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W T Schlapfer

Publications and source records attributed to W T Schlapfer.

At least 19 recordsLinked to original sources
PubMed1980

Separate serotonin and dopamine receptors modulate the duration of post-tetanic potentiation at an Aplysia synapse without affecting other aspects of synaptic transmission.

We have studied the effect of the biogenic amines, serotonin and dopamine, on post-tetanic potentiation (PTP) at an identified synapse in the abdominal ganglion of Aplysia californica. We found that: (1) 10(-7) M perfused serotonin doubles the rate constant of decay of PTP. The effect is specific in that neither the size of the non-potentiated (isolated) EPSP nor the amplitude of PTP is affected. As reported previously, higher doses of serotonin will also increase the amplitude of PTP and decrease the size of the isolated EPSP; (2) 5 X 10(-7) M dopamine in the perfusate increases the rate constant of decay of PTP by about 50%. The effect is also specific in that neither PTP amplitude nor the size of the isolated EPSP is affected; (3) SQ10,631, a serotonin antagonist, blocks the effect of perfused serotonin on PTP decay rate. It does not antagonize the dopamine effect. SQ10,631 also slows the endogenous decay of PTP in some preparations which exhibit an unusually fast PTP decay rate, suggesting a naturally occurring source of serotonin within the ganglion capable of affecting the rate constant of PTP decay; (4) (+)-butaclamol, a dopamine antagonist, blocks the effect of dopamine on the rate constant of PTP decay, whereas (-)-butaclamol has little effect. Butaclamol does not block the effect of serotonin on the rate constant of PTP decay; (5) phosphodiesterase inhibitors potentiate the effect of serotonin on the rate constant of PTP decay, and cyclic AMP analogues mimic the effect of the biogenic amines, suggesting that the aminergic modulation of the rate of decay of PTP is coupled with activation of adenylate cyclase and accumulation of cyclic AMP; and (6) the evidence presented is consistent with the hypothesis that serotonin and dopamine are capable of specifically modifying the rate of change in the efficacy of transmitter release which underlies PTP. It also suggests that the two biogenic amines operate separately and in parallel via presynaptic receptor mechanisms.

Animals↗
PubMed1980

Heterosynaptic stimulation modulates the duration of post-tetanic potentiation at an Aplysia synapse without affecting other aspects of synaptic transmission.

Repetitive stimulation of an axon in the right visceropleural connective to the abdominal ganglion of Aplysia californica produces post-tetanic potentiation (PTP) of a unitary monosynaptic EPSP recorded from cell R15. PTP decays within one half hour following cessation of repatitive stimulation. Stimulation of the left visceropleural connective speeds the rate of decay of PTP, but does not affect the amount of potentiation which is developed or the size of the non-potentiated EPSP. The effect of heterosynaptic left connective stimulation is similar to the previously reported effects of low doses of serotonin but different from the effects of heterosynaptic branchial nerve stimulation. As previously reported, branchial nerve stimulation causes a reduction in the size of the EPSP, and can also speed the rate of decay of PTP. Effects of branchial nerve and left connective stimulation are blocked by SQ10,631, a serotonin antagonist. The left connective effect on the rate of decay of PTP, like the serotonin effect, appears to be mediated by a cyclic nucleotide. The data are consistent with the existence of two separable serotonergic receptors presynaptic to the homosynaptic pathway; one receptor mediates a change in the rate of decay of PTP, one mediates a change in the size of the EPSP. The possible physiological significance of heterosynaptic control of PTP is considered.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1980

Stimulation is necessary for the development of tolerance to a neuronal effect of ethanol.

Ethanol accelerates the decay of post-tetanic potentiation at an identified synapse in Aplysia. We have previously shown that with repeated exposures the ethanol effect diminishes, a development termed "tolerance." Here we present evidence that the establishment of tolerance depends on a adequate stimulation of the presynaptic terminal in the presence of ethanol. Elevated magnesium in the perfusion medium prevents tolerance, whereas elevated calcium in the perfusion medium reduces the amount of stimulation required for tolerance to develop.

Animals↗
PubMed1979

The amplitude of post-tetanic potentiation of the EPSP RC1-R15 in Aplysia is modulated by environmental parameters.

Evidence is presented that the EPSP called RC1-R15, which is recorded from cell R15 of the abdominal ganglion of Aplysia californica upon appropriate stimulation of the right connective, is endogenously active. In previous studies we showed that after repetitive stimulation the amplitude of this EPSP increases and then slowly decays over many minutes, a phenomenon called post-tetanic potentiation (PTP). The rate of endogenous firing of this EPSP varies with time of day and tonicity of the animal's external environment. It is shown that this endogenous firing increases the magnitude of the PTP component of the amplitude of the EPSP. The degree of this potentiation varies with the endogenous firing rate. In general, daytime or a hypertonic external environment increases the firing rate of the EPSP and its degree of potentiation. Since the degree of this PTP reflects time of day and environmental tonicity, it is inferred that it conveys physiologically significant information to the postsynaptic cell R15.

Animals↗
PubMed1978

Amplitude and rate of decay of post-tetanic potentiation are controlled by different mechanisms.

Evidence is presented that post-tetanic potentiation (PTP) of the cholinergic, fast, Cl- dependent IPSP seen in cell L5 of the abdominal ganglion of Aplysia californica upon eliciting a spoke in cell L10 is due to an increase in spike-evoked transmitter release. The magnitude of the post-tetanic change in spike-evoked release is inversely correlated with the amount of transmitter released by an isolated presynaptic spike. This was found whether the latter was increased by injection of tetraethyl ammonium (TEA) into the soma of L10 or decreased by hyperpolarization of the soma of L10. Neither of these manipulations affected the rate of decay of PTP. The magnitude of PTP was increased and the rate of decay reduced by increasing either the number or frequency of stimuli in the tetanus. Under all conditions PTP decayed with a single exponential time course, asymptotically approaching the unpotentiated magnitude. It is concluded that while both the amplitude and rate of decay of PTP are affected by the frequency and number of stimuli in the tetanus, the underlying mechanism controlling the amplitude of PTP is different from the mechanism controlling the rate of decay of PTP.

Action Potentials↗
PubMed1976

Sustained tolerance to a specific effect of ethanol on posttetanic potentiation in Aplysia.

Perfusion with 0.8 molar ethanol in a seawater specifically accelerates the rate of decay of posttetanic potentiation observed after repetitive electrical stimulation of an identified synapse in the abdominal ganglion of Aplysia californica. Repeated perfusion with seawater alternately with and without ethanol leads to a progressive diminution of this specific effect of ethanol, such that after the third application ethanol no longer has any effect on the rate constant of decay of posttetanic poteniation. This tolerance to the specific effects of ethanol persists for at least 11 hours after the last application of ethanol.

Animals↗
PubMed1976

Frequency facilitation and post-tetanic potentiation of a unitary synaptic potential in Aplysia californica are limited by different processes.

Post-tetanic potentiation (PTP) of the monosynaptic and unitary excitatory postsynaptic potential (EPSP) recorded in cell R15 of the abdominal ganglion of Aplysia californica was observed after repetitive stimulation of the right visceropleural connective. PTP at this synapse developed after a few pulses (about 20) and after trains of low frequency stimulation (1/2 sec) under normal physiological conditions of media and temperature. No phase of post-tetanic depression was observed. Evidence is presented that the PTP is due to an increase in transmitter release. The amplitude of the PTP was a function of the frequency and number of stimuli in the preceding train. The PTP was observed to decay, with a single exponential time course, to the size of an isolated EPSP. The rate constant of PTP decay depended upon both the frequency and number of stimuli in the preceding train. The magnitude of the various types of synaptic plasticities seen at this junction, i.e., synaptic depression, frequency facilitation and PTP, correlated with the size of an isolated EPSP as well as with each other. Based on the analysis of the data in terms of a flow model of transmitter release, it is concluded that: (a) during a train of repetitive stimulation the net rate of transmitter supply into the immediately available pool (net transmitter mobilization) increases, the efficiency of the release mechanism (fractional release) increases, and the pool of immediately available transmitter depletes; (b) upon the cessation of the train, as the peak amplitude of PTP is approached, the increased but diminishing rate of net transmitter mobilization refills the available pool to its equilibrium size, while the fractional release is still elevated; (c) during the PTP period after the peak potentiation, the elevated fractional release slowly decays with a single exponential time course; (d) the size of the facilitated EPSPs during the train is limited by the net rate of transmitter supply, although the efficiency of release is also increased; while the size of the EPSPs during the falling phase of the PTP period is determined solely by an increased efficiency of the release mechanism; and (e) the rising phase of the PTP observed in the period shortly after termination of the train is produced by the refilling of the depleted pool of available transmitter in the presence of an elevated release efficiency.

Animals↗
PubMed1976

Resting and stimulated values of model parameters governing transmitter release at a synapse in Aplysia californica.

Transmitter release (R) at a synpase in Aplysia californica can be analyzed in terms of a model with the following parameters: A, the available pool of transmitter; F, the fraction of available pool released by a presynaptic action potential; M, the rate of transmitter mobilization into the available pool; D, the rate constant of demobilization of transmitter from the available pool. In the present paper we show that: (1) beginning with an analysis of the recovery from depression of the second of a pair of disolated EPSPs separated by a series of intervals of about 10-60 sec, and assuming that the recovery is due to refilling of a depleted A, it is possible to estimate resting equilibrium values of these parameters; (2) changes in these parameters when a new equilbrium state is reached after prolonged stimulation (e.g., 300 stimuli at 1/sec) can then be quantitatively determined; (3) the increased rate of transmitter release observed during and after repetitive stimulation is the consequence of increases in F and M with changes in A passively following; and (4) there are significant correlations among certain resting parameters and between the values of certain resting parameters and these parameters upon stimulation. Preparations with a large resting F tend to have a relatively small resting A. Preparations with a large resting F or M tend to increase these less with stimulation than preparations with smaller resting values of these parameters. Preparations with large stimulus-dependent increases in F tend to have large stimulus-dependent increases in M.

Animals↗
PubMed1976

Synaptic depression at a synapse in Aplysia californica: analysis in terms of a material flow model of neurotransmitter.

When a pair of stimuli separated by an appropriate interval is given to the right visceropleural connective of Aplysia californica the amplitude of the second EPSP elicited in cell R15 is usually smaller than the amplitude of the first EPSP. In the present paper we show that this phenomenon, synaptic depression, can be analyzed in terms of the material flow model of neurotransmitter economics developed in our preceding publications. We specifically show how changes in the 4 model parameters; A, the available pool of transmitter; F, the fraction of the available pool released by a presynaptic action potential; M, the rate of transmitter mobilization into the available pool; and D, the rate constant of demobilization of transmitter from the available pool, all effect synaptic depression. In addition, we show how transient changes in F and M, that are observed immediately and for seconds after a stimulus, influence the time course of synaptic depression. Using this analysis we then tested our previous inferences about changes in the model parameters produced either by pharmacological manipulations or repetitive stimulation, by comparing the observed effects of these manipulations on synaptic depression with the theoretical predictions. The theoretical and experimental findings agreed, thereby strengthening both our previous conclusions of the mode of action of these manipulations and the model itself.

Animals↗
PubMed1976

Dopamine, serotonin and related compounds: presynaptic effects on synaptic depression, frequency facilitation, and post-tetanic potentiation at a synapse in Aplysia californica.

Dopamine, serotonin and related compounds (referred to collectively as biogenic amines) were found to modify transmission at the presumably cholinergic synapse made by an axon in the right visceropleural connective onto cell R15 of the abdominal ganglion of Aplysia californica. (1) With chronic application, dopamine hyperpolarizes R15, and serotonin depolarizes R15. Both actions upon the membrane potential desensitize in 10 min. All the actions described below were studied with chronic perfusion of the biogenic amines after desensitization of this postsynaptic action. (2) The biogenic amines drastically reduce the size of the EPSP evoked at the synapse under investigation; but they do not alter the ACh potential evoked in the soma of R15. (3) The biogenic amines reduce the amplitude of synaptic depression. The relationship between the effects of the amines on the size of an isolated EPSP and on synaptic depression differed from this relationship as affected by post-tetanic potentiation (PTP) or by changes in the Ca2+-Mg2+ balance. (4) The biogenic amines increase frequency facilitation, when the latter is defined as the ratio of the facilitated to the isolated EPSP. However, the absolute magnitude of the facilitated EPSP is always reduced at long times after introduction of the agent; shortly after introduction of the biogenic amines the absolute magnitude of the facilitated EPSP is unaffected in most preparations.

Animals↗
PubMed1976

Heterosynaptic inhibition modifies the presynaptic plasticities of the transmission process at the synapse in Aplysia californica.

The monosynaptic and unitary excitatory postsynpatic potential (EPSP) observed in cell R15 of the abdominal ganglion of Aplysia californica upon minimal stimulation of the right visceropleural connective exhibits several presynaptic plasticities (synaptic depression, frequency facilitation, post-tetanic potentiation). We studiied effects of branchial nerve stimulation (heterosynaptic stimulation) on these plasticities of the homosynaptic (right connective) path. A burst of heterosynaptic stimulation (20 pulses at 4/sec) decreased the amplitude of an isolated homosynaptic EPSP. The rate of recovery from heterosynaptic inhibition (HSI) was a function of the rate of stimulation of the homosynaptic path so that at a stimulus frequency of 1 pulse/sec to the right connective (RC) the HSI lasted less than 20 sec while at a RC stimulus frequency of 1/10 sec the HSI persisted for more than 60 sec. While the frequency facilitated EPSP (during homosynaptic stimulation at 1/sec) was only transiently affected by heterosynaptic stimulation the effect on the subsequent post-tetanic potentiation was much more pronounced and longer lasting (more than 30 min). This suggests a specific effect of HSI on the rate constant of decay of elevated fractional release, as observed upon bath applications of biogenic amines. Heterosynaptic stimulation also reduces synaptic depression but the reduction in the depression is more than would be caused by comparable reduction of the first EPSP of a pair of high Mg2+, low Ca2+ or the addition of carbachol to the perfusion medium. The duration of the effect on synaptic depression was the same as the effect on EPSP1.

Animals↗
PubMed1975

Cholinergic agents affect two receptors that modulate transmitter release at a central synapse in Aplsia californica.

A unitary, monosynaptic and presumably cholinergic EPSP recorded in cell R15 of the abdominal ganglion of Aplysia californica undergoes depression followed by facilitation when the presynaptic axon is repetitively stimulated at a rate of 1-3 pulses/sec. During trains of stimulation which produced this sequence of phenomena, the effects of a large number of agents known to affect cholinergic transmission in other systems were studied. The agents could be divided into 4 classes: (1) agents having no effect upon transmission at this cholinergic junction; (2) agents of a class typified by curare, which depressed all EPSPs of a train to the same extent, and which are believed to be acting in this system solely as competitive postsynaptic blockers; (3) agents typified by acetylcholine and carbachol (ACh class), which selectively depressed earlier EPSPs of a train more than later EPSPs and which appear to act by reducing the fractional release of transmitter; (4) agents typified by trimethidinium (trimethidinium class), which selectively depress later EPSPs of a train more than earlier EPSPs and which appear to act by reducing the rate of transmitter supply into the readily releasable pool. Neither the ACh class nor the trimethidinium class produced these selective effects on different pulses in the train by changes in the postsynaptic membrane potential or membrane resistance. Nor did they act by stimulating or inhibiting other recorded inputs onto R15. Iontophoretic application of acetylcholine onto R15 indicated that the effect of trimethidinium could not be explained by an alteration in desensitization of a postsynaptic acetylcholine receptor. The structural specificity of the presynaptic receptors mediating the action of the ACh and trimethidinium classes was demonstrated by the use of a larger number of structurally related compounds.

Acetylcholine↗