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J D Lambert

Publications and source records attributed to J D Lambert.

At least 19 recordsLinked to original sources
PubMed1995

Regenerative properties of pyramidal cell dendrites in area CA1 of the rat hippocampus.

1. Intracellular recordings were obtained from 184 distal apical dendrites and twenty-six somata of CA1 pyramidal neurones in the rat hippocampal slice preparation. In the presence of 3.25 mM K+ 200 ms suprathreshold current pulses evoked three different types of firing patterns in the apical dendrites, all of which were distinct from regular somatic firing. Fast tetrodotoxin (TTX)-sensitive spiking was evoked in 38.8% of the dendrites. Compound spiking, consisting of an initial fast spike followed by one or more secondary slow spikes of variable amplitude and duration, was seen in 44.1% of dendrites. 'Classical' burst firing, resembling intrinsic somatic bursts, was evoked in 17.1% of the dendrites. 2. In fast spiking dendrites, the spikes evoked by long depolarizing pulses were rarely overshooting, showed prominent accommodation and declined progressively to about one-third of the initial amplitude. The amplitude of single dendritic fast spikes (50.6 +/- 1.5 mV; mean +/- S.E.M.) was smaller than that of somatic spikes (82.2 +/- 1.9 mV) and their rate of rise (81.3 +/- 4.3 V s-1) was markedly slower than that of somatic spikes (291.5 +/- 17.8 V s-1). However, the thresholds were not significantly different (dendrites, -49.8 +/- 0.8 mV; somata, -50.8 +/- 1.3 mV). These results indicate that fast spikes in the distal parts of apical dendrites are generated by a local regenerative Na+ current. 3. 4-Aminopyridine (4-AP, 0.1-0.5 mM) caused a dose-dependent slowing of the repolarization of the fast spikes, while tetraethylammonium (TEA, 2 mM) and Co2+ (2 mM) induced a slowing of the late phase of the repolarization. These results indicate that the transient outward K+ current, IA, and the Ca(2+)-activated K+ current, IC, are involved in the repolarization of dendritic Na(+)-dependent spikes. 4. Compound spiking was completely blocked by TTX (0.5-1 microM). The secondary slow spikes within the complex were blocked by Co2+ (2 mM), nifedipine (10 microM) and high concentrations (> 50 microM) of verapamil, while Ni2+ (100-300 microM) had no effect. Thus, compound spiking consists of an initial Na(+)-dependent spike followed by one or more slow Ca(2+)-dependent spikes mediated by L-type Ca2+ channels located in the apical dendrites. 5. In fast spiking dendrites, 4-AP (0.5-2.5 mM) changed the firing pattern from regular fast spiking to compound spiking. In the presence of 4-AP (0.1-0.5 mM), the single fast spike evoked by a short (20 ms), threshold current pulse, was followed by secondary slow spikes of variable amplitude and duration.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1995

Increased NMDA receptor and calcium channel activity underlying ethanol withdrawal hyperexcitability.

Withdrawal from chronic ethanol administration results in hyperexcitability. In the hippocampus, evoked bursting activity and spontaneous epileptiform events are seen. The present study investigated the effect of ethanol withdrawal on N-methyl-D-aspartate (NMDA) receptor-mediated postsynaptic potentials and on voltage-gated calcium currents, in mouse hippocampal pyramidal cells. The NMDA receptor-mediated component of synaptic excitation was increased during withdrawal, accompanied by an increase in synaptic activation of calcium spikes. Evidence for a direct effect of ethanol withdrawal on calcium channel function was seen in voltage clamp recordings of isolated, slowly inactivating calcium currents. A synergistic effect of increased NMDA receptor and calcium channel function is therefore suggested to contribute to hyperexcitability during ethanol withdrawal.

Animals↗
PubMed1994

Factors contributing to the decay of the stimulus-evoked IPSC in rat hippocampal CA1 neurons.

1. Monosynaptic gamma-aminobutyric acid-A (GABAA)-mediated inhibitory postsynaptic currents (IPSCs) were evoked in CA1 pyramidal neurons in the hippocampal slice preparation by direct stimulation of the interneurons in the presence of glutamatergic blockers and intracellular QX-314 to block GABAB-mediated postsynaptic inhibition. 2. Paired-pulse stimulation was used to activate presynaptic GABAB autoreceptors and thereby reduce the amount of transmitter release. This caused paired-pulse depression, persisting for > 3 s, and maximal at interpulse intervals between 100 and 250 ms where peak current (Ipeak) was decreased by 29.7% and decay time (t1/2) was decreased by 44.7%. There was clear correlation between changes in Ipeak and t1/2 at all interpulse intervals. 3. With paired-pulse stimulation, the decay of the second IPSC in most cells (12/18) could be resolved into two components, Ifast and Islow, each decaying monoexponentially with tau fast = 14.10 ms and tau slow = 58.87 ms. The faster decay during paired-pulse depression was predominantly caused by a larger Ifast fraction, which accounted for 27.5% of Ipeak in a single control IPSC and 79.3% at an interpulse interval of 250 ms. 4. Reducing the probability for transmitter release at all active sites by reducing [Ca2+]o from 2 mM to 1 mM decreased Ipeak by 49.7%, reduced paired-pulse depression, and partly mimicked the changes in decay kinetics seen after activation of presynaptic GABAB receptors. Lowering the stimulating intensity to 10% of the maximal value decreased Ipeak by 73.8%, but hardly affected the decay of the IPSC and the paired-pulse depression. 5. Application of the selective blocker of GABA uptake, tiagabine (20-50 microM), increased t1/2 of a single IPSC by 114% without affecting Ipeak. The increase was caused solely by an increase in tau slow of 141%. On the other hand, the benzodiazepine agonist midazolam (2 microM), selectively increased tau fast. It therefore is suggested that tau fast reflects the kinetics of the GABAA receptor/ionophore complex and tau slow the efficiency of the GABA uptake system. 6. The findings show that GABA activates postsynaptic receptors throughout the tail of a single IPSC. This could be caused by reactivation of synaptic receptors or activation of extrasynaptic receptors. The decay therefore is limited mainly by the efficiency of the uptake system. An IPSC that is maximally depressed by paired-pulse stimulation is mediated primarily by a single activation of synaptic receptors, and the decay is limited mainly by the kinetics of the GABAA receptor/ionophore complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Comparison of the effect of the GABA uptake blockers, tiagabine and nipecotic acid, on inhibitory synaptic efficacy in hippocampal CA1 neurones.

The action of the novel gamma-aminobutyric acid (GABA) uptake blocker, tiagabine, has been studied on isolated GABAergic fast inhibitory postsynaptic potentials (IPSP) and currents (IPSC) in rat hippocampal CA1 pyramidal cells in the slice preparation. Tiagabine (20-50 microM) had little effect on the peak amplitude of the IPSC, but caused a robust increase in the half-width (by 109 +/- 15%). These results contrasted with those obtained using the established uptake blocker, nipecotic acid (100 microM to 1 mM), which reduced the amplitude of the IPSC by 35 +/- 6% and caused only a modest prolongation of the recovery phase. These effects, which were poorly reversible, are probably explained by the fact that nipecotic acid is a substrate for the GABA-uptake carrier and can act as a false transmitter. Tiagabine is not transported by the GABA carrier and results with this substance demonstrate the role of uptake in determining the kinetics of activation of GABAA receptors. Tiagabine is proposed as the blocker of choice for the GABA uptake system.

Animals↗
PubMed1992

Chronic treatment with a benzodiazepine agonist in vivo increases the actions of the benzodiazepine partial inverse agonist, FG7142, on the hippocampal slice in vitro.

We have shown previously that chronic treatment of mice with a benzodiazepine agonist, flurazepam, increased the pharmacological actions of the partial inverse agonist, FG7142. We have investigated the neurophysiological basis for this using extracellular recordings of evoked field potentials in area CA1 of isolated hippocampal slices. The slices were prepared 48 h after the end of the chronic in vivo treatment, a time when no evidence of residual benzodiazepine agonist activity was found in the CNS. During perfusion with standard Ringer solution, no significant differences were seen between the field potentials in slices from flurazepam-treated mice and those from control animals. When FG7142 was added to the perfusion medium there was an increase in the secondary discharges that followed the initial population spikes, and an increase in paired pulse potentiation. These increases were significantly greater in slices from flurazepam-treated mice, compared with controls. The results show that the effects of the partial inverse agonist, FG7142, on an isolated neuronal preparation, were increased by chronic administration of a benzodiazepine agonist in vivo. This effect is suggested to be due to a decrease in GABAergic inhibition.

Animals↗
PubMed1992

Changes in intrinsic inhibition in isolated hippocampal slices during ethanol withdrawal; lack of correlation with withdrawal hyperexcitability.

1. Intracellular recordings were made from pyramidal cells in area CA1 in mouse isolated hippocampal slices, after chronic ethanol treatment in vivo. 2. Fast i.p.s.ps were isolated by injection of the impaled neurones with QX314 (to block fast sodium currents and the slow i.p.s.p.) and stimulating the interneurones in the presence of the glutamatergic blockers, CNQX and APV. 3. The isolated fast-inhibitory postsynaptic potential (f.-i.p.s.p.) was measured at intervals during the 7 h withdrawal period. The reversal potential and sensitivity to bicuculline suggested that the isolated f.-i.p.s.p. was mediated by activation of the GABAA receptor-chloride ionophore complex. 4. Measurement of stimulus-response relationships for the f.-i.p.s.ps revealed an initial increase in the maximum size of the i.p.s.p., evoked from a membrane potential of -50 mV, seen at 2 h into ethanol withdrawal. This was attributed to a negative shift in the reversal potential, Ei.p.s.p., with no observed change in conductance, Gi.p.s.p. 5. No differences in f.-i.p.s.ps evoked during ethanol withdrawal or in control slices were seen at 4 h or 6 h. At these times, epileptiform activity was seen in previous field potential recordings. 6. Paired pulse depression of the f.-i.p.s.p. was significantly increased at 2 h into withdrawal, when a 150 ms pulse interval was used. No differences were seen at later times in the ethanol withdrawal period. 7. The results suggest that ethanol withdrawal hyperexcitability in isolated hippocampal slices is not caused by primary decreases in inhibition mediated by the GABAA receptor-chloride ionophore complex.4. Measurement of stimulus-response relationships for the f.-i.p.s.ps revealed an initial increase in the maximum size of the i.p.s.p., evoked from a membrane potential of - 50 mV, seen at 2 h into ethanol withdrawal. This was attributed to a negative shift in the reversal potential, Ejp.sp with no observed change in conductance, Gj ps p.5. No differences in f.-i.p.s.ps evoked during ethanol withdrawal or in control slices were seen at 4 h or 6 h. At these times, epileptiform activity was seen in previous field potential recordings.6. Paired pulse depression of the f.-i.p.s.p. was significantly increased at 2 h into withdrawal, when a 150 ms pulse interval was used. No differences were seen at later times in the ethanol withdrawal period.7. The results suggest that ethanol withdrawal hyperexcitability in isolated hippocampal slices is not caused by primary decreases in inhibition mediated by the GABAA receptor-chloride ionophore complex.The increase in the f.-i.p.s.p. during the initial stages of the withdrawal might prevent the overt expression of epileptiform activity at this time.

Animals↗
PubMed1991

Electrophysiological recordings from rat hippocampus slices following in vivo brain ischemia.

Pyramidal neurons in area CA1 of the septal hippocampus degenerate 2-3 days after an episode of transient global cerebral ischemia. The purpose of this study was to investigate synaptic transmission and passive neuronal properties in the post-ischemic period prior to neuronal death. Electrophysiological recordings were made from area CA1 in hippocampal slices prepared from rats which had survived a period of 20 min of ischemia for up to 5 days. In septal slices, field responses were in area CA1 unaltered up to 24 h after the ischemic insult. Forty-eight hours after ischemia, the mean amplitude of the population spike, but not the field-EPSP, was significantly reduced. In septal slices prepared more than 48 h after ischemia field potentials were absent or strongly attenuated, whereas they were intact in slices prepared from the temporal pole. No spontaneous discharges were detected in slices prepared at any time from post-ischemic rats. Intracellular recordings were obtained from slices up to 48 h after the ischemic episode. There was no significant difference in the resting membrane potential or input resistance between these neurons and those from control slices. Action potentials followed by a fast afterhyperpolarization and spike accommodation were preserved in all post-ischemic neurons. In all neurons investigated, orthodromic stimulation evoked an EPSP followed by a fast- and then a slow-IPSP. One hour after ischemia, the slow-IPSP was reduced. Forty-eight hours after ischemia, the fast-IPSP was significantly increased. The EPSP was markedly attenuated by the non N-methyl-D-aspartate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). The residual depolarizing component was amplified by perfusing with Mg(2+)-free medium and blocked by the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid. Paired-pulse facilitation of the EPSP was also preserved. As in control slices, the slow-IPSP and paired-pulse depression of the fast-IPSP were blocked by 1 microM baclofen. The present experiments provide no evidence that overt alteration of excitatory synaptic transmission or neuronal properties favouring hyperexcitability precede the ischemically induced death of CA1 pyramidal cells.

Animals↗
PubMed1991

Inhibition in postischemic rat hippocampus: GABA receptors, GABA release, and inhibitory postsynaptic potentials.

We have investigated the GABAergic system in rat hippocampus at 1 hour and up to 21 days following 20 min of global cerebral ischemia. Distribution of 3H-GABA (in excess of unlabeled baclofen) and 3H-Ro-15-1788 (benzodiazepine antagonist) binding sites in hippocampus was studied utilizing quantitative autoradiography. The 3H-GABA binding was unchanged (p greater than 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p less than 0.01) in all hippocampal subfields 1-21 days after ischemia. Using microdialysis in CA1, we found that K(+)-stimulated GABA release at 1 hour and 1 day after ischemia was unchanged (p greater than 0.01) in comparison to preischemic controls. Electrophysiological recordings were made from CA1 of hippocampal slices prepared from rats sacrificed 1 hour, 1 day and 2 days after ischemia. Field potentials evoked by stimulation of the Schaffer collaterals showed no differences (p greater than 0.01) from those taken from controls. Postischemic intracellular recordings from the CA1 pyramidal cells showed that fast and slow inhibitory postsynaptic potentials were readily evoked on orthodromic stimulation. Together with our previous morphological results, demonstrating survival of hippocampal interneurons following ischemia, we conclude that hippocampal GABAergic interneurons preserve their inhibitory potential in the period preceding delayed CA1 pyramidal cell death. This conclusion taken together with the observation that postischemic 3H-Ro-15-1788 binding in hippocampus declined, suggest that benzodiazepines (by increasing the receptor affinity), GABA analogs, and GABA uptake inhibitors may be useful in the treatment of ischemic CA1 pyramidal cell death in the rat.

Animals↗
PubMed1991

Endod: safety evaluation of a plant molluscicide.

Toxicity tests, in accordance with the Minimal Data Requirements (Tier 1) of the OECD Guidelines for Pre-Market Chemicals, were conducted on a standard extract (Endod-S) from the unripe berries of Phytolacca dodecandra, a potent botanical molluscicide of potential importance in the control of schistosomiasis. In acute mammalian toxicity tests, except for the eye irritation toxicity test which indicated severe irritancy, all test results were classified as either nontoxic or slightly toxic. Eye protection is therefore recommended during berry crushing and handling of dry powders. Ecotoxicity tests indicated that Endod is no more toxic than currently recommended synthetic molluscicides; however, environmental fate and additional local ecotoxicity tests are recommended for nontarget aquatic organisms present in the endemic situations of field trials. Given these toxicological data and recognizing the need for an affordable, locally cultivated, botanical molluscicide, it is concluded that field trials of Endod in schistosomiasis control are now justifiable.

Animals↗
PubMed1991

Electrophysiological studies of the GABAA receptor ligand, 4-PIOL, on cultured hippocampal neurones.

1. Whole-cell, patch-clamp recordings from cultured hippocampal neurones have been used to characterize the action of the GABAA ligand, 5-(4-piperidyl)isoxazol-3-ol (4-PIOL). The action of 4-PIOL was compared with that of the established GABAA agonist, isoguvacine. 2. With a symmetrical Cl- gradient across the membrane and a holding potential of -60mV, both isoguvacine and 4-PIOL evoked an inward current. The reversal potentials of the responses to both agents were identical (+8.8 mV, n = 4) and the current/voltage relationships showed outward-going rectification. 3. The response to 300 microM 4-PIOL was completely blocked by the GABAA antagonist, bicuculline methobromide (BMB, 10 microM). The pA2 of BMB was greater than 6.46. With 2 mM 4-PIOL about 15% of the response remained in the presence of 100 microM BMB. This may represent a non-specific component of the response to large concentrations of 4-PIOL. 4. 4-PIOL was about 200 times less potent as an agonist than isoguvacine. because of the rapid fade (desensitization) of isoguvacine-induced currents, the maximum response to this agonist was not determined. However, the response to 2 mM 4-PIOL was only a small fraction of that evoked by submaximal concentrations of isoguvacine. 5. Setting the response to 1 mM 4-PIOL as maximum, the EC50 for 4-PIOL was 91 microM (95% confidence limits:73-114 microM). 6. 4-PIOL antagonized the response to isoguvacine with a parallel shift to the right of the dose-response curve. The antagonist action of 4-PIOL was about 30 times weaker than that of BMB. When allowance was made for the intrinsic agonist action of 4-PIOL, the Ki was 116p microM (95% confidence limits: 102-130 microM). This was not significantly different from EC5, (P = 0.86; non-parametric Mann-Whitney test).7. It is concluded that 4-PIOL is a partial agonist at the GABAA receptor on cultured hippocampal neurones.

Animals↗
PubMed1991

Noradrenaline receptors participate in the regulation of GABAergic inhibition in area CA1 of the rat hippocampus.

1. Standard intracellular recordings from CA1 pyramidal neurones in in vitro hippocampal slices have been used to investigate the effects of excitatory amino acid antagonists and adrenergic agents on evoked synaptic potentials. 2. Ortho- and antidromic stimulation were conducted with remotely placed electrodes in order to minimize the possibility of stimulating the interneurones directly. In addition to the excitatory postsynaptic potential (EPSP), orthodromic stimulation evoked an inhibitory sequence consisting of a fast and slow inhibitory postsynaptic potential (IPSP). The slow-IPSP was blocked by intracellular injection of QX 314. Antidromic stimulation evoked a relatively pure fast-IPSP. 3. In seven neurones the differential effects of glutamatergic receptor blockers on the fast-IPSP were investigated. The N-methyl-D-aspartate (NMDA) receptor blocker, DL-2-amino-5-phosphonovaleric acid (APV) was added after the full effect of the non-NMDA receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) had been achieved. In three neurones, APV had no additional blocking effect, while in the remaining four neurones, both the ortho- and antidromically evoked IPSPs were reduced by 20-50%. This suggests that NMDA receptors participate in the activation of some GABAergic interneurones, which was further confirmed by showing that the IPSP was enhanced by Mg(2+)-free medium. 4. In the presence of CNQX (10 microM) and APV (50 microM) together, the ortho- and antidromically evoked fast-IPSPs were greatly reduced. A small 'residual' IPSP remained which was best studied by depolarizing the neurone to around -50 mV. With maximum stimulation, this amounted to 26.3 +/- 15.4% (mean +/- S.E.M., n = 15) of the control IPSP evoked by orthodromic stimulation and 41 +/- 14.6% of the control IPSP evoked by antidromic stimulation. The following statements apply equally to the ortho- and antidromically activated residual IPSPs. 5. The residual IPSP was completely blocked by low concentrations of bicuculline, indicating that it is mediated by GABAA receptors. When compared with a control IPSP of similar amplitude, the residual IPSP was found to have a faster rise time and time-to-peak, but a similar decay time. 6. Neither the muscarinic cholinergic antagonist, atropine nor the presynaptic glutamate agonist, L-2-amino-4-phosphonobutyric acid (L-APB) had any effect on the residual IPSP. 7. The residual IPSP was completely blocked by the adrenergic beta-receptor antagonist, L-propranolol (50-100 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1991

Depression of the fast IPSP underlies paired-pulse facilitation in area CA1 of the rat hippocampus.

1. Intracellular recordings from CA1 pyramidal neurons in the rat hippocampal slice have been used to study synaptic transmission after maximal orthodromic stimulation of the Schaffer collateral-commissural fibers. Paired-pulse stimulation was used to investigate how the first (conditioning) stimulation influenced the response to the second (test) stimulation. 2. When the test stimulation was delivered up to approximately 4 s after the conditioning stimulation, the late phase of the excitatory postsynaptic synaptic potential (EPSP) was increased ("late-phase facilitation") whereas the fast (f-) and the slow (s-) inhibitory postsynaptic potentials (IPSPs) were depressed. 3. In terms of appearance and time course, facilitation of the intracellularly recorded EPSP was similar to that of the extracellularly recorded field EPSP in stratum radiatum. 4. The s-IPSP is not involved in facilitation of the EPSP. To show this, we counteracted the s-IPSP either by repolarizing the membrane potential to the resting level or by intracellularly injecting the quaternary lignocaine derivative QX 314. Facilitation of the late phase of the EPSP was unaffected by either procedure. 5. The conditioned response was modified in two ways when the stimulation was delivered at the equilibrium potential for the f-IPSP (Ef-IPSP) and the s-IPSP had been blocked by intracellular injection of QX 314. The amplitude of the EPSP was increased, and the repolarizing phase was delayed with an apparent depolarizing shift of Ef-IPSP. This effect was present at pulse intervals greater than 20 ms and was maximal after 150 ms. Facilitation could be detected at interpulse intervals of up to 4 s. 6. The gamma-aminobutyric acid-B (GABAB) agonist baclofen (1 microM) reduced late-phase facilitation by preferentially increasing the unconditioned response, such that this came to resemble a conditioned response in control medium. 7. The f-IPSP was isolated pharmacologically to investigate its role in the facilitation of the EPSP. This was done by blocking the s-IPSP with QX314 and the EPSP with a mixture of the N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovaleric acid (APV, 50 microM), and the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). An f-IPSP was then evoked by stimulating the interneurons directly. This potential could be blocked by the GABAA receptor antagonist bicuculline (20 microM), thereby confirming the successful isolation of GABAAergic transmission. 8. With paired-pulse stimulation, the amplitude of the conditioned f-IPSP was depressed.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1990

GABAB receptors play a major role in paired-pulse facilitation in area CA1 of the rat hippocampus.

Extracellular recordings of field potentials in area CA1 of the rat hippocampal slice have been used to investigate paired-pulse facilitation. Field potentials were evoked by maximal stimulation of the Schaffer collateral/commissural fibres. The height of the population spike (PS) in stratum pyramidale (str. pyr.) and the area under the field excitatory postsynaptic potential (EPSP) following the PS in the stratum radiatum (str. rad.) were quantified. These values were used to describe the time course of paired-pulse facilitation. Facilitation of the PS was maximal 50 ms after the conditioning pulse and was present over a period of about 500 ms. However, facilitation of the late area (LA) of the field EPSP was maximal afer 125 ms and had an overall duration of 1-2 s. The N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), had no effect on paired-pulse facilitation of either the LA or the PS. The gamma-aminobutyric acid-B (GABAB) agonist baclofen increased facilitation of the PS. This was mainly due to a reduction of the unconditioned response. Facilitation of the LA was reduced by both baclofen and the GABAB antagonist, 2-OH-saclofen. Baclofen increased the LA of the unconditioned response, while this was unaffected by 2-OH-saclofen. The LA of facilitated responses was decreased by 2-OH-saclofen while the effect of baclofen on these responses was more complex. Baclofen reduced the LA of maximally facilitated responses, while the LA of slightly facilitated responses was increased. The results show that different mechanisms are involved in the facilitation of the LA and the PS. Furthermore, activation of GABAB receptors makes a large contribution to paired-pulse facilitation of the field EPSP. It is also suggested that recording of extracellular fields in str. rad. in response to paired-pulse stimulation provides a simple electrophysiological model for testing the effect of agents which act at the GABAB receptor.

2-Amino-5-phosphonovalerate↗
PubMed1990

The slow inhibitory postsynaptic potential in rat hippocampal CA1 neurones is blocked by intracellular injection of QX-314.

Intracellular recordings were made from CA1 pyramidal neurones in the rat hippocampus slice preparation. The recording electrodes contained potassium acetate (4 M) with or without the quaternary lidocaine derivative, QX-314 (50 mM). Both fast (f) and slow (s) inhibitory postsynaptic potentials (IPSP) were evoked by low-frequency orthodromic stimulation. The s-IPSP was rapidly reduced by QX-314 injection. It decreased along a similar time course to the dV/dt of the action potential (AP). The f-IPSP and excitatory postsynaptic potential were not significantly reduced in size at a time when the s-IPSP was virtually abolished by QX-314. It is concluded that conductance through the K+ channels which are coupled to GABAB receptors is readily blocked by QX-314, while the Cl- channels which are coupled to GABAA receptors and the cation channels coupled to the glutamate receptors are relatively resistant to the local anaesthetic.

Action Potentials↗
PubMed1990

Effects of lowering [Na+]o and [K+]o and of ouabain on quisqualate-induced ionic changes in area CA1 of rat hippocampal slices.

Changes in extracellular ([Na+]o) and calcium ([Ca2+]o) concentration evoked by quisqualate (Quis), applied iontophoretically, were measured in rat hippocampal slices. Following an initial decrease in [Ca2+]o, Quis causes a post-application overshoot, which may reflect Ca2+ extrusion from cells by the Na+/Ca2+ exchanger. To test this hypothesis, the effects of directly and indirectly reduced transmembrane Na+ gradients on these Quis-induced Ca2+ overshoots were investigated. In all cases the post-application overshoots were reduced. This suggests that the Na+/Ca2+ exchanger is involved in the production of these Quis-induced Ca2+ overshoots which may have important implications for understanding how various types of glutamate receptors differ in their capability to trigger Ca2(+)-activated processes.

Animals↗
PubMed1990

The role of excitatory amino acid receptors in the propagation of epileptiform discharges from the entorhinal cortex to the dentate gyrus in vitro.

The relationship between epileptiform events in the medial entorhinal cortex (MEC) and the dentate gyrus was investigated using a slice preparation from rat brain. Simultaneous intracellular recordings were made from neurones in layer II of the MEC and neurones in the granule cell layer of the dentate gyrus (DGC). Epileptiform activity was induced by perfusion with Mg+(+)-free medium or GABAA-receptor blockers. Epileptiform discharges in MEC cells were reflected on a one-to-one basis and at a latency of 1-3 ms by depolarizing events in DGC. The latter rarely gave rise to action potentials. Bath perfusion of the N-methyl-D-aspartate (NMDA) receptor blocker, 2-aminophosphonovalerate (2-AP5) abolished the Mg+(+)-free induced events in MEC cells and the corresponding depolarizations in the DGC but local application of 2-AP5 to the dentate gyrus only reduced the depolarizations. The non-NMDA-receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whether bath applied or applied locally to the DG, had little effect on the cortical events but strongly reduced the depolarizations of the DGC. The discharges induced in MEC cells by GABA-blockers were reduced by bath applied 2-AP5 but abolished by CNQX. These effects were mirrored in the dentate gyrus by a reduction in the depolarizing events by 2-AP5 and their abolition by CNQX. Local application of either antagonist to the dentate gyrus reduced but did not abolish the depolarizations. Thus, Mg+(+)-free induced events in MEC depend mainly on enhanced NMDA-receptor activity, while events induced by bicuculline are primarily dependant on non-NMDA receptors. The depolarizing events in the DGC which reflect the activity in the EC are mediated by both types of receptor, although non-NMDA receptors play a much greater role.

2-Amino-5-phosphonovalerate↗