bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seizures induced by aminooxyacetic acid in mice: Pharmacolgical characteristics
Authors: Turski Waldemar A. , Dziki Marek , Urbanska Ewa , Calderazzo‐Filho Lineu S. , Cavalheiro Esper A. 
Published: December 2004

AbstractSystemic (s.c.) administration of aminooxyacetic acid (AOAA) in mice triggered clonic convulsions with a CD50 (convulsive dose) of 68 mg/kg (range 54–86). AOAA also induced clonic covulsions in mice subjected to intracerebroventricular administration of the drug with a CD50 of 0.04 μmol (range 0.028–0.06). At the onset of convulsions induced by systemic AOAA (CD97; 150 mg/kg), the GAD activity in the frontal cortex and hippocampus was not affected. GABA mimetic drugs, progabide and gabaculine, had no effect on covulsions induced by AOAA. Convulsions induced by systemic administration of AOAA were blocked by diazepam, phenobarbital, and valproate. Ethosuximide, trimethadione, acetazolamide, diphenylhydantion, and carbamazepine remained ineffective. L‐Phenylisopropyladenosine was also found to protect mice against AOAA‐induced convulsions, whereas atropine and baclofen had no effect. The seizures induced by intracerebroventricular administration of AOAA (CD97; 0.1 μmol) were blocked by coadministration of preferential N‐methyl‐D‐aspartate antagonists, D‐(−)‐2‐aminophosphonoheptanoic (AP7), 3‐((±)‐2‐carboxypiperazinv4‐yl)‐propyl‐1‐phosphonic (CPP), and kynurenic acid (KYNA); preferential quisqualate/kainate antagonists, 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione and γ‐D‐glutamylaminomethylsulphonic acid, remained inactive in the range of dosages sufficient to block seizures induced by quisqualic acid or kainic acid.The antagonistic action of antiepileptic drugs effective against seizures induced by excitatory amino acids (diazepam and valproate), and drugs acting on excitatory amino acid receptors (AP7, CPP, and KYNA) upon seizures induced by AOAA suggests an involvement of excitatory neurotransmission in the covulsant action of the drug.
Effects of protein kinase C activators and inhibitors on membrane properties, synaptic responses, and cholinergic actions in CA1 subfield of rat hippocampus in situ an in vitro
Authors: Agopyan N. , Agopyan I. 
Published: December 2004

AbstractActivation and inhibition of protein kinase C(PKC) has been reported to induce several effects in hippocampus in vitro. It has been also proposed that, in hippocampus, phorbol esters mimic the effects of acetylcholine. To test whether the actions produced by PKC activators and inhibitors in situ are comparable to those induced in vitro preparations, we studied in CA1 region of the hippocampus both in situ and in vitro, the responses produced by activation and inhibition of protein kinase C. Once the effects of various PKC activators and inhibitors were established their interaction with muscarinic agonists was studied. The main findings were as follows: (I) Extracellular studies in situ: (1)Phorbol diacetate (PDAc) enhanced the population spike and dendritic field amplitudes. Unlike ACh, it never induced disfacilitation or disinhibition. (2) The effects produced by mascarinic agonists were not occluded by prolonged PDAc applications. (3) Inhibition of PKC with H‐7 induced a strong excitation manifested by induction of multiple spikes and broadening of the dendritic field response. This excitation was associated with blockade of IPSPs, represented by positive waves, at a presynaptic site, which was antagonised by PDAc suggesting the involvement of PKC. (4) Sphingosine, a dual PKC/‐calciumcalmodulin‐dependent kinase inhibitor, did not reproduce H‐7‐induced responses. However, it did prevent the actions of muscarinic agonists. (II) Intracellular studies in vitro: (1) PDAc application by either iontophoresis or superfusion produced a (i) depolarization; (ii) increase in input resistance (RN); (iii) blockade of the anomalous rectification (“sag”)(iv) increase in the fast—but decrease in the slow—after hyperpolarization (AHP);and (v) reduction in excitability, measured by the repetitive firing evoked by depolarizing pulses. (2) During local (iontophoretic) applications of PDAc, the reversal shifted toward more positive values. (3) Iontophoresis of H‐7 caused a decrease in RN, hyperpolarization, and blockade of IPSPs. In conclusion, in the hippocampus, PKC can modulate the IPSPs, the anomalous rectification, and the membrane potential, but PKC is unlikely to be the major intracellular mediator of the excitatory actions of acetulcholine. The possible involvement of calcium‐calmodulinvdependent kinase is discussed.
Evidence that changes in spine neck resistance are not responsible for expression of LTP
Authors: Jung Min W. , Larson John , Lynch Gary 
Published: December 2004

AbstractFrom modeling studies it is known that changes in spine neck resistance can influence the shape of the non‐linear curve relating synaptic current to synaptic conductance if the resistance of the neck approaches the synaptic input resistance. Such work also indicates that the effects of resistance will be much more pronounced for fast rather than slow synaptic currents. Accordingly, a reduction in neck resistance could produce an increase in the rapid responses generated by the quisqualate/AMPA class of glutamate receptors while only minimally affecting the slower NMDA receptor‐mediated responses and thus account for the pattern of changes known to be associated with long‐term potentiation (LTP). This hypothesis predicts that large reductions in synaptic conductance should have disproportionate effects on potentiated versus control responses. This was tested by using field potential recordings of synaptic currents in CA1 pyramidal cells in hippocampal slices in response to stimulation of Schaffer/commissural inputs that either received LTP‐inducing stimulation or did not. Two manipulations were used to systematically reduce synaptic conductances: reductions of extracellular Ca++ and partial blockade of postsynaptic receptors. Reductions jof synaptic field potentials by 40–75% by either method at control synapses were accompanied by equivalent reductions at priviously potentiated synapses. These results suggest that LTP expression is not due to a predicted by the curves relating synaptic current to synaptic conductance as would be predicted by the spine resistance hypotheses.
Regulation of spontaneous activity and oscillatory spike firing in rat midbrain dopamine neurons recorded in vitro
Authors: Grace Anthony A. 
Published: December 2004

AbstractIntracellular recordings were obtained from identified dopamine (DA) neurons in rat midbrain slices maintained in vitro. DA neuron membranes exhibited pronounced instantaneous and time‐dependent anomalous rectification that showed evidence of maximal activation at average membrane potentials of −63 and −78 mV, respectively. Action potentials were followed by prominent afterhyperpolarizations (AHP) that consisted of two components. The fast component showed evidence of inactivation at −63 mV independent of the initial membrane potential, whereas the longer‐duration, later component increased in amplitude at hyperpolarized potentials. Unlike DA neurons recorded in vivo, there was no evidence of spike frequency adaptation or summation of AHPs with prolonged depolarization‐induced spike trains. Spontaneous spike discharge occurred via an endogenous pacemaker potential that was dependent on both TTX‐sensitive and cobalt‐sensitive processes. Hyperpolarizing prepulses could activate rebound pacemaker discharge, but this rebound activity was progressively blocked with larger‐amplitude hyperpolarizing prepulses.DA neurons recorded in the ansthetized animal, freely moving animal, and in vitro preparations have been shown to exist in two states of activity: (1) spontaneously discharging action potentials or (2) hyperpolarized, quiescent, and non firing. Further‐more, although it is rare to find DA neurons in the untreated animal in transitional states of activity, quiescent neurons can be activated by stimuli that place a demand on the DA system. The evidence presented here is consistent with the hypothesis that the special combination of membrane properties of DA neurons contribute to the segregtion of their activity into active or inactive states.
Synaptic plasticity at crayfish neuromuscular junctions: Facilitation and augmentation
Authors: Bittner George D. , Baxter Douglas A. 
Published: December 2004

AbstractSimultaneous intracellular recordings from presynaptic nerve terminals and postsynaptic muscle fibers were used to investigate the extent to which changes in presynaptic voltage may contribute to short‐term facilitation and augmentation of transmitter release at neuromuscular junctions of the crayfish (Procambarus simulans) opener muscle. Presynaptic nerve terminals have an average resting membrane potential of about–80 mV, single action potentials have an average foot‐to‐peak amplitude of about 98 mV, and single action potentials are followed by a depolarizing after potential (DAP) of about 10 mV. During stimulus trains of 9–16 impulses at 100 Hz, amplitudes of excitatory postsynaptic potentials (EPSPs) continuously facilitate up to 100‐fold. This dramatic facilitation is associated with oly slight increases in the peak voltage and duration of APs for first 2–4 pulses in such a stimulus train. Foot‐to‐peak total amplitude of APs usually decreases after the first pulse in a stimulus train. The data strongly suggest that short‐term facilitation is not due to changes in the amplitude or duration of APs invading the presynaptic terminal. Upon cessation of a longer stimulus train, the presnaptic terminal exh‐ibits a hyperpolarizing after potential (HAP) up to 16 mV in amplitude depending upon the frequency (10–100 Hz) and duration (1–10 sec) of the tetanic stimulation. This post‐tetanic HAP decays with a time constant of 10–20 sec, which is approximately equal to the third time constant of decay in EPSP amplitude (augmentation) following tetanic stimulation. Hence, presynaptic voltage changes and/or processes associated with these voltage changes (e.g., acumulation of ions, changes in ionic conductances, etc.) may be responsible for augmentation of EPSP amplitudes.
Competitive (AP7) and non‐competitive (MK‐801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex
Authors: Clow Daniel W. , Lee Shay J. , Hammer Ronald P. 
Published: December 2004

AbstractThe effects of D, L‐2‐amino‐7‐phosphonoheptanoic acid (AP7), a competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist, and MK‐801, a non‐competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative [14C]2‐deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose‐dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK‐801 (0.1 or 1.0 mg/kg) resulted in a dose‐dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK‐801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK‐801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK‐801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK‐801 administration also decreased metabolic activity in granular SI relative to dysgranular SI and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non‐competitive NMDA receptor antagonist suppressed activity form extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions while the competitive NMDA antagonist depressed metabolic activity in all cortical regions. These selective laminar and regional changes in metabolic activity may be due to an enhanced susceptibility of certain cortical circuits to non‐competitive NMDA receptor antagonists.
Bursting response to current‐evoked depolarization in rat ca1 pyramidal neurons is correlated with lucifer yellow dye coupling but not with the presence of calbindin‐D28k
Authors: Baimbridge Kenneth G. , Peet Martin J. , McLennan Hugh , Church John 
Published: December 2004

AbstractCalbindin‐D28k (CaBP) immunohistochemistry has been combined with electrophysiological recording and Lucifer Yellow (LY) Cell identification in the CA1 region of the rat hippocampal formation. CaBP is shown to be contained within a distinct sub‐population of CA1 pyramidal cells which is equivalent to the superficial layer described by Lorente de Nó (1934). The neurogenesis of these CaBP‐Positive neurons occurs 1–2 days later than the CaBP‐negative neurons in the deep pyramidal cell layer, as shown by 3H‐thymidine autoradiography. No correlation could be found between the presence or absence of CaBP and the type of electrophysiological response to current‐evoked depolarizing pulses. The latter could be separated into bursting or non‐bursting types and the bursting‐type response was nearly always found to be associated with the presence of LY dye coupling. Furthermore, when dye coupling involved three neurons, a characteristic pattern was observed which may represent the coupling of phenotypically identical neurons into distinct functional units within the CA1 pyramidal cell layer. In this particular casse the three neurons were all likely to be CaBP‐positive.
Neurophysiological maturation of cat caudate neurons: Evidence from in vitro studies
Authors: Cepeda Carlos , Walsh John P. , Buchwald Nathaniel A. , Levine Michael S. 
Published: December 2004

AbstractThe membrane properties and synaptic physiology of developing cat caudate (Cd) nucleus neurons were studied in in vitro slice preparations. Recordings were obtained from 98 cells in kittens from fetal day (F) 56 to postnatal day (P) 90. With increasing age, the following maturational changes occurred; resting membrane potentials became more negative, action potential rise times decreased, action potential amplitudes increased, and action potential durations and input resistances decreased. The frequency of occurrence of afterhyperpolarizations and of of anomalous rectification increased with age. The primary response to local extracellular stimulation was depolarization usually accompanied by an action potential. Evoked hyperpolarizing responses were seen after P28 but only occurred if the membrane was depolarized by intracellular current injection. Cells identified by intracellular injection of Lucifer yellow were primarily medium‐sized spiny neurons although it was not always possible to determine the cell type in slices from animals < P5. Somatic diameter, dendritic length, and spine density increased with age. Dye‐coupling occurred in slices < P20. Its frequency decreased with age. These results show that Cd neurons undergo significant maturation during late pernatal and early postnatal periods. In contrast, substantia nigra neurons mature more rapidly and should be capable of influencing the less mature Cd neurons during development (Walsh et al., Synapse, 7:291–300, 1991).
Modulation of Mg2+‐dependent [3H]TCP binding by L‐glutamate, glycine, and guanine nucleotides in rat cerebral cortex
Authors: Hori Takafumi , Yamamoto Toshifumi , Hatta Kotaro , Moroji Takashi 
Published: December 2004

AbstractBiochemical and electrophysiological studies have demonstrated that phencyclidine (PCP) recognition site exists in the ion channel of the N‐methyl‐D‐aspartate (NMDA) receptor in ion channel complex. Using an extensively washed rat cortical membrane preparation, the effects of Mg2+ and guanylylimidodiphosphate (GppNHp) were examined on the binding of [3H]‐N‐[1‐(2‐thienyl)cyclohexyl]‐3, 4‐piperidine ([3H]TCP). Low concentrations of Mg2+ (EC50 = 11μM) stimulated [3H]TCP binding under the basal condition and high concentrations of Mg2+ (IC50 = 1 mM) inhibited it. In the presence of 10 μM L‐glutamate and 10 μM glycine, their EC50 values for Mg2+ enhancement of [3H]TCP binding were markedly reduced (to 1.9 μM or 8.4 μM), respectively. By contrast, the IC50 values for Mg2+ inhibition of [3H]TCP binding were reduced in the presence of L‐glutamate, but not glycine. Furthermore, a stimulatory effect of Mg2+ on [3H]TCP binding was additional to the [3H]TCP binding stimulated by a maximally effective concentration of L‐glutamate (10 μM) or glycine (10 μM). In the kinetic study, 300 μM Mg2+ produced an increase in the rates of both association and dissociation of [3H]TCP. Similar results were obtained with L‐glutamate (10 μM) and glycine (10 μM); 10 mM Mg2+ also caused an acceleration of the association rate but strongly decreased [3H]TCP binding at equilibrium. Compared with [3H]TCP binding under the basal condition, K+ (10 mM) alone decreased the maximal binding without producing any change in the association rate; 10 mM K+ also significantly decreased Mg2+ ‐stimulated [3H]TCP binding but caused no change no change in the acceleration of the association rate caused by Mg2+. At 100 μM, GppNHp resulted in a rightward shift in the Mg2+ dose–response curve of [3H]TCP binding to a high affinity site for Mg2+ under the basal condition and in the presence of glycine. The observations presented here strongly suggest that a Mg2+ recognition site with high affinity (a high affinity Mg2+ site) is distinct not only from the L‐glutamate and glycine binding sites but also from the Mg2+ recognition site with low affinity located in the ion channel and that the high affinity Mg2+ site may be associated with a GTP binding site.
Correlation of 125I‐LSD autoradiographic labeling with serotonin voltage clamp responses in Aplysia neurons
Authors: Evans Martyn L. , Kadan Michael J. , Hartig Paul R. , Carpenter David O. 
Published: December 2004

AbstractAutoradiographic receptor binding studies using 125I‐LSD (2‐[125I]lysergic acid diethyamide) revealed intense labelling on the soma of a symmetrically located pair of cells in the abdominal ganglion of Aplysia californica. This binding was blocked by micromolar concentrations of serotonin and lower concentrations of the serotonergic antagonists, cyproheptadine and mianserin (Kadan and Hartig, 1988). Electrophysiological investigation of responses to serotonin of neurons in the left upper quadrant, where one of the labeled neurons is located, revealed a range of serotonin responses. Cells L3 and L6 have a K+ conductance increase in response to serotonin that is not blocked by cyproheptadine or mianserin. Cells L2 and L4 have a biphasic response to serotonin: a Na+ conductance increase, which can be blocked by cyproheptadine and mianserin, followed by a voltage dependent Ca2+ conductance which is blocked by Cs2+ but not the serotonergic antagonists. Cell L1, and its symmetrical pair, R1, have in addition to the Na+ and Ca2+ responses observed in L2 and L4, a Cl− conductance increase blocked by LSD, cyproheptadine and mianserin. LSD had little effect on the other responses. We conclude that the symmetrically located cells L1 and R1 have a Cl− channel linked to a cyproheptadine‐ and mianserin‐sensitive serotonin receptor that is selectively labelled by 125I‐LSD. This receptor has many properties in common with the mammalian serotonin 1C receptor.
Effects of serotonergic denervation on the density and plasticity of brain muscarinic receptors in the rat
Authors: Alonso Richard , Soubrie Philippe 
Published: December 2004

AbstractThis study investigated whether serotonergic lesion may affect density, sensitivity, and of muscarinic receptors in hippocampus and cerebral cortex. Intracerebroventricular injection of 5, 7‐dihydroxytryptamine (5, 7‐DHT) in rats produced a 90% reduction in cortical and hippocampal 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) contents. In these brain areas, the 5, 7‐DHT lesion did not affect the overall density of muscarinic receptors or those of M1 and non‐M1 muscarinic receptor subtypes as assayed using [3H]N‐methylscopolamine ([3H]NMS), [3]pirenzepine, and [3H]NMS in the presence of pirenzepine, respectively. In addition, the binding of the muscarinic agonist [3H]oxotremorine‐M (OXO‐M), taken as an indirect index of coupling efficiency of non‐M1 receptors with G‐proteins, did not change significantly in cortex and hippocampus of 5, 7‐DHT‐lesione rats. Similarly, carbachol‐induced accumulation of [3H]inositol phosphates (InPs) in hippocampal miniprisms showed no significant differences between tissues from 5, 7‐DHT‐lesioned and sham‐operated rats. In sham‐operated rats, an intraperitoneal (i.p) injection of scopolamine (10 mg/kg once daily) during 21 days caused an increased density of [3H]NMS binding sites in cortex (+20%) and hippocampus (+26%). This up‐regulation was restricted to non‐M1 receptors subtypes. In 5, 7‐DHT‐lesioned rats, chronic scopolamine failed to modify significantly the density of cortical or hippocampal M1 or non‐M1 receptors. These results suggest (1) that 5‐HT denervation did not affect the density and sensitivity of muscarinic receptors and (2) that the ability of cortical and hippocampal non‐M1 receptors to up‐regulate following repeated injection of scopolamine requires the integrity of 5‐HT neurons terminating in these brain structures.
GABA depolarizes neurons in the rat striatum: An in vivo study
Authors: Mercuri Nicola Biagio , Calabresi Paolo , Stefani Alessandro , Stratta Francesca , Bernardi Giorgio 
Published: December 2004

AbstractGABA, applied by iontophoresis to striatal neurons of the rat in an in vivo prepartion, depolarized the membrane potential and decreased the input resistance in a dose‐dependent manner. The null potential of the GABA depolarization was about –50 mV. In addition, a fading of the GABA‐induced response was observed for prolonged and relatively high amino acid application. We conclude that GABA has a depolarizing effect on striatal cells. This is in line with recent in vitro works describing a depolarizing effect of GABA in the rat neostriatum.
Rapid alteration of synaptic number and postsynaptic thickening length by NMDA: An electorn microscopic study in the occipital cortex of postnatral rats
Authors: Brooks William J. , Petit Ted L. , Leboutillier Janelle C. , Lo Robert 
Published: December 2004

AbstractThe N‐methyl‐D‐aspartate (NMDA) receptor has been widely implicated in numerous activity‐dependent models of neural plasticity, learning, and memory. The formation of new synapses is a major assumption of the neural basis of learning. The current research was conducted to determine whether NMDA receptor activation could induce synaptic formation and, if so, whether this ability would mirror developmental changes in NMDA receptors. Rats at various developmental ages were given a single intraperitoneal injection of NMDA and sacrificed at various brief postinjection intervals (0.5–2 hr). The rats showed an age‐dependent decline in the behavioral response to NMDA, as evidenced by reduced seizure activity and duration. Quantitative electron microscopic observations on the molecular layer of the occipital cortex, an area rich in NMDA receptors, revealed a transient increase in the length of postsynaptic thickenings in 17‐ and 35‐day‐old animals, appearing within 0.5 hr of injection. At 1 and 2 hr postinjection, an increase in synaptic density (number of synapses) was observed in 8‐day‐old animals. These results provide evidence that NMDA administration alone is capable of rapidly inducing alterations in synaptic structure and the formation of new synapses, underscoring the importance of the NMDA receptor in synaptogenesis and synaptic structural plasticity.