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.     

Analysis of individual Ia-afferent EPSPs in a homonymous motoneuron pool with respect to muscle topography

The spike-triggered averaging technique (26) was used to determine whether the synaptic input from medial gastrocnemius (MG) Ia-afferent fibers to homonymous motoneurons is "topographically weighted" (22) by means of differences in projection frequency, excitatory postsynaptic potential (EPSP) amplitude, or a combination of both factors. Motoneurons were classified as either "same branch" or "other branch," depending on whether a Ia-afferent fiber and motor axon were contained in the same or different intramuscular nerve branches. No difference was found in the projection frequency of Ia-afferents to the same branch and other branch motoneurons (95 versus 94%, respectively). The mean EPSP amplitude was larger in the same branch group of motoneurons (92 +/- 8 (SE) microV; n = V; n = 97) than in the other branch group (77 +/- 7 microV; n = 79). This difference was most striking in high-rheobase (greater than or equal to 10 nA) motoneurons, for which the mean EPSP amplitude in the same branch group was 82 +/- 12 microV (n = 48), whereas that in the other branch group was 52 +/- 5 microV (n = 37). In 60 cases it was possible to compare the EPSPs produced by a same branch afferent and an other branch afferent in the same motoneuron. The same branch afferent produced the larger EPSP in 73% (44/60) of the cases. Moreover, the mean ratio of the same branch to the other branch EPSP amplitudes was 1.7, which was both statistically significant and consistent with analogous results from our preceding study of aggregate EPSPs (22). Mean rise times and half-widths of EPSPs in the same branch group were not significantly different from those in the other branch group. Furthermore, no significant differences in rise times or half-widths between the two groups were evident when motoneurons were segregated according to their rheobase values. This suggests that the segregation of Ia-afferent and motor axons across the intramuscular nerve branches is not reflected in the locations of Ia terminals on the motoneuron somadendritic surface and that other factors must account for observed EPSP amplitude differences. Our data suggest that the topographic weighting of homonymous Ia-afferent input to cat MG motoneurons is mediated by a gradient of EPSP amplitude rather than by a gradient of Ia connectivity and also suggest that the effect is most prominent in high-rheobase motoneurons.     

Modulation of synaptic effectiveness of Ia and descending fibers in cat spinal cord.

1. In the unanesthetized spinal cord, conditioning stimulation of low-threshold afferents (below 1.3 times threshold strength) in the biceps semitendinosus (BST) nerve often reduced the peak amplitude of the monosynaptic Ia EPSPs evoked in gastrocnemius motoneurons without affecting the monosynaptic component of the EPSPs evoked by stimulation of the ipsilateral ventral funiculus (VF) in the thoracic cord. 2. Volleys to the BST nerve comprising higher threshold afferents (usually above 1.4 times threshold strength) reduced the peak amplitude of the monosynaptic Ia and VF EPSPs and shortened their falling phase. 3. Conditioning volleys to low-threshold cutaneous afferents often increased the Ia-EPSP peak amplitude, sometimes without affecting the monosynaptic component of the VF EPSP. 4. In most cases the Ia nd VF monosynaptic EPSPs elicited in a given motoneuron summated nonlinearly. The amount of nonlinear summation between Ia and VF monosynaptic EPSPs was often reduced by low-threshold BST conditioning volleys. These observations suggest that in many instances, both species of fibers end in "electrotonically close" synaptic loci over the motoneuron surface. Therefore, amplitude changes of monosynaptic Ia EPSPs produced by conditioning afferent volleys without concomitant changes of monosynaptic VF EPSPs do not appear to result from postsynaptic remote conductance changes and may be attributed to a presynaptic mechanism. 5. At the time of occurrence of the Ia and VF monosynaptic EPSP the variance of the motoneuron membrane potential may be increased above base-line levels with a time course approximately matching the EPSP itself. Conditioning stimulation of BST afferents usually reduced Ia EPSP variance, often without affecting or even increasing the variance of the monosynaptic VF EPSPs. These observations provide additional evidence that Ia EPSP variability is introduced, at least in part, through the segmental pathways mediating primary afferent depolarization. 6. The possibility of a differential control of the information flow transmitted through two independent channels converging on a given cell ensemble is discussed.     

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)     

Influence of synaptic identity on single-Ia-afferent connectivity and EPSP amplitude in the adult cat: homonymous versus heteronymous connections.

1. This study makes use of the pattern of synaptic connections between motoneurons and Ia afferents of triceps surae muscles in the cat to test the relative importance of synaptic identity, neuronal size, and neuronal topography as determinants of Ia-afferent connectivity and excitatory postsynaptic potential (EPSP) amplitude. 2. The synaptic actions of single-Ia medial gastrocnemius (MG) afferents were measured by intracellular recording in MG and lateral gastrocnemius (LG) motoneurons. The spike-triggered averaging technique was used to measure EPSPs generated by homonymous or heteronymous Ia afferents and motoneurons, i.e., neurons supplying the same or different muscles, respectively. In agreement with earlier studies, the pooled sample showed that the number of functional connections and the size of EPSPs were both significantly greater for homonymous than for heteronymous neurons. 3. Afferent conduction velocity, motoneuron conduction velocity, rheobase current, and position of the motoneuron relative to the spinal cord afferent entry were all correlated with EPSP amplitude, but the amplitude difference between homonymous and heteronymous connections remained significant after the statistical removal analysis of covariance (ANCOVA) of the contribution of these variables. Stepwise multiple-regression analysis showed that synaptic identity explained the greatest fraction of the variance in EPSP amplitude (9%), with significant but smaller fractions accounted for by rheobase current or motoneuron conduction velocity. 4. In a separate experiment, the monosynaptic affects from both homonymous and heteronymous single-Ia afferents were examined in each of 88 MG or LG motoneurons. The single-Ia afferents used in this portion of the study were sampled from both MG and LG muscles and selected for similar conduction velocities and spinal cord entry points.(ABSTRACT TRUNCATED AT 250 WORDS)     

Posttetanic potentiation of group Ia EPSPs: possible mechanisms for differential distribution among medial gastrocnemius motoneurons

We have reinvestigated the phenomenon of posttetanic potentiation (PTP) of group Ia monosynaptic excitatory postsynaptic potentials (EPSPs) in medial gastrocnemius (MG) alpha-motoneurons of pentobarbital-anesthetized cats. The results generally confirm earlier reports by Lüscher and colleagues (43, 44) of a negative correlation between the maximum percentage potentiation of Ia EPSP amplitude (Pmax) and 1) the mean amplitude of the pretetanic control EPSP in the same cell and 2) the input resistance of the postsynaptic motoneuron. These negative correlations, which we will refer to as "differential distribution of PTP" within the MG motor pool, were less strong in the present work than reported by Lüscher et al. (43, 44). We also found a relatively strong negative correlation between posttetanic EPSP depression, assessed by the amplitude of the first posttetanic EPSP, and the level of Pmax subsequently attained. We found no evidence that posttetanic depression is caused by failure of presynaptic action potentials. We investigated a second type of depression, referred to as "specific" synaptic depression, in which the second EPSP of paired responses (interval 250 ms) is, on average, smaller in peak amplitude than the first EPSP. This phenomenon appears to reflect decreases in the probability of transmitter release from previously activated synapses. Specific synaptic depression was consistently increased when paired responses were conditioned by a high-frequency tetanus. This is most easily explained by postulating that PTP results, at least in part, from an increase in the statistical probability of transmitter liberation from group Ia synapses that are activated (i.e., presumably invaded by action potentials) both before and after afferent tetanization. On the basis of the present results and other available evidence, we conclude that the differential distribution of PTP can be explained by two main factors: 1) the nonlinear relation between conductance and voltage changes inherent in all chemical synapses and 2) systematic variations in the properties of group Ia synapses that innervated different motoneurons, which remain to be clarified.     

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)     

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.     

Acute effects of spinal transection on EPSPs produced by single homonymous Ia-fibers in soleus alpha-motoneurons in the cat

1. Excitatory postsynaptic potentials (EPSPs) generated in soleus motoneurons by single homonymous Ia-fibers were measured using intracellular recording and the spike-triggered averaging technique. Two groups of barbiturate-anesthetized adult cats were studied: one with the spinal cord intact and the other with the spinal cord severed at thoracic segment 13 (T13) several hours prior to recording. 2. In cord-transected cats, single homonymous Ia-fibers produced EPSPs in soleus motoneurons that were, on average, larger and faster rising relative to normal, as they are for those produced in medial gastrocnemius (MG) motoneurons (8, 12, 13, 40). Specifically, mean EPSP amplitude and rise time were, respectively, 261 +/- 22 microV and 0.65 +/- 0.05 ms for the transected group vs. 160 +/- 21 microV and 0.96 +/- 0.08 ms for the intact group. The group means for each parameter were significantly different (P less than 0.005). 3. The group difference in EPSP amplitude was largely due to a decrease in number of small EPSPs in the transected group (11% less than 100 microV compared with the normal 41%) and not due to the occurrence of unusually large ones. Ratios of the largest to smallest amplitude EPSPs produced in the same motoneuron were similarly distributed for intact and transected groups, implying that the effect of transection on EPSP size was uniform across different Ia-fiber synapses made with the same motoneuron. Mean EPSP amplitude for each transected cat (n = 5) was larger than normal, but in some cases the increase took greater than 10 h to express itself. 4. The normal tendency for EPSP rise time to decline on average with amplitude was absent in the transected group, wherein rise time was reduced to similar average values in all amplitude categories. This suggests that the decrease in rise time occurred independently of the increase in amplitude. In contrast, EPSP half-width, which tended tow ward lower than normal values [5.63 +/- 0.36 (SE) ms vs. 6.51 +/- 0.44 ms; P greater than 0.10], decreased in proportion with rise time as evidenced by the preservation of the normal relation between those parameters in transected cats. Normalizing EPSPs by motoneuron time constant (tau) reduced the group differences in rise time and half-width, suggesting that a fall in tau contributes to the abbreviation of EPSP time course. 5. The condition of the spinal cord best accounted for differences in synaptic strength between groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

Analysis of effective synaptic currents generated by homonymous Ia afferent fibers in motoneurons of the cat

1. We have developed a technique to measure the total amount of current from a synaptic input system that reaches the soma of a motoneuron under steady-state conditions. We refer to this quantity as the effective synaptic current (IN) because only that fraction of the synaptic current that actually reaches the soma and initial segment of the cell affects its recruitment threshold and firing frequency. 2. The advantage of this technique for analysis of synaptic inputs in comparison to the standard measurements of synaptic potentials is apparent from Ohm's law. Steady-state synaptic potentials recorded at the soma of a cell are the product of IN and input resistance (RN), which is determined by intrinsic cellular properties such as cell size and membrane resistivity. Measuring IN avoids the confounding effect of RN on the amplitudes of synaptic potentials and thus provides a more direct assessment of the magnitude of a synaptic input. 3. Steady-state synaptic inputs were generated in cat medial gastrocnemius (MG) motoneurons by using tendon vibration to activate homonymous Ia afferents. We found that the magnitude of the Ia effective synaptic current (Ia IN) was not the same in all MG cells. Instead, Ia IN covaried with RN (r = 0.64; P less than 0.001), being about twice as large on average in motoneurons with high RN values as in those with low RN values. Ia IN was also correlated with motoneuron rheobase, afterhyperpolarization duration, and axonal conduction velocity. 4. A comparison of transient Ia EPSPs with steady-state Ia EPSPs (Ia EPSPSS) evoked in the same cells suggested that the effective synaptic current that produces the transient Ia EPSP was also greater in motoneurons with high RN values than in those with low RN values. 5. The factors responsible for the Ia IN-RN covariance are uncertain. However, our finding greater values of Ia IN in high RN motoneurons is consistent with other evidence suggesting that Ia boutons on these motoneurons have a higher probability for neurotransmitter release than those on low RN motoneurons (19). 6. The neural mechanisms underlying orderly recruitment are discussed. The effect of the Ia input is to produce an approximately twofold expansion of the differences in motoneuron recruitment thresholds that are generated by intrinsic cellular properties. It is suggested that the higher efficacy of Ia input in low-threshold motoneurons confers particular importance on this input system in the control of vernier movements (7).     

Analysis of Ia-inhibitory synaptic input to cat spinal motoneurons evoked by vibration of antagonist muscles.

1. Steady-state inhibitory postsynaptic potentials (IPSPs) were evoked in tibialis anterior and extensor digitorum longus motoneurons of the cat by using tendon vibration to activate Ia-afferent fibers from the antagonist medial gastrocnemius muscle. 2. The effective synaptic currents (IN) underlying the steady-state IPSPs were measured by the use of a modified voltage-clamp technique. The amplitudes of the effective synaptic currents (1.62 +/- 0.66 nA, mean +/- SD; n = 20) extended over a fivefold range (0.5-2.7 nA) but were not correlated with the intrinsic properties of the motoneurons or with putative motor unit type. 3. We calculated the synaptic conductance (GS) underlying the steady-state Ia IPSPs from measurements of motoneuron input conductance during the activation of the Ia synaptic input. As was expected from Ohm's law, the Ia-inhibitory GS and IN were correlated (r = 0.49; P less than 0.05). Like IN, GS (175 +/- 202 nS, mean +/- SD; n = 20) was not correlated with the intrinsic properties of the motoneurons. 4. As has been reported previously for transient Ia IPSPs, the amplitudes of the steady-state IPSPs were correlated with motoneuron input resistance (r = 0.74; P less than 0.001) and homonymous Ia excitatory postsynaptic synaptic potential (EPSP) amplitude (r = 0.72; P less than 0.001). 5. The amplitudes of the steady-state Ia IPSPs and the homonymous Ia EPSPs were plotted on logarithmic axes. The slope (0.59) was significantly less than 1, which indicates that the gradient of Ia inhibition across the motoneuron pool is less steep than that of Ia excitation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of synaptic transmission at Ia-afferent fiber connections on motoneurons during high-frequency stimulation: role of postsynaptic target.

1. High-frequency stimulation of single group Ia-fibers results in modulation of excitatory postsynaptic potential (EPSP) amplitude recorded in target motoneurons. This can be either positive (EPSP amplitude increases in response to successive stimuli in the high-frequency burst) or negative (decrease in EPSP amplitude). We have investigated whether the magnitude of modulation is associated with the stimulated afferent, the responding motoneuron, or the amplitude of the EPSP. 2. In agreement with previous findings, we found that positive modulation tends to occur at connections generating small EPSPs and negative modulation, at those producing large EPSPs. Because large EPSPs generally are evoked in motoneurons with low values of rheobase, we found, as anticipated, that connections on low rheobase motoneurons are prone to negative modulation during high-frequency stimulation, whereas those on high rheobase motoneurons (which tend to generate small EPSPs) are prone to positive modulation. 3. In experiments where the projection of multiple afferents to a single motoneuron was studied, we found that amplitude modulation was similar despite differences in EPSP amplitude. Thus in a given motoneuron there is no relationship between modulation and amplitude, in contrast to the existence of such a relationship in the population of connections as a whole. 4. In the converse experiments where the projection of single afferents to multiple motoneurons was studied, we found marked variability in the modulation patterns with clear indications that amplitude and modulation are correlated as in the entire population of Ia/motoneuron connections. 5. We tested the constancy of modulation patterns evoked in a given motoneuron by comparing the modulation patterns evoked in motoneurons by single fibers, and by stimulation of the heteronymous nerve.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of axotomy on posttetanic potentiation of group Ia synapses in the cat

Posttetanic potentiation (PTP) of composite Ia excitatory postsynaptic potentials (EPSPs) has been studied in normal cat alpha-motoneurons and in motoneurons axotomized 2-3 wk earlier by ventral root section. The maximal amount of PTP of EPSP amplitude (expressed relative to unpotentiated amplitude) was considerably less in the axotomized population compared with the normal population. The decrease in PTP provoked by axotomy occurs in association with a postaxotomy increase of input resistance, the net effect being that PTP in axotomized cells was much the same as that observed by others in normal motoneurons possessing similarly high input resistance. In agreement with previous results, EPSP peak amplitudes were decreased after axotomy. This decrease seemed to be largely related to an absence of the largest EPSPs, since otherwise the EPSP distributions of normal and axotomized motoneurons showed considerable overlap. It is suggested that the observed decrease in PTP after axotomy is related to a change in synaptic release properties and not secondary to changes in the electrical properties of motoneurons. A previous analysis has suggested that axotomy causes an alteration of the distribution of passive electrical properties among motoneurons such that axotomized cells resemble normal high-resistance motoneurons. The present results suggest that axotomy may affect the distribution of Ia synaptic release properties in a similar manner, since PTP in axotomized motoneurons resembles that observed in normal high-resistance motoneurons.     

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.     

Synaptic strength between motoneurons and terminals of the dorsolateral funiculus is regulated by GABA receptors in the turtle spinal cord

The role of GABAA and GABAB receptors in modulation of excitatory synaptic transmission between motoneurons and terminals from dorsolateral funiculus (DLF) was studied in in vitro spinal cord slices of adult turtles. Muscimol--a GABAA receptor agonist--depressed the monosynaptic excitatory postsynaptic potential (EPSP) induced by stimulation of the DLF and shortened its duration. The input resistance and the membrane time constant also were strongly reduced. The input membrane resistance, the amplitude, and the half-width of the EPSP were reduced at the same rate in the presence of muscimol. Bicuculline--a GABAA receptor antagonist--increased the EPSPs amplitude and the input membrane resistance. The EPSP amplitude ratio elicited by a paired-pulse protocol did not change significantly. Our results suggest that muscimol acts mainly by activation of postsynaptic GABAA receptors located on the motoneuron and the synaptic strength on motoneurons may be modulated by tonic activation of postsynaptic GABAA receptors. Baclofen--a GABAB receptor agonist--also depressed DLF-motoneuron synaptic transmission. However, it did not affect the falling phase of the EPSPs or the motoneuron membrane time constant but induced a small decrement in input resistance. In the presence of baclofen, the amplitude ratio produced by a paired-pulse protocol increased significantly. This suggests that baclofen decreased the synaptic strength by inhibition of neurotransmitter release from the DLF terminals via activation of presynaptic GABAB receptors.     

Factors that control amplitude of EPSPs in dendritic neurons

We have used a computer-based mathematical model of alpha-motoneurons and of group Ia synaptic input to them, based on anatomical and electrophysiological data from the cat spinal cord, in order to examine the effects of variations in neuron size and input resistance and of conductance magnitude and duration on the generation of excitatory postsynaptic potentials (EPSPs). The first set of calculations were designed to test the possible role of nonlinear EPSP summation in producing a differential distribution of posttetanic potentiation of group Ia EPSPs, described in the preceding paper (25; see also Refs. 26, 27). The results suggest that the negative correlations observed between the degree of posttetanic potentiation of Ia EPSPs and initial (pretetanic) EPSP amplitude as well as with the input resistance of the postsynaptic motoneurons can be explained in part by the inherent non-linearity between conductance change and the resultant potential change at chemical synapses. In a second set of calculations, we used the same model system to evaluate the effects produced by variations in neuronal membrane area, input resistance, and specific membrane resistivity, as well as of the density of excitatory synaptic input on the peak amplitude of EPSPs. With parameters constrained to match the properties of alpha-motoneurons and group Ia synaptic input, EPSP amplitudes were most sensitive to changes in synaptic density and were much less sensitive to alterations in neuron input resistance and specific membrane resistivity when synaptic density was constant.     

The relationship between estimates of Ia-EPSP amplitude and conduction velocity in human soleus motoneurons

There are several parameters associated with motoneuron size, among which are the conduction velocity of the axon as well as the size of the excitatory postsynaptic potential (EPSP) induced by stimulation of Ia afferents in the corresponding muscle nerve. In particular, it has been established in animal experiments that small motoneurons with a low conduction velocity exhibit large Ia EPSPs, whereas large motoneurons with a high conduction velocity show small Ia EPSPs. Thus small motoneurons are recruited earlier than large ones. In this study, we investigated whether such a relationship between motoaxon conduction velocity and size of the Ia EPSPs could also be found for human soleus motoneurons. In total, 36 motor units from six healthy volunteers were activated by a slight voluntary contraction and exposed to 200 stimuli of the tibial nerve in the popliteal fossa. Stimuli were delivered using a special stimulus protocol ensuring a constant pre-stimulus spike density along with a constant rate of discharge of the investigated unit. From the stimulus-correlated spike train data a measure of Ia-EPSP amplitude was obtained, along with the single-unit H-reflex latency. Additionally, for each unit, the so-called surface macro EMG was recorded, which measures the complete electrical activity attributable to the unit investigated. From the macro EMG, the intramuscular delay from arrival of each action potential at the soleus muscle and the detection of the muscle-fiber action potential picked up by the recording needle electrode were measured. All single-unit H-reflex latencies were corrected for the corresponding intramuscular delays. From the corrected latencies, single-unit conduction velocities were obtained. It was found that there was a highly significant negative correlation between the estimate of the single-unit conduction velocity and the inferred size of the Ia EPSP. Thus, it was found that Ia-EPSP amplitudes in human soleus motoneurons follow the size principle.     

Potentiation of transmission at Ia-motoneuron connections induced by repeated short bursts of afferent activity

Single medial gastrocnemius Ia-afferent fibers and motoneurons to which they projected were simultaneously impaled in anesthetized cats. Each Ia-afferent fiber was electrically stimulated once every 2 s with short high-frequency bursts (32 shocks at 167 Hz) followed by 1-11 test shocks. The resulting motoneuron excitatory postsynaptic potentials (EPSPs) were recorded and averaged in register. The interval between the end of one burst and the beginning of the next was 2 s; therefore, the amplitude of the first EPSP in the burst was considered to be a measure of efficacy of transmission 2 s after the burst. At most connections (23/29) the mean amplitude of the first EPSP in the burst was equal to or larger than the mean amplitude of control EPSPs produced by low-frequency (18-Hz) stimulation. Enhancement of transmission was maximum 50-100 ms after the burst, and the amplitude of the test EPSP delivered at this time was always greater than that of the control. The period of enhanced transmission appeared to decay more rapidly at connections with small EPSPs. The greatest amount of EPSP amplitude enhancement at 50 or 100 ms after the burst was observed at connections at which EPSP amplitude increased during the burst. The shape (rise time, half width) of potentiated EPSPs was the same as control EPSPs averaged during low-frequency (18-Hz) stimulation. Multiple shocks delivered at low frequency between bursts revealed that enhanced transmission following the high-frequency burst is very sensitive to the effects of low-frequency test stimulation. Furthermore, increasing the number of shocks during the interval between bursts reduced the enhancement of the first EPSP in the burst. We suggest that modulation of synaptic transmission after high-frequency bursts differs across Ia-motoneuron connections. These time-dependent changes associated with short bursts of firing (which are similar in frequency to those observed in Ia-fibers supplying hind-limb muscles during stepping) emphasize the necessity to consider the history of the discharge pattern of the group Ia fiber in assessing efficacy at individual Ia-motoneuron connections.     

Effects of preventing reinnervation on axotomized spinal motoneurons in the cat. II. Changes in group Ia synaptic function

1. Composite excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of heteronymous group Ia afferents have been studied at various postoperative times in axotomized motoneurons that were denied the opportunity to reinnervate muscle. 2. The medial gastrocnemius (MG) nerve was transected and sutured onto the surface of the normally innervated lateral gastrocnemius (LG) muscle. The denervated MG muscle was excised thereby eliminating access of regenerating MG motor axons to vacant end-plates. 3. The mean amplitude of monosynaptic Ia EPSPs evoked by electrical stimulation of the LG-soleus (LGS) nerve and recorded in axotomized MG motoneurons showed an initial decline at 20 days postoperative (DPO) that was not significant. At 44 DPO, mean amplitude had declined significantly to 43% of the control mean amplitude. At 90 DPO, mean EPSP amplitude was not significantly different from control. At the latest postoperative time (150-180 DPO), mean amplitude was significantly less than the control amplitude. 4. Mean EPSP rise time (time-to-peak) was significantly increased (27%) at the earliest postoperative times (20-44 DPO). At later postoperative times (90-180), mean EPSP rise time was not significantly different from mean control rise time. 5. "Partial responses" superimposed on EPSPs were not observed at any postoperative time. 6. Mean posttetanic potentiation (PTP) of the LGS EPSP was significantly depressed at 20 DPO. At later postoperative times, PTP did not differ significantly from mean control PTP. 7. The possibility is considered that postaxotomy alterations in the electrical properties of motoneurons may explain these complex variations of mean EPSP amplitude and rise time.     

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.