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Implanting electrical devices in the nervous system to treat neural diseases is becoming very common. The success of these brain-machine interfaces depends on the electrodes that come into contact with the neural tissue. Here we show that conventional tungsten and stainless steel wire electrodes can be coated with carbon nanotubes using electrochemical techniques under ambient conditions. The carbon nanotube coating enhanced both recording and electrical stimulation of neurons in culture, rats and monkeys by decreasing the electrode impedance and increasing charge transfer. Carbon nanotube-coated electrodes are expected to improve current electrophysiological techniques and to facilitate the development of long-lasting brain-machine interface devices.

Adult adipose contains stromal progenitor cells with neurogenic potential. However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult Stromal (ADAS) cells and whether terminal neuronal differentiation is required for their consideration as alternatives in cell replacement strategies to treat neurological disorders is largely unknown. We investigated whether in vitro neural induction of ADAS cells determined their ability to neuroprotect or restore function in a lesioned dopaminergic pathway. In vitro-expanded naïve or differentiated ADAS cells were autologously transplanted into substantia nigra 1 week after an intrastriatal 6-hydroxydopamine injection. Neurochemical and behavioral measures demonstrated neuroprotective effects of both ADAS grafts against 6-hydroxydopamine-induced dopaminergic neuron death, suggesting that pre-transplantation differentiation of the cells does not determine their ability to survive or neuroprotect in vivo. Therefore, we investigated whether equivalent protection by naïve and neurally-induced ADAS grafts resulted from robust in situ differentiation of both graft types into dopaminergic fates. Immunohistological analyses revealed that ADAS cells did not adopt dopaminergic cell fates in situ, consistent with the limited ability of these cells to undergo terminal differentiation into electrically active neurons in vitro. Moreover, re-exposure of neurally-differentiated ADAS cells to serum-containing medium in vitro confirmed ADAS cell phenotypic instability (plasticity). Lastly, given that gene expression analyses of in vitro-expanded ADAS cells revealed that both naïve and differentiated ADAS cells express potent dopaminergic survival factors, ADAS transplants may have exerted neuroprotective effects by production of trophic factors at the lesion site. ADAS cells may be ideal for ex vivo gene transfer therapies in Parkinson's disease treatment.

The mechanisms that trigger or contribute to loss of dopaminergic (DA) neurons in Parkinson's disease (PD) remain unclear and controversial. Elevated levels of tumor necrosis factor (TNF) in CSF and postmortem brains of PD patients and animal models of PD implicate this proinflammatory cytokine in the pathophysiology of the disease; but a role for TNF in mediating loss of DA neurons in PD has not been clearly demonstrated. Here, we report that neutralization of soluble TNF (solTNF) in vivo with the engineered dominant-negative TNF compound XENP345 (a PEGylated version of the TNF variant A145R/I97T) reduced by 50% the retrograde nigral degeneration induced by a striatal injection of the oxidative neurotoxin 6-hydroxydopamine (6-OHDA). XENP345 was neuroprotective only when infused into the nigra, not the striatum. XENP345/6-OHDA rats displayed attenuated amphetamine-induced rotational behavior, indicating preservation of striatal dopamine levels. Similar protective effects were observed with chronic in vivo coinfusion of XENP345 with bacterial lipopolysaccharide (LPS) into the substantia nigra, confirming a role for solTNF-dependent neuroinflammation in nigral degeneration. In embryonic rat midbrain neuron/glia cell cultures exposed to LPS, even delayed administration of XENP345 prevented selective degeneration of DA neurons despite sustained microglia activation and secretion of solTNF. XENP345 also attenuated 6-OHDA-induced DA neuron toxicity in vitro. Collectively, our data demonstrate a role for TNF in vitro and in vivo in two models of PD, and raise the possibility that delaying the progressive degeneration of the nigrostriatal pathway in humans is therapeutically feasible with agents capable of blocking solTNF in early stages of PD.

1. The aim of this study was to examine the extent of muscle-unit force modulation due to motoneuron firing-rate variation in type-identified motor units of the cat medial gastrocnemius (MG) muscle, and to investigate the contribution of muscle-unit force modulation to whole-muscle force regulation. The motoneuron discharge patterns recorded from 8 pairs of motor units during 12 smoothly graded muscle contractions evoked by stimulation of the mesencephalic locomotor region (MLR) were used to reactivate those units in isolation to estimate what their force profiles would have been like during the evoked whole-muscle contractions. 2. For most motor units, muscle-unit force modulation was similar to motoneuron firing-rate modulation, in that muscle-unit force increased over a limited range (120-600 g) of increasing whole-muscle tension and was then maintained at a near maximal (> 70%) output level as muscle force continued to rise. Most muscle units also decreased their force outputs over a slightly larger range of declining whole-muscle force before relaxing. This second finding was best explained by the counterclockwise hysteresis recorded in the motor units' frequency-tension (f-t) relationships. 3. In those instances when whole-muscle force fluctuated just above the recruitment threshold of a motor unit, a substantial percentage (10-25%) of the change in whole-muscle force could be accounted for by force modulation in that motor unit alone. This finding suggested that few motor units in the pool were simultaneously simultaneously undergoing force modulation. To evaluate this possibility, the extent of parallel muscle-unit force modulation within the 8 pairs of simultaneously active motor units was evaluated. As with parallel motoneuron firing-rate modulation, the extent of parallel muscle-unit force modulation was limited to unit pairs of the same physiological type and recruitment threshold. In several instances, pairs of motor units displayed parallel motoneuron firing-rate modulation but did not show parallel muscle-unit force modulation because of the nature of the motor units' f-t relationships. 4. The limited extent of parallel muscle-unit force modulation seen in these experiments implies that the major strategy for force modulation in the cat MG muscle, involving contractions estimated to reach 30-40% of maximum, may be motor-unit recruitment rather than motor-unit firing-rate variation with resulting force modulation. Given, however, that the majority of motor units are already recruited at these output levels (< 40%), it is proposed that motor-unit firing-rate variation with resulting force modulation may take over as the major muscle force modulating strategy at higher output levels.

1. The recruitment order of 64 pairs of motor units, comprising 21 type-identified units, was studied during centrally evoked muscle contractions of the cat medial gastrocnemius (MG) muscle in an unanesthetized, high decerebrate preparation. Motor units were functionally isolated within the MG nerve by intra-axonal (or intramyelin) penetration with conventional glass microelectrodes. 2. Graded stimulation of the mesencephalic locomotor region (MLR) was used to evoke smoothly graded contractions, which under favorable conditions was estimated to reach 40% of maximum tetanic tension of the MG muscle. With this method of activation, 100% of slow twitch (type S) units, 95% of fast twitch, fatigue-resistant (type FR) units, 86% of fast twitch, fatigue-intermediate (type FI) units, and 49% of fast twitch, fatigable (type FF) units studied were recruited. 3. Motoneuron size as estimated by axonal conduction velocity (CV) was correlated with muscle-unit size as estimated by maximum tetanic tension (Po). Although the correlation between these properties was significant among type S and FR units, no significant correlation was found for these properties among type FI and FF units. 4. Motor-unit recruitment was ordered by physiological type (S > F, 100% of pairs; S > FR > FI > FF, 93% of pairs). Although none of the motor-unit properties studied predicted recruitment order perfectly, motor-unit recruitment was found to proceed by increasing Po (89% of pairs), decreasing contraction time (79% of pairs), decreasing fatigue index (80% of pairs), and increasing CV (76% of pairs). These percentages were significantly different from random (i.e., 50%). Statistically, all four motor-unit properties were equivalent in predicting recruitment order. These results are similar to those reported by other investigators for motor-unit recruitment order evoked from other supraspinal centers, as well as from peripheral sites. 5. When, however, motor-unit recruitment within pairs of motor units containing two fast-twitch (type F) units was examined, Po was a significantly better predictor of recruitment order than CV (85% vs. 52% of pairs). One explanation for this observation is that the correlation between Po and CV is high among type S, type FR units, and possibly among the lower-tension type FF units, but not among the remaining higher-tension type FF units. 6. The reproducibility of recruitment order in multiple contractions was investigated in 16 motor-unit pairs. Recruitment order was found to be variable in only three motor-unit pairs, all of which contained units of similar physiological type and recruitment threshold. 7. Analysis of recruitment order by pair-wise testing confirms the general conclusion reached in human studies that the muscle force level at recruitment for a motor unit is highly correlated with its strength. As an additional confirmation, the whole-muscle force level at recruitment for 41 units was measured in a series of contractions in which the rate of rise of muscle tension was limited to rates < 1,000 g/s. For these contractions, a significant correlation was found between muscle tension at recruitment and motor-unit Po.

1. The aim of this study was to examine the nature of motoneuron firing-rate modulation in type-identified motor units during smoothly graded contractions of the cat medial gastrocnemius (MG) muscle evoked by stimulation of the mesencephalic locomotor region (MLR). Motoneuron discharge patterns, firing rates, and the extent of firing-rate modulation in individual units were studied, as was the extent of concomitant changes in firing rates within pairs of simultaneously active units. 2. In 21 pairs of simultaneously active motor units, studied during 41 evoked contractions, the motoneurons' discharge rates and patterns were measured by processing the cells' recorded action potentials through windowing devices and storing their timing in computer memory. Once recruited, most motoneurons increased their firing rates over a limited range of increasing muscle tension and then maintained a fairly constant firing rate as muscle force continued to rise. Most motoneurons also decreased their firing rates over a slightly larger, but still limited, range of declining muscle force before they were derecruited. Although this was the most common discharge pattern recorded, several other interesting patterns were also seen. 3. The mean firing rate for slow twitch (type S) motor units (27.8 imp/s, 5,092 activations) was found to be significantly different from the mean firing rate for fast twitch (type F) motor units (48.4 imp/s, 11,272 activations; Student's t-test, P < 0.001). There was no significant difference between the mean firing rates of fast twitch, fatigue-resistant (type FR) and fast twitch, fatigable (type FF) motor units. When the relationship between motoneuron firing rate and whole-muscle force was analyzed, it was noted that, in general, smaller, lower threshold motor units began firing at lower rates and reached lower peak firing rates than did larger, higher threshold motor units. These results confirm both earlier experimental observations and predictions made by other investigators on the basis of computer simulations of the cat MG motor pool, but are in contrast to motor-unit discharge behavior recorded in some human motor-unit studies. 4. The extent of concomitant changes in firing rate within pairs of simultaneously active motor units was examined to estimate the extent of simultaneous motoneuron firing-rate modulation across the motoneuron pool. A smoothed (5 point sliding average) version of the two motoneurons' instantaneous firing rates was plotted against each other, and the slope and statistical significance of the relationship was determined. In 16 motor-unit pairs, the slope of the motoneurons' firing-rate relationship was significantly distinct from 0. Parallel firing-rate modulation (< 10-fold difference in firing rate change reflected by a slope of > 0.1) was noted only in pairs containing motor units of like physiological type and then only if they were of similar recruitment threshold. 5. Other investigators have demonstrated that changes in a motoneuron's "steady-state" firing rate predictably reflect changes in the amount of effective synaptic current that cell is receiving. The finding in the present study of limited parallel firing-rate modulation between simultaneously active motoneurons would suggest that changes in the synaptic drive to the various motoneurons of the pool is unevenly distributed. This finding, in addition to the findings of orderly motor-unit recruitment and the relationship between motor-unit recruitment threshold and motoneuron firing rate, cannot be adequately accommodated for by the existing models of the synaptic organization in motoneuron pools. Therefore a new model of the synaptic organization within the motoneuron pool has been proposed.

The loss of force production during sustained activity presents the CNS a unique control problem. Different tasks stress the neuromuscular system at different sites and times, and involve different cellular mechanisms. The functional organization of muscles and their motor units has evolved to avoid fatigue processes that impair motor performance. The purpose of this brief review is to examine the fatigue properties of type-identified motor units and to speculate what these properties reveal about the organization and control of muscle.

1. The endurance of slow-twitch motor units from the soleus (SOL) and medial gastrocnemius (MG) muscles of the cat were tested by determining the length of time (endurance time, Et) that a unit could maintain its tension output at 85% of maximum. Motor-unit tension was clamped at the target level by altering the stimulation rate of a unit's motor axon through computer feedback control. Tested in this way, units of both muscles displayed a wide range of Ets, approximately 40- to 50-fold. 2. Electromyographic (EMG) waveforms of motor units subjected to force-clamp contractions were analyzed to access whether any activity-dependent changes in their waveform shape might predict Et. Three measurements of waveform shape were determined: baseline-to-baseline duration, peak-to-peak amplitude, and area. Typically, amplitude decreased and duration increased as a contraction proceeded, whereas area remained fairly constant. Because changes in each measure were very similar for units of widely different Ets, it was concluded that neuromuscular junction failure and changes in the excitability of the sarcolemma (excluding the t-tubule system) play a minor role in determining Et. 3. Et was highly correlated with the mean stimulation rate (Et/number of stimuli) used during the force-clamp contractions. Mean rate was seen to progressively decrease with increasing Et. This correlation could not be explained by measures of isometric contractile speed or relaxation (e.g., twitch contraction time or half-relaxation time) measured before the force-clamp contractions. Both contraction time and half-relaxation time were found to be unrelated to both Et and the rate used to stimulate the unit during the force-clamp contraction. 4. Among type S units of SOL and MG, maximum tetanic tension and Et were not related. A significant relation (r = -0.49) was found between axonal conduction velocity and Et for SOL units (n = 38). In addition, a significant correlation (r = 0.47) was found between conduction velocity and tetanic tension for SOL units. Perhaps because of the small sample of type S units from MG (n = 10), conduction velocity was found not be related to either Et or tetanic tension. 5. Others have shown that a motor unit's maximum tetanic tension and axonal conduction velocity are correlated with its order of recruitment among motoneurons innervating a muscle. Recent work has further shown that among type F units the order in which a motoneuron is recruited is highly correlated with the fatigue resistance of its muscle unit.(ABSTRACT TRUNCATED AT 400 WORDS)

1. The aim of this study was to describe the control of tension by rate modulation of single motor units in reinnervated muscle. 2. Single fast-twitch motor units were isolated from medial gastrocnemius (MG) muscles in two groups of anesthetized adult cats: one in which the MG nerve was left untreated and another in which that nerve was sectioned and immediately sutured together 10-33 mo before study. Together with conventional measures of isometric contractile properties, units were tested with the use of computer-controlled feedback regulation of stimulation rate to maintain tension during continuous isometric contraction at a constant submaximal level [25% of maximal tension (Pmax)]. 3. For motor units from both groups, stimulation rate began to decline after target tension was attained and then settled at lower values for variable durations before rapidly increasing, usually within the last 5% of the contraction's duration, until reaching the experimentally selected limit of 100 pulses/s (pps). 4. Measures of the declining phase in stimulation rate occurring at the beginning of sustained contraction were not significantly different in comparison of untreated versus reinnervated muscles. These measures included 1) the magnitude of the decrease in rate, 2) the minimum rate attained, and 3) the time taken to reach minimum stimulation rate expressed as a fraction of endurance time (Et, total duration of the sustained contraction). 5. Most fast-twitch units from reinnervated muscles fell within normal limits for both endurance time and the number of stimuli applied over that period.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence is presented for the existence of a localization of monosynaptic Ia excitatory post-synaptic potentials (e.p.s.p.s) in the motor nucleus of a cat hind limb muscle. Intracellular recordings from biceps femoris motoneurones were made in anaesthetized low spinal cats of the effects of stimuli to the nerve branches supplying the anterior, middle, and posterior portions of the biceps femoris muscle. Recordings were also made during stimulation of nerves to semimembranosus and semitendinosus in order to provide a means of categorizing middle biceps cells as 'extensors' (middle biceps-extensor; i.e. like anterior biceps cells) or as 'flexors' (middle biceps-flexor; like posterior biceps). Homonymous nerve-branch (i.e. from anterior, middle or posterior biceps) monosynaptic Ia e.p.s.p.s were compared within unifunctional (flexor or extensor) groups of motoneurones. In three of four comparisons (anterior biceps nerve branch onto anterior and middle biceps-extensor cells, middle biceps onto middle biceps-flexor and posterior biceps, posterior biceps onto middle biceps-flexor and posterior biceps) the anterior, middle and posterior biceps nerve branches contributed larger e.p.s.p.s to their 'own' motoneurones than to motoneurones supplying other 'compartments' of the muscle. In the fourth case, middle biceps's input appeared to have similar effects onto anterior biceps and middle biceps-extensor cells. A normalization was performed to eliminate the possibility that the differences in e.p.s.p. sizes were due to differences in cell type within the four cell groupings (i.e. differences in the number of cells supplying FF, F(int.), FR and S muscle units). This normalization confirmed that the localization in the first three comparisons was not a consequence of differences in motoneurone type and, in addition, suggested that middle biceps may indeed have greater effects on middle biceps-extensor than anterior biceps cells. In addition to the asymmetrical effects of anterior and middle biceps nerve branches onto anterior biceps and middle biceps-extensor motoneurones, it was shown that while semitendinosus and posterior biceps contributed larger e.p.s.p.s to middle biceps-flexor than to middle biceps-extensor cells, the anterior biceps nerve branch and semimembranosus nerve contributed equally to the two middle biceps groups. Analysis of cell location in the spinal cord and rostro-caudal differences in group I volley sizes gave evidence of a topographic organization of the biceps femoris motor nucleus which could contribute to the observed localization. However, localization was also evident when comparing e.p.s.p. amplitudes in pairs of neighbouring cells of different category, indicating a role for neuronal recognition factors.

Intrafusal fibres from the rat soleus were investigated for representative histochemical profiles in sedentary animals and animals chronically exercised for 17 weeks on a treadmill. The pattern of myosin adenosine triphosphatase (ATPase) activity in the polar region revealed three intrafusal fibre types: (1) myosin ATPase-dark (MD) fibres, alkali- and acid-stabile; (2) myosin ATPase-light (ML) fibres, alkali- and acid-labile; and (3) myosin ATPase-reversible (MR) fibres, alkali-stabile and acid-labile. The three fibre types were correlated with the level of reduced NADH diaphorase activity, with MR, ML and MD fibres staining dark, moderate and light, respectively. In the equatorial region the morphological features of representative ML and MD fibres revealed that they were nuclear bag fibres, while representative MR fibres were identified as nuclear chain fibres. The MR fibres in the exercised animals had higher levels of myosin ATPase alkaline stability and acid lability than MR fibres in the sedentary animals, suggesting the MR fibre profiles are selectively influenced by chronic exercise. The mean cross-sectional area of MR fibres from the exercised animals was significantly less than the MR fibres from the sedentary animals. In contrast to the effect of endurance training on NADH diaphorase activity in extrafusal muscle fibres, there was evidence of less activity in the MD fibres of the exercised animals.

The effect of evoked muscle tension, active muscle mass, and fiber-type composition on the pressor reflex evoked by muscular contraction was examined in decerebrate and anesthetized cats. Muscular contraction was induced by stimulating the L7 and S1 ventral roots with 0.1-ms duration pulses three times motor threshold at various frequencies. The experiments were designed to isolate the variable under study as much as possible and included the use of selectively denervated preparations to limit contractions to specific muscles. It was found that altering the evoked tension by varying the resting muscle length had commensurate effects on the pressor reflex (greater evoked tension caused a larger reflex). In addition it was found that changing the amount of active muscle mass caused similar changes in the reflex (the smaller the muscle mass, the smaller the reflex). Finally, it was found that contrary to other accounts, pressor reflexes could be evoked by activation of the slow-twitch muscle soleus, composed exclusively of red (type I) fibers.

Phosphorylation of the P-light chain of myosin from skeletal muscle by myosin light chain kinase is dependent upon calmodulin and Ca2+. Investigations were performed to determine if the rapid Ca2+ transients that occur during low frequency repetitive stimulation are sufficient to activate myosin light chain kinase with significant P-light chain phosphorylation. In addition, P-light chain phosphorylation was correlated with potentiation of isomeric twitch tension (staircase phenomenon). Stimulation of rat gastrocnemius muscle at 5 Hz in situ results in a time-dependent phosphorylation of the P-light chain of myosin. Initially, there was a rapid rate of phosphorylation within the first 10 muscle twitches (0.19 to 0.40 mol of phosphate/mol of P-light chain) followed by a slower rate of phosphorylation. These data indicate that myosin light chain kinase can be activated during repetitive stimulation at a low frequency in the range that occurs in vivo, despite the fact that the muscle is in the relaxed state during most of the period between each stimulation. Potentiation of isometric twitch tension was found to be temporally correlated to light chain phosphorylation at 5 Hz. It is postulated that the transient changes in intracellular Ca2+ concentration associated with low frequency stimulation are sufficient to activate myosin light chain kinase, and, furthermore, the magnitude of the potentiation of isometric twitch tension may be related to the extent of phosphorylation of myosin during a stimulus train.

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)

Single muscle spindle afferent and motor unit EMG spike trains have been recorded simultaneously during periods of spontaneous motor activity in triceps surae muscles of decerebrate cats. The approximate time course and magnitude of the motor unit contractions were extracted from the whole muscle force record by spike-triggered averaging, and the functional interactions between motor unit contractions and spindle discharge were assessed by cross-correlating their respective spike trains. We have found that both spindle group Ia and II afferents are responsive to the contractions of single motor units in the presence of spontaneous motor activity, being strongly coupled to the activity of some motor units and indifferent to the contractions of others. Moreover, the cross-correlation analysis revealed modulation of a single motor unit's discharge pattern by the input of a single Ia afferent.

Discharge properties of cat cervical motoneurons innervating distal forelimb muscles were investigated by intracellular current injection. Values for rheobase current, afterhyperpolarization duration and several measures of repetitive discharge characteristics were in most respects similar to those obtained for hindlimb motoneurons.

1. Through computer feedback control, muscle-unit tension was maintained by altering the stimulation rate of a functionally isolated motor axon. The required stimulation patterns and fatigue properties of motor units from the flexor carpi radialis (FCR), flexor digitorum longus (FDL), and medial gastrocnemius (MG) muscles of the cat were studied when tension was maintained or "clamped" at a constant average level (25% of maximum tetanic tension). 2. In each muscle, two distinct stimulation patterns were observed during constant-tension contractions, one associated with slow-twitch units and the other with fast-twitch units. Once target tension was reached, slow-twitch units required fairly constant rates in order to maintain a constant force, whereas fast-twitch units displayed a marked decline in rate during the early phases of the contraction, averaging between 42 and 54% for the three muscles. The decline in rate most likely represented potentiation of the contractile response and slowing of contractile speed. In general, slow-twitch units responded with lower mean rates (approximately 14 pps less), averaged over the course of the contraction, than fast-twitch units. 3. For fast-twitch units of each muscle, resistance to fatigue varied continuously and over a wide range. The duration that tension could be maintained at 25% of maximum, defined as endurance time, ranged between 16 and 2063 s. No categorization of fast-twitch units into groups could be made on the basis of endurance time. Of the 5 slow-twitch units followed beyond 2700 s, only one failed to maintain tension during the observation period. 4. For hindlimb fast-twitch units, endurance was independent of the stimulation rate needed to maintain tension during the contraction. By contrast, there was a significant tendency for an inverse relation between endurance time and mean stimulation rate for FCR fast-twitch units. 5. Recovery of maximum tension was evaluated at 30 s, 1 min, 2 min, and 5 min following a constant-tension contraction. After a 5-min rest, fast-twitch units were able to produce an average of 80-85% of their maximum tetanic tension. By using the median endurance time (approximately 100 s) to divide the fast-twitch population into "low" and "high" endurance groups, recovery of tension was found not to be uniform among the two groups. High endurance units were able to recover a greater percentage of their original maximum tetanic tension. No difference was found between force recovery for low and high endurance units at 30 s.(ABSTRACT TRUNCATED AT 400 WORDS)

Motor units in the cat flexor carpi radialis (FCR) muscle, one of two primary wrist flexors, were classified into three groups: slow twitch, fatigue resistant (S); fast twitch, fatigue resistant (FR); and fast twitch, fatigue sensitive (FF). Classification was based on 1) the ratio of the tension-time area produced by a train of stimuli delivered at 40 pps and the maximum tension-time area (A40/Amax), and 2) the cumulative force index (CFI), calculated from a series of trains (40 pps) delivered intermittently for a period of 4 min. The CFI is defined as the ratio between the force accumulated in the last 2 min of stimulation to the first 2 min of stimulation. Motor units with values for A40/Amax greater than 0.50 were classified as type S units, and less than 0.50 as type F. A40/Amax is essentially equivalent to the "sag" profile of an unfused tetanus in its ability to separate units into "slow" and "fast" contracting units. In general, units with area ratios less than 0.50 had twitch contraction times less than 25 ms, whereas units with area ratios greater than 0.50 had contraction times greater than 25 ms. Separation of type F units into two groups was based on the CFI, with ratios less than or equal to 0.75 corresponding to type FF units and greater than 0.75 as type FR units. Type S units also had CFIs greater than 0.75. Based on this classification scheme, 40.4% of FCR motor units were type S, 37.5% type FR, and 22.1% type FF. The a priori assumption of three motor-unit types based on the distributions of A40/Amax and CFI was evaluated by cluster analysis. The analysis supported the assumption of three primary groups of motor units. Furthermore, when cluster formation proceeded to the point where only three clusters remained in the analysis, each of these clusters consisted exclusively of one type of unit (i.e., S, FR, or FF). The validity of the classification scheme was further tested by stepwise discriminant analysis. Units classified as types S, FR, and FF were predicted to be classified with 100% accuracy. All units had a high probability (a posteriori) of having group membership in their originally classified group (P greater than 0.99 for 129 units; P greater than 0.90 for 7 units). The duration of potentiated twitch contractions for type FR and FF units was found to be less than reported for most populations of hindlimb units.(ABSTRACT TRUNCATED AT 400 WORDS)

The static discharge characteristics of deefferented Ia and II spindle afferents in the cat medial gastrocnemius muscle have been compared with respect to incidence and firing rate of spontaneously firing units, length threshold of nonspontaneous units, linearity of the response to stretch, and position sensitivity. Measurements of the stretch response were taken 20s after each step increase in length so as to obtain the nearly fully adapted rate. Under this condition the frequency-length relationship was quite linear, especially for group II units. The mean position sensitivity of group II fibers exceeded that of Ia fibers in the ratio of 1.5: 1.0. The incidence of spontaneously discharging units was about 20% for both types of unit. The relationships between some of these measures and axonal conduction rate were examined. No correlation of position sensitivity with axonal conduction velocity was detected for either afferent type, but the length thresholds of the group II afferents showed a significant trend for slower conducting, that is, smaller fibers to be less sensitive. There was some indication of a direct relationship between conduction velocity and length threshold for Ia fibers. The contradiction to the "size principle" and mechanisms contributing to the static discharge behavior of the spindle are discussed.

Single motor units of the flexor carpi radialis (FCR) muscle were activated with a series of constant-rate stimulus trains to study the relation between the frequency of activation and isometric tension development (F-T relation). The tension produced by each stimulus train was expressed as a percentage of the maximum tension-time area (Amax) found for a given unit. Between 25 and 75% Amax a clear separation was seen in the rates needed to produce the same relative tension for the F-T curves of slow-twitch (type S) and fast-twitch (type F) units. Over the steepest portion of the F-T curve (25-50% Amax), where tension output was most sensitive to changes in activation rate, type F units required substantially higher stimulation rates (30 pps) to achieve the same relative tension output as type S units. Furthermore, the frequency range that corresponded to the steep portion of the curve was 2.3 times greater for type F units. For both type S and F units, twitch duration was deemed to be an important determinant of the F-T curve, as has been shown previously. A direct continuous relation was seen between the integrated twitch time (ITT) and the stimulus interval needed to produce 50% Amax (r = 0.94, P less than 0.001). Thus, units that had relatively brief twitches required higher activation rates to achieve the same relative percentage of Amax. Comparison of F-T curves from FCR with those derived by other investigators for cat hindlimb units (medial gastrocnemius and peroneus longus) revealed that significant differences in activation rates were needed to produce the same percentage of Amax throughout the midrange of the F-T curve. At 50% Amax, type F units in FCR required activation rates approximately 20 pps higher than type F units in the hindlimb. Type S units in FCR required only slightly higher rates (approximately equal to 5 pps). Based on a number of well-founded assumptions, F-T curves derived from FCR units were used to estimate the potential contribution of rate coding to total muscle tension by type S and F units. This analysis leads to the conclusion that rate modulation is a potentially important factor in the gradation of tension for the FCR muscle.

1. The relationships between maximum tetanic tension (P0), endurance time, and axonal conduction velocity (CV) were investigated in fast-twitch motor units of the cat flexor carpi radialis (FCR) and medial gastrocnemius (MG) muscles, and in one flexor digitorum longus (FDL) muscle. Endurance time was the length of time that a unit could maintain 25% of its maximum tetanic tension during a sustained contraction. Motor-unit tension was "clamped" at 25% of maximum by altering the stimulation rate of a unit's motor axon through computer feedback control. 2. In individual experiments, including the one investigated FDL muscle, an inverse relation was consistently found between maximum tension and endurance time. Pooled data from the FCR and MG muscles also resulted in significant correlations between maximum tetanic tension and endurance time. 3. Following the force-clamp contraction, some motor units were subjected to the standard fatigue test of Burke and colleagues (6). Motor units were classified as type FR (fast twitch, fatigue resistant) or type FF* (fast twitch, fast fatiguing after the force-clamp contraction). For both type FR and FF* units, maximum tetanic tension and endurance time were found to be inversely related. However, no correlation was found between maximum tetanic tension and fatigue index for type FR units. Only when all type F (FR + FF*) units were considered as a population was there a significant correlation between these two properties. 4. Other investigators have shown that maximum tetanic tension and axonal conduction velocity are highly correlated with the recruitment order of motoneurons (e.g., Refs. 2, 26). Endurance time was found to be more tightly coupled with contraction strength than with conduction velocity. In 12 of 14 experiments, significant Spearman rank correlation coefficients were found between endurance time and tension, whereas significant correlations were found in only 3 of 14 experiments for endurance time and conduction velocity. 5. Pairs of motor units isolated from the same muscle were formed to see if the unit with the smaller tension had the slower conduction velocity and the longer endurance time. Across all muscles, the probability that the unit with the smallest tension had the greatest endurance time was 0.91 (441 of 487 pairs). By contrast, the probability that the least forceful unit of the pair had the slowest conduction velocity was 0.61. 6. In four experiments, pairs of type-identified units were examined. Among FR-FR pairs, the least forceful unit had the greatest endurance time in 88% of 43 pairs. For FF*-FF* pairs, the percentage was somewhat lower, 72% of 29 pairs.(ABSTRACT TRUNCATED AT 400 WORDS)

Pressor reflexes evoked by muscle contraction following stimulation of the cut distal portions of the L7 and S1 ventral roots were studied in decerebrate unanesthetized cats. Reflex responses evoked by this simulated exercise persisted after lesions were made in the dorsolateral sulcus region of the T13-L1 spinal cord, indicating that this area is not essential for mediation of these reflexes. Additional evidence suggested that the pathway responsible for the exercise pressor reflex located in the surviving spinal cord is most likely bilateral.

Intracellular recordings form biceps femoris (BF) motoneurons were made in anesthetized low spinal cats during periods of electrical stimulation of the nerve branches supplying the anterior, middle and posterior portions of the BF muscle and the nerves to semimembranosus and semitendinosus. Measurements were made of each cell's composite intrahomonymous and heteronymous monosynaptic Ia-EPSP responses to stimulation of the test nerves (branches). We have found evidence for an intramuscular localization of these monosynaptic Ia reflex effects not only when comparing responses between the two functional components of the BF muscle as is well established [6] but, in addition, when comparing responses between different parts of each functional (hip extensor and knee flexor) component as well. It is argued that both somatotopic and neuronal recognition factors may contribute to the localization of these monosynaptic reflex effects.

Estimates were made of the changing volumes of discharge arising from the total populations of Ia and II spindle afferent fibers in the cat's deefferented medial gastrocnemius as the muscle was extended stepwise over its excursion range. The estimates were based on values reported elsewhere for (i) the incidence of active units and (ii) their rates of discharge at static muscle lengths normalized against the excursion range of the particular muscle, together with (iii) the numbers of Ia and II afferent fibers in the medial gastrocnemius as derived from a critical review of published information. Curves representing the total discharge of the two afferent types are similar and show three phases: an initial level of spontaneous activity, a somewhat curvilinear rise associated with early recruitment of units during stretch, and rectilinear increase after full recruitment. There was no appearance of saturation. Completion of recruitment of both types of units occurred about halfway in the extension range of the passive muscle. Over most of the excursion range, inflow from the group II population was about one-third greater than that from the Ia units.

Evidence is presented for a lack of localization of monosynaptic Ia excitatory post-synaptic potentials (e.p.s.p.s) in the motor nucleus supplying the atypical cat hind limb muscle semitendinosus, which has anatomically distinct in-series compartments. Recordings were made from dorsal root filaments containing functionally isolated Ia, spindle group II and Ib axons from the proximal and distal compartments of semitendinosus. Twitch of either of these in-series compartments resulted in accelerated discharge of Ia and spindle group II fibres in the other compartment. Ib fibres of either compartment showed an in-series response to twitch of a single compartment which was weaker than twitch of the whole muscle, a finding which was consistent with the diminished force produced by twitch of either compartment alone. In addition, intracellular recordings were made from semitendinosus motoneurones in anaesthetized low-spinal cats during electrical stimulation of the nerve branches to proximal semitendinosus and distal semitendinosus. Comparison of proximal semitendinosus and distal semitendinosus motoneurones failed to reveal any difference between the two cell groups with respect to the average Ia e.p.s.p. amplitude produced by either the proximal or distal semitendinosus nerve branch. However, e.p.s.p.s due to stimulation of distal semitendinosus were approximately 65% larger, on average, than those due to stimulation of proximal semitendinosus in either motoneurone group. Analysis of cell location along the rostro-caudal axis of the spinal cord indicated that the proximal and distal semitendinosus cell groups are largely co-extensive. Recordings of volleys in the proximal and distal semitendinosus nerve branches in response to stimulation of the L6, L7 and S1 dorsal roots showed that group I afferents from the proximal semitendinosus compartment tend to have a more rostral entry point to the spinal cord than do distal semitendinosus afferents. E.p.s.p. amplitude in either cell group due to stimulation of either nerve branch showed little dependence on cell location in the spinal cord. The results are discussed with respect to the relation between muscle function and the distribution of monosynaptic Ia connexions.

The pressor reflex evoked by muscular contraction (exercise pressor reflex) is one important model of cardiovascular adjustments during static exercise. The central nervous system (CNS) structures mediating this reflex have remained largely obscure. Therefore, we examined the contribution of selected levels of the neuraxis in mediating the pressor reflex evoked by muscular contraction from stimulation of ventral roots. Decerebrate cats exhibited larger pressor reflexes than those found in intact alpha-chloralose-anesthetized cats, a difference more apparent at low (5 Hz or repeated twitch) rather than at high (50 Hz or tetanic) stimulus frequencies. Although a depressor response to 5-Hz stimulation was observed in the intact anesthetized cats, it appeared to be primarily due to anesthetic level, since a depressor response was not observed in decerebrate animals (nonanesthetized). Cerebellectomy produced no changes in the reflexes of the decerebrate animal. Further transection of the neuraxis (caudal to the midcollicular level) attenuated the exercise pressor reflex. The spinal cat demonstrated slight evidence of exercise pressor reflex activity. These results provide clarification as to representation of this pressor reflex within the CNS and establish the reflex's characteristics at several levels of neuraxis integration.

Cell groups of the caudal brainstem were labeled with 2-[14C]deoxyglucose during the pressor response evoked by contraction of hindlimb muscles (exercise pressor reflex). The nuclear groups which were labeled in excess of control levels included: the lateral reticular nucleus, the inferior olive (medial accessory olive), and the lateral tegmental field (adjacent to the lateral reticular nucleus).

Significant differences in the properties of myosin light chain phosphorylation in skeletal and smooth muscles may be important in considering the role of myosin phosphorylation in contraction. Repetitive, low-frequency stimulation of fast-twitch skeletal muscle resulted in phosphorylation of myosin light chain. Some of the factors leading to phosphorylation under these conditions include 1) partial activation of myosin light chain kinase with each stimulus, 2) a slow rate (t1/2 = 1 s) of inactivation of the kinase activity, and 3) a very slow rate of dephosphorylation by myosin light chain phosphatase. Myosin light chain phosphorylation was correlated with potentiation of isometric twitch tension in posttetanic potentiation and staircase responses. Stimulation of contraction in bovine tracheal smooth muscle by the cholinergic agonist carbachol was correlated with phosphorylation of the myosin light chain. The initial rate and maximum extent of phosphorylation during the first minute of stimulation was dependent on the concentration of carbachol. Phosphate incorporation into light chain declined after 1 min whereas isometric tension was maintained. beta-Adrenergic inhibition of tension development was accompanied by a decrease in the rate and extent of phosphorylatable myosin light chain phosphorylation but was not associated with reduced affinity of myosin light chain kinase for calcium-calmodulin.