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At least 343 records · Page 19Linked to original sources
PubMed1993

NMDA receptors have a dominant role in population spike-paired pulse facilitation in the dentate gyrus of urethane-anesthetized rats.

Paired-pulse facilitation was studied at the perforant path-granule cell synapses in the dentate gyrus of urethane-anesthetized rats. Extracellular field potentials comprising excitatory postsynaptic potentials (EPSPs) and population spikes (PSs) were used to compare facilitation of both responses at interpulse intervals between 10 and 1000 ms. In this model system EPSPs, produced at stimulus intensities well below the PS threshold, exhibited paired-pulse facilitation (PPF) at intervals less than 40 ms. Between 40 and 100 ms both responses were of equal size and from 200 to 1000 ms the second response exhibited paired-pulse depression (PPD). With higher stimulus intensities, PSs exhibited early (10-30 ms) and late (400-1000 ms) PPD and intermediate interval (40-200 ms) PPF. The enhanced PS amplitude during facilitation was accompanied by a modest decrease in EPSP slope and increase in PS latencies to onset and to peak. If PS amplitude was increased to the same extent by simply increasing stimulus intensity, an increase in EPSP slope and decrease in PS latencies to onset and peak were observed. Current source-density analysis revealed that the current sink generated by synaptic activation of granule cell dendrites was indistinguishable between control and facilitated responses up to the onset of the PS. However, the facilitated response exhibited a marked increase in the duration and amplitude of current flowing into the dendrites during the late phase of the EPSP. PPF of the PS was attenuated or blocked by the administration of the known NMDA receptor-ion channel blockers, MK-801, dextromethorphan and ketamine. The depressant effects of these pharmacological agents on facilitation shared the same time course as facilitation itself, peaking at 60 ms and lasting approximately 200 ms. These data suggest that facilitation in this situation is due to postsynaptic rather than presynaptic modulations, and is based upon an increase in the NMDA-mediated component of the evoked response. No increase in transmitter release, per se, could be demonstrated.

Analysis of Variance↗
PubMed1994

Effects of an inhibitor for calcium/calmodulin-dependent protein phosphatase, calcineurin, on induction of long-term potentiation in rat visual cortex.

A role of Ca2+/calmodulin-dependent protein phosphatase (calcineurin) in induction of long-term potentiation (LTP) was investigated using its selective inhibitor, FK506, in visual cortical slices of young rats. Field potentials or excitatory postsynaptic potentials (EPSPs) to test stimulation of white matter were recorded extra- or intracellularly from layer 2/3, and tetanic stimulation (tetanus) was applied to the white matter at 5 Hz. During the application of FK506 (1 microM), short tetanus (6 s) which had rarely induced LTP in the normal medium, became effective in inducing LTP. Tetanus for 1 min in the presence of FK506 induced LTP with higher probability than in the normal medium. To test possible involvement of presynaptic mechanisms, paired pulses at 50 ms intervals were given to the white matter. The facilitation ratio of the second to first EPSPs was not significantly changed by FK506 and after the induction of LTP, suggesting that the action of FK506 may not be presynaptic. To confirm this, FK506 was injected directly into neurons through recording electrodes. In cases in which stable EPSPs were recorded, the probability of LTP induction became higher than that obtained with normal electrodes. These results suggest that calcineurin plays a role in processes antagonizing the induction of LTP in visual cortex.

Animals↗
PubMed1993

Synaptic organization of the vestibulo-collic pathways from six semicircular canals to motoneurons of different neck muscles.

The pattern of inputs from six semicircular canals to neck motoneurons was investigated by stimulating six ampullary nerves electrically and recording intracellular potentials from motoneurons of the rectus capitis dorsalis (RD), the complexus (COMP) and the obliquus capitis caudalis (OCA) muscles at the upper cervical cord of the cat. RD and COMP motoneurons received disynaptic excitation from bilateral anterior and contralateral horizontal ampullary nerves and disynaptic inhibition from bilateral posterior and ipsilateral horizontal ampullary nerves. OCA motoneurons received excitation from ipsilateral vertical and contralateral horizontal ampullary nerves and inhibition from contralateral vertical and ipsilateral horizontal ampullary nerves. Ipsilateral disynaptic inhibitory postsynaptic potentials and contralateral disynaptic excitatory postsynaptic potentials to these motoneurons were mediated by the medial longitudinal fasciculus (MLF) and the other postsynaptic potentials by the extra-MLF pathways. The results indicated that motoneurons of a neck muscle have its own characteristic pattern of inputs from six semicircular canals.

Animals↗
PubMed2001

Preferential potentiation of fast-releasing synaptic vesicles by cAMP at the calyx of Held.

We have studied the effects of cAMP on synaptic transmission at the calyx of Held and found that forskolin (an activator of adenylate cyclase) and 8-Br-cAMP (a membrane-permeable analog of cAMP) potentiated excitatory postsynaptic currents (EPSCs). Direct sampling of miniature EPSCs (mEPSCs) and nonstationary fluctuation analysis showed that mEPSCs were not modulated by cAMP, suggesting that the locus of modulation is presynaptic. Deconvolution was used to examine effects of cAMP on quantal-release rates. By using this method, it was shown recently that release probabilities of readily releasable vesicles are heterogeneous. Here, we show that cAMP selectively increases the number of vesicles with higher release probabilities, whereas a slow component of the EPSC, representing vesicles that fuse more slowly, is unchanged. cAMP increases the apparent Ca2+ sensitivity for secretion, but this increase does not reflect an increase in release probability necessarily but rather an increase in the number of highly sensitive vesicles.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Neural circuits for taste. Excitation, inhibition, and synaptic plasticity in the rostral gustatory zone of the nucleus of the solitary tract.

The rostral nucleus of the solitary tract (rNST) plays a key role in modulating, organizing and distributing the sensory information arriving at the central nervous system from gustatory receptors. However, except for some anatomical studies of rNST synapses, the neural circuits responsible for this first stage in synaptic processing of taste information are largely unknown. Over the past few years we have used an in vitro brain slice preparation of the rNST to study synaptic processing, and it has become apparent that the rNST is a very complex neural relay. Synaptic potentials recorded in rNST neurons resulting from stimulation of afferent taste fibers are a composite of excitatory and inhibitory post synaptic potentials. Pure excitatory postsynaptic potentials (EPSP) can be isolated by using gamma-aminobutyric acid type A (GABAA) receptor blockers to eliminate the inhibitory postsynaptic potentials (IPSP). Application of glutamate ionotropic receptor blockers effectively eliminates all postsynaptic activity, indicating that glutamate is the transmitter at the first central synapse in the taste pathway. Stimulation of the afferent taste fibers originating from the anterior (chorda tympani) and posterior (glossopharyngeal) tongue results in a postsynaptic potential that is a complex sum of the two individual potentials. Thus, rNST neurons receive convergent synaptic input from the anterior and posterior tongue. The IPSP component of the synaptic potentials in rNST results from stimulation of interneurons. If these IPSPs are initiated by tetanic stimulation they undergo both short-term and long-term changes. Short-term changes result in the development of biphasic depolarizing IPSPs, and long-term changes result in potentiation of the IPSPs that can last over an hr in some neurons. This remarkable synaptic plasticity may be involved in the mechanism of learned taste behaviors. Synaptic transmission in rNST consists of excitation combined with inhibition. The inhibition does not simply depress excitation but probably serves many roles such as shaping and limiting excitation, coordinating the timing of synaptic events and participating in synaptic plasticity. Knowledge of these synaptic mechanisms is essential to understanding how the rNST processes taste information.

Animals↗
PubMed1986

Effects of 4-aminopyridine on the action potential and the after-hyperpolarization of cat spinal motoneurons.

In cats under pentobarbital anaesthesia, intramotoneuronal administrations of 4-aminopyridine significantly prolong the falling phase of the antidromic action potential but have much less effect on the orthodromic action potential. 4-aminopyridine probably blocks the fast K channels involved in the repolarization of the membrane and indirectly activates ionic channels through enhancement of synaptic transmission, also suggested by the potentiation of excitatory postsynaptic potentials. In many cells, 4-aminopyridine depresses the amplitude and prolongs the time course of the after-hyperpolarization; therefore 4-aminopyridine may also partly block Ca2+-activated K+ channels.

4-Aminopyridine↗
PubMed1995

Neurophysiological consequences of nitroxide antioxidants.

Nitroxides are antioxidant compounds that have been shown to provide radioprotection in vivo and in vitro. Radioprotection in vivo is limited by toxicity, which appears to be neurologic in nature. To further evaluate the toxicity of these compounds, three representative nitroxides, Tempol, Tempamine, and Tempo, were examined in slices of guinea pig hippocampus. Each nitroxide increased the population spike and caused potentiation of excitatory postsynaptic potential--spike coupling. Repetitive activity and epileptiform activity were observed at the highest concentrations of Tempo and Tempamine. Tempol was the least toxic compound in this system, followed by Tempamine and Tempo. Additional studies are necessary to further define the effects of nitroxides on the central nervous system and to develop strategies to mitigate these effects.

Animals↗
PubMed1995

Electrical properties of the cerebral prothoracicotropic hormone cells in diapausing and non-diapausing pupae of the tobacco hornworm, Manduca sexta.

Prothoracicotropic hormone (PTTH) is an insect brain neuropeptide that is a primary factor regulating an insect development. Curtailment of its release is thought to be responsible for the pupal diapause of tobacco hornworm, Manduca sexta. The cell synthesizing and secreting the PTTH has been identified as a pair of neurosecretory cells in the pars lateralis on each brain hemisphere. Using intracellular recording techniques, we have demonstrated electrical properties of the PTTH cells in different physiological status, i.e., diapausing and developing pupae. In diapausing pupae, they showed threshold value increasing and input resistance decreasing with the progress of diapausing state, indicating that they were getting unexcitable. Spontaneous action potentials and excitatory postsynaptic potentials (EPSPs) were rarely observed in deeply diapausing state. Non-diapausing PTTH cells were almost silent except day-2, showing rather constant values of electrical properties. On day-2, a significant proportion of the cells had spontaneous action potentials, showing less negative membrane potential values than inactive cells. Exclusively inhibitory postsynaptic potentials (IPSPs) were observed in significant numbers of the cells during the period from day-2 to day-5. On the basis of the results obtained, we proposed a working hypothesis that electrical activities of the PTTH cell may be primarily regulated by its membrane properties which are further modulated by the synaptic mediation.

Animals↗
PubMedDate not supplied

Perspectives on physiological monitoring: junctional-type potentials in the food ventricle.

1. Many toads monitored throughout survival with no support other than protection against drying, pass terminally through a remarkable evolution which is described here in the full details of a single experiment lasting some 40 hours. 2. The essential features of this particular sequence is block of the Luciani-Wenckebach type affecting SA, AV, and intraventricular conduction. SA block was apparently the major cause of periods of arrest and of cycles of heart beats. Periodically PR delay based on progressive AV block was observed but it was not an outstanding feature. 3. Progressive, rate-determined intraventricular block during the cycles of ventricular beats was the first new feature of these observations. 4. As intraventricular block progressed, an initial ventricular deflection separated itself from the rest of QRS. 5. This initial deflection diminished in amplitude throughout each cycle of ventricular beats, its rate of rise diminished, and the interval separating it from the rest of the ventricular complex increased until the whole initial deflection was revealed. 6. Thereafter, with a small decrease in amplitude of the initial deflection, the remainder of the ventricular electrogram failed to follow and the complex stood alone. 7. Its polarity indicated its origin at the base of the ventricle, the interval separating it from the origin of P indicated that it was downstream from the AV conduction mechanism. 8. This deflection, now a local ventricular potential (LVP) then progressively declined in amplitude and disappeared. 9. The possibility has been discussed that the potential represents (a) a true action potential localized by block or (b) a local, nonpropagated potential akin to junctional potentials like: (1) end-plate potentials, (2) generator potentials, (3) excitatory postsynaptic potentials (EPSPs), or (c) a pacemaker potential. The experiments that have revealed the phenomenon have not provided other than suggestive but inconclusive information about its nature. 10. The observations are new or certainly not well known and further study should shed light on the problem of intracardial impulse formation and conduction.

Animals↗
PubMed1999

Evidence for an ephaptic feedback in cortical synapses: postsynaptic hyperpolarization alters the number of response failures and quantal content.

The amplitude of excitatory postsynaptic potentials and currents increases with membrane potential hyperpolarization. This has been attributed to an increase in the driving force when the membrane potential deviates from the equilibrium potential of the respective ions. Here we report that in a subset of neocortical and hippocampal synapses, postsynaptic hyperpolarization affects traditional measures of transmitter release: the number of failures, coefficient of variation of response amplitudes, and quantal content, suggesting increased presynaptic release. The result is compatible with the hypothesis of Byzov on the existence of electrical (or "ephaptic") linking in purely chemical synapses. The linking, although negligible at neuromuscular junctions, could be functionally significant in influencing transmitter release at synapses with high resistance along the synaptic cleft. Our findings necessitate reconsideration of classical amplitude-voltage relations for such synapses. Thus, synaptic strength may be enhanced by hyperpolarization of the postsynaptic membrane potential. The positive ephaptic feedback could account for "all-or-none" excitatory postsynaptic potentials at some cortical synapses, large evoked and spontaneous multiquantal events and a high efficacy of large "perforated" synapses whose number increases following behavioural learning or the induction of long-term potentiation.

2-Amino-5-phosphonovalerate↗
PubMed2002

Short-term dynamics of synaptic transmission within the excitatory neuronal network of rat layer 4 barrel cortex.

The short-term plasticity of synaptic transmission between excitatory neurons within a barrel of layer 4 rat somatosensory neocortex was investigated. Action potentials in presynaptic neurons at frequencies ranging from 1 to 100 Hz evoked depressing postsynaptic excitatory postsynaptic potentials (EPSPs). Recovery from synaptic depression followed an exponential time course with best-fit parameters that differed greatly between individual synaptic connections. The average maximal short-term depression was close to 0.5 with a recovery time constant of around 500 ms. Analysis of each individual sweep showed that there was a correlation between the amplitude of the response to the first and second action potentials such that large first EPSPs were followed by smaller than average second EPSPs and vice versa. Short-term depression between excitatory layer 4 neurons can thus be termed use dependent. A simple model describing use-dependent short-term plasticity was able to closely simulate the experimentally observed dynamic behavior of these synapses for regular spike trains. More complex irregular trains of 10 action potentials occurring within 500 ms were initially well described, but during the train errors increased. Thus for short periods of time the dynamic behavior of these synapses can be predicted accurately. In conjunction with data describing the connectivity, this forms a first step toward computational modeling of the excitatory neuronal network of layer 4 barrel cortex. Simulation of whisking-evoked activity suggests that short-term depression may provide a mechanism for enhancing the detection of objects within the whisker space.

Action Potentials↗
PubMed1997

Lamotrigine inhibits tetraethylammonium-induced synaptic plasticity in the rat amygdala.

Although long-term potentiation was generally initiated by a brief tetanus, in the hippocampus, it could also be evoked by application of the K+ channel blocker tetraethylammonium. The present study was aimed at investigating the effect of lamotrigine, a new anticonvulsant, on the tetraethylammonium-induced potentiation in brain slices of the rat amygdala using intracellular recording techniques. Bath application of tetraethylammonium (20 mM) for 10 min resulted in a long-lasting enhancement of the amplitude of excitatory postsynaptic potentials to 235 +/- 12% of control (n = 6, P < 0.001). Pretreatment of the slices with nifedipine (10 microM) abolished the potentiation, suggesting that tetraethylammonium long-term potentiation in the amygdala is due to Ca2+ influx through voltage-dependent Ca2+ channels. By contrast, N-methyl-D-aspartate receptor activation was not required because D-2-amino-5-phosphonovalerate (50 microM) did not prevent the tetraehylammonium long-term potentiation. Superfusion of lamotrigine (50 microM) depressed the excitatory postsynaptic potential to 53.8 +/- 3.9% of control. Tetraethylammonium was subsequently added in the presence of lamotrigine but failed to enhance the excitatory postsynaptic potential. Bursts of Ca2+ spikes evoked by a depolarizing pulse or by synaptic stimulation under tetraethylammonium were depressed by lamotrigine. It is concluded that lamotrigine is capable of inhibiting tetraethylammonium-induced synaptic plasticity. The underlying mechanism is likely due to lamotrigine's inhibition of postsynaptic voltage-dependent Ca2+ channels. Considering that tetraethylammonium is a convulsant agent and brief seizure episodes induced long-term potentiation, fibre sprouting and the development of aberrant synaptic contacts, lamotrigine could be a potential neuroprotective agent, especially in pathological situations where excessive glutamate release occurs.

Amygdala↗
PubMed2000

Group II and group III metabotropic glutamate receptor agonists depress synaptic transmission in the rat spinal cord dorsal horn.

The effects of group II and group III metabotropic glutamate receptor agonists on synaptic responses evoked by primary afferent stimulation in the dorsal horn, but mostly substantia gelatinosa, neurons were studied in the spinal cord slice preparation using conventional intracellular recording technique. Bath application of a potent metabotropic glutamate receptor 2- and 3-selective agonist (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine reversibly suppressed monosynaptic and polysynaptic excitatory postsynaptic potentials evoked by A primary afferent fibers stimulation, the effect likely mediated by mGlu3 receptor subtype. This suppressing effect of (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine on primary afferent neurotransmission was dose dependent and reduced by (S)-alpha-ethylglutamate, a group II metabotropic glutamate receptor antagonist. (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine suppressed excitatory postsynaptic potentials without inducing detectable changes of postsynaptic membrane potential and neuronal input resistance in dorsal horn neurons. The paired-pulse depression at excitatory synapses between primary afferent fibers and dorsal horn neurons was reduced by (2S,1'R,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl) glycine application, suggesting a presynaptic site of action. The selective group III metabotropic glutamate receptor agonist (S)-2-amino-4-phosphonobutanoate also depressed A afferent fibers-evoked monosynaptic and polysynaptic excitatory postsynaptic potentials in a dose-dependent and reversible manner. The concentration-dependence of (S)-2-amino-4-phosphonobutanoate-mediated depression was most consistent with activation of mGlu receptor subtypes 4 and 7. However, on the basis of anatomical distribution of mGlu 4 and 7 subtypes, it is also possible that the (S)-2-amino-4-phosphonobatanoate effect is due to interaction with mGlu 7 receptor alone. (RS)-alpha-cyclopropyl-4-phosphonophenylglycine a preferential antagonist at group III metabotropic glutamate receptors, completely reversed the depressant effects of (S)-2-amino-4-phosphonobutanoate on both monosynaptic and polysynaptic responses. (S)-2-amino-4-phosphonobutanoate reduced the paired-pulse depression at excitatory synapses between primary afferent fibers and dorsal horn neurons, but did not alter their postsynaptic membrane potential and input resistance. A clear facilitation of the (S)-2-amino-4-phosphonobutanoate-induced depression of monosynaptic and polysynaptic excitatory postsynaptic potentials in the absence of gamma-aminobutyric acid-subtype A receptor- and glycine-mediated synaptic inhibition was shown. Besides the depressant effect on excitatory synaptic transmission, inhibitory actions of group II and III metabotropic glutamate receptor agonists on the inhibitory postsynaptic potentials evoked by primary afferent stimulation in dorsal horn neurons were observed. These results suggest that group II and group III metabotropic glutamate receptors are expressed at primary afferent synapses in the dorsal horn region, and activation of the receptors suppresses synaptic transmission by an action on the presynaptic site.

Animals↗
PubMed1994

Synaptic potentiation and depression in slices of mediorostral neostriatum-hyperstriatum complex, an auditory imprinting-relevant area in chick forebrain.

Long-term potentiation, a tetanic stimulation-evoked, persistent increase in synaptic efficiency, is the most extensively studied form of synaptic plasticity. Intracellular correlates of long-term potentiation have been analysed in mammalian hippocampus and cortex, but not in bird cortical analogues. We present here studies on long-term potentiation in slices of the chick forebrain area mediorostral neostriatum-hyperstriatum complex which receives thalamic afferents and is relevant for auditory filial imprinting. Following afferent tetanic stimulation, population spike potentiation was extracellularly recorded in 25% of the tested neurons for longer than 40 min. Using intracellular recordings, the membrane potential, the amplitude of excitatory postsynaptic potentials, the latency between the test stimulus and the evoked action potentials, and the cellular excitability (excitatory postsynaptic potential-spike relationship) were found to change after the tetanus. A long-term depression following the tetanus was also seen in some units in this area. Furthermore, the mechanisms underlying long-term potentiation were investigated. A large depolarization of resting membrane potential (approx. 36 mV) was characteristic after the tetanic stimulation. N-methyl-D-aspartate receptor channels are necessary for induction of this depolarization, as well as for long-term potentiation, as demonstrated by the effect of DL-2-amino-5-phosphonovaleric acid. After intracellular recordings, the cells were injected with Lucifer Yellow. The combination of electrophysiological characterization and morphological identification suggested that the potentiation came chiefly from type I neurons, which have the largest soma among the neuron types in this area and up to eight dendrites. The results demonstrate that the recognized major phenomena of long-term potentiation are found in an auditory imprinting-relevant area of the chick forebrain, and that this potentiation is dependent on N-methyl-D-aspartate receptor channels. It is noteworthy that behavioural imprinting was previously shown to induce a reduction of up to 47% of the spine frequency of type I neurons and a growth of the remaining spine synapses, all resembling a synaptic selection process. Therefore, the intriguing possibility emerges that mechanisms underlying long-term potentiation are instrumental for this selection process, which involves regressive and proliferative morphological changes.

Acoustic Stimulation↗
PubMed1986

Amino acid receptor-mediated transmission at primary afferent synapses in rat spinal cord.

Intracellular recording techniques have been used to provide information on the identity of excitatory transmitters released at synapses formed between dorsal root ganglion (DRG) and spinal cord neurones in two in vitro preparations. Explants of embryonic rat DRG were added to dissociated cultures of embryonic dorsal horn neurones and synaptic potentials recorded intracellularly from dorsal horn neurones after DRG explant stimulation. More than 80% of dorsal horn neurones received at least one fast, DRG-evoked, monosynaptic input. In the presence of high divalent cation concentrations (5 mmol l-1 Ca2+, 3 mmol l-1 Mg2+) the acidic amino acid receptor agonists, L-glutamate, kainate (KA) and quisqualate (QUIS) excited all dorsal horn neurones which received a monosynaptic DRG neurone input, whereas L-aspartate and N-methyl-D-aspartate (NMDA) had little or no action. 2-Amino-5-phosphonovalerate (APV), a selective NMDA receptor antagonist, was relatively ineffective at antagonizing DRG-evoked synaptic potentials and L-glutamate-evoked responses. In contrast, kynurenate was found to be a potent antagonist of amino acid-evoked responses and of synaptic transmission at all DRG-dorsal horn synapses examined. The blockade of synaptic transmission by kynurenate appeared to result from a postsynaptic action on dorsal horn neurones. Intracellular recordings from motoneurones in new-born rat spinal cord were used to study the sensitivity of the Ia excitatory postsynaptic potential (EPSP) to antagonists of excitatory amino acids. Superfusion of the spinal cord with APV did not inhibit the Ia EPSP but did suppress later, polysynaptic components of the afferent-evoked response. Kynurenate was a potent and selective inhibitor of the Ia EPSP, acting via a postsynaptic mechanism. These findings indicate that L-glutamate, or a glutamate-like compound, but not L-aspartate, is likely to be the predominant excitatory transmitter that mediates fast excitatory postsynaptic potentials at primary afferent synapses with both dorsal horn neurones and motoneurones.

Afferent Pathways↗
PubMed1993

The impaired long-term potentiation in the CA1 field of the hippocampus of cognitive deficient microencephalic rats is restored by D-serine.

Rat embryos exposed on gestational day 15 to methyl-azoxymethanol acetate develop a microencephaly characterized primarily by a hypoplasia of the neocortex and CA fields of the hippocampus that in adulthood is associated with disturbances in learning. In brain slices prepared from microencephalic rats, we have examined the field excitatory postsynaptic potentials and population spike in the CA1 field of the hippocampus evoked by stimulation of the stratum radiatum. These parameters did not differ from those obtained in slices from control rats. High frequency stimulation of the stratum radiatum afferent fibres, which readily induced long-term potentiation of the field excitatory postsynaptic potentials and population spike in the CA1 field of the hippocampus of control rats, failed to induce long-term potentiation in that of microencephalic rats. High frequency stimulation of the perforant path readily elicited long-term potentiation in the dentate gyrus of both control and microencephalic rats. Picrotoxin had no apparent effect on field excitatory postsynaptic potentials and population spike in the CA1 field of the microencephalic rats, indicating that little GABAergic inhibition was present in slices from these rats. D-2-Amino-phosphonovalerate suppressed the field potentials in slices from microencephalic rats by more than 50%, suggesting that N-methyl-D-aspartate receptors contributed markedly to the synaptic responses evoked by single stimuli. D-Serine, but not picrotoxin, restored long-term potentiation in the CA1 field of the microencephalic rats. The D-serine effect was prevented by pretreating the slices with either 7-chloro-kynurenate or D-2-amino-phosphonovalerate. The failure to induce long-term potentiation, if also found in vivo, may be among the factors related to the learning deficits displayed by these rats.

2-Amino-5-phosphonovalerate↗
PubMed1975

Molecular model of postsynaptic potential.

A molecular model of the excitatory postsynaptic membrane is given in terms of two biochemical cycles intimately associated: an acetylcholine cycle and a calcium cycle. The acetylcholine controls the Na ionophores while calcium ions control the tk ionophore. The two ionophores are spatially separated but interact in such a way that the variation in K conductance precedes that in Na conductance. Digital simulation shows that our model accounts quantitatively for both the evolution of excitatory postsynaptic potential and current in a variety of experimental conditions.

Acetylcholine↗
PubMed1998

Subtype-specific involvement of metabotropic glutamate receptors in two forms of long-term potentiation in the dentate gyrus of freely moving rats.

In this study, the role of metabotropic glutamate receptors in N-methyl-D-aspartate receptor-dependent and voltage-gated calcium channel-dependent long-term potentiation in the dentate gyrus of freely moving rats was investigated. Antagonists for group 1 metabotropic glutamate receptors ((S)-4-carboxyphenylglycine), group 1/2 metabotropic glutamate receptors ((RS)-alpha-methyl-4-carboxyphenylglycine) and group 2 metabotropic glutamate receptors ((RS)-alpha-methylserine O-phosphate monophenylester) were used. The N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, and the L-type voltage-gated calcium channel antagonist, methoxyverapamil were used to investigate the N-methyl-D-aspartate receptor and voltage-gated calcium channel contribution to the long-term potentiation recorded. Field excitatory postsynaptic potential slope and population spike amplitude were measured. Drugs were applied, prior to tetanus, via a cannula implanted into the lateral cerebral ventricle. 200 Hz tetanization produces a long-term potentiation which is inhibited by application of D(-)-2-amino-5-phosphonopentanoic acid and (RS)-alpha-methyl-4-carboxyphenylglycine. In this study, a dose-dependent inhibition of 200 Hz long-term potentiation expression was obtained with (S)-4-carboxyphenylglycine. Long-term potentiation induced by 400 Hz tetanization was not inhibited by D(-)-2-amino-5-phosphonopentanoic acid, although the amplitude of short-term potentiation was reduced. (RS)-alpha-methyl-4-carboxyphenylglycine and (S)-4-carboxyphenylglycine, both in the presence and absence of D(-)-2-amino-5-phosphonopentanoic acid, inhibited the development of 400 Hz long-term potentiation. (RS)-alpha-methylserine O-phosphate monophenylester had no significant effect on long-term potentiation induced by either 200 or 400 Hz tetanization. Application of methoxyverapamil significantly inhibited 400 Hz long-term potentiation, but had no effect on 200 Hz long-term potentiation. These data suggest that 400 Hz long-term potentiation, induced in the presence of D(-)-2-amino-5-phosphonopentanoic acid, requires activation of L-type calcium channels. Furthermore, these results strongly support a critical role for group 1 metabotropic glutamate receptors in both N-methyl-D-aspartate receptor- and voltage-gated calcium channel-dependent long-term potentiation.

2-Amino-5-phosphonovalerate↗