SEARCH · PubMed Health

Results for “Inhibitory Postsynaptic Potentials”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

PubMed1978

Vestibulo-ocular reflex from the posterior canal nerve to extraocular motoneurons in the cat.

In the anesthetized cat, the posterior canal nerve (PCN) was stimulated by electric pulses and synaptic responses were recorded intracellularly in the three antagonistic pairs of extraocular motoneurons. Pure reciprocal effects were obtained in the motoneurons innervating the antagonistic pair of ipsilateral oblique muscles and the antagonistic pair of contralateral vertical rectus muscles. These responses consisted of low threshold disynaptic excitatory postsynaptic potentials (EPSPs) in either the contralateral superior oblique (c--SO) (trochlear) or contralateral inferior rectus (c--IR) motoneurons and of disynaptic inhibitory postsynaptic potentials (IPSPs) in either the ipsilateral inferior oblique (i--IO) or ipsilateral superior rectus (i--SR) motoneurons. In addition, disynaptic IPSPs were also found in (i--SO) motoneurons. Mixtures of low threshold (di or trisynaptic) EPSPs and IPSPs were found in all other extraocular motoneurons except for the contralateral lateral rectus (c--LR) motoneurons. These results may afford a basis for the characteristic eye movements induced by vertical canal nerve stimulation.

Animals↗

PubMed2003

Hyperpolarization-activated current (Ih) in the inferior colliculus: distribution and contribution to temporal processing.

Neurons in the inferior colliculus (IC) process acoustic information converging from inputs from almost all nuclei of the auditory brain stem. Despite its importance in auditory processing, little is known about the distribution of ion currents in IC neurons, namely the hyperpolarization-activated current Ih. This current, as shown in neurons of the auditory brain stem, contributes to the precise analysis of temporal information. Distribution and properties of the Ih current and its contribution to membrane properties and synaptic integration were examined by current- and voltage-clamp recordings obtained from IC neurons in acute slices of rats (P17-P19). Based on firing patterns to positive current injection, three basic response types were distinguished: onset, adapting, and sustained firing neurons. Onset and adapting cells showed an Ih-dependent depolarizing sag and had a more depolarized resting membrane potential and lower input resistance than sustained neurons. Ih amplitudes were largest in onset, medium in adapting, and small in sustained neurons. Ih activation kinetics was voltage dependent in all neurons and faster in onset and adapting compared with sustained neurons. Injecting trains of simulated synaptic currents into the neurons or evoking inhibitory postsynaptic potentials (IPSPs) by stimulating the lemniscal tract showed that Ih reduced temporal summation of excitatory and inhibitory potentials in onset but not in sustained neurons. Blocking Ih also abolished afterhyperpolarization and rebound spiking. These results suggest that, in a large proportion of IC cells, namely the onset and adapting neurons, Ih improves precise temporal processing and contributes to the temporal analysis of input patterns.

Animals↗

PubMed1994

Sympathetic input to ganglia of the guinea pig sphincter of Oddi.

Intracellular recording and immunohistochemical staining techniques were used to establish whether sphincter of Oddi (SO) ganglia are a target of sympathetic input to this region. Norepinephrine (0.01-10.0 microM) decreased the amplitude of the nicotinic fast excitatory postsynaptic potential (EPSP) evoked by stimulation of interganglionic fiber tracts, with a half-maximal inhibitory concentration (EC50) of 300 nM. Norepinephrine did not alter the responsiveness of the neurons to acetylcholine. The alpha 2-adrenoreceptor agonist UK-14304 mimicked the norepinephrine-induced effect with a EC50 of 2.5 nM, whereas alpha 1- and beta-adrenoreceptor agonists had no effect on the EPSP. The alpha 2-adrenoreceptor antagonist idazoxan (1.0 microM) inhibited the UK-14304 response, with a dissociation constant of 1.0 nM. Release of endogenous catecholamines, by the addition of tyramine (100 microM) to the bath, caused an idazoxan-sensitive decrease in the amplitude of the fast EPSP. In the minority of SO neurons that exhibited inhibitory postsynaptic potentials (IPSPs), norepinephrine caused a hyperpolarization of the membrane potential. The IPSP and the norepinephrine-induced hyperpolarization were inhibited by alpha 2-adrenoreceptor antagonists. Desipramine (1.0 microM), an uptake inhibitor, reversibly increased the amplitude of the IPSP. Immunoreactivities for tyrosine hydroxylase and dopamine beta-hydroxylase were coexistent in nerve fibers and nonexistent in cell bodies in the ganglionated plexus of the SO. The results of this study indicate that norepinephrine acts pre- and postsynaptically as an inhibitory neurotransmitter in SO ganglia.

Acetylcholine↗

PubMed1972

Effect of black widow spider venom on the lobster neuromuscular junctions.

The effect of black widow spider venom (BWSV) on the junctions of the lobster nerve-muscle preparation was studied by intracellular recordings. After application of BWSV both excitatory and inhibitory postsynaptic potentials (epsp and ipsp) were augmented then suppressed. The frequency of miniature potentials was markedly increased by BWSV. Summated postsynaptic conductance changes appeared to be responsible for the membrane depolarization and the decrease in effective membrane resistance seen in the early stages of the venom action. In the later stages both excitatory and inhibitory "giant miniature potentials" were evoked. No discernible changes were found in the reversal potential of the epsp and ipsp and in the sensitivity of the postsynaptic membrane. The results indicate that BWSV has a presynaptic action at crustacean neuromuscular junctions.

Animals↗

PubMed1996

Uncrossed disynaptic inhibition of second-order vestibular neurons and its interaction with monosynaptic excitation from vestibular nerve afferent fibers in the frog.

1. Eighth nerve evoked responses in central vestibular neurons (n = 146) were studied in the isolated brain stem of frogs. Ninety percent of these neurons responded with a monosynaptic excitatory postsynaptic potential (EPSP) after electrical stimulation of the ipsilateral VIIIth nerve. In 5% of these neurons, the EPSP was truncated by a disynaptic inhibitory postsynaptic potential (IPSP), and in 5% of these neurons a pure disynaptic IPSP was evoked. 2. Disynaptic IPSPs superimposed upon apparently pure EPSPs were revealed by bath application of the glycine receptor antagonist strychnine (0.5-5 microM) or of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (0.5-2 microM). The evoked EPSP increased in most central vestibular neurons (strychnine: 15 out of 16 neurons; bicuculline 26 out of 29 neurons). At higher stimulus intensities, the evoked spike discharge increased from 2 to 3 spikes before up to 8-10 spikes per electrical pulse during the application of blocking agents. The unmasked disynaptic inhibitory component increased with stimulus intensity to a different extent in different neurons. 3. Lesion studies demonstrated that these inhibitory components were generated ipsilaterally with respect to the recording side. The disynaptic strychnine-sensitive inhibition was mediated by neurons located either in the ventral vestibular nuclear complex (VNC) or in the adjacent reticular formation. The spatial distribution of the disynaptic inhibition was investigated by simultaneous recordings of VIIIth nerve-evoked field potentials at different rostrocaudal locations of the VNC. A significant strychnine-sensitive component was detected in the middle and caudal parts but not in the rostral part of the VNC. A bicuculline-sensitive component was detected in the rostral and in the caudal parts but not in the middle part of the VNC. In view of a similar rostrocaudal distribution of glycineor GABA-immunoreactive neurons in the VNC of frogs, our results suggest that part of the disynaptic inhibition is mediated by local interneurons with a spatially restricted projection area. 4. The monosynaptic EPSP of second-order vestibular neurons was mediated in part by N-methyl-D-aspartate (NMDA) and in part by non-NMDA receptors. The relative contribution of the NMDA receptor-mediated component of the EPSP decreased with stronger stimuli. This negative correlation could have resulted from a preferential activation of NMDA receptors via thick vestibular nerve afferent fibers. Alternatively, the activation of NMDA receptors became disfacilitated at higher stimulus intensities due to the recruitment of disynaptic inhibitory inputs. Comparison of data obtained in the presence and in the absence of these glycine and GABAA receptor blockers indicates a preferential activation of NMDA receptors via larger-diameter vestibular nerve afferent fibers. 5. The kinetics of NMDA receptors (delay, rise time) activated by afferent nerve inputs were relatively fast. These fast kinetics were independent of superimposed IPSPs. The association of these receptors with large-diameter vestibular nerve afferent fibers suggests that fast NMDA receptor kinetics might be matched to the more phasic response dynamics of the large diameter vestibular afferent neurons to natural head accelerations.

Afferent Pathways↗

PubMed1996

Pharmacological properties of peripherally induced postsynaptic potentials in bulbar respiratory neurons of decerebrate cats.

Intracellular recordings of bulbar inspiratory and post-inspiratory neurons, combined with extracellular iontophoresis of antagonists of putative neurotransmitters, were performed in decerebrate cats. Inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of the superior laryngeal nerve or vagus nerve were depressed by bicuculline in all 22 neurons tested, but not modified by strychnine. The non-N-methyl-D-aspartate (NMDA) glutamate antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) decreased the neurally evoked excitatory postsynaptic potentials (EPSPs) in 23 out of 26 neurons tested, while the NMDA antagonist dizocilpine had no notable effect. The present results suggest that the peripherally induced IPSPs are mediated through gamma-aminobutyric acid (GABA)A receptors and the EPSPs through non-NMDA glutamate receptors in bulbar respiratory neurons.

Animals↗

PubMed1989

Specific suppression of pentylenetetrazol-induced epileptiform discharges in CA3 neurons (hippocampal slice, guinea pig) by the organic calcium antagonists flunarizine and verapamil.

Antiepileptic actions of the organic calcium antagonists flunarizine (cinnarizine derivate) and verapamil (papaverin derivat) on pentylenetetrazol-induced epileptic bioelectric activity were tested in CA3 neurones of hippocampal slices. In all experiments both calcium antagonists reduced the amplitudes and/or durations of paroxysmal depolarizations as well as their rate of occurrence, when the bath concentrations of flunarizine or verapamil exceeded 20 mumol/l. When they were added to the bath solution before pentylenetetrazol application, recordings of the resting membrane potential, of the membrane resistance, of action potentials and of spontaneous as well as of evoked excitatory and inhibitory postsynaptic potentials gave no indication that the antiepileptic effects of these drugs are due to unspecific depressive actions on neuronal excitability or spread of excitation.

Animals↗

PubMed1984

Hyperpolarizing potentials in guinea pig hippocampal CA3 neurons.

There is a bewildering variety of hyperpolarizing potentials which control activity in hippocampal pyramidal cells. These include an inhibitory postsynaptic potential (IPSP) with early and late components, voltage- and calcium-dependent potassium conductances, a voltage-dependent potassium conductance modulated by muscarinic agents (the M-current), and a complex and poorly understood afterhyperpolarization following epileptiform bursts. In hippocampal CA3 pyramidal cells, mossy fiber stimulation elicits an IPSP which is made up of two readily separable components. Using the in vitro slice preparation, we investigated the underlying ionic basis of these IPSP components and compared them to other hyperpolarizing potentials characteristic of the CA3 neurons. Intracellular recordings were obtained and then tissue was exposed to bathing medium low in chloride concentration or high in potassium concentration; the ion "blockers" EGTA (intracellular); tetraethylammonium (TEA) (intra- and extracellular), and barium and cobalt (extracellular); and the gamma-aminobutyric acid (GABA)/chloride antagonists penicillin, bicuculline and picrotoxin.

Animals↗

PubMed1987

Papain effects on rat hippocampal neurons in the slice preparation.

Intracellular recordings were made from the CA1 stratum pyramidale region of rat hippocampal slices. Papain was applied to the cells via bath perfusion, and its effects on membrane properties, synaptic potentials and responses to pressure application of gamma-aminobutyric acid (GABA) were assessed. Papain did not markedly affect neuronal input resistance, resting potential or action potentials with treatment times lasting over one hour. Synaptic potentials were initially enhanced and then gradually abolished, with the fast inhibitory postsynaptic potential being the most sensitive and the late, potassium-dependent hyperpolarization being the most resistant to enzyme. Responses to GABA were enhanced by papain, the GABA-activated conductance increased, and a slow depolarizing wave appeared which resembled the effect caused by pentobarbital on these neurons. This study indicates that the use of papain in the acutely dissociated neuron preparation is not responsible for the dramatic increase in resting input resistance seen in these neurons. The GABA-activated conductance may be affected by the enzyme.

Action Potentials↗

PubMed1999

Potassium channels of myenteric neurons in guinea-pig small intestine.

Patch-clamp recording was used to study rectifying K+ currents in myenteric neurons in short-term culture. In conditions that suppressed Ca2+ -activated K+ current, three kinds of voltage-activated K+ currents were identified by their voltage range of activation, inactivation, kinetics and pharmacology. These were A-type current, delayed outwardly rectifying current (I(K),dr) and inwardly rectifying current (I(K),ir). I(K),ir consisted of an instantaneous component followed by a time-dependent current that rapidly increased at potentials negative to -80 mV. Time-constant of activation was voltage-dependent with an e-fold decrease for a 31-mV hyperpolarization amounting to a decrease from 800 to 145 ms between -80 and -100 mV. I(K),ir did not inactivate. I(K),ir was abolished in K+ -free solution. Increases in external K+ increased I(K),ir conductance in direct relation to the square root of external K+ concentration. Activation kinetics were accelerated and the activation range shifted to more positive K+ equilibrium potentials. I(K),ir was suppressed by external Cs+ and Ba2+ in a concentration-dependent manner. Ca2+ and Mg+ were less effective than Ba2+. I(K),ir was unaffected by tetraethylammonium ions. I(K),dr was activated at membrane potentials positive to - 30 mV with an e-fold decrease in time-constant of activation from 145 to 16 ms between -20 and 30 mV. It was half-activated at 5 mV and fully activated at 50 mV. Inactivation was indiscernible during 2.5 s test pulses. I(K),dr was suppressed in a concentration-, but not voltage-dependent manner by either tetraethylammonium or 4-aminopyridine and was insensitive to Cs+. The results suggest that I(K),ir may be important in maintaining the high resting membrane potentials found in afterhyperpolarization-type enteric neurons. They also suggest importance of I(K),ir channels in augmentation of the large hyperpolarizing after-potentials in afterhyperpolarization-type neurons and the hyperpolarization associated with inhibitory postsynaptic potentials. I(K),dr in afterhyperpolarization-type enteric neurons has overall kinetics and voltage behaviour like delayed rectifier currents in other excitable cells where the currents can also be distinguished from A-type and Ca2+ -activated K+ current.

Animals↗

PubMed1994

A role for potassium currents in the generation of the swimming motor pattern of Xenopus embryos.

1. To assess the role that K+ currents play in the production of the swimming motor pattern in the Xenopus embryo, we have used low doses of the K+ channel blockers, 3,4-diaminopyridine (3,4-DAP; 25-100 microM) and tetraethylammonium (TEA; 500 microM), to reduce K+ currents and investigated the effects on motor output. 2. To confirm that 3,4-DAP and TEA block K+ currents and characterize their actions, we made whole-cell voltage-clamp recordings from acutely isolated spinal neurons. Both 25-100 microM 3,4-DAP and 100-500 microM TEA blocked the sustained K+ current in a dose-dependent manner. 3. Because TEA can block acetylcholine nicotinic receptors on autonomic ganglia, and nicotinic acetylcholine receptors have recently been shown to be present on Xenopus spinal neurons, we have tested both 3,4-DAP and TEA for antagonist action against the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP). Although 500 microM TEA blocked the DMPP-induced depolarization, 25 microM 3,4-DAP did not. 4. In the intact embryo, application of 25-100 microM 3,4-DAP or 500 microM TEA disrupted both the left and right alternation of ventral root discharge and the motor pattern recorded intracellularly from spinal neurons during swimming. Both blockers allowed the firing of an extra action potential at midcycle, which led to a number of different patterns. These patterns were categorized as follows: type A, cycles with midcycle action potentials; type B, the simultaneous firing of neurons on both sides of the cord; and type C, in which one side was active, whereas the other side was inhibited. In both 3,4-DAP and TEA these abnormalities tended to occur at the beginning of swimming episodes. Both blockers also caused a significant increase in the cycle period. Because both 3,4-DAP and TEA produced very similar affects to the motor pattern, we conclude that the perturbations are probably a result of reducing K+ current amplitude. 5. To investigate whether 3,4-DAP and TEA were producing disruptions in the motor pattern by increasing synaptic drive through the broadening of action potentials, we made measurements of spike width, tonic depolarization, and midcycle inhibitory postsynaptic potential (IPSP) amplitude during swimming. Both 3,4-DAP and TEA caused significant but modest spike broadening (20.8 and 29.8%, respectively); however, their effects on tonic depolarization were inconsistent although both blockers increased midcycle IPSP amplitude. 6. To test whether a reduction in K+ currents could plausibly produce the specific motor pattern perturbations that were seen, we have made computer simulations of simplified spinal networks.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed2001

Zinc and copper influence excitability of rat olfactory bulb neurons by multiple mechanisms.

Zinc and copper are highly concentrated in several mammalian brain regions, including the olfactory bulb and hippocampus. Whole cell electrophysiological recordings were made from rat olfactory bulb neurons in primary culture to compare the effects of zinc and copper on synaptic transmission and voltage-gated ion channels. Application of either zinc or copper eliminated GABA-mediated spontaneous inhibitory postsynaptic potentials. However, in contrast to the similarity of their effects on inhibitory transmission, spontaneous glutamate-mediated excitatory synaptic activity was completely blocked by copper but only inhibited by zinc. Among voltage-gated ion channels, zinc or copper inhibited TTX-sensitive sodium channels and delayed rectifier-type potassium channels but did not prevent the firing of evoked single action potentials or dramatically alter their kinetics. Zinc and copper had distinct effects on transient A-type potassium currents. Whereas copper only inhibited the A-type current, zinc modulation of A-type currents resulted in either potentiation or inhibition of the current depending on the membrane potential. The effects of zinc and copper on potassium channels likely underlie their effects on repetitive firing in response to long-duration step depolarizations. Copper reduced repetitive firing independent of the initial membrane voltage. In contrast, whereas zinc reduced repetitive firing at membrane potentials associated with zinc-mediated enhancement of the A-type current (-50 mV), in a significant proportion of neurons, zinc increased repetitive firing at membrane potentials associated with zinc-mediated inhibition of the A-type current (-90 mV). Application of zinc or copper also inhibited voltage-gated Ca(2+) channels, suggesting a possible role for presynaptic modulation of neurotransmitter release. Despite similarities between the effects of zinc and copper on some ligand- and voltage-gated ion channels, these data suggest that their net effects likely contribute to differential modulation of neuronal excitability.

Action Potentials↗

PubMed1985

Vertical spread of neuronal activity within the cat motor cortex investigated with epicortical stimulation and intracellular recording.

In the encéphale isolé cat preparation the surface of precruciate cortex was electrically stimulated. Intracellular responses underneath the stimulated site were recorded to assess the vertical spread of activities across the cortical layers. To the epicortical stimulation (EPICS) with intensity adjusted to evoke a pure negative wave in the direct cortical response (DCR), only some neurons in relatively superficial layers responded with excitatory postsynaptic potentials (EPSPs). Stimuli intensified to evoke both the negative and subsequent positive waves in DCR produced in all tested cells either EPSPs, inhibitory postsynaptic potentials (IPSPs), or both. Direct or axonal antidromic excitation of the cell was observed only infrequently. Cells with EPSPs distributed through all the layers with two peak populations in laminae II and V-VI. Those with IPSPs were located mainly in the upper half of lamina III with a few in more superficial as well as in deeper layers. Both EPSPs and IPSPs showed mono- or oligosynaptic latencies (0.6-10 msec) that tended to become longer in deep than in superficial layers. Some deep layer cells including fast and slow pyramidal tract cells showed slowly rising monosynaptic EPSPs of dendritic origin. Further late responses consisted of EPSPs, IPSPs, disfacilitation (DF), and disinhibition (DI). DF or DI occurred in some deep layer cells. Two modes of vertical spread of activities were postulated: one the cascade transmissions which increased response repertoire toward the depths, and the other the electrotonic spread of EPSPs along dendrites.

Animals↗

PubMed2006

[Long-term alteration of gamma-aminobutyric acid B receptor subunits in immature rats after recurrent febrile seizures].

OBJECTIVE: Febrile seizure (FS) is closely related to an altered transmission of gamma-aminobutyric acid (GABA). GABA exerts its effects through ionotropic receptors (GABA(AR) and GABA(CR)) and metabotropic receptors (GABA(BR)). GABA(BRs) are located at pre- and postsynaptic sites. Stimulation of postsynaptic receptors generates long-lasting inhibitory postsynaptic potentials (IPSPs) that are important for the fine-tuning of inhibitory neurotransmission and caused by an increase in K(+) conductance. At presynaptic sites, GABA(BRs) mediate a suppression on the release of neurotransmitters such as of GABA or glutamate by inhibiting voltage-sensitive Ca(2+) channels. The present study aimed to explore the long-term changes of GABA(B) receptor subunits in immature rats after recurrent febrile seizures. METHODS: Rats were randomly divided into control group and hyperthermia treatment group. The control rats (n = 64) were put into 37 degrees C water for 5 minutes. Rats with hyperthermia treatment were put into 44.8 degrees C water for 5 minutes. If a rat in hyperthermia treatment group showed seizure within 5 min, the rat was taken out of the water as soon as the seizure occurred. Water-immersion was carried out 10 times, once every 2 days. Rats showing 10 seizures (FS(10), n = 64) were studied. Rats exposed to hyperthermia for 10 times without seizure were also studied as hyperthermia-only (H, n = 64) group. Rats showing one seizure at the last time of 10 times of hyperthermia treatment were studied as one-seizure group (FS(1), n = 64). The other rats were studied for other research. The changes of GABA(B)R(1) and GABA(B)R(2) co-localization were detected by double fluorescence;the quantitative alteration of GABA(B)R(1) and GABA(B)R(2) were detected by quantitative RT-PCR; the binding of GABA(B)R(2) to GABA(B)R(1) was detected by immunoprecipitation/Western blot. RESULTS: GABA(B)R(1), GABA(B)R(2), and the binding of GABA(B)R(2) to GABA(B)R(1) decreased after the last febrile seizure in FS(10) group, the expression of GABA(B)R(1) returned to normal in later phase while GABA(B)R(2) and the binding of them did not. CONCLUSION: Recurrent FS down-regulated the expression of GABA(B)R subunits in a long term.

Age Factors↗

PubMed1992

Postsynaptic potentials in cat visual cortex: dependence on polarization.

During the investigation of visually evoked postsynaptic potentials (PSPs) of visual cortical neurons, we recorded cell activity under different levels of membrane potential. In some cases, however, dependence of these PSPs on the level of membrane polarization appears to be inconsistent with the conventional scheme. One disagreement was the reduction, instead of an increase, of excitatory potentials during hyperpolarization of the cell. The other point was that depolarization of the cell often leads to increase of the amplitude of both excitatory and inhibitory postsynaptic potentials. This inconsistency may suggest the involvement of voltage-dependent ion channels in generating PSPs to visual stimuli. A possible way of separating the excitatory and inhibitory components of the response by polarization of the cell in spite of the presence of voltage-dependent channels and possible implications of this mechanism in the visual cortex are discussed.

Animals↗

PubMed1990

[Effect of verapamil independent of its calcium channel antagonist action on hippocampal pyramidal neurons in rats].

The effects of verapamil, the phenylalkylamine calcium channel antagonist, have been studied on rat hippocampal pyramidal neurons, using intracellular recordings in an in vitro slice preparation. At low concentrations (1-10 microM), verapamil had no effect on these neurons. At higher concentrations (100-150 microM), it induced a progressive blockade of the slow component of the after-hyperpolarizing potential (AHP), but did not affect the fast one. Verapamil also blocked the slow inhibitory postsynaptic potential (sIPSP), but not the fast one. Pharmacological responses to the application of baclofen and serotonin were abolished, while the response to GABA was not. In addition, the size of the calcium spike was increased by verapamil, while the AHP and the sIPSP were already blocked. These results suggest that verapamil, applied at high concentrations, has an inhibitory effect on potassium conductances, independent of its calcium antagonist property.

Action Potentials↗

PubMed1994

Modulation of GABA-mediated synaptic transmission by endogenous zinc in the immature rat hippocampus in vitro.

1. Intracellular recordings from postnatal 2- to 12-day-old (P2-12) rat hippocampal CA3 pyramidal neurones exhibited spontaneous synaptic potentials mediated by GABAA receptors. These potentials can be separated on the basis of amplitude into two classes which are referred to as small and large. 2. The large depolarizing potentials were reversibly inhibited by the Zn2+ chelator 1,2-diethyl-3-hydroxypyridin-4-one (CP94). The small inhibitory postsynaptic potentials. (IPSPs) were apparently unaffected. 3. Stimulation of the mossy fibre pathway evoked composite excitatory postsynaptic potentials (EPSPs) and IPSPs. Threshold stimulus-evoked synaptic potentials were mediated by GABAA receptors and were reversibly blocked by CP94. The responses evoked by suprathreshold stimulation and persisting in the presence of bicuculline or CP94 were partially inhibited by 2-amino-5-phosphonopropionic acid (AP5) and were completely blocked with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 4. L-Histidine, which preferentially forms complexes with Cu2+ > Zn2+ > Fe2+ > Mn2+, inhibited both naturally occurring spontaneous and evoked GABAA-mediated large synaptic potentials without affecting the neuronal resting membrane properties. Exogenously applied Zn2+ induced large spontaneous synaptic potentials and prolonged the duration of the evoked potentials. These effects were reversibly blocked by histidine. 5. The metal chelating agent diethyldithiocarbamate had little effect on the large amplitude synaptic potentials. 6. The transition metal divalent cations Fe2+ and Mn2+ did not initiate large synaptic potentials in CA3 neurones; however, Cu2+ depolarized the membrane and enhanced both excitatory and inhibitory synaptic transmission, resulting in a transient increase in the frequency of the large amplitude events. In comparison, zinc increased the frequency of the large potentials and also induced such events in neurons (P4-21) where innate potentials were absent. The postsynaptic response to ionophoretically applied GABA was either unaffected or slightly enhanced by Zn2+. 7. Under conditions favouring the activation of non-NMDA receptors, excitatory synaptic transmission was unaffected by CP94 but was depressed by Zn2+. Responses to ionophoretically applied glutamate were not inhibited by Zn2+, indicating that Zn2+ affects excitatory synaptic transmission via a presynaptic mechanism. 8. We conclude that the naturally occurring large synaptic potentials in young CA3 neurones are apparently induced by endogenous Zn2+ which can promote or synchronize the release of GABA in the immature hippocampus.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1993

Epileptic focus induced in rat by intrahippocampal cholera toxin: neuronal properties in vitro.

Injecting 0.5-1.0 microgram of cholera toxin into rat hippocampus induces a chronic epileptic focus which generates interictal discharges and brief epileptic seizures intermittently over the following seven to 10 days. Here we examined the electrophysiological properties of hippocampal slices prepared from these rats three to four days after injection, at the height of the epileptic syndrome. These slices generated epileptic discharges in response to electrical stimulation of afferent pathways. In many cases epileptic discharges occurred spontaneously in the CA3 subregion; these usually lasted < 200 ms, but they could last < 0.6 s. Intracellular recordings from pyramidal layer cells revealed depolarization shifts synchronous with the epileptic field potentials. These depolarization shifts had slow onsets compared with those induced by blocking inhibition with bicuculline (depolarizations started a mean of 57 ms before, and reached 5.2 mV by, the onset of the cholera toxin epileptic field potential, compared with 12 ms and 3.6 mV respectively for 70 microM bicuculline methiodide). Extracellular unit recordings showed that the slow predepolarization seen in the cholera toxin focus was associated with an acceleration of the firing of other pyramidal layer neurons. The epileptic activity in this model cannot be attributed to the loss of synaptic inhibition, because inhibitory postsynaptic potentials could be evoked when the synchronous bursts were blocked by increasing [Ca2+]o from 2 to 8 mM. Observations of monosynaptic inhibitory postsynaptic currents isolated by application of 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione, 50 microM DL-2-amino-5-phosphonovaleric acid and 100-200 microM 3-amino-2-(4-chlorophenyl)-2-hydroxy-propylsulphonic acid showed a small effect of the toxin only on the time course of the inhibitory postsynaptic current. On the other hand, there were significant changes in the intrinsic properties of individual neurons. The membrane potentials of cells in the cholera toxin focus did not differ from those in slices from rats injected with vehicle solution, but their input resistances were significantly increased. Unlike the other cellular changes in this model, the increase in input resistance was not seen in slices exposed acutely to 1 micrograms/ml cholera toxin for 30 min, suggesting there may be morphological changes in the chronic focus. Action potential accommodation and the slow afterhyperpolarization were depressed in both acute and chronic epileptic tissue, indicating impairments of Ca(2+)- and/or voltage-dependent K+ currents, and we conclude that these provide the most likely basis for cholera toxin epileptogenesis.

2-Amino-5-phosphonovalerate↗