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R Miles

Publications and source records attributed to R Miles.

At least 55 records · Page 3Linked to original sources
PubMed1993

Precision and variability in postsynaptic target selection of inhibitory cells in the hippocampal CA3 region.

Non-pyramidal cells were filled intracellularly with biocytin in the CA3 region of the guinea-pig hippocampus in vitro, within or close to stratum pyramidale. On the basis of camera lucida reconstructions and electron microscopy, six different cell types with distinct laminar distribution of axon terminals could be distinguished. The axon of three axo-axonic cells, three typical basket cells, and atypical basket cells of two types arborized in the perisomatic and proximal dendritic region of CA3 pyramidal cells. Two cells with axons innervating the distal dendritic segments of pyramidal cells were also found; one terminated in stratum radiatum and the other in stratum lacunosum-moleculare. Electron microscopy demonstrated that symmetrical synapses were formed by the labelled boutons on axon initial segments, somata, and proximal or distal dendrites of mostly pyramidal neurons. Axo-axonic cells showed absolute target selectivity for axon initial segments, whereas for the other cells the distribution of contacted elements was determined by the laminar distribution of axon terminals. In two cases, where additional cells were labelled with biocytin, multiple (up to nine) light microscopically identified contacts (presumed synaptic contacts) were established by the interneurons on several pyramidal cells and on an axo-axonic cell. Our results show that a restricted set of inhibitory cells, with somata within or close to CA3 stratum pyramidale, possess variable patterns of axonal arborization. Various types of postsynaptic elements are contacted, but precision in selecting certain targets and ignoring others is maintained within a particular cell type and layer. In contrast to the diversity of axonal arbors the structure of the dendritic trees shows no consistent differences, suggesting that the cells may be activated by a similar set of afferents. It seems probable that the innervation of precise regions of postsynaptic pyramidal cells by different types of interneurons--often in conjunction with particular excitatory afferents (Han et al., Eur. J. Neurosci., 5, 395-410, 1993)--underlies functional differences in inhibitory synaptic actions.

Animals↗
PubMed1993

Synaptic and intrinsic conductances shape picrotoxin-induced synchronized after-discharges in the guinea-pig hippocampal slice.

1. A computer model was constructed of the guinea-pig hippocampal region in vitro, containing 100 pyramidal neurones. This approach has contributed to the understanding of brief (usually less than 100 ms) epileptic events known as 'interictal spikes'. The present study addresses the cellular mechanisms of more prolonged epileptic events, lasting 200 ms and more, that may represent short-duration seizures. Each neurone was simulated with a nineteen-compartment model using six voltage-dependent ionic conductances. The neurones were randomly interconnected with excitatory synapses, each synapse exerting a fast voltage-independent alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) component and a slower voltage-dependent N-methyl-D-aspartate (NMDA) component. Each neurone received input from twenty other neurones. 2. This model was able to generate, in response to synaptic noise or to stimulation of one neurone, a series of synchronized population bursts, the initial (primary) burst being longer than later (secondary) bursts, terminating in a prolonged after-hyperpolarization. The simulated after-discharge potentials resemble those recorded experimentally from pyramidal neurones during perfusion of the hippocampal slice with media containing picrotoxin, a blocker of synaptic inhibition mediated by GABAA receptors. 3. Simulated after-discharges agree with the following experiments: over a certain range of total NMDA conductance, blockade of AMPA receptors will prevent the occurrence of synchronized firing, whereas, blockade of NMDA receptors will, in contrast, abolish the secondary bursts, leaving a shortened and somewhat smaller primary burst. Dendritic potential oscillations occur in phase with somatic oscillations. When interneurones (some generating GABAA-mediated IPSPs, others generating GABAB IPSPS) are included in the model, the occurrence of synchronized events was suppressed, the most significant suppressant effect coming from GABAA IPSPS. 4. The model predicts that: a dendritic calcium spike occurs during each secondary burst; AMPA receptors serve to maintain the synchrony of secondary bursts, as well as to initiate the primary burst; and that with sufficient total NMDA conductance, synchronized firing can occur even with AMPA receptors blocked. 5. The model suggests, in addition, that the duration of the initial burst is determined in part by the experimentally observed delay between Ca2+ entry and peaking of the after-hyperpolarization (AHP) conductance, and hence reflects properties of the individual pyramidal neurones. Specifically, a pattern of a long initial burst followed by brief secondary bursts is elicited in single-cell simulations by injection of a steady depolarizing current into the apical dendrite. The same pattern is produced when the single-cell model includes only calcium and calcium-dependent conductances.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Metabotropic glutamate receptors mediate a post-tetanic excitation of guinea-pig hippocampal inhibitory neurones.

1. Inhibitory cell activity and inhibitory postsynaptic potentials impinging spontaneously on pyramidal cells were recorded in the CA3 region of hippocampal slices from guinea-pig. We compared the effects on synaptic inhibition, of tetanic stimuli in the presence of antagonists of ionotropic excitatory amino acid receptors, and of application of agonists of metabotropic glutamate receptors. 2. Tetanic stimulation of afferent fibres caused an increase, of duration 0.5-2.5 min, in the frequency of spontaneous Cl(-)-mediated IPSPs. Inhibitory cell firing increased due to a depolarization and a reduction of after-hyperpolarizing potentials. 3. Tetanic stimulation induced, in some experiments, rhythmic bursts of IPSPs and transformed the firing pattern of some inhibitory cells from a discharge of single action potentials to rhythmic bursts of three to five action potentials. 4. Application of the metabotropic glutamate receptor agonist, trans-1-amino-cyclopentane-1,3-dicarboxylic acid (tACPD), at concentrations from 3-10 microM increased the frequency of spontaneous IPSPs. In some slices tACPD caused IPSPs to occur rhythmically. IPSP frequency did not continue to increase with concentrations of tACPD above 20 microM. 5. tACPD depolarized inhibitory cells and reduced after-hyperpolarizing potentials. High concentrations (50-100 microM) of tACPD excited inhibitory cells to potentials at which they no longer discharged fast action potentials. 6. Both tetanic stimulation and tACPD led to the appearance in pyramidal cell pairs of simultaneous IPSPs which were not previously observed, suggesting that the same group of inhibitory cells was excited in both cases. 7. Low concentrations of tACPD (3-10 microM) enhanced IPSP responses to tetanic stimuli, while the effects of tetanic stimuli were occluded in the presence of high concentrations (20-30 microM) of tACPD. 8. We suggest that activation of metabotropic glutamate receptors during tetanic stimulation leads to a post-tetanic excitation of inhibitory cells that mediate Cl(-)-dependent IPSPs.

2-Amino-5-phosphonovalerate↗
PubMed1993

Analysis of the propagation of disinhibition-induced after-discharges along the guinea-pig hippocampal slice in vitro.

1. A model has been proposed of picrotoxin-induced hippocampal in vitro after-discharges; it depends critically upon alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the recurrent excitatory connections between pyramidal neurones, and upon the ability of pyramidal neurones to generate bursts at about 10 Hz when their dendrites are sufficiently depolarized. 2. We study here the question of whether this model can account for spatial--as well as temporal--aspects of after-discharges in guinea-pig hippocampal slices. For example, can the model explain the propagation along a transverse slice of the initial burst and the secondary bursts at about the same velocity, approximately 0.10-0.20 m s-1? Under what conditions might the secondary bursts exhibit a different spatial pattern to the initial burst, as we now show can occur in longitudinal slices? To examine these questions, we increased the number of cells in our model from 100 to 8000 (in a 20 x 400 array), arranging the excitatory synaptic connections in a spatially restricted fashion, with an average extent of 1.0 mm (as suggested experimentally). 3. Our model suggests that both AMPA and NMDA receptors contribute to the propagation pattern and velocity of the initial and the secondary bursts in an after-discharge. 4. When unitary AMPA and NMDA conductances are in the range where the primary burst lasts for 100-200 ms, and there are three or four secondary bursts, then both primary and secondary bursts propagate near to the experimentally observed velocity for transverse slices. In the model, however, secondary bursts propagate at somewhat slower velocities than the initial burst. 5. The mechanisms of propagation are different for the initial and for the secondary bursts: propagation of the primary burst depends upon the initiation of electrogenesis in 'resting' dendrites by AMPA and NMDA inputs that are rapidly increasing in time. Propagation of secondary bursts depends upon the timing of calcium spikes in depolarized dendrites with slowly varying NMDA inputs; the timing of calcium spikes can be influenced by a 'wave' of AMPA input, but calcium spikes--we predict--should occur even without the AMPA input, once the after-discharge has been initiated. The blockade of firing in an intermediate region of the disinhibited slice is predicted to have different effects on the primary burst and on secondary bursts distal to the region of blockade.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Current trends in the usage of the Adaptability Rating for Military Aviation (ARMA) among USAF flight surgeons.

The Adaptability Rating for Military Aviation (ARMA) is that portion of the initial flight physical that assesses an aviator candidate's motivation for and potential adaptability toward an aviation career. A survey was mailed to all USAF operational flight surgeons in the continental U.S. to describe the frequency and distribution of ARMA usage and attitudes. Descriptive statistics suggest that the ARMA is used suboptimally in accordance with current USAF regulation. ARMA training, flight surgeon satisfaction and lack of regulation clarity are described and discussed. More flight surgeons are dissatisfied with the ARMA than are satisfied, and the regulation is perceived as unclear in the area of final disposition for candidates with equivocal ARMA's. A post-hoc analysis to rule out the influences of rank, gender, experience and residency training was performed. Residency training in Aerospace Medicine is beneficial in terms of doing an ARMA, when required, and covering recommended areas. Females and those with less than 1 year experience perform an ARMA more frequently than males and experienced flight surgeons. Despite the limitations of the current ARMA, it should not be abandoned. Recommendations to improve it are provided. Doing better ARMA's can lead to decreased illness, injury, accidents, and attrition.

Adaptation, Psychological↗
PubMed1992

Computer simulation of carbachol-driven rhythmic population oscillations in the CA3 region of the in vitro rat hippocampus.

1. We used simulations of the in vitro CA3 region of the hippocampus to analyse the 5 Hz population oscillations recorded experimentally in carbachol. 2. A simulation model of the in vitro CA3 region was constructed with 1000 pyramidal neurones and 200 inhibitory neurones (100 producing fast inhibitory postsynaptic potentials (IPSPs) and 100 producing slow IPSPs of delayed onset). Each neurone contained nineteen soma-dendritic compartments. Pyramidal neurones contained six voltage- and/or calcium-dependent ionic currents, whose kinetics were consistent with voltage-clamp data. The connectivity and waveform of unitary synaptic events for excitatory and fast inhibitory synapses were consistent with dual intracellular recordings. This network was shown to generate previously described network oscillations, including synchronized bursts recorded in the presence of GABAA blockers, and synchronized synaptic potentials observed during partial blockade of GABAA inhibition. 3. The model generated 5 Hz oscillations as recorded in carbachol under the following conditions: (a) excitatory synaptic conductance was within a limited range; (b) there was blockade of fast and slow IPSPs (consistent with the experimental lack of effect of bicuculline and phaclofen on carbachol oscillations and the known depression of IPSPs by acetylcholine); (c) the after hyperpolarization (AHP) conductance was reduced (consistent with the known pharmacology of carbachol); (d) the apical dendrites of the pyramidal cells were depolarized, as suggested by the carbachol-induced depolarization of pyramidal neurones. Each oscillation was associated in pyramidal cells with a burst of action potentials riding on a depolarizing wave. The N-methyl-D-aspartate (NMDA) type of excitatory synapse was not necessary for the oscillations to occur. 4. Progressive reduction of excitatory synaptic strength led to an oscillation of the same frequency, with bursts riding on smaller EPSPs (consistent with the experiment). Further reduction of excitatory synaptic strength abolished the population oscillation by uncoupling the neurones. When excitatory synaptic conductance was too large, population oscillations were attenuated as the cells switched from a bursting mode to a repetitively firing mode. 5. Increasing the AHP conductance prolonged the interburst interval as expected. Inclusion of slow IPSPs exerted a similar effect. 6. When fast IPSPs were included, an oscillation with different characteristics emerged: a 10 Hz oscillation that was gated by compound GABAA IPSPs. On any oscillatory wave, few pyramidal neurones fired, and the firing of individual neurones was irregular.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Teicoplanin in open fractures: a preliminary report.

The occurrence of infection following open fractures varies with the severity of the fracture and associated soft tissue damage. In order to study the effect of antibiotics given prophylactically, teicoplanin has been used in a prospective study. On admission, fractures were graded according to the severity of the tissue damage: Type I--soft tissue injury less than 1 cm Type II--soft tissue injury more than 1 cm. Type III fractures characterized by extensive soft tissue and bone damage were not included in the study. Type I patients were given a single dose of teicoplanin, 400 mg i.v.; Type II patients were given a single dose of teicoplanin, 400 mg i.v., followed by two further intravenous injections at 12 and 24 hours. Patients were assessed for the presence of wound and bone infections and follow up was for 1 year. Preliminary results, predominantly from Type II fractures involving long bones, show that teicoplanin is effective in lowering the incidence of infection following open fractures.

Adolescent↗
PubMed1991

CA 125 levels in abruptio placentae.

The diagnosis of abruptio placentae is frequently difficult despite ultrasonography; additional diagnostic parameters would be useful. Maternal serum CA 125, which is believed to derive from the decidua, is elevated in the first trimester and immediately after delivery when placental separation occurs, possibly because of decidual disruption. Serum CA 125 was measured in 27 patients beyond 20 weeks' gestation who were first seen with vaginal bleeding and in 17 control patients of similar gestational age and labor status. Mean (+/- SD) CA 125 levels were higher (p less than 0.01) among patients with abruptio placentae (105.9 +/- 115 U/ml) than among those with alternate sources of bleeding (13.7 +/- 10 U/ml) or control patients (18.2 +/- 11.7 U/ml). Mean (+/- SD) serum CA 125 levels in seven control patients within 6 hours post partum (194 +/- 80.5 U/ml) were higher than those among patients first seen with abruptio placentae (p less than 0.01). Sensitivity and specificity of CA 125 for abruptio placentae were 70% and 94%, respectively. Our data support a decidual source for CA 125 and may indicate utility of CA 125 as a marker for abruptio placentae.

Abruptio Placentae↗
PubMed1991

Migration to Britain: the significance of a historical approach.

The author discusses migration to Great Britain since 1945, with a focus on the importance of taking a historical approach in order to understand long-held assumptions regarding migration from the British Caribbean and the Indian subcontinent. Causes and consequences of non-European migrants being considered members of distinct and inferior races are analyzed. The author concludes that "when seeking to explain the nature and significance of racism in contemporary Europe, we might usefully begin by focussing on the processes involved in the construction and reproduction of the Nation-State...." (SUMMARY IN FRE AND SPA)

Americas↗
PubMed1991

Tetanic stimuli induce a short-term enhancement of recurrent inhibition in the CA3 region of guinea-pig hippocampus in vitro.

1. Recordings were made from pre- and postsynaptic cells at synapses involved in generating synaptic inhibition in the CA3 region of slices from guinea-pig hippocampus to examine the short-term effects of tetanic stimuli on recurrent inhibitory circuits. 2. Disynaptic inhibitory interactions were facilitated for a period of 2-5 min after tetanic stimulation of afferent fibres. The facilitation was due to an increase in the probability that IPSPs were transmitted. The amplitude of IPSPs that were evoked did not change. 3. IPSPs elicited by single action potentials in inhibitory cells were not changed immediately after tetanic stimulation. 4. There was no short-term change in the amplitude of unitary or spontaneously occurring EPSPs recorded from inhibitory cells. 5. The frequency of spontaneous IPSPs recorded in CA3 pyramidal cells increased transiently after tetanic stimuli delivered in the presence of excitatory amino acid receptor antagonists. 6. Tetanic stimuli caused a voltage-dependent increase in excitability of CA3 inhibitory cells. Little effect was apparent at hyperpolarized potentials. Near resting potential, tetanic stimuli enhanced inhibitory cells firing frequency partly by increasing the rate of membrane repolarization after an action potential. 7. These findings suggest tetanic stimulation releases a transmitter or other factor that alters intrinsic currents of CA3 inhibitory cells for several minutes, increasing their excitability and resulting in a transient facilitation of recurrent synaptic inhibition.

2-Amino-5-phosphonovalerate↗
PubMed1991

A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances.

1. We have developed a 19-compartment cable model of a guinea pig CA3 pyramidal neuron. Each compartment is allowed to contain six active ionic conductances: gNa, gCa, gK(DR) (where DR stands for delayed rectifier), gK(A), gK(AHP), and gK(C). THe conductance gCa is of the high-voltage activated type. The model kinetics for the first five of these conductances incorporate voltage-clamp data obtained from isolated hippocampal pyramidal neurons. The kinetics of gK(C) are based on data from bullfrog sympathetic neurons. The time constant for decay of submembrane calcium derives from optical imaging of Ca signals in Purkinje cell dendrites. 2. To construct the model from available voltage-clamp data, we first reproduced current-clamp records from a model isolated neuron (soma plus proximal dendrites). We next assumed that ionic channel kinetics in the dendrites were the same as in the soma. In accord with dendritic recordings and calcium-imaging data, we also assumed that significant gCa occurs in dendrites. We then attached sections of basilar and apical dendritic cable. By trial and error, we found a distribution (not necessarily unique) of ionic conductance densities that was consistent with current-clamp records from the soma and dendrites of whole neurons and from isolated apical dendrites. 3. The resulting model reproduces the Ca(2+)-dependent spike depolarizing afterpotential (DAP) recorded after a stimulus subthreshold for burst elicitation. 4. The model also reproduces the behavior of CA3 pyramidal neurons injected with increasing somatic depolarizing currents: low-frequency (0.3-1.0 Hz) rhythmic bursting for small currents, with burst frequency increasing with current magnitude; then more irregular bursts followed by afterhyperpolarizations (AHPs) interspersed with brief bursts without AHPs; and finally, rhythmic action potentials without bursts. 5. The model predicts the existence of still another firing pattern during tonic depolarizing dendritic stimulation: brief bursts at less than 1 to approximately 12 Hz, a pattern not observed during somatic stimulation. These bursts correspond to rhythmic dendritic calcium spikes. 6. The model CA3 pyramidal neuron can be made to resemble functionally a CA1 pyramidal neuron by increasing gK(DR) and decreasing dendritic gCa and gK(C). Specifically, after these alterations, tonic depolarization of the soma leads to adapting repetitive firing, whereas stimulation of the distal dendrites leads to bursting. 7. A critical set of parameters concerns the regulation of the pool of intracellular [Ca2+] that interacts with membrane channels (gK(C) and gK(AHP)), particularly in the dendrites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

A 31P-NMR study of the mechanism of and salt effect on Mg2(+)-ATP exchange.

The study of exchange between free and metal-bound ligands by NMR methods is discussed with reference to differentiation between unimolecular dissociation of the metal-bound complex and biomolecular exchange of metal ion between two ligands. This is applied to exchange of ATP4- between the free and Mg2(+)-bound states and problems of interpretation in the presence of a strong kinetic salt effect are discussed. Contrary to a previous report, exchange is inferred to occur mainly via unimolecular dissociation of MgATP2- over a range of temperatures, concentrations, and pH values, which include those expected in vivo. For the model system Mg2(+)-tripolyphosphate, an activation energy of 52 +/- 5 kJ.mol-1, inferred to be that for dissociation of MgTPPH2-, is found for the exchange process.

Biological Transport↗
PubMed1990

Synaptic excitation of inhibitory cells by single CA3 hippocampal pyramidal cells of the guinea-pig in vitro.

1. In simultaneous recordings from pairs of neurones in hippocampal slices from guinea-pigs, single action potentials fired by CA3 pyramidal cells could initiate inhibitory postsynaptic potentials (IPSPs) in nearby pyramidal cells. 2. The latencies of these IPSPs could be as short as 3 ms. However, they were mediated disynaptically via chemical, excitatory synapses, since inhibitory coupling was suppressed by an excitatory amino acid antagonist. 3. The properties of excitatory synapses made onto inhibitory cells were examined to assess the basis for this strong coupling. Inhibitory cells were identified either by showing that they inhibited another cell or by their characteristic firing pattern. 4. Excitatory postsynaptic potentials (EPSPs) elicited by single pyramidal cell action potentials had a mean amplitude of 1-4 mV and a time to peak of 1.5-4 ms. In most cases they decayed with a time constant similar to that of the inhibitory cell membrane. 5. EPSP amplitude increased with hyperpolarization of the postsynaptic membrane. Membrane polarization had little effect on EPSP shape. 6. EPSPs fluctuated in amplitude and transmission sometimes failed, suggesting transmission was quantal and that few quanta were released. 7. When presynaptic cells were made to fire bursts of action potentials, EPSPs in inhibitory cells were initially potentiated. 8. EPSPs could cause inhibitory cells to fire. The interval between pre- and postsynaptic spikes could be as short as 2.5 ms and the probability of spike transmission could be as high as 0.6. Some inhibitory cells which received feedback excitation were also excited in feedforward fashion by mossy fibre stimuli. 9. One pyramidal cell could activate several disynaptic inhibitory pathways terminating on another pyramidal cell. This suggests that excitatory synapses made by pyramidal cell axon collaterals onto inhibitory cells are divergent. 10. This strong, divergent excitation of inhibitory cells ensures recurrent inhibition is sufficiently widespread, rapid and potent to control the spread of activity by recurrent excitatory connections between CA3 pyramidal cells.

Action Potentials↗
PubMed1990

Characteristics of miniature inhibitory postsynaptic currents in CA1 pyramidal neurones of rat hippocampus.

1. Recordings were made in vitro from chloride-loaded CA1 rat hippocampal pyramidal neurones in the presence of tetrodotoxin (TTX) to examine miniature inhibitory postsynaptic currents (IPSCs). 2. Most spontaneous synaptic events recorded before TTX was applied, and all events that were resolved in the presence of TTX, were blocked by the GABAA receptor antagonist bicuculline. 3. At 25 degrees C, averaged miniature IPSCs had time to peak of about 3 ms and in most cases decayed with a single time constant close to 25 ms. 4. With a driving force for chloride ions between 70 and 80 mV, the mean miniature IPSC amplitude was 19.6-27.9 pA, yielding a conductance of 258-326 pS. The mean amplitude of unitary IPSCs recorded before TTX was applied was in the range of 31-73 pA. 5. When intervals between miniature IPSCs were compared with an exponential distribution, there was an excess of events at intervals shorter than 5 ms. Some individual events appeared to represent the nearly simultaneous release of two inhibitory quanta. 6. Miniature IPSC amplitude distributions were better fitted with the sum of two Gaussians than with one Gaussian. The variance in amplitude of a single quantal event exceeded that of the baseline noise. 7. Comparison of the conductance changes corresponding to the first Gaussian distribution with single GABA channel data suggests that one inhibitory quantum opens twelve to twenty chloride channels and that GABA molecules bind once to a postsynaptic receptor.

Animals↗
PubMed1990

Variation in strength of inhibitory synapses in the CA3 region of guinea-pig hippocampus in vitro.

1. Simultaneous recordings were made from inhibitory cells located close to the stratum pyramidale and from pyramidal cells in the CA3 region of guinea-pig hippocampal slices, to examine inhibitory synaptic interactions. 2. The average amplitude of inhibitory postsynaptic potentials (IPSPs) initiated by single action potentials at different synapses varied between 0.3 and 2.6 mV. Experiments were performed to investigate the source of this variation. 3. Unitary IPSPs reversed at similar potentials to the first phase of the synaptic inhibition elicited by afferent fibre stimulation. IPSPs evoked by single action potentials or repetitive inhibitory cell firing were suppressed by picrotoxin, a gamma-aminobutyric acid (GABAA) receptor antagonists. 4. The time to peak and amplitude of averaged IPSPs were not related as predicted if amplitude variations resulted simply from different electrotonic locations of inhibitory terminals. 5. Transmission failures could be resolved at connections which generated small averaged IPSPs, but were not apparent at connections where averaged IPSPs were large. 6. IPSPs elicited by the same inhibitory cell in several pyramidal cells were of similar amplitude. The amplitudes of simultaneous IPSPs impinging on pairs of neighboring pyramidal cells were positively correlated. 7. Thus, the variation in efficacy of inhibitory synapses may result from differences in transmitter release from different inhibitory cells and not from postsynaptic factors.

2-Amino-5-phosphonovalerate↗
PubMed1990

Excitatory amino acid receptors of guinea pig medial nucleus tractus solitarius neurons.

Neurons isolated from the medial subnuclei of nucleus tractus solitarius in adult guinea pigs were studied for responses to the excitatory amino acid glutamate and its analogues using the whole cell tight-seal voltage clamp technique. In 80% of the cells studied (n = 60) 100 microM glutamate produced inward currents at negative voltages. To further characterize the glutamate response, the agonists for three glutamate receptor subtypes, N-methyl-D-aspartate (NMDA), kainate, and quisqualate, were examined for their effects on membrane conductance. NMDA (25-250 microM) activated currents in 85% of the neurons tested (n = 30). NMDA currents were generally very small in amplitude. Of the neurons tested, 84% responded to kainate (10-30 microM, n = 19) and only 50% to quisqualate (25-50 microM, n = 26). The conductance activated by NMDA was outwardly rectifying. The conductance activated by kainate was voltage independent, while that activated by quisqualate showed varying degrees of outward rectification. Responses to NMDA were specifically antagonized by DL-2-amino-5-phosphonovaleric acid (AP-5, 50-100 microM). Kainate responses were blocked by kynurenate at concentrations (0.5-1.5 mM) ineffective on quisqualate-induced current. Glutamic acid diethyl ester (GDEE, 2-15 mM) was effective in reducing quisqualate responses at concentrations that had no effect on kainate responses. This characterization of the glutamate receptor subtypes and effective antagonists provides a basis for future determination of the specific receptor of glutamate responsible for mediation of the excitatory postsynaptic potentials produced by activation of the baroreceptor input.

Amino Acids↗