SEARCH · PubMed Health

Results for “Excitatory 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 271 records · Page 15Linked to original sources

PubMed1996

Synaptic long-term depression alters recovery from, and frequency dependency of, short-term depression in Helix pomatia.

Kinetic properties of synaptic depression were analysed for excitatory postsynaptic potentials in neuron number 3 in the right pallial ganglion of Helix pomatia. It was observed that long-term depression did not only suppress the amplitudes of excitatory postsynaptic potentials but also changed the kinetics of short-term depression. Early during each experiment (before the induction of long-term depression), the degree of short-term depression was inversely related to the frequency of excitatory postsynaptic potentials (contrary to most earlier reports). Later in the experiments, after the formation of long-term depression induced by four spaced excitatory postsynaptic potential series, the inverse frequency dependency had changed into a direct proportionality between short-term depression and frequency. This change was associated with, and could be at least partially explained by, an alternation of recovery from short-term depression induced by long-term depression: early in experiments, recovery showed a transient phase of large recovery between excitatory postsynaptic potentials separated by 3 to 45 s. After the induction of long-term depression, this large and transient recovery was absent. The relationship between the amount of long-term depression formed and the number of preceding excitatory postsynaptic potentials inducing the depression was analysed, and it was observed that a significant long-term depression was present 10 min after only six excitatory postsynaptic potentials. The results point towards the implication that many previous investigations of the kinetics of short-term depression observed in experiments involving a high number of excitatory postsynaptic potentials have been performed under the influence of variable degrees of long-term depression. Since long-term depression (at least in Helix) induced substantial alterations of the kinetic properties of short-term depression, such changes may have significantly influenced the conclusions of earlier reports.

Animals↗

PubMed2000

Linear to supralinear summation of AMPA-mediated EPSPs in neocortical pyramidal neurons.

It has been hypothesized that voltage-sensitive conductances present on the dendrites of neurons can influence summation of excitatory postsynaptic potentials (EPSPs) and hence affect how neurons compile information. Greater than linear summation of EPSPs has been postulated to facilitate coincidence detection by cortical neurons. This study examined whether the summation of subthreshold AMPA-mediated EPSPs generated on layer V neocortical pyramidal neurons in vitro was linear and if any nonlinearities could be attributed to dendritic conductances. Evoked EPSPs (1-12 mV) were recorded somatically by means of intracellular sharp electrodes in the presence of 100 microM amino-5-phosphonopentanoic acid (AP-5) and 3 microM bicuculline. Two independent EPSPs were evoked by a stimulating electrode in layer I and another in layers III-V. The areas of stimulation were isolated from each other by a horizontal cut below layer I. By subtracting the algebraic sum of the individual EPSPs from the evoked response when both EPSPs were evoked simultaneously, we determined that they summed linearly to supralinearly. Supralinear summation was more likely when the soma was hyperpolarized by DC current injection. Summation was predominantly linear when postsynaptic conductances (i.e., Na(+) and Ca(2+)) were blocked with intracellular QX-314. The supralinear summation of EPSPs (without QX-314) decreased as the time between inputs was increased from 0 to 30 ms. To determine the role of dendrites in nonlinear summation, we substituted a current pulse (simulated EPSP) delivered at the soma for either or both of the evoked EPSPs. Simulated EPSPs combined with either an evoked EPSP or another simulated EPSP showed significantly less supralinear summation than two evoked EPSPs, indicating that the dendritic conductances were largely responsible for the observed supralinear summation.

Anesthetics, Local↗

PubMed1999

Complement-mediated lesion of sympathetic ganglia in vitro with acetylcholinesterase antibodies.

When administered to rats, antibodies against acetylcholinesterase (AChE) selectively destroy presynaptic inputs to sympathetic ganglia. To investigate the mechanism of this immunolesion, we created an in vitro system in which relevant components could be manipulated. Freshly dissected rat superior cervical ganglia (SCG) were incubated 15-20 h at 37 degrees C in fresh human serum (a potent source of complement) with continuous oxygenation. More than 96% of neurons in six control ganglia retained synaptic inputs, as defined by action potentials or excitatory postsynaptic potentials (EPSP) upon stimulation of the preganglionic trunk. However, when anti-AChE antibodies were present (0.16 mg/ml), none of 61 neurons from six incubated ganglia showed synaptic responses although membrane potential and input resistance remained normal. Staining for AChE and synaptophysin (a synaptic vesicle marker) was also disrupted in ganglia exposed to AChE antibodies in complement-sufficient serum. When complement was eliminated by substituting serum that was heat-inactivated or deficient in C3, synaptic input was retained in 60-90% of neurons incubated with AChE antibodies. Choline acetyltransferase activity (ChAT), an enzymatic marker of cholinergic cytoplasm in sympathetic ganglia, was largely lost after incubation with AChE antibodies and serum. However, incubation with AChE antibodies in heat-inactivated serum, or serum that was deficient in C3 or C8, caused no measurable loss of ganglionic ChAT activity. These findings strongly implicate the complement cascade in the destruction of preganglionic sympathetic terminals that follows binding of AChE antibodies.

Acetylcholinesterase↗

PubMed1999

Methyl bromide decreases excitability without having immediate toxic effects in rat hippocampal CA1 neurons in vitro.

Methyl bromide, a disinfectant gas amply used worldwide, is neurotoxic in humans and other mammals. To study its short-term effects on neurons, it was applied in aqueous solution to hippocampal slices of young rats (1.4 and 0.7 mM; for 8 minutes). Extracellular field recordings and intracellular microelectrode recordings from CA1 pyramidal neurons showed that the neurons stay viable for at least one hour after application of the mono-halomethane. However, a moderate, but consistent, irreversible decrease in synaptic excitability was observed. The intracellular recordings indicate that this may be attributed to a decrease in excitatory postsynaptic potentials. No effects were observed at 0.7 mM methyl bromide. Bromide, in a dose-dependent, partly reversible manner (during one hour), produced a similar decrease in excitability. Quantitatively, the action of bromide at 0.5 mM resembled the one seen with methyl bromide at the concentration of 1.4 mM. Since methyl bromide did not induce electrophysiologic changes consistent with evidence of neurotoxicity during one hour of observation it is concluded that it lacks immediate toxic effects on hippocampal rat neurons. Its neurotoxicity may be entirely due to metabolites or other indirect effects. The slight decrease in excitability may be due to the effect of bromide that is set free as tissue proteins and other cell molecules are methylated.

Animals↗

PubMed1997

Structure-dependent differences in the effects of the Aconitum alkaloids lappaconitine, N-desacetyllappaconitine and lappaconidine in rat hippocampal slices.

Lappaconitine, a C19 diterpenoid alkaloid from Aconitum sinomontanum has been reported to possess analgesic and antiinflammatory properties in vivo and to inhibit neuronal activity in brain slices. In the present study the effect of lappaconitine has been compared with the effects of its main metabolite N-desacetyllappaconitine and the structurally related alkaloid lappaconidine. For comparison of drug effects population spikes and field excitatory postsynaptic potentials (EPSPs) evoked by stimulation of stratum radiatum or the alveus were studied in normal rat hippocampal slices and in slices treated with low Mg2+-medium. At concentrations of 3-100 microM, both lappaconitine and N-desacetyllappaconitine inhibited population spikes elicited by stratum radiatum and alvear stimulation as well as the field EPSP recorded in CA1 stratum radiatum. The drug-induced depression of field potential responses was increased with rising stimulus frequency, indicating an activity-dependent mode of action. The effect of N-desacetyllappaconitine on each parameter investigated was significantly stronger than the effect of lappaconitine. Despite the structural relationship, lappaconidine failed to affect neuronal excitability in concentration below 100 microM, and an increase in stimulus frequency did not potentiate its effect. Moreover, lappaconitine and N-desacetyllappaconitine suppressed epileptiform activity induced by bicuculline or by omission of Mg2+ from the bathing medium.

Aconitine↗

PubMed2002

Effects of paired-pulse and repetitive stimulation on neurons in the rat medial geniculate body.

Many behaviorally relevant sounds, including language, are composed of brief, rapid, repetitive acoustic features. Recent studies suggest that abnormalities in producing and understanding spoken language are correlated with abnormal neural responsiveness to such auditory stimuli at higher auditory levels [Tallal et al., Science 271 (1996) 81-84; Wright et al., Nature 387 (1997) 176-178; Nagarajan et al., Proc. Natl. Acad. Sci. USA 96 (1999) 6483-6488] and with abnormal anatomical features in the auditory thalamus [Galaburda et al., Proc. Natl. Acad. Sci. USA 91 (1994) 8010-8013]. To begin to understand potential mechanisms for normal and abnormal transfer of sensory information to the cortex, we recorded the intracellular responses of medial geniculate body thalamocortical neurons in a rat brain slice preparation. Inferior colliculus or corticothalamic axons were excited by pairs or trains of electrical stimuli. Neurons receiving only excitatory collicular input had tufted dendritic morphology and displayed strong paired-pulse depression of their large, short-latency excitatory postsynaptic potentials. In contrast, geniculate neurons receiving excitatory and inhibitory collicular inputs could have stellate or tufted morphology and displayed much weaker depression or even paired-pulse facilitation of their smaller, longer-latency excitatory postsynaptic potentials. Depression was not blocked by ionotropic glutamate, GABA(A) or GABA(B) receptor antagonists. Facilitation was unaffected by GABA(A) receptor antagonists but was diminished by N-methyl-D-aspartate (NMDA) receptor blockade. Similar stimulation of the corticothalamic input always elicited paired-pulse facilitation. The NMDA-independent facilitation of the second cortical excitatory postsynaptic potential lasted longer and was more pronounced than that seen for the excitatory collicular inputs. Paired-pulse stimulation of isolated collicular inhibitory postsynaptic potentials generated little change in the second GABA(A) potential amplitude measured from the resting potential, but the GABA(B) amplitude was sensitive to the interstimulus interval. Train stimuli applied to collicular or cortical inputs generated intra-train responses that were often predicted by their paired-pulse behavior. Long-lasting responses following train stimulation of the collicular inputs were uncommon. In contrast, corticothalamic inputs often generated long-lasting depolarizing responses that were dependent on activation of a metabotropic glutamate receptor. Our results demonstrate that during repetitive afferent firing there are input-specific mechanisms controlling synaptic strength and membrane potential over short and long time scales. Furthermore, they suggest that there may be two classes of excitatory collicular input to medial geniculate neurons and a single class of small-terminal corticothalamic inputs, each of which has distinct features.

Animals↗

PubMed1998

Transient neurophysiological changes in CA3 neurons and dentate granule cells after severe forebrain ischemia in vivo.

Transient neurophysiological changes in CA3 neurons and dentate granule cells after severe forebrain ischemia in vivo. J. Neurophysiol. 80: 2860-2869, 1998. The spontaneous activities, evoked synaptic responses, and membrane properties of CA3 pyramidal neurons and dentate granule cells in rat hippocampus were compared before ischemia and </=7 days after reperfusion with intracellular recording and staining techniques in vivo. A four-vessel occlusion method was used to induce approximately 14 min of ischemic depolarization. No significant change in spontaneous firing rate was observed in both cell types after reperfusion. The amplitude and slope of excitatory postsynaptic potentials (EPSPs) in CA3 neurons decreased to 50% of control values during the first 12 h reperfusion and returned to preischemic levels 24 h after reperfusion. The amplitude and slope of EPSPs in granule cells slightly decreased 24-36 h after reperfusion. The amplitude of inhibitory postsynaptic potentials in CA3 neurons transiently increased 24 h after reperfusion, whereas that in granule cells showed a transient decrease 24-36 h after reperfusion. The duration of spike width of CA3 and granule cells became longer than that of control values during the first 12 h reperfusion. The spike threshold of both cell types significantly increased 24-36 h after reperfusion, whereas the frequency of repetitive firing evoked by depolarizing current pulse was decreased during this period. No significant change in rheobase and input resistance was observed in CA3 neurons. A transient increase in rheobase and a transient decrease in input resistance were detected in granule cells 24-36 h after reperfusion. The amplitude of fast afterhyperpolarization in both cell types increased for 2 days after ischemia and returned to normal values 7 days after reperfusion. The results from this study indicate that the neuronal excitability and synaptic transmission in CA3 and granule cells are transiently suppressed after severe forebrain ischemia. The depression of synaptic transmission and neuronal excitability may provide protection for neurons after ischemic insult.

Animals↗

PubMed1995

Comparison of long-term potentiation in the proximal versus distal stratum radiatum of hippocampal field CA1.

Recent studies indicate that long-term potentiation is accompanied by changes in the waveform of field excitatory postsynaptic potentials in the CA1 field of disinhibited hippocampal slices, suggesting that long-term potentiation alters the kinetics of the glutamate receptor channels that mediate excitatory synaptic responses. The present study examined the effects of stimulating and recording location within stratum radiatum on the magnitude of long-term potentiation and the associated waveform changes. Stimulation of stratum radiatum proximal to the cell body layer evoked field excitatory postsynaptic potentials in proximal stratum radiatum that had decay phases well-fit by single exponentials; long-term potentiation reduced the decay time constant of these potentials, as reported previously. Stimulation of distal stratum radiatum evoked field excitatory postsynaptic potentials in distal stratum radiatum that were contaminated by positive after-potentials; meaningful estimates of decay time constants for these responses could not be obtained. Long-term potentiation of distal responses tended to be smaller than that obtained proximally. Comparisons were also made between responses recorded distally and proximally for either distal or proximal stimulation. For both stimulation loci, the distally-recorded responses had positive after-potentials and the proximally-recorded responses did not. The decay time constants for proximally-recorded responses to distal stimulation decreased significantly after long-term potentiation. Proximal and distal stimulation both produced greater long-term potentiation recorded proximally than distally and the difference was significantly greater for proximal stimulation. When long-term potentiation was induced by stimulation of proximal and distal sites simultaneously, the difference between proximally- and distally-recorded long-term potentiation was significantly reduced. Paired-pulse facilitation was greater when recorded proximally but the variation in facilitation with stimulation and recording position was different from that obtained for long-term potentiation. Paired-pulse facilitation of response amplitude was slightly reduced after long-term potentiation, but the change did not depend on the stimulation-recording arrangement; facilitation of response slope was not reliably affected by long-term potentiation. These results indicate that the shape of the dendritic field excitatory postsynaptic potential is influenced by the relative position of recording electrodes in stratum radiatum; when the position is such that after-potentials are minimized, long-term potentiation produces a decrease in the decay time constant of the synaptic field potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1982

Synaptic excitation of the second and third order auditory neurons in the avian brain stem.

Synaptic potentials were examined in the second- and third-order auditory neurons of nucleus magnocellularis and nucleus laminaris in the chick. Brain stems of mature chick embryos were explanted and maintained in vitro for 4 to 8 h. Field potentials, extracellular spike potentials and intracellular potentials evoked by 8th-nerve stimulation were examined. Eighth-nerve stimulation reliability elicited four identifiable field potentials which could be attributed to: (i) the afferent volley of the 8th-nerve axons, (ii) postsynaptic responses of n. magnocellularis neurons, and (iii) ipsilaterally and, (iv) contralaterally-evoked n. laminaris postsynaptic responses. Intracellular-recorded postsynaptic potentials were characterized by a rapid rise time and short duration. They were apparently monosynaptic with a synaptic delay of 0.4 ms. In each n. magnocellularis neuron the 'fast' excitatory postsynaptic potentials were composed of 1 to 3 all-or-none components. 'Slow' excitatory postsynaptic potentials were characterized by a longer latency, a longer duration and graded amplitude variation in proportion to the intensity of 8th-nerve stimulation. Both 'fast' and 'slow' excitatory postsynaptic potentials had similar reversal potentials. Since the 8th nerve makes monosynaptic connection with n. magnocellularis neurons, it is likely that at this synapse the 'fast' excitatory postsynaptic potentials were produced, while the 'slow' potential may be attributable to the convergence of many boutonal synapses of unknown origin. Intracellular injections of horseradish peroxidase into n. magnocellularis revealed that its efferents bifurcate below the nucleus and send one axon to the contralateral n. laminaris while the other axon forms a highly divergent projection to the ipsilateral laminar nucleus. The intracellular records obtained from n. laminaris are consistent with this anatomical finding in that graded excitatory postsynaptic potentials were elicited by 8th-nerve stimulation.

Animals↗

PubMed1999

Antagonism of the aconitine-induced inexcitability by the structurally related Aconitum alkaloids, lappaconitine and ajacine.

Aconitine, lappaconitine and ajacine are structurally related alkaloids occurring in several species of the Aconitum genus. While aconitine is known to activate the voltage-dependent sodium channel, lappaconitine has been reported to block this channel. To investigate a possible antagonism of the aconitine action on neuronal activity by lappaconitine and the closely related alkaloid ajacine, we have performed extracellular recordings of stimulus evoked population spikes and field excitatory postsynaptic potential (EPSP) in rat hippocampal slices. Aconitine (10-100 nM) diminished the amplitude of the orthodromic population spike in a concentration-dependent manner. When aconitine was applied in presence of 10 microM lappaconitine, the concentration-response curve was shifted to the right. Furthermore, the complete suppression of the population spike evoked by 100 nM aconitine was reversed by 10 microM lappaconitine. The action of lappaconitine was mimicked by ajacine, however, the latter alkaloid was less potent. Both lappaconitine and ajacine shifted the input-output relationship of the presynaptic fiber spike as function of the stimulation intensity and of the field EPSP as function of the presynaptic fiber spike to the right. After pharmacological isolation, the presynaptic fiber spike was decreased by both compounds in a frequency-dependent manner indicative for a use-dependent action. Thus, electrophysiologically these alkaloids seem to inhibit predominantly the excitability of the afferent fibres and, in consequence, neurotransmission between Schaffer collaterals and the CA1 neurons, thereby suppressing the firing of the latter. Ajacine and lappaconitine inhibited stimulus-triggered epileptiform population bursts in area CA1 elicited by omission of Mg(2+) as well as spontaneously occurring epileptiform discharges in area CA3 elicited by omission of Mg(2+) and elevation of K(+). It is concluded that the inhibitory and antiepileptiform effect of ajacine and lappaconitine is mediated by a frequency-dependent inhibition of the voltage-dependent sodium channel, thereby decreasing the excitability which might be important for filtering high frequency bursts of action potentials characteristic for epileptiform activity in the hippocampus. Moreover, these alkaloids are naturally occurring antagonists of the sodium channel activator aconitine.

Aconitine↗

PubMed1999

Postsynaptic glutamate receptors and integrative properties of fast-spiking interneurons in the rat neocortex.

The glutamate-mediated synaptic responses of neocortical pyramidal cell to fast-spiking interneuron (pyramidal-FS) connections were studied by performing paired recordings at 30-33 degrees C in acute slices of 14- to 35-day-old rats (n = 39). Postsynaptic fast-spiking (FS) cells were recorded in whole cell configuration with a patch pipette, and presynaptic pyramidal cells were impaled with sharp intracellular electrodes. At a holding potential of -72 mV (near the resting membrane potential), unitary excitatory postsynaptic potentials (EPSPs) had a mean amplitude of 2.1 +/- 1.3 mV and a mean width at half-amplitude of 10.5 +/- 3.7 ms (n = 18). Bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist D(-)2-amino-5-phosphonovaleric acid (D-AP5) had minor effects on both the amplitude and the duration of unitary EPSPs, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) almost completely blocked the synaptic responses. In voltage-clamp mode, the selective antagonist of AMPA receptors 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl-7,8-methylenedioxy-3, 4-dihydro-5H-2,3-benzodiazepine (GYKI 53655; 40-66 microM) blocked 96 +/- 1.9% of D-AP5-insensitive unitary excitatory postsynaptic currents (EPSCs), confirming the predominance of AMPA receptors, as opposed to kainate receptors, at pyramidal-FS connections (n = 3). Unitary EPSCs mediated by AMPA receptors had fast rise times (0.29 +/- 0.04 ms) and amplitude-weighted decay time constants (2 +/- 0.8 ms; n = 16). In the presence of intracellular spermine, these currents showed the characteristic rectifying current-voltage (I-V) curve of calcium-permeable AMPA receptors. A slower component mediated by NMDA receptors was observed when unitary synaptic currents were recorded at a membrane potential more positive than -50 mV. In response to short trains of moderately high-frequency (67 Hz) presynaptic action potentials, we observed only a limited temporal summation of unitary EPSPs, probably because of the rapid kinetics of AMPA receptors and the absence of NMDA component in these subthreshold synaptic responses. By combining paired recordings with extracellular stimulations (n = 11), we demonstrated that EPSPs elicited by two different inputs were summed linearly by FS interneurons at membrane potentials below the action potential threshold. We estimated that, in our in vitro recording conditions, 8 +/- 5 pyramidal cells (n = 18) should be activated simultaneously to make FS interneurons fire an action potential from -72 mV. The low level of temporal summation and the linear summation of excitatory inputs in FS cells favor the role of coincidence detectors of these interneurons in neocortical circuits.

Action Potentials↗

PubMed2001

Enhanced excitatory synaptic transmission in spiny neurons of rat striatum after unilateral dopamine denervation.

The synaptic transmission and intrinsic membrane properties of spiny neurons in rat neostriatum were studied after unilateral dopamine depletion using in vivo intracellular recording and staining techniques. Two to four weeks after dopamine denervation, the spontaneous firing rate of spiny neurons increased and the spontaneous membrane potential fluctuation stayed at a more depolarized state for longer periods of time. The amplitude of cortically evoked initial excitatory postsynaptic potentials increased and a late excitatory postsynaptic potential that was occasionally found in control neurons was elicited from 23% of spiny neurons after dopamine denervation. No significant changes in intrinsic membrane properties of spiny neurons were observed after dopamine denervation. These results suggest that dopamine inhibits excitatory synaptic transmission of spiny neurons in naïve animals.

Animals↗

PubMed1995

Synaptic feed-backs mediated by potassium ions.

Repetitive activity of the neuromuscular system and of neuronal centers leads to K+ efflux from excited cells and to its accumulation within extracellular spaces and synaptic clefts, especially during the generation of postsynaptic responses such as end-plate potentials or excitatory postsynaptic potentials. K+ ions accumulated within the synaptic cleft during activity modulate the transmitter secretion from motor nerve terminals. Depending on the concentration, K+ can either increase the transmitter release due to a specific presynaptic action or decrease it due to depolarization of the presynaptic membrane. The dual antidromic action of K+ can be the basis of functional self-regulation of the synapse. The significance of the positive presynaptic action of K+ can be assumed to enhance the reliability of the synaptic transmission at moderate activation rates. The negative presynaptic action of K+, which predominates at high-frequency activities or during neuromuscular fatigue, leads to randomized failures of transmissions at individual synapses, the overall pattern of activation of the entire system being reproduced. This might save the general capability of the system and protect its weakest elements. The positive antidromic action of K+ can be assumed to be essential to the mechanism of heterosynaptic facilitation and long-term potentiation at learning synapses of the brain.

Adaptation, Physiological↗

PubMed2001

Synchronized Ca2+ signals mediated by Ca2+ action potentials in the hippocampal neuron network in vitro.

Periodic, synchronized Ca2+ signals appeared 30-120 min after the application of tetrodotoxin, 4-aminopyridine and Cs+, and became stable in interval (6-47s) for hours. The Ca2+ signals were accompanied by excitatory or inhibitory postsynaptic potentials (excitatory postsynaptic currents (EPSCs) for the former) and blocked by the simultaneous application of 6-cyano-7-nitroquinoxaline-2,3-dione and 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid or treatment with Ca2+ -free solution, nicardipine, or omega-conotoxin MVIIC (omegaCTX), but not with ryanodine, caffeine, thapsigargin or CPP alone. Nicardipine largely, but omegaCTX less, blocked Ca2+ action potentials or voltage pulse-induced Ca2+ currents at the cell soma, while omegaCTX completely blocked autaptic EPSCs. Ca2+ signals within a neuron occurred almost simultaneously in the cell soma and all the processes (> 200 microm), while the latency between Ca2+ signals of neighbouring neurons varied over hundreds of ms like that of Ca2 action potential induction from EPSPs. Ca2+ signals propagated in random directions throughout neural circuits. Thus, when Na+ and K+ channels are blocked, Ca2+ action potentials spontaneously occur somewhere in a neuron, eventually propagate via the cell soma to the presynaptic terminals and activate excitatory synaptic transmission, causing synchronized Ca2+ signals. The results further suggest that the axon of hippocampal neurones have the potential ability to convey coded information via Ca2+ action potentials.

4-Aminopyridine↗

PubMed1989

Interaction of telenzepine with muscarinic receptors in mammalian sympathetic ganglia.

The interaction of the antimuscarinic drug telenzepine with muscarinic receptors was studied in rabbit and rat isolated superior cervical sympathetic ganglia. Radioligand binding demonstrated two muscarinic receptor sites in rabbit ganglia, with the characteristics of M1- and M2-receptors. Telenzepine bound to the M1 sites with a KI of 0.94 nmol/l and to the M2 sites with a KI of 17.8 nmol/l; the corresponding values for pirenzepine were 18.6 and 588 nmol/l; for AF-DX 116 the values were 891 and 33 nmol/l respectively. [3H]Telenzepine dissociated from the M1-receptors with a half time of 46 min at 37 degrees C. Electrophysiological experiments demonstrated that telenzepine reduced the amplitude of the extracellularly recorded slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential (ED50: 38 and 253 nmol/l respectively). In rat ganglia, application of muscarine or the M1-receptor agonist McN-A-343 increased the amplitude of submaximal population action potentials. This facilitation of synaptic transmission was potently blocked by telenzepine and pirenzepine but only weakly by AF-DX 116 (ED50: ca. 30, 150 and 20 mumol/l, respectively). It is concluded that telenzepine blocks the generation of the slow excitatory postsynaptic potential and the excitatory action of muscarine and McN-A-343 via an action on muscarinic M1-receptors.

Animals↗

PubMed1982

Postsynaptic factors controlling the shape of potentials at the squid giant synapse.

The roles of rectification and cable properties of the squid giant axon in determining the shape of synaptic potentials generated at the giant synapse were investigated. Excitatory postsynaptic potentials were recorded in response to selective stimulation of the main presynaptic axon at various temperatures. Excitatory postsynaptic potentials elicited at low temperatures (less than 18 degrees C) exhibited a marked after-hyperpolarization or undershoot, while those recorded at higher temperatures did not. The postsynaptic current, recorded under voltage clamp conditions, did not show an undershoot. Furthermore, intracellular injection of tetraethylammonium chloride, to block the voltage-dependent rise in potassium conductance, also eliminated the undershoot of the excitatory postsynaptic potential. These results indicate that the duration of synaptic potentials at the squid giant synapse is reduced by rectification due to a delayed rise in potassium conductance. Computer simulations of these synaptic potentials suggested that the effects of rectification will be more prominent in spherical (isopotential) cells than in cells with more complicated geometries.

Animals↗

PubMed1993

Co-activation of metabotropic glutamate and N-methyl-D-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal CA1 neurons.

Slices of hippocampal area CA1 in the rat were employed to test the hypothesis that the activation of metabotropic glutamate receptors during tetanization is necessary for the late maintenance of long-term potentiation. If the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionate was present during tetanization, post-tetanic and early long-term potentiation of the population spike as well as field excitatory postsynaptic potential developed almost normally. However, 100 min after tetanization, long-term potentiation of the field excitatory postsynaptic potential decreased in an irreversible manner. The same concentration of D-2-amino-3-phosphonopropionate was ineffective. If L-2-amino-3-phosphonopropionate was applied 120 min after tetanization, it did not influence long-term potentiation. The presence of the metabotropic glutamate receptor agonist trans-D,L-1-aminocyclopentane-1,3-dicarboxylic acid during tetanization weakly enhanced the slope of field excitatory postsynaptic potential long-term potentiation. The influence of L-2-amino-3-phosphonopropionate and D,L-1-aminocyclopentane-1,3-dicarboxylic acid on ionotropic glutamate receptors was studied using whole-cell voltage-clamp and pressure application techniques. No effect of L-2-amino-3-phosphonopropionate on either early or late components of excitatory postsynaptic currents could be detected at the concentration used to block long-term potentiation. It is therefore unlikely that the effect of L-2-amino-3-phosphonopropionate on long-term potentiation is due to an interaction with N-methyl-D-aspartate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors. However, bath-applied 1S,3R-D,L-1-aminocyclopentane-1,3-dicarboxylic acid facilitated the N-methyl-D-aspartate-induced depolarization in response to N-methyl-D-aspartate pressure application in a reversible manner. These data suggest that besides the involvement of N-methyl-D-aspartate receptors the activation of a 2-amino-3-phosphonopropionate-sensitive metabotropic glutamate receptors during or immediately after tetanization is necessary for subsequent mechanisms responsible for the maintenance of long-term potentiation. A link between metabotropic glutamate receptors and protein kinase C activation during long-term potentiation is discussed considering the similar time course of long-term potentiation blockade after application of L-2-amino-3-phosphonopropionate and protein kinase C inhibitors.

Alanine↗

PubMed1983

Lumbar spinal cord responses to limb vein distention.

The purpose of this study was to determine if central neural responses were elicited by distention of limb veins, and to compare the pattern of these response to those produced in previous studies using electrical stimulation to excite limb venous afferent fibers. Spinal evoked potentials were measured in response to stretch of the wall of a segment of the femoral-saphenous vein by perfusion-distention or by mechanical stretch. These studies revealed that spinal cord evoked potentials were elicited by these procedures, and that the activated venous afferent fibers coursed through the saphenous nerve and entered the sixth lumber spinal cord segment. The minimum stretches which were required to elicit spinal evoked potentials were produced by perfusion pressures starting at 2-3 mm Hg, or by mechanical stretch of the wall of 5 micron/mm. A vein wall proprioceptor hypothesis is proposed and discussed in the light of these findings. In addition to the cord dorsum evoked potentials, distention or stretch of the vein wall elicited ventral root potentials (excitatory postsynaptic population potentials) which are known to be produced by excitatory inputs to motoneurons. A venous afferent mediated muscle-tonus venopressor mechanism hypothesis is proposed and discussed in the light of these and previous findings.

Afferent Pathways↗