bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal patterns of γ frequency oscillations tetanically induced in the rat hippocampal slice
Authors: Whittington Miles A. , Stanford Ian M. , Colling Simon B. , Jefferys John G. R. , Traub Roger D. 
Published: September 2004

We used transverse and longitudinal rat hippocampal slices to study the synchronization of γ frequency (> 20 Hz) oscillations, across distances of up to 4.5 mm. γ oscillations were evoked in the CA1 region by tetanic stimulation at one or two sites simultaneously, and were associated with population spikes. Tetanic stimuli that were strong enough to induce oscillations were associated with depolarization of both pyramidal cells and interneurones, largely produced by activation of metabotropic glutamate receptors.
Computer simulations of γ oscillations were also performed in a model with pyramidal cells and interneurones, arranged in a chain of five cell groups. This model had suggested previously that interneurone networks alone could generate synchronous γ oscillations locally, but that pyramidal cell firing, by inducing spike doublets in interneurones, was necessary for the occurrence of highly correlated oscillations with small phase lag (< 2.5 ms), in a distributed network possessing long axon conduction delays.
In both experiment and model, pyramidal cell spikes occurred in phase with local population spikes, as did the first spike of the interneurone doublet.
The conductance of the interneurone α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor‐mediated conductance was manipulated in the model, while the relation between oscillations at opposite ends of the chain was examined. When the conductance was large enough for doublet firing to be synaptically induced in interneurones, oscillation phase lags were < 2.25 ms across the chain. As predicted, experimental blockade of AMPA receptors resulted in increased phase lags between two sites oscillating simultaneously, compared with control conditions.
Both in model and in experiment, when stimuli to the two ends of the network were slightly different, cross‐network synchronization occurred with a shorter phase lag at high frequencies than at lower frequencies.
These data suggest that, while interneurone networks alone can generate locally synchronized γ oscillations, firing of pyramidal cells, and the synaptically induced doublet firing in interneurones, contribute to the stability and tight synchrony of the oscillations in distributed networks.
Functional differences in Na+ channel gating between fast‐spiking interneurones and principal neurones of rat hippocampus
Authors: Martina Marco , Jonas Peter 
Published: September 2004

GABAergic interneurones differ from glutamatergic principal neurones in their ability to discharge high‐frequency trains of action potentials without adaptation. To examine whether Na+ channel gating contributed to these differences, Na+ currents were recorded in nucleated patches from interneurones (dentate gyrus basket cells, BCs) and principal neurones (CA1 pyramidal cells, PCs) of rat hippocampal slices.
The voltage dependence of Na+ channel activation in BCs and PCs was similar. The slope factors of the activation curves, fitted with Boltzmann functions raised to the third power, were 11.5 and 11.8 mV, and the mid‐point potentials were −25.1 and −23.9 mV, respectively.
Whereas the time course of Na+ channel activation (−30 to +40 mV) was similar, the deactivation kinetics (−100 to −40 mV) were faster in BCs than in PCs (tail current decay time constants, 0.13 and 0.20 ms, respectively, at −40 mV).
Na+ channels in BCs and PCs differed in the voltage dependence of inactivation. The slope factors of the steady‐state inactivation curves fitted with Boltzmann functions were 6.7 and 10.7 mV, and the mid‐point potentials were −58.3 and −62.9 mV, respectively.
The onset of Na+ channel inactivation at −55 mV was slower in BCs than in PCs; the inactivation time constants were 18.6 and 9.3 ms, respectively. At more positive potentials the differences in inactivation onset were smaller.
The time course of recovery of Na+ channels from inactivation induced by a 30 ms pulse was fast and mono‐exponential (τ= 2.0 ms at −120 mV) in BCs, whereas it was slower and bi‐exponential in PCs (τ1= 2.0 ms and τ2= 133 ms; amplitude contribution of the slow component, 15%).
We conclude that Na+ channels of BCs and PCs differ in gating properties that contribute to the characteristic action potential patterns of the two types of neurones.
Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation
Authors: Hussy Nicolas , Deleuze Charlotte , Pantaloni Antoine , Desarménien Michel G. , Moos Françoise 
Published: September 2004

To evaluate the implication of taurine in the physiology of supraoptic neurones, we (i) investigated the agonist properties of taurine on glycine and GABAA receptors of supraoptic magnocellular neurones acutely dissociated from adult rats, using whole‐cell voltage clamp, (ii) studied the effects of taurine and strychnine in vivo by extracellular recordings of supraoptic vasopressin neurones in anaesthetized rats, and (iii) measured the osmolarity‐dependent release of endogenous taurine from isolated supraoptic nuclei by HPLC.
GABA, glycine and taurine evoked rapidly activating currents that all reversed close to the equilibrium potential for Cl−, indicating activation of Cl− selective channels. Glycine‐activated currents were reversibly blocked by strychnine (IC50 of 35 nM with 100μm glycine), but were unaffected by the GABAA antagonist gabazine (1–3 μm). GABA‐activated currents were reversibly antagonized by 3 μm gabazine, but not by strychnine (up to 1 μm).
Responses to 1 mm taurine were blocked by strychnine but not by gabazine and showed no additivity with glycine‐induced currents, indicating selective activation of glycine receptors. Responses to 10 mm taurine were partially antagonized by gabazine, the residual current being blocked by strychnine. Thus, taurine is also a weak agonist of GABAA receptors.
In the presence of gabazine, taurine activated glycine receptors with an EC50 of 406 μm. Taurine activated at most 70% of maximal glycine currents, suggesting that it is a partial agonist of glycine receptors.
In vivo, locally applied strychnine (300 mm) increased and taurine (1 mm) decreased the basal electrical activity of vasopressin neurones in normally hydrated rats. The effect of strychnine was markedly more pronounced in water‐loaded rats.
Taurine, which is concentrated in supraoptic glial cells, could be released from isolated supraoptic nuclei upon hyposmotic stimulation. Decreases in osmolarity of 15 and 30% specifically enhanced basal release of taurine by 42 and 124%, respectively.
We conclude that supraoptic neurones express high amounts of glycine receptors, of which taurine may be regarded as a major natural agonist. We postulate that taurine, which can be released in hyposmotic situations, acts on glycine receptors to exert an inhibitory control on magnocellular neurones during alterations of body fluid homeostasis, implicating an active participation of glial cells in this neuroendocrine regulatory loop.
Interchangeable discharge patterns of neurons in caudal nucleus tractus solitarii in rat slices: role of GABA and NMDA
Authors: Yen J. C. , Chan Samuel H. H. 
Published: September 2004

We characterized in rat brain slices the discharge patterns of spontaneously active neurons in the caudal region of the nucleus tractus solitarii (cNTS) and the neuromodulatory role of GABA and glutamate, via GABAA and NMDA receptors.
Spontaneous action potentials recorded intracellularly from cNTS neurons manifested either a regular or an irregular discharge pattern, alongside characteristic waveforms of the action potentials. These discharge patterns were interchangeable, and were highly sensitive to fluctuations in membrane potentials. In addition, the repolarizing rate of the after‐hyper‐polarization (AHP) in cNTS neurons that exhibited a regular discharge pattern was significantly higher than that of neurons that displayed irregular discharges.
cNTS neurons that manifested a regular discharge pattern were converted to irregular discharges upon superfusion with GABA (200 μm). This was accompanied by a reduction in the repolarizing rate of the AHP of both spontaneous and evoked action potentials. Conversion of discharge patterns in the opposite direction was elicited by superfusion with NMDA(6.8/μm).
The irregular discharges of spontaneous or evoked cNTS neurons were converted to a regular discharge pattern by bicuculline (200 μm). Subsequent application of d(–)‐2‐amino‐5‐phosphonopentanoic acid (250 μm) essentially led the neuronal discharges to revert to an irregular pattern.
Our results support the presence of two interchangeable modes of electrophysiological manifestations from the same cNTS neuronal population. They also showed that GABA and glutamate, via GABAA and NMDA receptors, may provide a novel form of neuromodulation at the cNTS by switching the patterns of neuronal discharges.
Two components of blood‐brain barrier disruption in the rat
Authors: Easton A. S. , Sarker M. H. , Fraser P. A. 
Published: September 2004

Permeability of pial venular capillaries to Lucifer Yellow (Ply) was measured using the single microvessel occlusion technique.
P

ly
was extremely low, when measured shortly after the removal of the meninges, consistent with an intact blood‐brain barrier, but rose spontaneously to (1.65 ± 060)× 10−6cms−1 (mean ±s.d.) within 20–‐60 min. This first phase of spontaneous disruption lasted 44–164 min. A second phase started when Ply rose sharply, and was characterized by rapid permeability fluctuations with a mean of (12.31 ± 15.14) × 1CT−6 cm s−1.
The first phase could be mimicked by applying the divalent cation ionophore A23187 in the presence of Ca2+, when Ply rose by (1.47±0–25) × 10−6 cm s−1 (mean±s.e.m.). Application of histamine (10 μm) to tight vessels increased Ply by (2.41 ± 0.22) × 10−6 cm s−1.
Substances that raised intraendothelial cAMP of vessels during the first phase of disruption reduced Ply to the initial blood‐brain barrier level.
The second phase could be prevented by applying catalase. Similar high and fluctuating Ply values could be produced reversibly by applying arachidonic acid or NH4C1.
This is the first report of two distinct types of permeability increase in the cerebral microvasculature, and reasons for this are discussed.
Onset of Bursting in Oxytocin Cells in Suckled Rats
Authors: Brown David , Moos Françoise 
Published: September 2004

We tested whether firing characteristics are associated with the onset of bursting in oxytocin cells during suckling. Extracellular electrical activity of paraventricular and supraoptic oxytocin cells was recorded in lactating rats from the beginning of suckling up to the first milk‐ejection burst, which occurred either within less than 1 h of suckling (bursting cells) or after injecting facilitatory drugs (non‐bursting cells).Significant differences in the distributions of firing rate (using low, intermediate and high categories, ≤ 1, 1–3 and > 3 spikes s−1, respectively) of bursting and non‐bursting cells were observed during suckling. Thirty minutes after pup application, most bursting cells (56%) had an intermediate firing rate, whereas non‐bursting cells had either a low (36%) or high (40%) firing rate.Thirty minutes after applying the pups, probability of bursting was highest for cells firing at 1–4 spikes s−1, and lowest for those firing above 5 spikes s−1.Bursting cells with high initial firing rate decreased their firing rate substantially during suckling while most of those with low initial firing rate showed increases. For non‐bursting cells, activity was maintained.There were marked differences in firing rate and its evolution between paired bursting cells. The firing rates for non‐bursting cell pairs were similar (mostly either low or high), and remained stable during suckling.In conclusion, we suggest that, as suckling proceeds, probability of bursting is related to the firing rate of oxytocin cells within the whole population, more specifically to the proportion of cells within the animal initially or subsequently displaying a critical firing rate (between 1 and 3 spikes s−1). The firing rates of cells which eventually burst and which are firing outside this range change in a direction which brings them into the preferred range for bursting.We suggest that when bursting occurs unaided, a majority of oxytocin cells fire in the preferred bursting range and facilitate the bursting of cells outside this range. Since such cooperativity does not develop between non‐bursting cells, it might be due to centrally released oxytocin.
Different roles for GABAA and GABAB receptors in visual processing in the rat superior colliculus
Authors: Binns K. E. , Salt T. E. 
Published: September 2004

The superficial grey layer of the superior colliculus (SGS) contains a high proportion of GABAergic inhibitory neurones. We have investigated the role of GABA receptors in synaptic transmission of aspects of visual activity in the SGS that may be driven by inhibitory mechanisms, such as surround inhibition and response habituation.
Multi‐barrel glass iontophoretic pipettes were used to record single neuronal activity in the SGS of urethane‐anaesthetized rats. Visual stimulation was provided by the display of moving bars and stationary spots of light on a monitor placed in the receptive field.
Both ejection of GABA and the GABAB agonist baclofen reduced responses to moving bars (interstimulus intervals ≥ 8 s). The effects of GABA were reversed by the GABAA antagonist bicuculline, and the effects of baclofen were antagonized by the GABAB antagonist CGP 35348.
Surround inhibition was estimated by plotting the response to flashed spots of increasing diameter. In controls, expanding the spot diameter beyond the excitatory receptive field caused a decrease in the response. This inhibitory surround was reversibly reduced by bicuculline, but CGP 35348 had no effect.
Response habituation is the progressive reduction in the visual response during repetitive stimulus presentation. In controls, the visual response was reduced to 44 ± 3% of its initial level when a stimulus (moving bar) was presented 5 times with an interstimulus interval of 0.5 s. During CGP 35348 ejection, response habituation was reversibly reduced. Bicuculline had no effect on response habituation.
The effects of bicuculline on surround inhibition in the superior colliculus are consistent with similar studies in the lateral geniculate nucleus which indicate that GABAA receptors mediate this effect. The function of GABAB receptors in the visual system is less well researched. The reduction of response habituation with CGP 35348 demonstrates that, at least in the SGS, GABAB receptors have an important role in visual transmission which is distinct from that of GABAA receptors.
Identification of a Zn2+ binding site on the marine gABAA receptor complex: Dependence on the Second transmembrane domain of β subunits
Authors: Wooltorton Julian R. A. , McDonald Bernard J. , Moss Stephen J. , Smart Trevor G. 
Published: September 2004

Whole‐cell currents were recorded from Xenopus laevis oocytes expressing wild‐type and mutant recombinant GABAA receptors to locate a binding site for Zn2+ ions in the β3 subunit.
The Cl−‐selective current, spontaneously gated by β3 subunit homomers, was enhanced by pentobarbitone and inhibited by picrotoxinin. The potencies of these agents were minimally affected by mutating histidine (H) 292 to alanine (A) in the second transmembrane domain (TM2).
Zn2+ inhibited the β3 subunit‐gated conductance (IC50, 0.31 μm); the inhibition was voltage insensitive. The H292A mutation in β3 subunits caused a 1000‐fold reduction in Zn2+ potency (IC50, 307 μm).
GABA‐activated responses recorded from heteromeric α1β3 GABAA receptors were also inhibited by Zn2+ (IC50, 0.11 μm). This inhibition was reduced by mutating H292A in the β3 subunit (IC50, 22.8 μm).
H292 in TM2 of the β3 subunit is an important determinant of a Zn2+ binding site on the GABAA receptor. Its location in the presumed ion channel lining suggests that Zn2+ can penetrate into an anion‐selective channel and that the ionic selectivity filter and channel gate are located beyond H292.
Nitric Oxide Contributes to Substance P‐Induced Increases in Lung Rapidly Adapting Receptor Activity in Guinea‐Pigs
Authors: Joad Jesse P. , Kott Kayleen S. , Bonham Ann C. 
Published: September 2004

Substance P induces fluid flux via nitric oxide, and fluid flux stimulates lung rapidly adapting receptors (RARs). We therefore proposed that nitric oxide contributes to substance P‐evoked increases in RAR activity. Since substance P decreases dynamic compliance (Cdyn), which can stimulate RARs, we also determined whether nitric oxide contributed to substance P‐induced effects on pulmonary function.
In anaesthetized guinea‐pigs, the effects of substance P on RAR activity, Cdyn, pulmonary resistance (RL), and arterial blood pressure were measured before and after i.v. infusion of NG‐methyl‐l‐arginine (l–NMMA; a nitric oxide synthase inhibitor), or l–NMMA followed by l‐arginine (a nitric oxide precursor which reverses the effects of l–NMMA).
Substance P‐evoked increases in RAR activity were blunted by l–NMMA (P= 0.006) but not by l–NMMA–l‐arginine (P= 0.42).
Substance P‐evoked decreases in Cdyn were slightly inhibited by l–NMMA (P= 0.02) and slightly enhanced by l‐NMM A–l‐arginine (P= 0.004). However, at the time at which l–NMMA maximally reduced substance P‐induced RAR stimulation (the first 30 s), it did not change substance P‐induced decreases in Cdyn.
Substance P‐evoked increases in RL were not changed by l–NMMA (P= 0.10) and were enhanced by l‐NMM A–l‐arginine (P= 0.03).
l–NMMA‐evoked increases in mean arterial blood pressure were reversed by l‐arginine. Substance P‐evoked decreases in mean arterial blood pressure were not changed by l–NMMA or by l–NMMA–l‐arginine.
We conclude that nitric oxide contributes to substance P‐evoked increases in RAR activity and that the increases are most probably independent of decreases in Cdyn.
Fluid transport across cultures of human tracheal glands is altered in cystic fibrosis
Authors: Jiang C. , Finkbeiner W. E. , Widdicombe J. H. , Miller S. S. 
Published: September 2004

There is evidence that defective submucosal gland secretion contributes to the airway pathology of cystic fibrosis (CF). Using a capacitance probe technique, we have compared fluid transport across submucosal gland cultures from individuals with and without CF.
Under baseline conditions, ∼60% of non‐CF cultures secreted fluid; the rest absorbed. In secreting tissues, amiloride increased secretion, whereas in absorbing tissues it reduced or reversed absorption. 5‐Mtro‐2‐(3‐ phenylpropylamino)‐benzoate (NPPB) a blocker of the CF transmembrane conductance regulator (CFTR), converted secretion to absorption. Thus, the direction and magnitude of baseline fluid movement depended on a balance between active absorption of Na+ and cAMP‐dependent secretion of CI−.
8‐(4‐Chlorophenylthio)‐adenosine 3',5'‐cyclic monophosphate (CPT‐cAMP), methacholine and luminal uridine 5'‐triphosphate (UTP) all induced or increased fluid secretion across non‐CF cultures. Results with NPPB and with 4,4'‐diisothiocyanatostilbene‐2,2'‐disulphonate (DIDS), a blocker of Ca2+ ‐activated CI− channels, suggested that fluid secretion induced by CPT‐cAMP was mediated primarily by CFTR; UTP acted entirely via Ca2+ ‐activated CI− channels, and methacholine activated both pathways.
All CF cultures showed baseline fluid absorption, which was abolished by amiloride.
CF cultures showed a normal secretory response to UTP, a reduced response to methacholine, and no response to CPT‐cAMP.
Thus, the absorptive processes of airway glands are retained in CF, but the cAMP‐dependent secretory process is lost. This would markedly reduce the water content of gland secretions. The resulting change in viscosity would contribute to the accumulation of airway mucus which is characteristic of this disease.
Inhibition of ATP‐activated current by zinc in dorsal root ganglion neurones of bullfrog
Authors: Li Chaoying , Peoples Robert W. , Weight Forrest F. 
Published: September 2004

The effect of Zn2+ on ATP‐activated current was studied in bullfrog dorsal root ganglion (DRG) neurones using the whole‐cell patch‐clamp technique.
Zn2+ (2–800 μm) inhibited current activated by submaximal concentrations of ATP. The Zn2+ concentration that produced 50% inhibition (IC50) of current activated by 2.5 μm ATP was 61 ± 9.8 μm. When ATP concentrations were adjusted to account for chelation of Zn2+, the IC50 of Zn2+ was 86 ± 18 μm.
The inhibitory action of Zn2+ on ATP‐gated channels did not appear to be due to a decrease in the concentration of one or more species of ATP.
Zn2+ inhibition of ATP‐activated current was independent of membrane potential between −80 and +40 mV, and did not involve a shift in the reversal potential of the current.
Zn2+ (100 μm) shifted the ATP concentration‐response curve to the right in a parallel manner, increasing the EC50 for ATP from 2.5 ± 0.5 μm to 5.5 ± 0.4 μm.
Zn2+ decreased the time constant of deactivation of ATP‐gated ion channels without affecting the time constant of activation or desensitization.
Dithiothreitol (DTT) reversed Zn2+ inhibition of ATP‐activated current.
2‐Methylthio ATP, α,β‐methylene ATP and ADP activated current with EC50 values of 2.4 ± 0.3, 50.1 ± 5.8 and 303.1 ± 53.9 μm, respectively. Adenosine, AMP or β,γ‐methylene ATP did not evoke detectable current.
Reactive Blue 2 and pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid inhibited ATP‐activated current.
The results suggest that Zn2+ can inhibit P2X purinoceptor function by decreasing the affinity of the binding site for ATP. These observations provide the first evidence for this action of Zn2+ on a neurotransmitter‐gated ion channel. Furthermore, the receptor‐channel in these neurones appears to be a novel member of the P2X purinoceptor class.
Desensitization shortens the high‐quantal‐content endplate current time course in frog muscle with intact cholinesterase
Authors: Giniatullin R. A. , Talantova M. , Vyskočil F. 
Published: September 2004

The desensitization induced by bath‐applied carbachol or acetylcholine (ACh) and potentiated by proadifen (SKF 525A) was studied in the frog sartorius with intact synaptic acetylcholinesterase (AChE).
The reduction in the density and number of postsynaptic receptors produced by desensitization lowered the amplitude of the endplate currents (EPCs) and shortened the EPC decay when the quantal content (m) of the EPC was about 170 and when multiple release of quanta at single active zones was highly probable. The shortening of high‐quantal‐content EPCs persisted for at least 15 min after the wash‐out of agonists, at a time when the amplitude had recovered fully.
The decay times of the low‐quantal‐content EPCs recorded from preparations pretreated with 5 mm Mg2+ (m≈ 70) and single‐quantum miniature endplate currents (MEPCs) were not affected by carbachol, ACh or proadifen.
The desensitization of ACh receptors potentiated by proadifen, prevented completely the 6‐ to 8‐fold prolongation of EPC which was induced by neostigmine inhibition of synaptic AChE.
It is assumed that high‐quantal‐content EPCs increase the incidence of multiple quanta release at single active zones and the probability of repetitive binding of ACh molecules which leads to EPC prolongation. The shortening which persists after complete recovery of the amplitude during wash‐out of the exogenous agonist is probably due to ‘trapping’ of ACh molecules onto rapidly desensitized receptors and the reduced density of functional AChRs during the quantum action.