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PubMed1986

Fast and slow synaptic potentials produced in a mammalian sympathetic ganglion by colon distension.

Radial distension of the large intestine produced a slow depolarization in a population of neurons in the inferior mesenteric ganglion of the guinea pig. The slow potentials often occurred simultaneously with cholinergic fast potentials [( excitatory postsynaptic potentials (EPSPs]) yet persisted in the presence of nicotinic and muscarinic cholinergic antagonists when all fast EPSPs were absent. The amplitude of the distension-induced noncholinergic slow depolarization increased with increasing distension pressure. For distensions of 1-min duration at pressures of 10-20 cm of water, the mean depolarization amplitude was 3.4 mV. The slow depolarization was associated with an increase in membrane resistance, and prolonged periods of colon distension resulted in a tachyphylaxis of the depolarization. Desensitization of ganglion cells to the peptide substance P attenuated the distension-induced slow potential by an average of 49% +/- 17%. Thus, two colonic mechanosensory afferent pathways converge on principal ganglion cells in the inferior mesenteric ganglion: one was previously described to be mediated by acetylcholine, and the other is described here, whose transmitter remains to be determined but which preliminary evidence suggests is mediated in part by substance P. The noncholinergic afferent pathway may enhance the intestinal inhibitory reflex mediated by cholinergic mechanosensory afferent input to the abdominal prevertebral sympathetic ganglia.

Animals↗
PubMed1990

Phencyclidine actions measured intracellularly in hippocampal CA1 neurons.

The electrophysiological effects of phencyclidine (PCP) were measured intracellularly in guinea pig hippocampal CA1 neurons in vitro. At all doses tested (0.2 microM - 10 mM), PCP increased the width of action potentials (APs). Doses of 10 microM and higher were associated with decreased action potential amplitude. PCP decreased inhibitory postsynaptic potentials and excitatory postsynaptic potentials but did not alter responses to focally applied GABA. At the lowest dose (0.2 microM), PCP decreased the input resistance (Rin), while at all other doses Rin was increased. PCP decreased post-spike train afterhyperpolarizations at low and medium doses. PCP effects persisted in low calcium medium and also in medium containing 10(-6) M tetrodotoxin. It is concluded that in these central neurons, PCP primarily blocks potassium conductances at all doses and, at anesthetic doses, depresses sodium-dependent spikes.

Action Potentials↗
PubMed1988

Non-cholinergic synaptic potentials mediated by lumbar colonic nerve in the guinea-pig inferior mesenteric ganglion in vitro.

Non-cholinergic slow synaptic potentials mediated by the lumbar colonic nerve have been investigated using an in vitro preparation of the guinea-pig inferior mesenteric ganglion attached to a distal colonic segment. Non-cholinergic potential responses to colonic nerve stimulation, colonic distension and chemical activation of sensory afferents were recorded intracellularly from neurons in the inferior mesenteric ganglion. Electrical stimulation of the lumbar colonic nerve produced either a slow excitatory postsynaptic potential, or a slow inhibitory postsynaptic potential followed by a slow excitatory postsynaptic potential. The extrapolated reversal potential of the slow excitatory postsynaptic potential was in the range of 0 to -20 mV and that of the slow inhibitory postsynaptic potential was -90 to 110 mV. The slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential were reversibly abolished by perfusion of the ganglion with tetrodotoxin (1 microM), or perfusion with low calcium (200 microM), high magnesium (12 mM) containing solution. Capsaicin (1 microM) evoked a reversible depolarization of inferior mesenteric ganglion cells after which desensitization occurred and the slow excitatory postsynaptic potential was abolished but the slow inhibitory postsynaptic potential was enhanced in amplitude and prolonged in duration. Bath application of substance P (2 microM) evoked a prolonged depolarization of inferior mesenteric ganglion neurons, during which the slow excitatory postsynaptic potential but not the slow inhibitory postsynaptic potential was abolished. Distensions of the colon to pressures in the range of 2-25 cm of water produced a stimulus graded non-cholinergic slow depolarization which was occasionally followed by a late slow hyperpolarization. Both types of response were abolished by tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1968

Effects of physostigmine on the afterdischarge and slow postsynaptic potentials of bullfrog sympathetic ganglia.

1. The effects of anticholinesterases (anti-ChEs) (physostigmine, prostigmine and TEPP) on the afterdischarges and the extracellular and intracellular slow potentials of bullfrog sympathetic ganglia were studied.2. The anti-ChEs augmented the early afterdischarge, the late negative potential and the slow excitatory postsynaptic potential. This indicated that the nature of the early afterdischarge was cholinergic (muscarinic) and that the late negative potential or the slow excitatory postsynaptic potential generated the early afterdischarge.3. Since the anti-ChEs increased the positive potential, the depression of the early afterdischarge observed in the presence of an antiChE was explained to be caused by the increased inhibitory effect of the enhanced positive potential.4. Prostigmine and tetraethyl pyrophosphate did not show any appreciable effects on the late afterdischarge, the late late negative potential nor the late slow excitatory postsynaptic potential. This indicated that the nature of the late afterdischarge was non-cholinergic and that the late late negative potential or the late slow excitatory postsynaptic potential generated the late afterdischarge.5. Physostigmine reversibly depressed the late afterdischarge, the late late negative potential and the late slow excitatory postsynaptic potential. The depressant action of physostigmine was not due to its anti-ChE action.

Animals↗
PubMed1995

Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog.

The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the vertebrate neuromuscular junction. The major differences between these two synapses are the neurotransmitters and the higher resting release rate and higher sensitivity of release to increased K+ concentrations of the hair cells over that of motor nerve terminals. These differences reflect the functional roles of the two synapses: the motor nerve terminal response in an all-or-nothing signal consequent from action potential invasion, while the hair cell releases transmitter in a graded fashion, proportionate to the extent of stereocilial deflection. Despite these differences between the two junctions, the similar actions of these elemental cations upon synaptic function at each implies that these ions may participate similarly in the operations of other synapses, independent of the neurotransmitter type.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1977

The presynaptic site of action of norepinephrine in the superior cervical ganglion of guinea pig.

Supramaximal preganglionic volleys did not elicit detectable postsynaptic potential in the curare-treated superior cervical ganglion cell of the guinea pig whereas, a tetanic stimulation (10-30 Hz, 1-5 seconds) consistently evoked a monophasic depolarizing potential resembling the slow excitatory postsynaptic potential. The depolarizing potential was not preceded by a detectable hyperpolarization. In non-curare-treated preparations, norepinephrine in concentrations of 1 to 10 muM consistently and reversibly suppressed the fast excitatory postsynaptic potential elicited by submaximal preganglionic stimulation without appreciably affecting the resting membrane potential, the total membrane resistance or the cell membrane excitability. Pretreating the ganglion with phenoxybenzamine (10 muM) completely prevented, whereas propranolol (30 muM) failed to antagonize, the ganglionic depressant action of norepinephrine. The amplitude and time course of the iontophoretically induced acetylcholine potential were not significantly altered by norepinephrine in concentrations which markedly attenuated the response of the fast excitatory postsynaptic potential. The frequency but not the amplitude of the miniature excitatory postsynaptic potentials was significantly reduced by norepinephrine (1-10 muM). These results demonstrate that norepinephrine inhibits ganglionic transmission in the guinea pig principally by reducing the output of acetylcholine from the presynaptic nerve terminals. These data are discussed with respect to their relation to the presence in the guinea pig superior cervical ganglion of norepinephrine-containing small intensely fluorescent cells which are not connected synaptically with the postganglionic neurons.

Acetylcholine↗
PubMed1999

Changes in membrane properties of CA1 pyramidal neurons after transient forebrain ischemia in vivo.

We have previously identified three distinct populations of CA1 pyramidal neurons after reperfusion based on differences in synaptic response, and named these late depolarizing postsynaptic potential neurons (enhanced synaptic transmission), non-late depolarizing postsynaptic potential and small excitatory postsynaptic neurons (depressed synaptic transmission). In the present study, spontaneous activity and membrane properties of CA1 neurons were examined up to 48 h following approximately 14 min ischemic depolarization using intracellular recording and staining techniques in vivo. In comparison with preischemic properties, the spontaneous firing rate and the spontaneous synaptic activity of CA1 neurons decreased significantly during reperfusion; spontaneous synaptic activity ceased completely 36-48 h after reperfusion, except for a low level of activity which persisted in non-late depolarizing postsynaptic potential neurons. Neuronal hyperactivity as indicated by increasing firing rate was never observed in the present study. The membrane input resistance and time constant decreased significantly in late depolarizing postsynaptic potential neurons at 24-48 h reperfusion. In contrast, similar changes were not observed in non-late depolarizing postsynaptic potential neurons. The rheobase, spike threshold and spike frequency adaptation in late depolarizing postsynaptic potential neurons increased progressively following reperfusion. Only a transient increase in rheobase and spike threshold was detected in non-late depolarizing postsynaptic potential neurons and spike frequency adaptation remained unchanged in these neurons. The amplitude of fast afterhyperpolarization increased in all neurons after reperfusion, with the smallest increment in non-late depolarizing postsynaptic potential neurons. Small excitatory postsynaptic potential neurons shared similar changes to those of late depolarizing postsynaptic potential neurons. These results suggest that the enhancement and depression of synaptic transmission following ischemia are probably due to changes in synaptic efficacy rather than changes in intrinsic membrane properties. The neurons with enhanced synaptic transmission following ischemia are probably the degenerating neurons, while the neurons with depressed synaptic transmission may survive the ischemic insult.

Animals↗
PubMed1989

Effects of cisapride on cholinergic neurotransmission and propulsive motility in the guinea pig ileum.

The actions of cisapride on electrical behavior of single myenteric neurons and on the propulsive activity of segments of ileum were studied in vitro. Cisapride (10-300 nM) did not affect the membrane potential, resting properties, or active properties of S neurons. The amplitude of fast nicotinic excitatory postsynaptic potentials recorded from S cells was increased by cisapride in the concentration range of 10 nM to 1 microM. Higher cisapride concentrations (3-10 microM) reduced the amplitude of fast excitatory postsynaptic potentials. Potentiation of fast excitatory postsynaptic potentials by cisapride was antagonized by ICS 205-930 (1 microM) but was unaffected by GR 38032F (1 microM), both compounds being 5-HT3-receptor antagonists. Cisapride did not modify the electrical behavior of AH neurons except at the highest concentrations (3-10 microM), which caused hyperpolarization of some neurons. The propulsive efficiency (i.e., number of peristalses and total amount of fluid ejected per unit of time) of isolated segments of ileum was enhanced by cisapride (100 nM to 3 microM). Higher cisapride concentrations (6 or 10 microM) had a depressant action on propulsive activity. The stimulatory effect of cisapride on propulsion was not antagonized by ICS 205-930 (300 nM or 1 microM). These data indicate that cisapride facilitates cholinergic transmission in the myenteric plexus of guinea pig ileum and that this effect may be at least partially responsible for the increased propulsive efficiency observed in ileal segments.

Acetylcholine↗
PubMed1989

Selective antagonism of muscarinic potentials on the superior cervical ganglion of the rat.

Selective antagonists have been used to classify the muscarinic receptors involved in the slow excitatory postsynaptic potential and slow inhibitory postsynaptic potential of the superior cervical ganglia of the rat, as recorded in 1 microM neostigmine, using a grease-gap method. Cardioselective M2 antagonists, e.g. AF-DX 116, depressed the slow inhibitory postsynaptic potential and enhanced the slow excitatory postsynaptic potential. The M1 selective antagonist pirenzepine depressed both potentials equally. The high potency of pirenzepine against the slow excitatory postsynaptic potential, however, indicates that it is mediated by M1 receptors. The slow excitatory and inhibitory postsynaptic potentials were found to be pharmacologically similar to the muscarinic agonist-induced depolarisation and hyperpolarisation of this preparation, respectively. The actions of two muscarinic agonists on the postsynaptic potentials were also studied. It is concluded that the slow excitatory postsynaptic potential is mediated by M1 receptors and the slow inhibitory postsynaptic potential by cardiac-like M2 receptors.

Animals↗
PubMed1997

Optical recording of trisynaptic pathway in rat hippocampal slices with a voltage-sensitive dye.

Changes in membrane potentials were recorded from rat hippocampal slices with a voltage-sensitive dye using a real-time optical recording system, which had high spatial resolution of 128 x 128 points with a high time resolution of 0.6 ms. Serial excitatory propagation was recorded in the dentate gyrus. CA3 and CA1 after stimulation of the perforant pathway, and the optical signals were clearly divided into two components in the dentate gyrus adjacent to the stimulus site. The slow component was suppressed in Ca(2+)-free solution, but the fast component in the molecular layer was not affected. However, the application of 1 microM tetrodotoxin fully abolished both components. These results suggest that the fast and slow components mainly reflect Na(+)-dependent action potentials and excitatory postsynaptic potentials, respectively. The excitatory response duration in the stratum radiatum of CA3 was significantly longer than that in other hippocampal areas. The long-lasting excitation in CA3 is probably related to the CA3 associational projections, because direct stimulation of CA3 pyramidal cell layer also produced similar results. The long-lasting dendritic excitation is probably important to integrate synaptic transmission and may be related to epileptogenesis. When long-term potentiation was induced by a tetanic stimulation (100 Hz for 1 s), the onset latency in the stratum radiatum of CA1 was reduced to as much as 65%, suggesting an increase of excitatory propagation. The analysis of the spatial-temporal optical signals contributes to understanding information processes in the hippocampus, related to learning and memory including long-term potentiation.

Animals↗
PubMed1999

Calcium channels controlling acetylcholine release in the guinea-pig isolated anterior pelvic ganglion: an electropharmacological study.

An electropharmacological analysis of the type(s) of calcium channel controlling neurotransmitter release in preganglionic sympathetic nerve terminals in the guinea-pig anterior pelvic ganglion has been carried out. Conventional intracellular recording techniques were used to record excitatory postsynaptic potentials as a measure of neurotransmitter release. Excitatory postsynaptic potentials were abolished by hexamethonium (30-100 microM) and are therefore mediated by acetylcholine acting at nicotinic receptors. In studies of more than 150 cells, the N-type calcium channel blocker omega-conotoxin GVIA (100-300 nM) failed to block the initiation of the nerve impulse by the excitatory postsynaptic potential. In single-cell studies, omega-conotoxin GVIA (1 microM) sometimes altered the configuration of the excitatory postsynaptic potential/cell body nerve action potential complex, but on only one occasion was the excitatory postsynaptic potential reduced below the threshold required to initiate the action potential. Nifedipine (10 microM), omega-agatoxin IVA (100 nM) and omega-conotoxin MVIIC (300 nM), applied alone or in combination with omega-conotoxin GVIA (300 nM), were also ineffective. However, excitatory postsynaptic potentials evoked by trains of stimuli (0.1-0.5 Hz) were markedly reduced or abolished by the non-specific calcium channel blocker omega-grammotoxin SIA (300 nM). When trains of stimuli were delivered at higher frequencies (4 Hz), the block induced by omega-grammotoxin SIA could be overcome, and excitatory postsynaptic potentials were able to initiate action potentials even when omega-conotoxin GVIA, omega-agatoxin IVA and omega-conotoxin MVIIC were also present. The calcium channel(s) controlling acetylcholine release was (were) blocked by low concentrations of cadmium ions (30 microM) at all stimulation frequencies studied (0.1-50 Hz). Thus, the dominant calcium channels controlling acetylcholine release in sympathetic ganglia are not the L, N, P or Q types. At low frequencies of stimulation, omega-grammotoxin SIA-sensitive calcium channels play a dominant role in acetylcholine release, but at higher stimulation frequencies yet another pharmacologically distinct calcium channel (or subtype) supports neurotransmitter release.

Acetylcholine↗
PubMed1992

Ca2+ entry via postsynaptic voltage-sensitive Ca2+ channels can transiently potentiate excitatory synaptic transmission in the hippocampus.

We have studied the role of Ca2+ entry via voltage-sensitive Ca2+ channels in long-term potentiation (LTP) in the CA1 region of the hippocampus. Repeated depolarizing pulses, in the presence of the NMDA receptor antagonist D-APV and without synaptic stimulation, resulted in a potentiation of excitatory postsynaptic potentials (EPSPs) or currents (EPSCs). This depolarization-induced potentiation was augmented in raised extracellular Ca2+ and was blocked by intracellular BAPTA, a Ca2+ chelator, or by nifedipine, a Ca2+ channel antagonist, indicating that the effect was mediated by Ca2+ entry via voltage-sensitive Ca2+ channels. Although the peak potentiation could be as large as 3-fold, the EPSP(C)s decayed back to baseline values within approximately 30 min. However, synaptic activation paired with depolarizing pulses in the presence of D-APV converted the transient potentiation into a sustained form. These results indicate that a rise in postsynaptic Ca2+ via voltage-sensitive Ca2+ channels can transiently potentiate synaptic transmission, but that another factor associated with synaptic transmission may be required for LTP.

2-Amino-5-phosphonovalerate↗
PubMed1994

Interaction between paired-pulse facilitation and long-term potentiation in area CA1 of guinea-pig hippocampal slices: application of quantal analysis.

The aim of the study was to further specify mechanisms of maintenance of hippocampal long-term potentiation. Previous analysis of excitatory postsynaptic potentials showed increases in quantal content (mean number of neurotransmitter quanta released by every testing pulse) with smaller increases in quantal size (effect of one transmitter quantum) following long-term potentiation induction. Here we recorded intracellularly excitatory postsynaptic potentials from CA1 pyramidal neurons of guinea-pig hippocampal slices after minimal paired-pulse stimulation of monosynaptic inputs. Statistical parameters underlying excitatory postsynaptic potential fluctuations were estimated by a deconvolution procedure using a quantal model. The parameters of excitatory postsynaptic potentials following paired-pulse stimulation were studied before and after induction of long-term potentiation. Under both conditions, paired-pulse facilitation was found to be accompanied by increases in quantal content and quantal size. During long-term potentiation, paired-pulse facilitation of amplitude and quantal content was lower. The respective changes in the paired-pulse facilitation ratios correlated with long-term potentiation magnitude. In contrast, the paired-pulse facilitation of quantal size did not change significantly following long-term potentiation induction. The results are compatible with the existence of two separate mechanisms of long-term potentiation maintenance. They support the suggestion that changes in quantal content are mainly due to presynaptic mechanisms which are shared by long-term potentiation and paired-pulse facilitation. The mechanisms underlying changes in quantal size are of a different nature for long-term potentiation and paired-pulse facilitation. For long-term potentiation they might be located postsynaptically.

Animals↗
PubMed1998

Reversal of excitatory postsynaptic potential/spike potentiation in the CA1 area of the rat hippocampus.

In the CA1 area of the hippocampus, low frequency and tetanic conditioning stimuli are known to trigger long-term depression and potentiation of synaptic responses respectively and to produce irreversible excitatory postsynaptic potential/spike potentiation, i.e. an increase of the probability of discharge of the neurons. Using simultaneous extracellular recordings in stratum radiatum and stratum pyramidale in the CA1 area of the rat hippocampus, brief application of the K+ channel blocker tetraethylammonium resulted both in long-term potentiation of synaptic responses and in excitatory postsynaptic potential/spike potentiation that could be reversed by subsequent low frequency or tetanic stimuli. Excitatory postsynaptic potential/spike potentiation and its subsequent reversal by an electrical conditioning stimulus were found to have an N-methyl-D-aspartate receptor-independent component. We conclude that the reversal of excitatory postsynaptic potential/spike potentiation can occur and that it does not require the induction of long-term modification of synaptic responses.

2-Amino-5-phosphonovalerate↗
PubMed1988

Pharmacological studies in frog sympathetic ganglion: support for the cholinergic monosynaptic hypothesis for slow IPSP mediation.

The slow inhibitory postsynaptic potential (slow IPSP), the slow excitatory postsynaptic potential (slow EPSP), the late slow excitatory postsynaptic potential (late slow EPSP), and the fast excitatory postsynaptic potential/compound action potential (fast EPSP) were recorded from the 9th or 10th paravertebral sympathetic ganglia of bullfrogs (and some Rana pipiens frogs) by the sucrose-gap technique. The adrenergic antagonists phentolamine, dihydroergotamine and propranolol did not show any antagonistic effect on the slow IPSP when used at concentrations of up to 10, 100 and 10 microM, respectively. U-0521 (3',4'-dihydroxy-2-methylpropriophenone, 50 micrograms/ml), a specific inhibitor of catechol-O-methyltransferase, did not show any potentiating effect on the slow IPSP. The cholinesterase inhibitor neostigmine (0.5-1 microM) induced a large increase in the duration and amplitude of slow IPSP. When phentolamine and propranolol at concentrations greater than 10 microM were used the slow IPSP (and all other synaptic potentials) were non-specifically reduced in amplitude by these drugs. The results reported in this paper do not lend any support to the hypothesis that the slow IPSP in frog sympathetic ganglia is mediated by an adrenergic interneuron. The results are consistent with the proposal that the slow IPSP in this ganglion is mediated by a direct action of acetylcholine released from cholinergic preganglionic fibers.

Action Potentials↗
PubMed1993

Synaptic activation of N-methyl-D-aspartate receptors induces short-term potentiation at excitatory synapses in the striatum of the rat.

We examined the effect of augmenting the activation of N-methyl-D-aspartate receptors during tetanic stimulation of the corpus callosum. Excitatory postsynaptic potentials were recorded from striatal neurons in an in vitro brain slice bathed in either normal or Mg(2+)-free artificial cerebrospinal fluid. Post-tetanic potentiation was followed by a long-lasting depression of the excitatory postsynaptic potential in normal artificial cerebral spinal fluid. Mg(2+)-free artificial cerebrospinal fluid increased the duration of the pretetanus excitatory postsynaptic potential and the amplitude and duration of the direct response to the tetanus. Mg(2+)-free artificial cerebrospinal fluid also enabled the expression of a short-term potentiation of the excitatory postsynaptic potential amplitude and duration. N-methyl-D-aspartate receptor antagonists blocked the induction of all tetanus-induced excitatory postsynaptic potential changes specific to the Mg(2+)-free artificial cerebral spinal fluid. These results indicate that maintained activation of N-methyl-D-aspartate receptors by synaptically released glutamate can produce a sustained enhancement of the excitatory postsynaptic potential. This use-dependent increase in synaptic efficacy may contribute to basal ganglia-related motor performance.

Animals↗
PubMed1997

Local synaptic release of glutamate from neurons in the rat hypothalamic arcuate nucleus.

1. The hypothalamic arcuate nucleus (ARC) contains neuroendocrine neurons that regulate endocrine secretions by releasing substances which control anterior pituitary hormonal release into the portal blood stream. Many neuroactive substances have been identified in the ARC, but the existence of excitatory neurons in the ARC and the identity of an excitatory transmitter have not been investigated physiologically. 2. In the present experiments using whole-cell current- and voltage-clamp recording of neurons from cultures and slices of the ARC, we demonstrate for the first time that some of the neurons in the ARC secrete glutamate as their transmitter. 3. Using microdrop stimulation of presynaptic neurons in ARC slices, we found that local axons from these glutamatergic neurons make local synaptic contact with other neurons in the ARC and that all evoked excitatory postsynaptic potentials could be blocked by the selective ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) and D,L-2-amino-5-phosphonovalerate (AP5; 100 microM). To determine the identity of ARC neurons postsynaptic to local glutamatergic neurons, we used antidromic stimulation to reveal that many of these cells were neuroendocrine neurons by virtue of their maintaining axon terminals in the median eminence. 4. In ARC cultures, postsynaptic potentials, both excitatory and inhibitory, were virtually eliminated by the glutamate receptor antagonists AP5 and CNQX, underlining the functional importance of glutamate within this part of the neuroendocrine brain. 5. GABA was secreted by a subset of ARC neurons from local axons. The GABAA receptor antagonist bicuculline released glutamatergic neurons from chronic inhibition mediated by synaptically released GABA, resulting in further depolarization and an increase in the amplitude and frequency of glutamate-mediated excitatory postsynaptic potentials.

2-Amino-5-phosphonovalerate↗
PubMed1997

The role of long-term potentiation in persistent epileptiform burst-induced hyperexcitability following GABAA receptor blockade.

Persistent hyperexcitability follows synchronized bursting induced in the CA3 region of hippocampal slices by perfusion with high concentrations (2000 IU/ml) of the GABAA antagonist, penicillin. This hyperexcitable state is characterized by: i) slow recovery from bursting following penicillin washout; ii) persistent "post-burst" field potential oscillations and iii) increased probability of spontaneous bursting with ordinarily sub-convulsant doses of GABAA antagonists. An N-methyl-D-aspartate-independent type of long-term potentiation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate excitatory postsynaptic potentials occurred following bursting. However, similar increases in excitatory postsynaptic potential magnitude also occurred after a subconvulsant dose of penicillin (500 IU/ml) which did not produce the other features of persistent hyperexcitability. Furthermore, long-term potentiation either increased or remained stable after bursting stopped, whereas, post-burst oscillations gradually diminished with time. Low doses of the AMPA/kainate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, which restored the potentiated excitatory postsynaptic potentials to control levels, reduced but did not eliminate the post-burst oscillation. Tetanus-induced long-term potentiation did not reproduce the hyperexcitable state seen after bursting. These findings indicate that the epileptiform bursting caused by blocking GABAA-mediated inhibition induces long-term potentiation which is partially responsible for persistent burst-induced hyperexcitability but is not sufficient to entirely explain it. The hippocampus which is critical for normal memory is also frequently the generator of intractable epileptic seizures. Seizure-like discharges in the hippocampus induced long-lasting increases in synaptic efficacy similar to those thought to underlie normal memory. This form of long-term potentiation contributed to the network oscillations characteristics of the hyperexcitable state persisting after epileptiform activity but was not sufficient to entirely explain them. Epileptic seizures may engage normal memory mechanisms which increase neuronal excitability and predispose the hippocampal network to further seizures. This may, in part, account for the propensity for hippocampal seizure foci to become intractable.

Animals↗