural cutaneous stimulation before and during local anaesthetic‐induced deafferentation. Two types of cells were found which exhibited different electrophysiological features at rest and in response to stimulation of their receptive fields (RFs). Low‐frequency (LF) neurons (77%) had very low spontaneous activity, and most could be antidromically activated from the medial lemniscus. High‐frequency (HF) cells (23%) had a much higher spontaneous discharge rate, with shorter spike duration, and did not project through the lemniscus. Both cell types generated phasic responses with similar latencies following cutaneous stimulation. Recordings of lemniscal axons had similar characteristics to those of LF neurons. Within minutes after anaesthetizing the functional centre of the RF, the LF and HF cells displayed new RFs, and enhanced responses to stimuli delivered at the periphery of the original fields. Firing rates increased during anaesthesia, but only in LF cells. Using a paired‐stimulation paradigm, many LF neurons displayed during anaesthesia a decrease of the normal inhibition that the conditioning stimulus evoked on the responses to the test stimulus; the opposite effect was observed in all HF cells. These results suggest that (i) LF neurons correspond to thalamic projection cells, and HF neurons may be inhibitory interneurons; (ii) by disinhibiting LF (but not HF) cells, temporary deafferentation may increase neuronal responsiveness to peripheral stimulation, and thus contribute to reveal new RFs, and (iii) these changes in the nucleus gracilis may partly account for the reorganization of representational maps at higher levels of the somatosensory pathways.
Interneurons in the Hippocampal Dentate Gyrus: an In Vivo intracellular Study
Authors: Sik Attila , Penttonen Markku , Buzsáki György 
Published: April 2006

AbstractInterneurons in the dentate area were characterized physiologically and filled with biocytin in urethane‐anaesthetized rats. On the basis of axonal targets the following groups could be distinguished. (i) Large multipolar interneurons with spiny dendrites in the deep hilar region densely innervated the outer molecular layer and contacted both granule cells and parvalbumin‐positive neurons (hilar interneuron with perforant pathway‐associated axon terminals; HIPP cells). (ii) A pyramidal‐shaped neuron with a cell body located in the subgranular layer innervated mostly the inner molecular layer and the granule cell layer (hilar interneuron with commissural‐associational pathway‐associated axon terminals; HICAP cell). It contacted both granule cells and interneurons. Axon collaterals of HIPP and HICAP neurons covered virtually the entire Septo‐temporal extent of the dorsal dentate gyrus. (iii) Calbindin‐immunoreactive neurons with horizontal dendrites in stratum oriens of the CA3c region gave rise to a rich axon arbor in strata oriens, pyramidale and radiatum and innervated almost the entire extent of the dorsal hippocampus, with some collaterals entering the subicular area (putative trilaminar cell). (iv) Hilar basket cells innervated mostly the granule cell layer and to some extent the inner molecular layer and the CA3c pyramidal layer. HIPP and trilaminar interneurons could be antidromically activated by stimulation of the fimbria. Only the HICAP cells could be monosynaptically discharged by the perforant path input. All interneurons examined showed phase‐locked activity to the extracellularly recorded theta/gamma oscillations or to irregular dentate electroencephalogram spikes. These observations indicate that the interconnected interneuronal system plays a critical role in coordinating population activity of the dentate gyrus and Ammon's horn.
Effects of a Cognition‐enhancer, Linopirdine (DuP 996), on M‐type Potassium Currents (IK(M)) Some Other Voltage‐ and Ligand‐gated Membrane Currents in Rat Sympathetic Neurons
Authors: Lamas J. Antonio , Selyanko A. A. , Brown D. A. 
Published: April 2006

AbstractLinopirdine is a cognition enhancer which augments depolarization‐induced transmitter release in the cortex and which is under consideration for potential treatment of Alzheimer's disease. It has previously been reported to inhibit M‐type K+ currents in rat hippocampal neurons. In the present experiments we have tested its effect on whole‐cell M‐currents and single M‐channels, and on a range of other membrane currents, in dissociated rat superior cervical sympathetic ganglion cells. Linopirdine inhibited the whole‐cell M‐current with an IC50 of 3.4 μM and blocked M‐channels recorded in excised outside‐out membrane patches but not in inside‐out patches. This suggests that linopirdine directly blocks M‐channels from the outside. It was much less effective in inhibiting other voltage‐gated potassium currents [delayed rectifier (IK(v)), IC50 63 μM; transient (IA) current, IC50 69 μM] and produced no detectable inhibition of the fast and slow Ca2+‐activated K+ currents Ic and IAHP or of a hyperpolarization‐activated cation current (IQ/Ih), at 10–30 μM. However, it reduced acetylcholine‐activated nicotinic currents and GABA‐activated Cl‐ currents with IC50 values of 7.6 and 26 μM respectively. It is concluded that linopirdine shows some 20–fold selectivity for M‐channels among different K+ channels but can also block some transmitter‐gated channels. The relationship between M‐channel block and the central actions of linopirdine are discussed.
Pharmacological and Physiological Characterization of Murine Homomeric β3 GABAA Receptors
Authors: Wooltorton Julian R. A. , Moss Stephen J. , Smart Trevor G. 
Published: April 2006

Abstractγ‐Aminobutyric acid (GABAa) receptor β3 subunits were expressed in Xenopus laevis oocytes and studied using two‐electrode voltage clamp. Injected oocytes exhibited an increased resting membrane conductance and more depolarized membrane potentials compared to uninjected control cells. Oocytes expressing β3 subunits were insensitive to GABA and muscimol, but pentobarbitone increased the membrane conductance in a concentration‐dependent manner. The membrane current response to pentobarbitone reversed at the Cl−equilibrium potential and at relatively high concentrations (>500 μM), a rebound CI− current was induced following the removal of pentobarbitone. In transfected human embryonic kidney (HEK) cells, the rebound current amplitude was reduced by desensitizing the β3 receptor with increased durations of ligand application. Both picrotoxin (0.5 nM to 10 μM) and Zn2+ (10 nM to 100 μM) reduced the resting membrane conductance for β3 cDNA‐injected oocytes. These oocytes were insensitive to flurazepam (5 μM) and alphaxalone (10 μM), but responded with increased membrane conductance to propofol (10 μM) and pregnanolone (50 nM to 5 μM). The antagonists, bicuculline (10 μM) and strychnine (50 nM to 100 μM), also induced conductance increases in a concentration dependent manner; however, glycine (1 mM) was inactive. It was concluded that β3 subunits form spontaneously opening ion channels that can be up‐regulated by some allosteric modulators, principally by pentobarbitone and propofol and, surprisingly, by bicuculline and strychnine, whilst picrotoxin and Zn2+ acted as antagonists. Computer modelling of some kinetic schemes was used to describe the rebound current observed in transfected HEK cells. This indicated that pentobarbitone, after modulation of the conductance, is potentially capable of further binding to the β3 receptor complex ‘driving’ the receptor into one or more desensitized states. This phenomenon may be of some importance for native neuronal GABAA receptors, where pentobarbitone can also evoke rebound current activation.
Neurosteroids: Expression of Functional 3β‐Hydroxysteroid Dehydrogenase by Rat Sensory Neurons and Schwann Cells
Authors: Guennoun R. , Schumacher M. , Robert F. , Delespierre B. , Gouézou M. , Eychenne B. , Akwa Y. , Robel P , Baulieu E. E. 
Published: April 2006

AbstractSteroids which are synthesized within the nervous system, such as progesterone, have been termed ‘neurosteroids’. Levels of progesterone are much larger in peripheral nerves of rats and mice than in plasma, and persist after removal of the steroidogenic endocrine glands. Schwann cells are a source of progesterone: when isolated from embryonic dorsal root ganglia, they can synthesize progesterone from pregnenolone, the obligate precursor of all steroids. Locally produced progesterone has been shown to play an important role in myelination of peripheral nerve. We show here that sensory neurons from embryonic dorsal root ganglia also express 3β‐hydroxysteroid dehydrogenase and can convert [3H]pregnenolone to [3H]progesterone. Moreover, when cultured under different conditions and incubated for 24 h in the presence of 100 nM [3H]pregnenolone, they produce 5–10 times more [3H]progesterone than Schwann cells. The conversion of pregnenolone to progesterone by neurons is further increased by a diffusible factor produced by Schwann cells. Sensory neurons can also metabolize progesterone to 5α‐dihydroprogesterone, but unlike Schwann cells, they do not produce 3α,5α‐tetrahydroprogesterone, a potent positive allosteric modulator of γ‐aminobutyric acid type A receptors. We also show that cells isolated from the adult nervous system still have the capacity to convert [3H]pregnenolone to progesterone and its 5α‐reduced metabolites: neurons and Schwann cells purified from dorsal root ganglia of 6 week old male rats show a similar pattern of pregnenolone metabolism to cells isolated from 18 day old embryos. These findings further support the important role of progesterone in the development and regeneration of the peripheral nervous system.
Interneurons Immunoreactive for Vasoactive Intestinal Polypeptide (VIP) are Extensively Innervated by Parvalbumin‐Containing Boutons in Rat Primary Somatosensory Cortex
Authors: Staiger Jochen F. , Freund Tamás F. , Zilles Karl 
Published: April 2006

AbstractSensory perception results from the synchronized action of large ensembles of cortical neurons. Receptive field properties of such neurons in sensory areas strongly depend on circuits utilizing the inhibitory amino acid transmitter γ‐aminobutyric acid (GABA). GABAergic neurons often co‐localize neuropeptides and/or calcium‐binding proteins in a cell‐type specific manner. We have taken advantage of this fact to study the synaptic circuitry involving presynaptic parvalbumin‐containing boutons (originating from horizontally extensive basket cells) and postsynaptic VlP‐immunoreactive GABAergic targets which mostly have a vertically oriented axonal field. Abundant appositions between parvalbumin‐immunoreactive boutons and all VIP‐stained neurons were observed at the light microscopic level. The numbers of contacts ranged between three and well over 20 for single VIP cells. The higher numbers were especially frequent in the supragranular and granular layers contacting the numerous bipolar, as well as multipolar VIP cells located there; but the VlP‐immunoreactive neurons in the infragranular layers were also targeted by parvalbumin‐immunoreactive boutons without exception, albeit in more variable, mostly lower numbers. Correlated electron microscopic investigations revealed that virtually all of these light microscopically observed appositions resembled symmetric synaptic specializations. The vast majority were located on the soma or proximal dendrites of the VIP‐positive neurons. Since pyramidal cells, in turn, represent a major target for the parvalbumin and VIP synapses, the activation of these synapses may lead to coherent oscillations providing the necessary clock function to synchronize pyramidal cell discharges, both across and within cortical columns.
Evidence That Agrin directly Influences Presynaptic Differentiation at Neuromuscular Junctions In Vitro
Authors: Campagna Jason A. , Ruegg Markus A. , Bixby John L. 
Published: April 2006

AbstractThe synaptic protein agrin is required for aspects of both pre‐ and postsynaptic differentiation at neuromuscular junctions. Although a direct effect of agrin on postsynaptic differentiation, presumably through the MuSK receptor, is established, it is not clear whether agrin directly affects the presynaptic nerve. To provide evidence on this point, we used anti‐agrin IgG to disrupt agrin function in chick ciliary ganglion (CG) neuron/myotube cocultures. In cocultures grown in the presence of 200 μg/ml anti‐agrin IgG, clustering of acetylcholine receptors (AChRs), extracellular matrix proteins, and the synaptic vesicle protein synaptotagmin (syt) at nerve‐muscle contacts was inhibited. Syt clustering was still inhibited in the presence of 100 μg/ml blocking antibody, while the postsynaptic clustering of AChRs, heparan sulphate proteoglycan, and s‐laminin was retained. Additionally, in CG neurons cultured with COS cells expressing agrin A0B0, which lacks the ability to signal postsynaptic differentiation, syt clustering was induced and this clustering was also blocked by anti‐agrin IgG. Our results demonstrate that agrin function is acutely required for pre‐ and postsynaptic differentiation in vitro, and strongly suggest that agrin is directly involved in the induction of presynaptic differentiation.
Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption
Authors: Oitzl Melly S. , de Kloet E. Ron , Joëls Marian , Schmid Wolfgang , Cole Timothy J. 
Published: April 2006

AbstractPrevious studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild‐type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform‐directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild‐type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor‐related long‐term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor‐mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor‐mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site‐specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor‐knockout mice present the only animal model for the study of corticosteroid‐mediated effects in the complete absence of a functional receptor.
Stabilization of Dendritic mRNAs by Nitric Oxide Allows Localized, Activity‐dependent Enhancement of Hippocampal Protein Synthesis
Authors: Morris Brian J. 
Published: April 2006

AbstractA small number of mRNA species are not restricted to the neuronal cell body, but are also present in neuronal dendrites. The levels of two of these dendritic mRNAs, encoding the microtubule‐associated protein MAP2 and the a subunit of calcium/calmodulin‐dependent protein kinase II (CamKllα), are increased rapidly by high‐frequency synaptic activity or by release of nitric oxide. To test the hypothesis that post‐transcriptional mechanisms might contribute to this modulation, primary cultures of rat hippocampal neurons were exposed tos‐nitroso‐N‐acetyl penicillamine (SNAP, 200 μM) or vehicle, and mRNA stability was determined. The stability of both CamKllá mRNA and MAP2 mRNA was increased by SNAP treatment, whereas the stabilities of tubulin T26 mRNA and proenkephalin mRNA were unaffected. When the intensity of staining for MAP2 immunoreactivity and CamKllα immunoreactivity was monitored in cultured hippocampal neurons, nitric oxide‐releasing agents induced increases in staining intensity that were dependent on protein synthesis but not on mRNA synthesis. These results show that nitric oxide can selectively stabilize CamKllα mRNA and MAP2 mRNA, leading to increased synthesis of the corresponding proteins. This demonstrates a mechanism whereby the presence of a particular mRNA in the vicinity of a synapse permits the levels of the protein product to be regulated by synaptic activity in a manner that is both prolonged and also highly localized to the region of stimulation. Thus, the dependence of sustained synaptic plasticity onde novoprotein synthesis need not entail a loss of anatomical specificity.
Membrane Currents Influencing Action Potential Latency in Granule Neurons of the Rat Cochlear Nucleus
Authors: Rusznák Zoltán , Forsythe Ian D. , Brew Helen M. , Stanfield Peter R. 
Published: April 2006

AbstractGranule cells are the most numerous neurons in the cochlear nucleus, but, because of their small size, little information on their membrane properties and ionic currents is available. We used an in vitro slice preparation of the rat ventral cochlear nucleus to make whole‐cell recordings from these cells. Under current clamp, some granule neurons fired spontaneous action potentials and all generated a train of action potentials on depolarization (threshold current, 10–35 pA). Hyperpolarization increased the latency to the first action potential evoked during a subsequent depolarization. We examined which voltage‐gated currents might underlie this latency shift. In addition to a fast inward Na+ current, depolarization activated two outward potassium currents. A transient current was rapidly inactivated by membrane potentials positive to ‐60 mV, while a second, more slowly inactivating current was observed following the decay of the transient current. No hyperpolarization‐activated conductances were observed in these cells. Modelling of the currents suggests that removal of inactivation on hyperpolarization accounts for the increased action potential latency in granule cells. Such a mechanism could account for the ‘pauser’‐type firing patterns of the fusiform cells which receive a prominent projection from the granule cells in the dorsal cochlear nucleus.
Glutamate Metabotropic Receptor Agonists Depress Excitatory and Inhibitory Transmission on Rat Mesencephalic Principal Neurons
Authors: Bonci Antonello , Grillner Pernilla , Siniscalchi Antonio , Mercuri Nicola B. , Bernardi Giorgio 
Published: April 2006

Abstractlntracellular and whole‐cell patch‐clamp recordings were used to evaluate the actions of different metabotropic glutamate receptor (mGluR) agonists on the synaptic inputs evoked on principal cells of the rat mesencephalon. Bath application of the group Ill mGluR agonists l‐2‐amino‐4‐phosphonobutyric acid (l‐AP4) and l‐serine‐O‐phosphonobutanoate (l‐SOP) did not change the holding current of the cells held at resting potential (‐60 mV) but produced a dose‐dependent inhibition of the amplitude of the excitatory and inhibitory events. l‐AP4 and l‐SOP were more effective at inhibiting the excitatory postsynaptic currents (EPSCs) than the GABAA and GABAB inhibitory postsynaptic currents (IPSCs). The suppressing effects of l‐AP4 and l‐SOP were antagonized by (S)‐2‐amino‐2‐methyl‐4‐phosphonobutanoic acid (MAP‐4) but not by ±‐α‐methyl‐4‐carboxyphenylglycine (MCPG). Moreover, the group II agonist (2S, 1′S, 2′S)‐(carboxycyclopropyl)glycine (l‐CCG1) and the group I agonist (RS)‐3,5‐dihydrophenylglycine (3,5‐DHPG) depressed in a dose‐related manner the EPSC, the GABAA IPSC and the GABAB IPSC. The suppressing effect of the two mGluRs agonists was partially antagonized by MCPG but not by MAP‐4. In addition, both l‐CCG1 and 3,5‐DHPG caused an inward shift of the holding current. To characterize the site of action of the metabotropic receptor agonists, experiments were performed to examine the amplitude and ratio of EPSC and GABAA IPSC pairs. The increase of the s2/sl ratio caused by the agonists suggests that the location of the inhibitory mGluRs was presynaptic. These results indicate that the activation of presynaptic mGluRs controls the release of excitatory and inhibitory transmitters on presumed dopaminergic cells within the ventral mesencephalon.