bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABAA receptor‐mediated IPSCs in rat thalamic sensory nuclei: patterns of discharge and tonic modulation by GABAB autoreceptors
Authors: Le Feuvre Y. , Fricker D. , Leresche N. 
Published: September 2004

The patterns of discharge of spontaneous GABAA‐mediated inhibitory postsynaptic currents (sIPSCs), originating from the nucleus reticularis thalami (NRT), and their modulation by GABAg autoreceptors, were studied in rat thalamocortical (TO) neurones using whole‐cell voltage‐clamp recordings in brain slices.
sIPSCs were recorded in all ventro‐basal (VB) and dorsal lateral geniculate (LGN) neurones. In VB neurones, in the presence of tetraethylammonium (TEA, 5 mm), these sIPSCs can occur in bursts at frequencies of either 0.1 or 1–2 Hz. In the presence of tetrodotoxin (TTX), these bursting activities are replaced by the continuous discharge of miniature IPSCs (mIPSCs), recorded in the absence of TEA, at a frequency of 4 Hz. The kinetic properties of mIPSCs were similar in VB and LGN TC neurones.
In VB TC neurones the GABAB receptor agonist (±)‐baclofen, at a concentration of 0.05 μm, decreased the mIPSC frequency by 22% without affecting their amplitude distribution. Increasing the (±)‐baclofen concentration to 1 and 10 μm caused similar reductions (41 and 47%, respectively) in the mIPSCs frequency: these values were significantly different from the one observed with 0.05 μm (±)‐baclofen. In LGN TC neurones, where mIPSCs originate from both NRT and local interneurone terminals, 1 μm (±)‐baclofen produced a 66% reduction in the mIPSC frequency.
The GABAB receptor antagonist CGP55845A (50 nm) not only blocked the baclofen‐mediated decrease in mIPSC frequency, but also produced a 52% increase in the mIPSC frequency compared with control in three out of seven neurones. Application of CGP55845A (50–500 nm) alone produced a 77 % increase in the mIPSC frequency in three out of nine VB neurones, and in the LGN, CGP55845A (100 nm) produced a 53% increase in four out of nine neurones. CGP55845A (100 nm) also reversibly increased the amplitude of evoked GABAA IPSCs by 74 and 57 % in three out of three VB and three out of five LGN neurones, respectively.
Application of GABA (1.5–5 μm) decreased the mIPSC frequency in VB TC neurones by a similar extent (48%) as 1–10 μm (±)‐baclofen.
In the presence of 100 μm Cd2+, (±)‐baclofen still decreased the mIPSC frequency by about 40%, indicating that the effect of presynaptic GABAB receptor activation on spontaneous GABA release did not occur through a reduction of voltage‐dependent Ca2+ currents.
Cd2+ (100 μm) decreased the amplitude of both mIPSCs and isoguvacine‐induced current by 30 and 19%, respectively, indicating an effect of this divalent cation on postsynaptic GABAA receptors.
We conclude that GABAB autoreceptors are present on the GABAergic terminals within the thalamic sensory nuclei and that these receptors can be tonically activated by the ambient GABA.
Metabotropic synaptic regulation of intrinsic response properties of turtle spinal motoneurones
Authors: Delgado‐Lezama Rodolfo , Perrier Jean‐Francois , Nedergaard Steen , Svirskis Gytis , Hounsgaard Jørn 
Published: September 2004

The effect of a brief train of electric stimuli in the dorsolateral funiculus on the intrinsic response properties of turtle motoneurones was investigated in transverse sections of the spinal cord in vitro.
Even when glutamatergic, GABAergic and glycinergic ionotropic synaptic transmission was blocked by antagonists of AMPA, NMDA, glycine and GABA receptors, dorsolateral funiculus (DLF) stimulation induced a facilitation of plateau potentials during current clamp and the underlying inward current in voltage clamp. This facilitation lasted more than 10 s.
The plateau potential and the facilitation by DLF stimulation was absent in the presence of 10 μm nifedipine. The DLF‐induced facilitation was reduced by antagonists of 5‐HT1a, group 1 metabotropic glutamate receptors and muscarine receptors.
These findings suggest that the intrinsic properties of spinal motoneurones are dynamically regulated by afferent synaptic activity. These afferents can be of spinal and extraspinal origin. Continuous regulation of intrinsic response properties could be a mechanism for motor flexibility.
Protein kinase A‐dependent and ‐independent stimulation of exocytosis by cAMP in mouse pancreatic B‐cells
Authors: Renström E. , Eliasson Lena , Rorsman P. 
Published: September 2004

The mechanisms by which cAMP stimulates Ca2+‐dependent insulin secretion were investigated by combining measurements of whole‐cell Ca2+ currents, the cytoplasmic free Ca2+ concentration ([Ca2+]i) and membrane capacitance in single mouse B‐cells maintained in tissue culture.
Cyclic AMP stimulated exocytosis > 4‐fold in whole‐cell experiments in which secretion was evoked by intracellular dialysis with a Ca2+‐EGTA buffer with a [Ca2+]i of 1.5μm. This effect was antagonized by inhibitors of protein kinase A (PKA).
Photorelease of cAMP from a caged precursor potentiated exocytosis at Ca2+ concentrations which were themselves stimulatory (≥60 nm), but was without effect in the complete absence of Ca2+.
Elevation of intracellular cAMP (by exposure to forskolin) evoked a 6‐fold PKA‐dependent enhancement of the maximal exocytotic response (determined as the maximum increase in cell capacitance that could be elicited by a train of depolarizations) in perforated‐patch whole‐cell recordings.
Exocytosis triggered by single depolarizations in standard whole‐cell recordings was strongly potentiated by cAMP, but in this case the effect was unaffected by PKA inhibition.
When exocytosis was triggered by Ca2+ released from Ca2+‐NP‐EGTA (‘caged Ca2+), cAMP exerted a dual stimulatory effect on secretion: a rapid (initiated within 80 ms) PKA‐independent phase and a late PKA‐dependent component.
We conclude that cAMP stimulates insulin secretion both by increasing the release probability of secretory granules already in the readily releasable pool and by accelerating the refilling of this pool.
cAMP‐dependent reversal of opioid‐ and prostaglandin‐mediated depression of the isolated respiratory network in newborn rats
Authors: Ballanyi K. , Lalley P. M. , Hoch B. , Richter D. W. 
Published: September 2004

Membrane potential (Vm) and resistance (Rm) of ventral respiratory group (VRG) neurons were measured in the isolated brainstem–spinal cord from newborn rats during bath application of the opioid receptor agonists fentanyl or [D‐Ala2, D‐Leu5]‐enkephalin (Ala‐Leu‐Enk) and of the prostaglandin Et (PGE1).
PGE1 (0.1–3 μm) and fentanyl or Ala‐Leu‐Enk (1–50 μm) produced depression and, at higher doses, block of inspiratory nerve activity and respiration‐related postsynaptic potentials. This apnoea was associated with hyperpolarization and Rm fall in 25% of thirty‐two VRG neurons tested, whereas resting Vm and Rm were not changed in the other cells.
The selective μ‐ and δ‐receptor blockers naloxonazine (10–20 μm) and naltrindole (50–100 μM) antagonized the effects of 5 μm fentanyl and 50 μM Ala‐Leu‐Enk, respectively.
Opioid‐ and PGE1‐evoked respiratory depression was reversed upon elevation of endogenous cAMP levels by stimulating adenylyl cyclase with 100 μM forskolin, activating dopamine D1 receptors with 50–100 μm 6‐chloro‐7,8‐dihydroxy‐3‐allyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine (6‐chloro‐APB) or preventing cAMP breakdown with 50–100 μm isobutylmethylxanthine.
The results indicate that opioid‐ or prostaglandin‐induced respiratory depression is due to a fall in cAMP levels in cells responsible for generation of rhythm or providing a tonic drive to the respiratory network.
We suggest that elevation of cAMP levels is an effective antidote in neonates against such forms of respiratory depression.
Activity‐dependent properties of synaptic transmission at two classes of connections made by rat neocortical pyramidal axons in vitro
Authors: Thomson Alex M. 
Published: September 2004

To compare the dynamics of synaptic transmission at different types of connection, dual intracellular recordings were made from pairs of neurones in slices of adult rat neocortex. Excitatory postsynaptic potentials (EPSPs) were elicited by single spikes, spike pairs and brief spike trains in presynaptic pyramidal cells and responses recorded in postsynaptic pyramidal cells and in inter neurones.
Pyramid–pyramid EPSPs were strongly voltage dependent and this resulted in a range of paired pulse effects. At thirty‐two of sixty‐nine pyramid–pyramid connections, the 2nd EPSP was the same shape as the 1st, indicating minimal interaction between active synapses. In these thirty‐two connections, paired pulse depression (PPD) was apparent (2nd EPSP integral 46 ± 21% of the 1st, at 5–20 ms), which recovered within 60–70 ms.
In eleven additional pyramid–pyramid pairs, the 2nd EPSP was also the same shape as the 1st, but paired pulse facilitation (PPF, 149 ± 32%) decaying within 50–60 ms was apparent. Even these connections displayed frequency‐dependent depression, however, as 3rd EPSPs were smaller than 1st EPSPs at intervals < 100 ms.
At twenty‐five pyramid–pyramid connections, 2nd EPSPs were broader than 1st EPSPs and in sixteen of these, voltage‐ and NMDA receptor‐dependent enhancement was large enough to obscure the underlying PPD. PPD was revealed by postsynaptic hyperpolarization (4 pairs), N‐methyl‐D‐aspartate (NMDA) receptor blockade (3 pairs), or if Mg2+ was removed (in the one case studied). If synapse location allowed significant depolarization of one active site by another, voltage‐dependent enhancement could produce supralinear EPSP summation and overcome PPD. Third EPSPs were, however, consistently smaller than 1st EPSPs.
In striking contrast, profound frequency‐dependent facilitation, independent of voltage or NMDA receptors was seen at fifteen connections involving two classes of postsynaptic inter neurones.
At these pyramid–interneurone connections, facilitation of the 2nd EPSP (655 ± 380% at 5–20 ms) decayed rapidly, within 50–60 ms. Third and fourth EPSPs showed additional facilitation which decayed more slowly, within 90 ms and 2 s, respectively. Facilitation due to five to six spike trains was still apparent at 3 s. Therefore, once initiated by a brief high frequency spike train, facilitation was maintained at lower frequencies.
Fusimotor Influence on Jaw Muscle Spindle Activity during Swallowing‐Related Movements in the Cat
Authors: Taylor A. , Hidaka O. , Durbaba R. , Ellaway P. H. 
Published: September 2004

The activity patterns of muscle spindle afferents in jaw‐closer muscles were studied during reflex swallowing movements in anaesthetized cats. Simultaneous records were made of the electromyogram (EMG) in masseter and anterior digastric muscles and of the unloaded jaw movements. The underlying patterns of fusimotor activity were deduced by comparing afferent discharges occurring during active swallowing with those occurring when exactly the same movements were imposed passively. The interpretation of spindle behaviour was greatly facilitated by characterizing the afferents according to the evidence for their contact with the various intrafusal muscle fibres, derived from testing with succinylcholine. It was also valuable to have two different types of afferent recorded simultaneously.
There was clear evidence of fusimotor activity occurring during active jaw closing so as to oppose the spindle silencing. This effect was most marked in b2c‐type afferents (probably secondaries) and was therefore attributed to a modulation of static fusimotor discharge approximately in parallel with α‐activity.
Afferents with evidence of bag1 fibre contacts (primaries) showed much greater sensitivity to muscle lengthening during active movement than when the movement was imposed. This difference was exaggerated when anaesthesia was deepened for the passive movements. This was interpreted as evidence for a higher level of dynamic fusimotor activity maintained during active movements than at rest.
The results support the view that for a variety of active jaw movements, static fusimotor neurone firing is modulated roughly in parallel with α‐activity but leading it so as to counteract spindle unloading. Dynamic fusimotor neurone firing appears to be set at a raised level during active movements. Anaesthesia appears to depress activity in the α‐motoneurones more than in γ‐motoneurones.
Mechanism of oxidative stress‐induced intracellular acidosis in rat cerebellar astrocytes and C6 glioma cells
Authors: Tsai Ke‐Li , Wang Seu‐Mei , Chen Ching‐Chow , Fong Tsorng‐Harn , Wu Mei‐Lin 
Published: September 2004

Following ischaemic reperfusion, large amounts of superoxide anion (.O2−), hydroxyl radical (.OH) and H2O2 are produced, resulting in brain oedema and changes in cerebral vascular permeability. We have found that H2O2 (100 μm) induces a significant intracellular acidosis in both cultured rat cerebellar astrocytes (0.37 ± 0.04 pH units) and C6 glioma cells (0.33 ± 0.07 pH units).
Two membrane‐crossing ferrous iron chelators, phenanthroline and deferoxamine, almost completely inhibited H2O2‐induced intracellular acidosis, while the non‐membrane‐crossing iron chelator apo‐transferrin had no effect. Furthermore, the acidosis was completely inhibited by two potent membrane‐crossing .OH scavengers, N‐(2‐mercaptopropionyl)‐grycine (N‐MPG) and dimethyl thiourea (DMTU). Since .OH can be produced during iron‐catalysed H2O2 breakdown (Fenton reaction), we have shown that a large reduction in pH1 in glial cells can result from the production of intracellular .OH via H2O2 oxidation.
We have ruled out the possible involvement of: (i) an increase in intracellular Ca2+ levels; and (ii) inhibition of oxidative phosphorylation.
Our results suggest that .OH inhibits glycolysis, leading to ATP hydrolysis and intracellular acidosis. This conclusion is based on the following observations: (i) in glucose‐free medium, or in the presence of iodoacetate or 2‐deoxy‐D‐glucose, H2O2‐induced acidosis is completely suppressed; (ii) H2O2 and iodoacetate both produce an increase in levels of intracellular free Mg2+, an indicator of ATP breakdown; and (iii) direct measurement of intracellular ATP levels and lactate production show 50 and 55% reductions in ATP content and lactate production, respectively, following treatment with 100 μm H2O2.
Inhibition of the pH1 regulators (i.e. the Na+–H+ exchange and possibly the Na+–HCO3−–dependent pH1 transporters) resulting from H2O2‐induced intracellular ATP reduction may also be involved in the H2O2‐evoked intracellular acidosis in glial cells.
The removal of acetylcholine by diffusion at nicotinic synapses in the rat otic ganglion
Authors: Callister Robert J. , Sah Pankaj 
Published: September 2004

We have examined the clearance of synaptically released acetylcholine in the otic ganglion when acetylcholinesterase was blocked with eserine.
Intracellular recordings were made from otic ganglion neurones, in vitro. The decay of the excitatory postsynaptic potential (EPSP), in response to stimulation of afferent fibres, was greatly prolonged in the presence of eserine. Low frequency (0.05–4 Hz) repetitive synaptic stimulation led to a slow depolarization of the postsynaptic cell that persisted throughout the period of stimulation. This slow depolarization was blocked by the nicotinic antagonists mecamylamine (100 μm) or (+)tubocurarine (100 μm), but was unaffected by atropine (1 μm), indicating that the response was due to the activation of nicotinic receptors.
Following 2 Hz synaptic stimulation (30 s), the rate of rise of the slow depolarization had a time constant of 3.1 ± 0.4 s and a peak amplitude of 12 ± 1 mV. Upon cessation of stimulation, the depolarization decayed to resting levels with a time constant of 18.3 ± 1.5 s (n= 23). At increasing stimulation frequencies the rate of rise of the depolarization increased. Lowering the probability of release, by adding cadmium to the perfusing solution or by lowering extracellular calcium, slowed the rise time of the response.
Both the onset and decay kinetics of the slow depolarization had a low temperature sensitivity, indicating that they reflect diffusional processes.
Repetitive stimulation (2 Hz) of the afferent nerve supplying the ganglion, in the presence of eserine, also caused a slow depolarization in cells in which we could not demonstrate a synaptic input. This indicates that synaptically released acetylcholine can spill over onto nearby neurones.
We conclude that at parasympathetic synapses, under physiological conditions, transmitter action is terminated by the enzymatic degradation of acetylcholine. When acetylcholinesterase is blocked, acetylcholine accumulates because its removal by diffusion is slow.
On‐going and reflex synaptic events in rat superior cervical ganglion cells
Authors: McLachlan Elspeth M. , Davies Philip J. , Häbler H.‐Joachim , Jamieson John 
Published: September 2004

Synaptic events evoked by brief noxious cutaneous stimuli were recorded in sympathetic neurones in the superior cervical ganglion of anaesthetized rats.
On‐going excitatory synaptic potentials (ESPs) and/or action potentials (APs) were recorded in 69% of neurones at mean frequencies that varied from 0.01 to 6.3 Hz in different cells. From histograms of ESP amplitude during membrane hyper polarization, it appears that most cells received one (52%), or two or more (36%), suprathreshold inputs and several subthreshold inputs with overlapping amplitudes.
Pinching the skin for 1–3 s evoked either a brief burst of synaptic events (lasting about 300 ms) preceding a few seconds of inhibition (burst–inhibitory (BI) neurones), or simply an excitation (excitatory (E) neurones), or no response (O neurones). In 60% of BI neurones, a second burst occurred after the end of the pinch.
BI neurones had a higher frequency of on‐going synaptic activity (2.9 ± 0.5 Hz, n= 15) than E neurones (0.2 ± 0.1 Hz, n= 5) or O (0.2 ± 0.1 Hz, n= 5) neurones. Most neurones with two or more suprathreshold inputs were BI neurones. In 20% of neurones (all BI with high rates of synaptic activity), several other inputs had ESPs with amplitudes close to threshold.
Subthreshold and suprathreshold inputs responded in the same way in only 45% of neurones, but suprathreshold inputs were excited in 73% of BI and all E neurones. The order of recruitment of different inputs varied from trial to trial. If classification was based only on suprathreshold responses, there were 36% BI, 32% E and 32% O neurones.
In the majority of neurones, postganglionic discharge was initiated exclusively by supra‐threshold inputs, even during reflex excitation.
Qualitatively similar, but smaller, responses were evoked by a puff of air on the abdomen in 71% of cells tested.
The data suggest that the natural discharge of SCG neurones is largely determined by the activity of one or two preganglionic inputs with high quantal contents. BI neurones may include vasoconstrictor neurones, whereas the other types include secretomotor, pilomotor and other neurones projecting to targets in the head.
Increased Sensitivity of Gastrin Cells to Gastric Distension following Antral Denervation in the Rat
Authors: Higham A. , Noble P. , Thompson D. G. , Dockray G. J. 
Published: September 2004

Secretion of the antral hormone gastrin is increased by protein in the gastric lumen and by nervous reflexes. We have examined the relative importance of luminal and neuronal mechanisms, by lesioning the antral innervation using benzalkonium chloride.
Benzalkonium chloride was applied to the serosa of the antrum in anaesthetized rats. In some animals, a stainless‐steel cannula was also implanted in the corpus. Animals were allowed 10 days to recover. Plasma gastrin was measured by radioimmunoassay and mRNAs encoding gastrin, somatostatin and histidine decarboxylase were measured by Northern blot.
Antral denervation was associated with gastric retention after fasting, and elevated plasma gastrin (28.4 ± 7 pM compared with 7.6 ± 1.0 pM in controls). When fasted control or denervated rats were refed, plasma gastrin increased 3‐fold in both cases. A gastrin‐releasing peptide antagonist inhibited the post‐prandial rise in plasma gastrin in control rats, but had no effect in antrally denervated rats.
In fasted, antrally denervated rats with a gastric fistula, basal gastric acid secretion was depressed 3‐fold, and plasma gastrin concentrations were similar to controls.
Distension of the stomach with peptone via a barostat attached to the gastric cannula (5 cmH2O, 30 min), produced 3‐fold increases in plasma gastrin in both control and denervated rats. However, distension with a non‐nutrient solution at pH 6.0 had no effect in controls, but increased gastrin to a similar extent to peptone in denervated rats; distension with 50 mM HCl had no effect in either control or denervated rats.
Somatostatin and gastrin mRNA abundances in the antrum were depressed by about 35% by antral denervation, but somatostatin mRNA in the corpus was unchanged; GAPDH mRNA abundance was unaffected by antral denervation.
The data suggest that luminal nutrient releases gastrin in the rat, in vivo, via activation of antral neurons secreting gastrin‐releasing peptide, and that the antral innervation normally inhibits G‐cell responses to non‐nutrient distension of the stomach. After antral denervation, gastric distension with a non‐nutrient solution is an adequate stimulus for gastrin release.
Hypoxia‐induced catecholamine secretion in isolated newborn rat adrenal chromaffin cells is mimicked by inhibition of mitochondrial respiration
Authors: Mojet Mart H. , Mills Elliott , Duchen Michael R. 
Published: September 2004

In newborn mammals, systemic hypoxia provokes catecholamine secretion from the adrenal medulla. In contrast to adults, this release is independent of sympathetic innervation. We have studied the cellular processes involved in hypoxia‐induced catecholamine secretion, employing fluorimetric techniques to measure changes in [Ca2+]i, NADH and mitochondrial potential, and voltammetric techniques to record changes inPO2and catecholamine secretion.In adrenal chromaffin cells freshly dissociated from newborn rats, severe hypoxia increased [Ca2+]iand secretion of catecholamines, indicating that the response of the newborn adrenal medulla to hypoxia is an intrinsic property of these cells. Discrete quantal secretory events were identifiable, suggesting an exocytotic mechanism of secretion.Hypoxia‐induced secretion was only seen whenPO2fell below 5 mmHg, similar to the threshold arterialPO2reported to stimulate releasein vivo.Such oxygen tensions also inhibited mitochondrial metabolism, shown by an increase in NADH autofluorescence. We therefore explored the involvement of mitochondria in oxygen sensing. Inhibition of mitochondrial respiration either by CN−at complex IV or by rotenone at complex I mimicked severe hypoxia, reversibly increasing both [Ca2+]iand catecholamine secretion. The CN−‐induced depolarization of the mitochondrial inner membrane potential preceded the increase in [Ca2]iby ∼6 s.The effects of severe hypoxia and CN−on [Ca2+]iand catecholamine secretion were not additive, suggesting a common mechanism.Chemical anoxia failed to increase [Ca2+]iin a significant proportion of cells dissociated from 2‐ to 4‐week‐old rats. Thus, the sensitivity to hypoxia is specific to adrenal chromaffin cells dissociated from newborn rats.These data indicate that hypoxia‐induced catecholamine secretion in the newborn adrenal medulla is mediated by reversible inhibition of mitochondrial respiration, leading to an increase in [Ca2+]iand catecholamine secretion.