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Many studies of synaptic transmission have assumed a parametric model to estimate the mean quantal content and size or the effect upon them of manipulations such as the induction of long-term potentiation. Classical tests of fit usually assume that model parameters have been selected independently of the data. Therefore, their use is problematic after parameters have been estimated. We hypothesized that Monte Carlo (MC) simulations of a quantal model could provide a table of parameter-independent critical values with which to test the fit after parameter estimation, emulating Lilliefors's tests. However, when we tested this hypothesis within a conventional quantal model, the empirical distributions of two conventional goodness-of-fit statistics were affected by the values of the quantal parameters, falsifying the hypothesis. Notably, the tests' critical values increased when the combined variances of the noise and quantal-size distributions were reduced, increasing the distinctness of quantal peaks. Our results support two conclusions. First, tests that use a predetermined critical value to assess the fit of a quantal model after parameter estimation may operate at a differing unknown level of significance for each experiment. Second, a MC test enables a valid assessment of the fit of a quantal model after parameter estimation.

Amygdala stimulation was shown to enhance the trisynaptic (fast, R1) component of the electromyogram recorded in the rat orbicularis oculi (oo) muscle, which is responsible for the active force generating eyelid closure. The eyeblink was elicited via direct electrical stimulation of the supraorbital branch of the trigeminal nerve. Possible mechanisms responsible for the effect of amygdala stimulation on the eyeblink reflex were evaluated by measuring the amount of R1 enhancement as a function of the interstimulus interval (ISI) between the onset of amygdala and trigeminal nerve stimulation. Amygdala stimulation produced significant R1 enhancement at ISIs that imply short-latency excitation of the eyeblink circuit by way of a fast-acting neurotransmitter.

1. We investigated the effects of metabotropic glutamate (mGlu) receptor activation on intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons. Changes in [Ca2+]i were measured using confocal imaging simultaneously with whole-cell recording techniques. Differences in [Ca2+]i were visualized as changes in the fluorescence of the Ca(2+)-sensitive dye Fluo-3. 2. Brief application of the specific mGlu receptor agonist (1S,3R)-ACPD to either the apical or basal dendrites produced initially localized increases in [Ca2+]i that subsequently propagated as waves throughout much of the neuron. These Ca2+ waves, which propagated at approximately 40 microns/s, were shown not to reflect intracellular Ca2+ diffusion or extracellular diffusion of ACPD and were always accompanied by small outward membrane currents. 3. Repetitive application of ACPD failed to trigger further Ca2+ release. We found that a threshold level of voltage-gated Ca2+ entry during trains of action potentials was needed to prime further mGlu-stimulated Ca2+ release. In contrast, the passage of time alone did not cause the mGlu-release system to reactivate--restoration of ACPD-stimulated Ca2+ release. The spike-mediated Ca2+ signal was unaffected by mGlu-stimulated depletion of intracellular stores. 4. These experiments demonstrate that specific mGlu receptor activation can mobilize Ca2+ in dendrites of CA1 neurons and trigger waves of Ca(2+)-induced Ca(2+)-release throughout the cell. A use-dependent relationship between voltage-gated Ca2+ entry during trains of action potentials and mGlu-stimulated Ca2+ release is suggested.

1. The quantal mechanism underlying the expression of long-term potentiation (LTP) was studied in the mossy-fiber (mf) synapses of the rat hippocampus. Whole-cell recordings were used to measure the excitatory postsynaptic currents (EPSCs) before and after LTP induction in brain slices maintained at 31 +/- 1 degrees C. 2. Evoked EPSCs were recorded from 473 CA3 pyramidal neurons. The mf synapses were stimulated using paired pulses (40-ms interpulse interval) repeated every 2-10 s. At least 400 pairs of mf responses were obtained before and during the expression of LTP, which was produced by high-frequency (100 Hz) mf stimulation. Sufficiently stationary data were obtained from five neurons that exhibited LTP and that also satisfied strict criteria and procedures that are necessary for eliciting and identifying unitary mf responses. 3. Three independent lines of evidence implicated a presynaptic component to the mechanism underlying mf LTP. The first was based on a graphical version of the classical method of variance. The graphical variance (GV) method was evaluated by clamping the cell at two different holding potentials during paired-pulse facilitation (PPF). The results indicated that the GV method can distinguish changes in mean quantal content m and mean quantal size q in rat mf synapses. The same analysis, when applied to PPF before and after LTP induction, indicated that both result from an increase in m. 4. The second line of evidence was based on the classical method of failures. Consistent with the inference that mf LTP is due to an increase in m, there was a statistically significant reduction in the number of quantal release failures.(ABSTRACT TRUNCATED AT 250 WORDS)

Brief tetanic stimulation of the preganglionic nerves to the superior cervical ganglion enhances the postganglionic response to single preganglionic stimuli for 1 to 3 hours. This long-term potentiation of transmission through the ganglion is apparently not attributable to a persistent muscarinic action of the preganglionic neurotransmitter, acetylcholine, since neither the magnitude nor the time course of the phenomenon is reduced by atropine. The decay of long-term potentiation can be described by a first-order kinetic process with a mean time constant of 80 minutes. We conclude that long-term potentiation, once considered a unique property of the hippocampus, is in fact a more general feature of synaptic function. This form of synaptic memory may significantly influence information processing and control in other regions of the nervous system, including autonomic ganglia.

It is well known that there are two types of neuronal burst discharges: endogenous and network driven. Frequently, the two types are similar in appearance. But careful analysis has shown them to be quite different mechanistically and to share few common properties. Endogenous bursts are a common feature of certain hippocampal neurons. Application of a convulsant agent to a hippocampal slice, however, results in the appearance of interictal discharges whose intracellular correlate is the paroxysmal depolarizing shift (PDS). In contrast to the normal endogenous burst, the PDS is a network-driven burst. It has been proposed that the underlying depolarization of the PDS constitutes a large, compound, excitatory synaptic potential. In support of this hypothesis, recent voltage clamp experiments have demonstrated that a large synaptic conductance underlies the PDS. In this report we review those experiments and others that have established the synaptic nature of epileptiform activity in the hippocampus.