Interaction of baseline synaptic noise and Ia EPSPs: evidence for appreciable negative correlation under physiological conditions

1. In the anesthetized cat, simultaneous intracellular recordings from pairs of spinal motoneurons were undertaken to see whether the amplitude of single-fiber excitatory postsynaptic potentials (EPSPs) in both cells fluctuated in a coordinated manner that would indicate correlative mechanisms at either pre- or post-synaptic level. Although these recordings revealed correlated fluctuations in the baseline, the single-fiber Ia/EPSPs recorded with the spike-triggered averaging technique exhibited no correlated fluctuations and, unexpectedly, virtually no increase in baseline variance associated with the EPSP. However, the fact that these experiments were carried out under conditions of high baseline synaptic noise (i.e., with muscle stretch) may have influenced the outcome because of interaction between EPSP and synaptic noise, and this possibility was evaluated explicitly. 2. A given connection was studied under low noise by electrically stimulating a single Ia fiber in the absence of muscle stretch. The same connection was analyzed under conditions of high noise by activating the fiber and all other stretch receptor afferents with muscle stretch and by using spike-triggered averaging to extract the EPSP. The differences in mean EPSP amplitude at a given connection under conditions of low noise and high noise were minimal. 3. Fluctuations in EPSP amplitude were then determined to see whether these were influenced by presence of baseline synaptic noise and whether the interaction was nonlinear. Two methods were used to measure EPSP fluctuations: measurement of the variance associated with the EPSP, and determination by the use of deconvolution methods of the discrete amplitude components associated with the EPSP. 4. An increase in baseline variance was observed during the EPSP evoked under low noise conditions at all six connections studied in this way. This increase disappeared at two of these connections when examined under high noise. This may help to explain the results obtained in pairs of motoneurons. 5. The deconvolution results were used to calculate the variance of the noise-free EPSP. This was found to differ from the variance of the EPSP amplitude distribution measured directly from the change in baseline variance associated with the EPSP. Analytic techniques suggested that this difference could be explained in most cases by negative correlation between the EPSP and baseline synaptic noise. These considerations led to an analytic method to assess the reliability of the deconvolution result. 6. Simulation studies revealed that the baseline variance increase associated with the EPSP is also highly dependent on the correlation between signal and noise.(ABSTRACT TRUNCATED AT 400 WORDS)     

A correlative physiological and morphological analysis of monosynaptically connected propriospinal axon-motoneuron pairs in the lumbar spinal cord of frogs

Intracellular stimulation of single propriospinal axons evoked excitatory postsynaptic potentials (EPSPs) in lumbar motoneurons. Mean EPSP amplitudes differed by two orders of magnitude when measured in different connections. After analyzing the distribution of mean amplitudes of 47 single-fiber EPSPs, two populations of responses could be defined: (1) those with mean amplitudes between 0.1 and 1.2 mV (mean+/-S.D.: 0.48+/-0.30 mV, 34 pairs), which is in the range of values typical for single-fiber EPSPs evoked by stimulation of supraspinal fibers and primary muscle afferents, (2) those with mean amplitudes between 1.6 and 8 mV (4.2+/-2.0 mV, 13 pairs). Both populations of responses had similarly short latencies and rise times and responded similarly to paired-pulse stimulation, consistent with monosynaptic transmission. However, the high-efficacy connections had significantly smaller coefficients of variation of EPSPs, as well as increased quantal content and quantal size. Tetanic stimulation gradually depressed the amplitude of large EPSPs by 81-86%, but did not affect small EPSPs. Recovery of large EPSPs was exponential with a time constant of 3-5.6 min. During post-tetanic depression the amplitude ratio between the test and conditioned EPSPs evoked by paired-pulse stimulation was not changed but the coefficient of variation was increased, suggesting that the depression was due to depletion of synaptic vesicles available for release.Intracellular labeling of seven electrophysiologically studied propriospinal axon-motoneuron pairs revealed that the number of axon varicosities establishing close appositions with dendrites of the labeled motoneuron was higher for connections where large-amplitude EPSPs were recorded. These varicosities were more often located on proximal dendrites of motoneurons than those of low-efficacy connections. In addition, the number of boutons in highly effective connections was several times lower than the maximal number of available quanta estimated from physiological data, implying that the large EPSPs may be generated by multivesicular release from presynaptic boutons.We conclude that the efficacy and related mode of use-dependent modulation of propriospinal connections is determined by a number of factors, including the number and position of synaptic contacts and the number of active zones or vesicles available for release.     

Synapsin I injected presynaptically into goldfish mauthner axons reduces quantal synaptic transmission

1. Synapsin I was injected into a vertebrate presynaptic axon to analyze its action on quantal synaptic transmission. Two microelectrodes were used for simultaneous intracellular recording from pairs of identified neurons in the goldfish brain. The postsynaptic electrode was placed in a cranial relay neuron (CRN) within 100 microns of its synapse with the Mauthner neuron. The presynaptic electrode impaled the Mauthner axon (M-axon) 50-200 microns from the first electrode. 2. Spontaneous miniature excitatory postsynaptic potentials (mEPSPs) and evoked postsynaptic potentials (EPSPs) were recorded at steady states before and after synapsin I was microinjected into the presynaptic M-axon. Responses were digitized and subsequently analyzed by computer for quantal parameters. 3. In 12 experiments, injection of synapsin I resulted in a reduction in transmission. The decrease in EPSP amplitude began approximately 30 s after the injection, reached a plateau within 10 min, and appeared to be reversible and dose dependent. 4. Injection of synapsin I decreased quantal content (m), with no effect on postsynaptic receptor sensitivity or on amount of transmitter per quantum. Further analysis based on the simplest binomial model for quantal release revealed that synapsin I consistently reduced the number of quantal units available for release (n) although the probability of release (p) was either unchanged or slightly increased. Injected synapsin I may thus bind to presynaptic vesicles and prevent transmitter quanta from entering a pool subject to evoked release.     

Analysis of fluctuations of “minimal” excitatory postsynaptic potentials during long-term potentiation in guinea pig hippocampal slices

Summary In previous studies, quantal analysis assuming a simple binomial model has shown that long-term potentiation (LTP) is accompanied by an increase in both mean quantal content (m) and quantal size (v), whereby the increase in m predominates. In the present study, compound binomial distributions with variable probabilities were convolved with Gaussian distributions in computer experiments to simulate amplitude histograms of intracellular excitatory postsynaptic potentials (EPSPs). A deconvolution procedure assuming equal quantal separation (v) between discrete components, but without assuming binomial statistics, was applied to the simulated distributions to determine v. It was found that with a small ratio of standard deviation of noise to v (S_n/v<0.4), a reliable estimate of v can be obtained even for small samples (N = 100). When S_n/v was larger (0.4–0.6), approximate v estimates (within±10–20% of the simulated v) could be obtained by averaging estimates from about 10 small samples (N = 100). Minimal EPSPs were recorded in area CA1 of guinea pig hippocampal slices. 37 EPSP amplitude samples of 9 neurones were measured before and up to 55 min after 10 tetanizations of stratum radiatum. In accordance with the previous data, the increase in v accounted for only about 10% of the average post-tetanic increase in EPSP amplitude and was not correlated with the latter. However, for an EPSP subset with small ETP magnitude, the increase in v accounted for an essential part of the LTP magnitude while the increase in m did not correlate with it. The results are in agreement with previous data obtained in the context of the simple binomial model and are interpreted as indicating primarily a presynaptic mechanism of LTP maintenance. The results suggest two types of synaptic mechanism of LTP maintenance related to the increases in m and v, respectively. The latter mechanism is saturated at about 10 to 30% increase in post-tetanic amplitude above the pretetanic EPSP amplitude.     

A revised method for generation of unitary postsynaptic potentials for quantal analysis in the hippocampus

For quantal analysis of excitatory postsynaptic potentials (EPSPs) in hippocampal CA3 neurons, a method was devised to evoke trains of unitary EPSPs at intended intervals and to control the number of unitary EPSPs composing each train at will. The amplitudes of the first EPSPs in EPSP trains evoked with this method were measured. From the mean and variance of the EPSP amplitudes, the mean number of quanta (m) released by a single impulse and the mean amplitude of EPSPs induced by individual quanta (q) were estimated in a standard solution and in a high calcium solution.     

Heterogeneity of group Ia synapses on homonymous alpha-motoneurons as revealed by high-frequency stimulation of Ia afferent fibers

Excitatory postsynaptic potentials (EPSPs) were recorded in medial gastrocnemius (MG) motoneurons following intraaxonal electrical stimulation of single spindle afferent fibers in anesthetized cats. High-frequency bursts of 32 shocks were delivered to the afferent axon and the EPSPs were averaged in the motoneuron. EPSP amplitude generally changed during the burst, in some cases increasing and in other cases decreasing, depending on the connection. Interpretation of these changes was complicated by potentiation of the initial EPSPs in the burst that occurred with the repeated bursts. The extent of the potentiation varied from connection to connection. The magnitude of facilitation or depression during a burst of standard frequency (167 Hz) was determined by comparison of EPSPs at the end of the burst with the mean EPSP obtained during low-frequency stimulation (18 Hz). Large amplitude EPSPs tended to depress, whereas the small amplitude EPSPs facilitated. Facilitation was more prevalent in motoneurons with large rheobases and depression was more often observed in small rheobase motoneurons. The use of partial correlations, which was necessary because of the inverse correlation between EPSP amplitude and motoneuron rheobase, revealed that facilitation-depression behavior during repetitive stimulation is correlated primarily with EPSP amplitude rather than with motoneuron rheobase. Acute transection of the spinal cord resulted in no change in motoneuron rheobase but considerable enlargement of mean EPSP amplitude at low frequencies of stimulation. A significant increase in the amount of depression during repetitive stimulation was noted under these conditions. These results indicate considerable heterogeneity in the response of individual connections to repetitive stimulation. We suggest that this heterogeneity results from differences in transmitter release at different connections. This heterogeneity must also have functional consequences related to susceptibility for firing of different motoneurons under various physiological conditions that can include afferent discharge frequencies equivalent to those used in this study.     

Estimates of EPSP amplitude based on changes in motoneuron discharge rate and probability

When motor units are discharging tonically, transient excitatory synaptic inputs produce an increase in the probability of spike occurrence and also increase the instantaneous discharge rate. Several researchers have proposed that these induced changes in discharge rate and probability can be used to estimate the amplitude of the underlying excitatory post-synaptic potential (EPSP). We tested two different methods of estimating EPSP amplitude by comparing the amplitude of simulated EPSPs with their effects on the discharge of rat hypoglossal motoneurons recorded in an in vitro brainstem slice preparation. The first estimation method (simplified-trajectory method) is based on the assumptions that the membrane potential trajectory between spikes can be approximated by a 10 mV post-spike hyperpolarization followed by a linear rise to the next spike and that EPSPs sum linearly with this trajectory. We hypothesized that this estimation method would not be accurate due to interspike variations in membrane conductance and firing threshold that are not included in the model and that an alternative method based on estimating the effective distance to threshold would provide more accurate estimates of EPSP amplitude. This second method (distance-to-threshold method) uses interspike interval statistics to estimate the effective distance to threshold throughout the interspike interval and incorporates this distance-to-threshold trajectory into a threshold-crossing model. We found that the first method systematically overestimated the amplitude of small (<5 mV) EPSPs and underestimated the amplitude of large (>5 mV EPSPs). For large EPSPs, the degree of underestimation increased with increasing background discharge rate. Estimates based on the second method were more accurate for small EPSPs than those based on the first model, but estimation errors were still large for large EPSPs. These errors were likely due to two factors: (1) the distance to threshold can only be directly estimated over a limited portion of the interspike interval and (2) the distance to threshold can be affected by the EPSP itself. Both methods provide the most accurate EPSP estimates for EPSP amplitudes less than 5 mV and moderate background discharge rates (~15 imp/s).     

Peptidergic inhibition of cholinergic transmission in bullfrog sympathetic ganglia

Intracellular and voltage-clamp recordings were made from sympathetic B neurons to investigate an interaction between peptidergic and cholinergic responses in bullfrog sympathetic ganglia. Stimulations of both 3rd-5th (0.2 Hz) and 8th (30 Hz) spinal nerves evoked the fast excitatory postsynaptic potential (EPSP) superimposed with the late slow EPSP at the same sympathetic neuron. The amplitude of fast EPSPs was decreased during the course of the late slow EPSP in a majority of sympathetic neurons. The mean depression of the fast EPSP amplitude was 51 +/- 4% (n = 24). The quantal content of the fast EPSP was also depressed by 54 +/- 3% (n = 10) during the late slow EPSP. Acetylcholine-induced depolarization (ACh potential) and current (ACh current) produced by an ionophoretic application of ACh were not reduced during the late slow EPSP. Bath-application of LH-RH (40 nM-4 microM) depressed the fast EPSP in a concentration-dependent manner; at a concentration of 1 microM, it produced a 63 +/- 8% (n = 8) depression of the quantal content of the fast EPSP. LH-RH (1-4 microM) depressed the frequency of the miniature (M) EPSPs by 25 +/- 4% (n = 5) of control. Antagonists for luteinizing hormone-releasing hormone (LH-RH) receptor, [D-Phe2,6, Pro3]-LH-RH and [D-pGlu1, D-Phe2, D-Trp3,6]-LH-RH, prevented the presynaptic inhibition of the fast EPSP induced by LH-RH. These results suggest that the fast EPSP is depressed during the late slow EPSP by decreasing the evoked release of ACh from presynaptic nerve terminals in bullfrog sympathetic ganglia.     

Variance analysis of excitatory postsynaptic potentials in cat spinal motoneurons during posttetanic potentiation

1. Fluctuations in the peak amplitudes of composite excitatory postsynaptic potentials (EPSPs) in cat spinal motoneurons were analyzed during posttetanic potentiation (PTP). Each of a series of identical tetanic stimulus trains delivered to a muscle nerve was followed by 45 test stimuli applied at 2-s intervals. The mean peak amplitude and mean peak variance were calculated for EPSPs evoked by all those stimuli following a tetanus with the same time interval. It was assumed that the variance arises primarily from the probabilistic all-or-none behavior of single synaptic boutons and background noise due to spontaneous synaptic activity and thermal noise in the recording system. The variance was corrected for the contribution from additive Gaussian background noise. 2. If it is assumed that individual synaptic boutons behave independently, corrected mean peak variance and mean peak amplitude are related by a parabolic function. The expected parabolic relationship was seen in 9 of 31 cases studied, and the parameters of the best parabolic fit to the data allowed estimation of some synaptic properties. From these parameters, the mean amplitude of the unit EPSP (v) was estimated to be 102.1 +/- 57.4 (SD) microV. An average of 3.7 boutons comprised each Ia-motoneuron contact system. 3. On average, only 27% of all synaptic boutons given off by the stimulated Ia fibers to one motoneuron were active and releasing transmitter during unpotentiated reflex transmission. The remaining 73% of the synapse population was intermittently silent. The population of boutons which took part in synaptic transmission could be divided into two subpopulations, one with a release probability P = 1 and a second with a mean release probability P = 0.13 +/- 0.086. 4. We conclude that synaptic boutons connecting Ia afferents to motoneurons exist in two populations, one having a high and one a low probability of transmitter release. Transmitter release is quantal, resulting in a unit EPSP of approximately 100 microV measured at the motoneuron soma.     

Control by Preynaptic Correlation: a mechanism affecting information transmission from Ia fibers to motoneurons.

1. In the unanesthetized spinal cord of the cat, simultaneous intracellular recordings were made from two motoneurons belonging to the gastronemius motor nucleus. 2. Supramaximal iterative stimulation of small branches of the gastrocnemius nerve produced monosynaptic EPSPs (Ia EPSPs) of varying amplitude superimposed on a fluctuating base line. 3. In most cases the variance of the motoneuron membrane potential was increased above base-line levels with a time course approximately matching the Ia EPSP. This suggests that Ia EPSP fluctuations are greater than can be accounted for by the base-line fluctuations alone. 4. For a given series of Ia EPSPs, the smaller responses in the series had about the same decay phase as the larger EPSPs, suggesting that most of the Ia EPSP fluctuations were not due to systematic changes in postsynaptic conductances produced by ongoing activity, but rather to a presynaptic mechanism. 5. Simultaneous recording from two motoneurons showed that base-line fluctuations were positively correlated. In most cases, however, there was an additional increased correlation above base-line levels resembling the time course of the Ia EPSPs, indicating positive correlation between EPSP fluctuations which is attributed to a presynaptic mechanism. 6. Conditioning volleys to group I muscle afferents or to low-threshold cutaneous afferents reduced the variance of the Ia EPSPs and also their correlation in motoneuron pairs, often without changing the mean Ia EPSPs. 7. It is concluded that, in the unanesthetized spinal cord, in addition to the random process which governs transmitter release intrinsic to a given synaptic terminal, there is another stochastic process affecting, in a correlated manner, transmitter release in large sets of Ia synaptic terminals. Most likely, the correlation in transmitter release is achieved by membrane potential fluctuations imposed on the Ia terminal arborizations by ongoing activity of the segmental mechanism mediating primary afferent depolarization. 8. The effects of such a correlating influence on cell firing behavior have been analyzed. The results suggest that this mechanism, referred to as control by presynaptic correlation, is able to modulate the information transmitted from Ia fibers to motoneurons.     

Relation between structural and release parameters at the young rat sensorimotor connection

The present work was carried out on isolated spinal cords of young rats. The aim of this study was the combined morphological and electrophysiological investigation of sensorimotor connections labelled with horseradish peroxidase and the evaluation of the relationship between their structural and functional properties. Sensorimotor contacts were widely distributed along the postsynaptic cell: from the soma and juxtasomatic dendrites to distal dendrites. The number of contacting boutons in the connection of a single afferent fibre and an individual motoneuron was about 10. The amplitude fluctuation patterns of the unitary and the minimal excitatory postsynaptic potentials of the motoneurons fitted with predictions based on a binomial model. A close correspondence was found between the estimated number of binomial release sites, n, and the number of contacting boutons. The calculated size of the quantal potential was about 100 microV. The difference in the organization of sensorimotor connections of the young rat and the frog is discussed.     

Changes in statistical parameters during facilitation at the crayfish neuromuscular junction

1. Transmitter release at excitatory neuromuscular junctions of the crayfish was studied at different frequencies of stimulation ranging from 1/sec to 20/sec.2. Over this frequency range the average number of quanta released per stimulus (m) increased with frequency by a factor of 6-7.3. Analysis of the fluctuations in quantal release using binomial statistics indicated that the increase in m was associated with increase in the average quantal release probability (p) at stimulation frequencies between 5/sec and 20/sec. Between 1/sec and 5/sec there was an apparent increase in the number of quanta available for release (n).     

The effects of calcium and magnesium on statistical release parameters at the crayfish neuromuscular junction

1. Transmitter release at excitatory neuromuscular junctions of crayfish muscle was studied at low temperature by recording synaptic potentials with extracellular micro-electrodes.2. Increasing the Ca concentration in the bathing solution produced an increase in the average number of quanta released per nerve stimulus (m). Increasing the Mg concentration resulted in a decrease in m.3. Statistical analysis of fluctuations in the quantal release from trial to trial, assuming binomial statistics, indicated that both the changes in m were due to changes in the average quantal release probability (p).     

Quantal analysis of long-term potentiation of “minimal” excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach

Summary Minimal excitatory postsynaptic potentials (EPSPs) were recorded from 13 neurones in area CA1 of guinea pig hippocampal slices after double-pulse stimulation of stratum radiatum (str. rad.) and stratum oriens (str. or.). Amplitudes of EPSPs significantly increased in 8 neurones 5 to 55 min after 9 tetanizations in str. rad. The increase was considered to represent long-term potentiation (LTP). Altogether 26 EPSPs (42 post-tetanic regions) were statistically analysed by four methods of the quantum hypothesis assuming the binomial model of transmitter release: the deconvolution (histogram), the variance, the failures, and the combined (variance-failures) methods. The mean quantal content (m) significantly increased after LTP induction according to all methods used. Quantal size (v) also tended to increase but according to some methods, the increase was not statistically significant and it did not correlate with LTP magnitude. However, for an EPSP subset with a LTP magnitude of < 1.55, the increase in v correlated with LTP magnitude, whereas the increase in m did not. The relative contribution of the increase in v to LTP magnitude was larger for cases with small LTP than for the whole EPSP set. In general, the increase in m corresponds to previous studies and favours the presynaptic location of major mechanisms of LTP maintenance, i.e. an increase in the average number of transmitter quanta released by each presynaptic volley. The post-tetanic increase in v might reflect some additional mechanisms which presumably include an increase in the amount of transmitter in one quantum.     

Statistical analysis of long-term potentiation of large excitatory postsynaptic potentials recorded in guinea pig hippocampal slices: binomial model

Summary Excitatory postsynaptic potentials (EPSPs) were recorded in guinea pig hippocampal slices (area CA1) from 15 neurones after stimulation of stratum radiatum (str. rad.) and stratum oriens. EPSP amplitudes increased in 8 neurones (10 post-tetanic regions) recorded 15 to 45 min after tetanic stimulation of str. rad. The increase was considered to represent long-term potentiation (LTP). Quantal analysis was performed by two methods assuming binomial statistics: the histogram method using deconvolution of noise and the variance method. According to both methods, LTP was associated with an increase in mean quantal content (m) which correlated with LTP magnitude. A statistically significant increase in quantal size (v) was found only by the histogram method and the increase was not correlated with LTP magnitude. A separate analysis of EPSPs with small LTP magnitude demonstrated that with the histogram method only v was increased but not m. A smaller increase in m for the pooled data of both methods did not correlate with LTP magnitude for this EPSP subset. The increase in m for the whole EPSP set corresponds to previous results on the quantal analysis of LTP in in vivo preparations and favours a presynaptic location of major mechanisms underlying LTP maintenance. The increase in v indicates the existence of another mechanism responsible for the maintenance of a small part of LTP. This mechanism might involve either pre- or postsynaptic changes or both.     

Synaptic actions produced by individual ventrolateral tract fibres in frog lumbar motoneurones

Excitatory post-synaptic potentials (EPSPs) were evoked in lumbar motoneurones of the isolated frog spinal cord by impulses in single ventrolateral tract fibres. In a few cases after recording an EPSP the fibre and the motoneurone involved were both filled with horseradish peroxidase (HRP) and the synaptic connexion between them was studied histologically. Monosynaptic EPSPs produced by direct stimulation of supraspinal (mainly reticulospinal) or unidentified (presumably propriospinal) fibres are mediated via chemical and, less frequently, dual-action synapses. The shape indices of chemical single-fibre EPSPs varied considerably in different connexions being, as a whole, similar to those of chemical components of EPSPs at synapses between primary afferents and motoneurones. Quantal analysis of the single-fibre EPSPs yielded quantal unit amplitude 18-113 microV and mean quantum content ranging from 1.14 to 16.4, the applicability of both Poisson and binomial models to transmitter release was revealed. Descending fibres electrically coupled with lumbar motoneurones were found to generate a depolarizing response to dorsal root stimulation. They were also characterized by a larger depolarization to superfused glutamate. The presence of electrical junctions between descending axons and spinal motoneurones suggests that the depolarization seen in these axons in response to synaptic excitation and glutamate could be the result of passive flow of depolarizing current from motoneurones electrically coupled to them. gamma-aminobutyric acid (GABA) did not produce conspicuous actions in axons forming both chemical and dual-action synapses. Axons injected with HRP have been followed to their site of termination in the lateral motor column. Synaptic boutons and varicosities were found to form contacts predominantly with dendrites of target motoneurones.     

Pericardial peptides enhance synaptic transmission and tension in phasic extensor muscles of crayfish

Two identified peptides, which are structurally related to FMRF-NH2 and are known to be associated with lobster pericardial organs, increase nerve-evoked tension and excitatory postsynaptic potentials (EPSPs) recorded from crayfish deep abdominal extensor muscles. At low stimulus frequencies, which produce marked depression of muscle twitches with successive stimuli, the peptides quickly and reversibly restore tension. Increased quantal content of transmitter release, rather than changes in postsynaptic input resistance, accounted for most of the increase in EPSP amplitude. The results support earlier suggestions that these two peptides may act as circulating neurohormones and provide the first evidence for peptidergic modulation of a phasic neuromuscular system in a crustacean.     

Computer simulation of group Ia EPSPs using morphologically realistic models of cat alpha-motoneurons

1. Morphological and electrophysiological data on the electrotonic structure of six triceps surae alpha-motoneurons and on the number and location of 202 Group Ia synapses making contact with ankle extensor motoneurons, previously obtained in this laboratory, were used to construct computer models to examine the generation of composite monosynaptic Group Ia excitatory postsynaptic potentials (EPSPs). 2. A total of 300 active synapses, each generating conductance transients based on voltage-clamp data and having activation times temporally dispersed (range approximately 1.3 ms) according to the conduction velocity profile of Group Ia-afferents, were used to generate composite EPSPs. 3. The shape indexes (foot-to-peak rise times and half widths) of simulated EPSPs matched those of experimentally observed Ia EPSPs reasonably well, although the rise times were, on average, approximately 0.25 ms longer in the simulated EPSPs. This may indicate that the effective temporal dispersion of actual Group Ia monosynaptic EPSPs is less than that the temporal asynchrony used in the simulations. 4. The peak amplitudes of simulated composite EPSPs (6-14 mV), as well as EPSPs produced by single somatic synapses (80-300 microV), were comparable to those found in experimental data. 5. Simulated EPSPs in motoneuron models with two forms of nonuniform Rm distribution ("step" increase from low values of Rm on the soma to much higher but uniform values in the dendrites, versus gradual monotonic "sigmoidal" increases from soma to distal dendrites) were similar in shape and amplitude. This prevented choosing one or the other Rm model as more "correct." 6. Transmembrane voltages at synaptic sites in motoneuron dendrites during generation of composite Ia EPSPs had peak amplitudes less than twice those of the somatic EPSP. The amount of nonlinearity during EPSP production was assessed by making the delivery of synaptic current independent of the local transmembrane voltage. This non-linearity was modest (less than 10%) during composite EPSP generation, consistent with previous experimental evidence. 7. The local voltages produced in various parts of different dendrites during composite EPSP generation depended on the number and location of active synapses and on the electrotonic structure of the particular dendrite. The results show that dendrites that project in different directions away from the motoneuron soma could, in principle, exhibit different degrees of interaction between Ia and other synaptic inputs. 8. Although produced by the same number of active synapses, the simulated composite Ia EPSPs varied over a two-fold range of peak amplitude in relation to motor-unit type, cell input resistance, and cell size (total membrane area).(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term facilitation alters transmitter releasing properties at the crayfish neuromuscular junction

Synaptic transmission at the neuromuscular junction of the excitatory axon supplying the crayfish opener muscle was examined before and after induction of long-term facilitation (LTF) by a 10-min period of stimulation at 20 Hz. Induction of LTF led to a period of enhanced synaptic transmission, which often persisted for many hours. The enhancement was entirely presynaptic in origin, since quantal unit size and time course were not altered, and quantal content of transmission (m) was increased. LTF was not associated with any persistent changes in action potential or presynaptic membrane potential recorded in the terminal region of the excitatory axon. The small muscle fibers of the walking-leg opener muscle were almost isopotential, and all quantal events could be recorded with an intracellular microelectrode. In addition, at low frequencies of stimulation, m was small. Thus it was possible to apply a binomial model of transmitter release to events recorded from individual muscle fibers and to calculate values for n (number of responding units involved in transmission) and p (probability of transmission for the population of responding units) before and after LTF. In the majority of preparations analyzed (6/10), amplitude histograms of evoked synaptic potentials could be described by a binomial distribution with a small n and moderately high p. LTF produced a significant increase in n, while p was slightly reduced. The results can be explained by a model in which the binomial parameter n represents the number of active synapses and parameter p the mean probability of release at a synapse. Provided that a pool of initially inactive synapses exists, one can postulate that LTF involves recruitment of synapses to the active state.