Input To Motoneurons Research Articles

Crossed Rhythmic Synaptic Input to Motoneurons during Selective Activation of the Contralateral Spinal Locomotor Network

To investigate the cellular mechanisms underlying locomotor-related left-right coordination, we monitored the crossed synaptic input to lumbar motoneurons during contralateral ventral root rhythmicity in the neonatal rat spinal cord in vitro. Using a longitudinal split-bath setup, one hemicord was kept in normal solution, whereas the contralateral hemicord was exposed to 5-HT and NMDA. With this approach, rhythmic bursting could be induced in the ventral roots on the agonist-exposed side, whereas the ventral roots on the agonist-free side remained silent. Intracellular recordings were made from L1-L3 motoneurons on the silent agonist-free side during rhythmic activity in the contralateral ventral roots. At the resting membrane potential, the typical crossed synaptic input was a rhythmic barrage of depolarizing IPSPs. This input modulated the frequency of spikes induced with depolarizing direct current by inhibiting firing in phase with the contralateral bursts. Intracellular chloride loading increased the amplitude of the IPSPs, suggesting that they were chloride-dependent. Strychnine but not bicuculline generally blocked the rhythmic inhibitory input when added to the agonist-free side during contralateral rhythmicity. APV and CNQX on the agonist-free side abolished the rhythmic inhibitory input in most motoneurons but not in all. We suggest that rat spinal motoneurons receive a mainly glycinergic rhythmic inhibition from the contralateral half of the locomotor network. Unlike in simpler vertebrates, the crossed inhibition often appears to be at least disynaptic, involving inhibitory premotor neurons located on the same side as the receiving motoneurons. These premotor neurons are rhythmically excited via a crossed pathway that depends on glutamatergic transmission.

A review of recent applications of cross-correlation methodologies to human motor unit recording

This article reviews some recent applications of time and frequency domain cross-correlation techniques to human motor unit recording. These techniques may be used to examine the pre-synaptic mechanisms involved in control of motoneuron activity during on-going motor tasks in man without the need for imposed and artificial perturbations of the system. In this review we examine, through several examples, areas in which insights have been gained into the basic neurophysiological processes that bring about motoneuron firing in man and illustrate how these processes are affected by central nervous system pathology. We will demonstrate that synchronization and coherence may be revealed between human motor unit discharges and give examples that support the hypothesis that these phenomena are generated by activity in a focused common corticospinal input to spinal motoneurons. Disruption of central motor pathways due to diseases of the nervous system leads to pathophysiological alterations in the activity of these pre-synaptic motoneuron inputs that can be revealed by cross-correlation analysis of motor unit discharges. The significance of these studies and outstanding questions in this field are discussed

Parapodial swim muscle in Aplysia brasiliana. I. Voltage-gated membrane currents in isolated muscle fibers.

1. We describe voltage-gated membrane currents present in single muscle fibers dissociated from the parapodia (swim appendages) of the marine gastropod mollusk Aplysia brasiliana. These muscles are utilized in swimming behavior and their activity is modulated by serotonin. It is necessary to characterize the innate membrane properties of these fibers before defining the mechanism of action of serotonin in facilitating muscle fiber responses to motoneuron input. 2. Freshly dissociated parapodial muscle fibers appear by morphological criteria to be a uniform population with an average length of 240 microns and width of 15 microns. The average resting potential of all fibers is -56 mV and the fibers contract in response to elevated extracellular K+ concentration or intracellular depolarization. 3. Muscle membrane currents were studied by single-electrode voltage clamp with the use of intracellular microelectrodes. The muscle fibers were found to fall into one of two groups, which we have classified as type I and type II, the former having two voltage-gated outward K+ currents and a small, less frequently seen Ca2+ current. Type II fibers display the same two K+ currents, a prominent Ca2+ current and, in addition, two Ca(2+)-dependent K+ currents, the latter described in a companion paper. 4. Membrane currents were characterized using 1-s voltage ramps and several voltage step protocols, including ones for analyzing K+ tail currents. Both fiber types had similar current-voltage relationships and input resistance of > or = 60 - 300 M omega. The current-voltage curves were quite flat at potentials more negative than resting potential, with no evidence of a voltage-gated, inwardly rectified (anomalous) potassium current. Outward K+ currents and a Ca2+ current were seen to appear at a threshold of near -40 mV. 5. Because type I fibers had no apparent Ca(2+)-activated K+ currents, the two voltage-gated outward K+ currents were most conveniently studied in these fibers. Compared with type II fibers, type I fibers display a relatively slowly rising total outward current with depolarization comprised of a delayed rectifier current and a transient A current (IA). These two currents were distinguished by slightly different thresholds for activation, by inactivation properties of IA, and by their partially selective sensitivity to tetraethylammonium and 4-aminopyridine. 6. Although contraction of all parapodial muscle fibers is dependent on extracellular Ca2+, an inward Ca2+ current was detected in only about one third of type I fibers, and the current was small. A similar and more prominent Ca2+ current was observed in all type II fibers and was analyzed more fully in these cells. This current had an activation threshold near -40 mV and peaked between -10 and 0 mV. It displayed little inactivation with depolarization steps of 80-200 ms, was blocked in the absence of Ca2+ or in the presence of Co2+, and was present, although not enhanced, when Ba2+ was substituted for Ca2+. This current was completely blocked by the dihydropyridine nifedipine (10 microM), and is therefore similar to an L-type Ca2+ current. 7. The voltage-gated membrane currents described in parapodial muscle fibers provide a framework for analyzing possible mechanisms by which serotonin facilitates neuromuscular output. This facilitatory mechanism will provide a better understanding of the role of serotonin in controlling locomotion.

Development of hypoglossal motoneurons.

Hypoglossal motoneurons (HMs) are brain stem motoneurons that innervate tongue muscles. Their function is critical in the control of the upper airway. Results from in vitro studies of rat HMs have shown that properties of HMs change during the postnatal period. For example, these studies have uncovered changes in HM morphology and electrical properties (both in ion channels and firing properties) as well as changes in chemical synaptic transmission to HMs during the postnatal period. Morphologically, a marked reduction in complexity of the dendritic tree takes place over the first 2 wk postnatal. In terms of electrical properties, a substantial and progressive fall in motoneuronal input resistance occurs during the first month of life, due to a decrease in specific membrane resistivity. This is primarily responsible for the progressive increase in rheobase and consequent reduction in cell excitability. In addition, the densities of at least two types of membrane ion channels are altered in early postnatal life, contributing to changes in their electroresponsive properties. On the one hand, the depolarizing mixed cationic current that is activated by membrane hyperpolarization was found to be approximately 10-fold larger in adult than in neonatal HMs. By contrast, neonatal HMs possess a transient low-voltage-activated T-type Ca2+ channel with a low single-channel conductance (approximately 7 pS), the density of which rapidly declines during the early postnatal period. The functional relevance of these and other changes occurring during the postnatal period is discussed.

Serine-1321-independent regulation of the mu 1 adult skeletal muscle Na+ channel by protein kinase C.

The adult skeletal muscle Na+ channel mu1 possesses a highly conserved segment between subunit domains III and IV containing a consensus protein kinase C (PKC) phosphorylation site that, in the neuronal isoform, acts as a master control for "convergent" regulation by PKC and cAMP-dependent protein kinase. It lacks an approximately 200-aa segment between domains I and II though to modulate channel gating. We here demonstrate that mu1 is regulated by PKC (but not cAMP-dependent protein kinase) in a manner distinct from that observed for the neuronal isoforms, suggesting that under the same conditions muscle excitation could be uncoupled from motor neuron input. Maximal phosphorylation by PKC, in the presence of phosphatase inhibitors, reduced peak Na+ currents by approximately 90% by decreasing the maximal conductance, caused a -15 mV shift in the midpoint of steady-state inactivation, and caused a slight speeding of inactivation. Surprisingly, these effects were not affected by mutation of the conserved serine (serine-1321) in the interdomain III-IV loop. the pattern of current suppression and gating modification by PKC resembles the response of muscle Na+ channels to inhibitory factors present in the serum and cerebrospinal fluid of patients with Guillain-Barré syndrome, multiple sclerosis, and idiopathic demyelinating polyradiculoneuritis.

Facilitation and depression at different branches of the same motor axon: evidence for presynaptic differences in release

This study provides evidence that a neuron can exhibit differences in activity-dependent transmitter release at two synaptic sites due to variations in the properties of its presynaptic terminals. Two muscles in the stomatogastric system of the lobster Homarus americanus are innervated by a single motor neuron but respond differently to that motor neuron's input, resulting in two different movements evoked by one motor neuron. During continued motor neuron stimulation, the gm8 muscle contracts slowly and maintains contraction, while the gm9 muscle contracts rapidly and then relaxes. These different muscle responses can be accounted for, in large part, by the properties of the respective neuromuscular synapses: the excitatory junctional potentials recorded in gm8 are initially small but summate and facilitate with repeated stimulation, while those in gm9 are initially large but depress with repeated stimulation. Presynaptic differences in neurotransmitter release contribute strongly to the divergent responses; reduction of the excitatory junction potential amplitude by partial postsynaptic receptor blockade or by desensitization does not change the amount of depression at gm9. However, reduction of neurotransmitter release with low-Ca2+, high-Mg2+ saline removes gm9 synaptic depression and reveals that both neuromuscular junctions exhibit frequency-dependent homosynaptic facilitation. Postsynaptic differences in muscle input resistance and muscle composition may enhance the effects of the divergent release properties, but are not responsible for the activity-dependent changes. Ultrastructural features of the nerve terminals on the two muscles are consistent with the differential output of the terminals; the synapses on gm9 are larger and have more presynaptic dense bars than their counterparts on gm8. These data suggest that the basis for the differences in transmitter release between the two muscles may be a higher density of release sites in the gm9 synapses that leads to a higher output of neurotransmitter, rapid depletion of transmitter stores, and synaptic depression.

Cholera Toxin B-HRP and Wheat Germ Agglutinin-HRP Tracing of Tensor Tympani Muscle Motorneurons and Processes in Rabbits

The brain stem position, organization and number of motoneurons innervating the rabbit tensor tympani muscle (TTM) were determined by retrograde axonal transport of cholera toxin B/horseradish peroxidase conjugate (CTB-HRP) and wheat germ agglutinin HRP conjugate (WGA-HRP) tracers. The synaptic input to the TTM motoneurons was examined with WGA-HRP. The results show the motoneurons of the TTM to be localized in a cluster ventro-lateral to the outer margin of the ipsilateral trigeminal motor nucleus (VMN) and dorso-lateral to the superior olive. The number of labeled cells was greater in the combined CTB-HRP/WGA-HRP injected cases. The TTM motoneurons were triangular and elongated in shape and smaller than those of the VMN. An extensive network of dendritic branches was present ventro-laterally in the vicinity of the superior olive. Similar, but less extensive collections of dendritic processes were observed to course dorso-medially, rostrally and caudally. Axons were observed to project first dorsally or laterally, towards the trigeminal motor root, then after a sharp turn coursed ventrally within the trigeminal motor root (VMR). Transneuronal transport of the WGA-HRP was not accomplished in any preparation, suggesting among other things, system or species differences in the effectiveness of the WGA-HRP conjugate as a transynaptic tracer. It is concluded that the TTM acoustic reflex in rabbits and other mammals, its threshold, prolonged contraction capacity, and its influence on middle ear sound transmission may be related to its demonstrated extensive synaptic field in the reflex chain, particularly in the area of the superior olive, while its many other physiological functions may be made possible by the number, location, and multi-dimensional orientation of its motoneurons and dendrites.

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)

Neural control of swimming in Aplysia brasiliana. III. Serotonergic modulatory neurons.

1. We describe a group of serotonergic neurons in the pedal ganglia of Aplysia brasiliana and characterize their modulatory effects on the motoneuron input to swimming muscles of the parapodia. Each pedal ganglion contains one cluster of large neurons near its dorsomedial surface that fires in phase with opening (downstroke) of the parapodia; these have been designated parapodial opener-phase (POP) cells. 2. POP cells are large, number 15-20 per ganglion, have peripheral axons in parapodial nerves, have distinctively shaped action potentials, and fire in bursts phasically with motoneurons during the opening, or downstroke portion, of parapodial movement during fictive swimming. Firing individual POP cells with intracellular current indicates that they have no direct detectable effect on muscle, causing neither junction potentials nor contractions. 3. 5,7-Dihydroxytryptamine (5,7-DHT) staining, immunocytochemistry using serotonin (5-HT) antibodies, and direct biochemical measurements revealed that POP cells are serotonergic. Serotonergic nerve endings were also seen in parapodial muscle. 4. Simultaneous intracellular recordings and use of altered divalent concentrations revealed that no detectable direct synaptic interactions exist between POP cells and motor neurons. 5. When POP cells and motoneurons were simultaneously recorded while measuring muscle contractions, it was found that POP cell activity enhances motoneuron-induced tension by 120-900%, averaging around 300%. Variability in the efficacy of individual POP cells suggests that they may influence specific regions or groups of muscle fibers. 6. POP cell activity also significantly increased the rate of relaxation of parapodial muscle contractions, averaging about a 40% reduction in the time required to relax to one-half peak tension. Increased relaxation rate implies a postsynaptic change in muscle behavior. 7. The effectiveness of POP cells to increase contraction tension and relaxation rate was positively correlated with POP cell spike frequency. These effects were slow (seconds) in onset and could persist for a minute or more after cessation of POP firing. Concurrent motoneuron activity is not required for modulation by POP cells. 8. Simultaneous intracellular recording from a POP cell, motoneuron, and muscle fiber revealed that POP cell activity enhanced the amplitude of motoneuron-induced excitatory junction potentials (EJPs). Activity of POP cells did not alter muscle fiber membrane potential, but the experiments left open the possibility that EJP enhancement is presynaptic, postsynaptic, or a combination.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of effective synaptic currents underlying recurrent inhibition in cat triceps surae motoneurons

1. Steady-state recurrent (Renshaw) inhibitory postsynaptic potentials (RIPSPs) were evoked in cat triceps surae motoneurons by stimulating the heteronymous muscle nerve at 100 Hz after dorsal root section. The effective synaptic currents (i.e., the net synaptic current measured at the soma, IN) underlying these inhibitory potentials were measured with a modified voltage-clamp technique. 2. The average value of the effective synaptic currents measured in medial gastrocnemius (MG) motoneurons was 0.4 nA. There was no significant correlation between the IN measured in individual cells and motoneuron input resistance (RN), rheobase (IR), duration of the spike afterhyperpolarization (AHPt1/2), or putative motor-unit type, although the steady-state inhibitory post-synaptic potential (IPSP) amplitudes were correlated with all of these parameters. 3. Steady-state recurrent inhibition was accompanied by a small (3.5%, on average) decrease in the resting input resistance of the motoneurons. The small magnitude of this measured change supports the hypothesis of Burke et al. that the site of synaptic contact between Renshaw cells and motoneurons is somewhat distal to the cell soma. 4. The absence of a differential distribution of the effective synaptic currents generated by Renshaw cells within the MG pool does not support the idea that recurrent inhibition mediates a selective reduction of the firing of small, low-threshold motoneurons by large, high-threshold motoneurons. The small amplitude of the effective synaptic currents we measured suggests that the contribution of recurrent inhibition to the direct modulation of motoneuron firing rate is subtle and that it is perhaps principally involved in the fine control and smooth production of muscle force.

Modulation of Neural Circuits in Crustacea

Recent research has shown that neuromodulators play important roles in shaping simple behaviors. They act at many different sites within the animal in a coordinated fashion, modulating the motor circuits in the central nervous system, altering motoneuron excitability, and modulating muscle response to motoneuron input. Within the central circuits that co-ordinate simple movements, neuromodulators play a dramatic sculpting role, changing the cells that participate in the circuit, altering their intrinsic properties, and affecting the strength of synaptic interactions that form the “wiring diagram” of the circuit. As a result, they are able to shape a family of related circuits out of a single anatomically identified network, each driving a unique variant on the basic motor theme. Examples of these actions from the Crustacea are described in this paper, focussing on the modulation of posture in the lobster, and on modulation of rhythmic motor programs for stomach movements in the stomatogastric ganglion of lobsters and crabs.

Dendrites of cat's spinal motoneurones: relationship between stem diameter and predicted input conductance.

1. The electroanatomy of motoneuronal dendrites was analysed using data from fifty-two dendritic trees of four completely reconstructed cat spinal motoneurones that had been labelled with intracellularly injected horseradish peroxidase. The cells belonged to m. triceps surae, and their physiological properties covered much of the known range for this muscle. 2. For each dendritic tree, the input conductance, as seen from the soma, was calculated by the method of Rall (1959), using anatomical measurements of the length and diameter of all branches and different assumed values for dendritic membrane resistivity. 3. There was a strong positive correlation between dendritic stem diameter and the calculated dendritic input conductance. Dendritic input conductance was approximately equal to a constant x (stem diameter)3/2 x (dendritic membrane resistivity)-0.76. 4. The relationship between dendritic stem diameter and computed input conductance was equal to that of Rall's equivalent-cylinder model of a dendritic tree. However, from a number of other points of view, the properties of the reconstructed dendrites differed from those of the model: (a) at branch points, the sum sigma(daughter diameters 3/2) was, on average, 19% greater than the 3/2 power of the parent diameter; (b) dendritic branches often showed a significant amount of tapering, and the mean overall degree of diameter decrease per branch was about 12%; (c) the termination of dendritic branches occurred at widely different distances from the soma within single dendritic trees (true for anatomical as well as for computed electrotonic distances). 5. When used in conjunction with previously published measurements of motoneuronal input resistance and proximal anatomy (Kernell & Zwaagstra, 1981), the present results gave further support to the conclusion that differences in membrane resistivity are of great importance for differences in motoneuronal input resistance. Furthermore, this conclusion was also confirmed by direct observation of the properties of the present four motoneurones: irrespective of the assumed ratio between somatic and dendritic membrane resistivity, there was a statistically significant positive correlation between the measured neuronal input resistance and the required membrane resistivity of soma and dendrites.

Motor activity in the isolated spinal cord of the chick embryo: synaptic drive and firing pattern of single motoneurons

The cellular mechanisms underlying embryonic motility were investigated using intracellular recording from motoneurons and electrotonic recording from muscle nerves during motor activity generated by an isolated spinal cord preparation of 12- to 15-d-old chick embryos. DC-coupled recordings from sartorius (a flexor) and femorotibialis (an extensor) muscle nerves revealed that both sets of motoneurons were depolarized at the same time in each cycle even when the motoneurons fired out of phase. Sartorius motoneurons fired briefly on the rising phase of the depolarization and then stopped firing before discharging a second burst of spikes as the depolarization decayed. By contrast, femorotibialis motoneurons fired at the peak of their depolarization, which was coincident with the interruption in sartorius activity. Intracellular recordings from antidromically identified motoneurons confirmed that flexor and extensor motoneurons were depolarized at the same time during each cycle of activity. The discharge of femorotibialis motoneurons, and others presumed to be extensors, followed changes in membrane potential so that maximal firing occurred during peak depolarization. The relationship between discharge and membrane potential was different in sartorius motoneurons (and in others presumed to be flexors) because they fired briefly on the rising phase of the depolarization and then stopped firing during peak depolarization. In some of these cells firing resumed as the membrane potential decayed back to rest. Intracellular injection of depolarizing current into sartorius motoneurons during motor activity reversed the direction of the membrane potential change from depolarizing to hyperpolarizing during the pause in sartorius discharge. In addition, the discharge evoked by the depolarizing current was blocked during the reversed part of the synaptic potential revealing its inhibitory nature. The occurrence of the IPSP was accompanied by a large reduction in motoneuronal input impedance. Injection of depolarizing current steps into motoneurons produced steady firing with no evidence of a pause in discharge, indicating that the depolarization accompanying synaptic activity was not responsible for the pause in firing of flexor motoneurons. These results suggest that flexor and extensor motoneurons receive a similar depolarizing drive from a common set of excitatory premotor interneurons. The alternating pattern of flexor and extensor discharge is produced, in part, by the timing of a depolarizing IPSP coincident with extensor activity that silences flexor discharge.(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).

Jendrassik maneuver facilitates soleus H-reflex without change in average soleus motoneuron pool membrane potential

Facilitation of spinal reflex amplitude by remote muscle contraction, otherwise known as the Jendrassik maneuver (JM), was first shown over 100 years ago, yet the mechanism by which this facilitation operates remains undetermined. Earlier work has eliminated participation of the muscle spindle in JM-induced spinal reflex facilitation, leaving changes in postsynaptic (e.g., change in average soleus motoneuron membrane potential) and presynaptic (e.g., inhibition of presynaptic inhibition) mechanisms as viable candidates. We recorded background EMG in the soleus muscle during JM-induced soleus H-reflex facilitation in humans. The JM in this experiment consisted of wrist muscle contraction. Soleus background EMG was maintained by the subject at either a zero level (e.g., relaxed) or a specified moderate level prior to and during the JM. The JM increased H-reflex amplitude by comparable amounts in both situations, but had no effect on soleus background EMG. Given the well-known relationship between the average motoneuron pool membrane potential and background EMG, we conclude that JM facilitation of the soleus H-reflex is not caused by an increase in background excitatory input to the soleus motoneuron pool. Remaining candidates for mediation of JM induced H-reflex facilitation include change in stimulus-evoked afferent input at some point proximal to the muscle spindle, such as reduction in presynaptic inhibition, or a change in motoneuron input resistance.

Activation of type B gamma-aminobutyric acid receptors in the intact mammalian spinal cord mimics the effects of reduced presynaptic Ca2+ influx.

Intracellular recordings from mammalian spinal motoneurons in vivo show that the type B gamma-aminobutyric acid receptor agonist, L-(-)-baclofen, when administered systemically to pentobarbital-anesthetized or decerebrate unanesthetized cats decreases the amplitude of monosynaptic group Ia excitatory postsynaptic potentials (EPSPs), markedly increases tetanic and posttetanic potentiation, and reduces or abolishes synaptic depression during high-frequency synaptic activation and in the posttetanic period. These changes occur without detectable alteration in motoneuron input resistance, EPSP shape, or the invasion of action potentials into the intraspinal group Ia terminal arborizations. The baclofen-induced effects are qualitatively similar to those observed in more accessible synaptic systems when presynaptic Ca2+ influx and, concomitantly, transmitter release are reduced. Based on these and other recent findings regarding the mechanism of action of baclofen and the distribution of its receptors in the spinal cord, we suggest that L-(-)-baclofen modifies frequency modulation of Ia synaptic transmission by reducing presynaptic Ca2+ influx and the concomitant level of transmitter release from Ia afferent terminals. The drug appears to be a useful tool in studies of the ionic mechanisms that control the release of transmitter and its frequency modulation at inaccessible mammalian synapses.

Cholinergic modulation of the synaptic transmission in the frog spinal cord

It was found during experiments on isolated frog spinal cord involving extracellular recording from the dorsal roots (sucrose bridging) and intracellular recording from motoneurons by microelectrodes that 10 mM of the M-cholinomimetic arecoline produces motoneuronal depolarization which is matched by depolarizing electronic ventral root potentials and a rise in motoneuronal input resistance. Arecoline changes synaptic transmission by increasing the amplitude of postsynaptic potentials during intracellular recording and that of motoneuronal reflex discharges in the ventral roots but reduces the duration of dorsal root potentials. In the presence of arecoline, L-glutamate-induced motoneuronal response increases. Facilitation of synaptic transmission produced by arecoline in the spinal cord is bound up with cholinergic M2- activation, since it is suppressed by atropine but not by low concentrations of pirenzipine; it is also coupled with a reduction in adenylcyclase activity. When motoneuronal postsynaptic response has been suppressed, as in the case of surplus calcium or theophylline, arecoline produces an inhibitory effect on the amplitude of motoneuronal monosynaptic reflex discharges which is suppressed by pirenzipine at a concentration of 1×10−7 M. This would indicate the presence at the primary afferent terminals of presynaptic cholinergic M1 receptors which mediate its inhibition of impulses of transmitter release. This effect is independent of changes in cyclic nucleotide concentration.

Motoneuron input-resistance changes during fictive locomotion produced by stimulation of the mesencephalic locomotor region.

Input-resistance changes during fictive locomotion were monitored in a variety of extensor and flexor hindlimb alpha-motoneurons in precollicular, postmammillary decerebrate cats induced to "walk" by electrical stimulation of the mesencephalic locomotor region (MLR). Using intracellular recording techniques and injected hyperpolarizing current pulses, the changes in the motoneuron input resistance recorded at the motoneuron soma were examined during nonlocomoting control periods as well as during the depolarized and hyperpolarized phases of the membrane potential oscillations (locomotor drive potentials, or LDPs) of fictive locomotion. In 28 of the 52 motoneurons examined, no change in the input resistance between the control and locomotor periods was observed. The remainder of the cells displayed a decrease (less than 20%) in input resistance when fictive stepping commenced. Over 80% of all the motoneurons depolarized (mean depolarization 4 mV), whereas only one LG motoneuron hyperpolarized (2 mV) with the onset of stimulation of the MLR. The remaining motoneurons did not display such changes. In 43 out of 52 motoneurons examined, no significant change in the input resistance could be observed between the depolarized and hyperpolarized phases of the step cycle. A decrease in the input resistance during the depolarized phase of the LDP was observed in four LG motoneurons, whereas five other motoneurons (2 LG, 1 TA, 1 PB, and 1 ST) displayed an increased input resistance during the depolarized phase compared with the hyperpolarized phase of locomotion. The data are consistent with the presence of an excitatory synaptic input alternating with an inhibitory input to the motoneuron during the fictive step cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of axotomy on the distribution of passive electrical properties of cat motoneurones.

Previously obtained experimental results concerning the effect of axotomy on motoneurone passive electrical properties have been re-analysed. As shown earlier, axotomy causes an average increase of motoneurone input resistance, membrane time constant and after-hyperpolarization duration. The present analysis suggests that the increased input resistance is related to a higher specific membrane resistivity, a decreased cell size and an altered dendritic geometry. The results also suggest that the change takes place only in neurones projecting to fast-twitch muscle units and produces in them passive electrical properties normally exhibited only by motoneurones projecting to slow-twitch units. Based on the notion that axotomy causes a 'dedifferentiation' of motoneurone properties, the present results might be taken to indicate that undifferentiated motoneurones are slow in character. A possible scheme in which a post-natal differentiation of motoneurone properties may lead to muscle differentiation is discussed.

Voltage threshold and excitability among variously sized cat hindlimb motoneurons.

Intracellular recording has been performed to examine whether any differences in apparent initial-segment voltage threshold exist between types F and S cat triceps surae motoneurons. Voltage threshold was estimated using orthodromic action potentials initiated by large, monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation. No significant differences in voltage threshold could be detected between types F and S motoneurons. Further, voltage thresholds did not covary with motoneuron input resistance, afterhyperpolarization duration, or the twitch contraction time of functionally isolated muscle units. Significant positive correlations were observed between voltage threshold and the motoneuron resting potential. Utilizing a compartmental neuron model, a theoretical analysis has been performed that examines the influence of specific passive membrane properties on current threshold for action potentials initiated by large, monosynaptic EPSPs. This analysis indicates that total membrane capacitance will be the primary determinant of these thresholds. Further analysis of available data suggests that active membrane properties will play a minimal role in setting these thresholds. Since specific membrane capacitance is likely to be similar among cat motoneurons, it is concluded that only size or surface area-related current threshold differences will exist among these cells for activation with brief currents such as those underlying large EPSPs. For motoneurons thus activated, it is suggested that variations in the excitatory/inhibitory balance or density of synaptic input would be the major mechanisms for producing differential recruitment thresholds among the motoneuron population. Other available evidence is discussed that indicates that factors intrinsic to the motoneurons themselves will contribute to the setting of functional recruitment thresholds for activation with longer duration currents.