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World population is forecast to grow from 7 to 9 billion by 2050, 1 in 6 is already hungry and food production must increase by 70-100% if it is to feed this growing population. No single solution will solve this problem but recent developments in the genetic technologies of plant breeding can help to increase agricultural efficiencies and save people from hunger in a sustainable manner, particularly in African nations where the need is greatest. These advances can rapidly incorporate new traits and tailor existing crops to meet new requirements and also greatly reduce the time and costs taken to improve local crop varieties. This book provides a collected, reliable, succinct review which deals expressly with the successful implementation of the new plant genetic sciences in emerging economies in the context of the interrelated key regulatory, social, ethical, political and trade matters.

1. The triceps surae (TS) stretch reflex was measured in decerebrate cats during crossed extensor stimulation and after spinalization during rhythmic locomotor activity induced by clonidine and manual perineal stimulation. The TS force in response to sinusoidal stretch was measured at a given contraction level before and after deafferentation, and the 'reflex force' was computed by subtracting these two responses. Reflex 'gain' was computed as the ratio of the reflex and deafferented force responses (a unitless estimate of the open loop feedback gain). 2. Prior to locomotion the spontaneous muscle activity was low (less than 15% of maximum), but the reflex gain was relatively high (close to 1.0 with a 5 Hz stretch). When locomotion commenced the reflex gain was markedly lowered when measured at the same contraction level as before locomotion (25% of the gain prior to locomotion). At higher contraction levels the reflex gain was not significantly increased. The reflex force and EMG responses to stretch increased with the contraction level, but their effect on the total reflex gain was cancelled by an associated increase in the intrinsic muscle stiffness. 3. In the decerebrate cat, during weak tonic contractions (spontaneous), the reflex gain was high and comparable with the gain in the resting spinal cat. However, with increased tonic contractions produced by crossed extensor stimulation the reflex gain dropped. At higher contraction levels the gain was not significantly different from the gain during spinal locomotion. 4. When the frequency of stretch was increased from 3 to 20 Hz, EMG responses to stretch increased, but the reflex force decreased, since a more fused contraction developed with the more frequent reflex activations. Overall, the reflex gain decreased with frequency in both spinal and decerebrate cats. The phase lag of the reflex force, relative to the intrinsic muscle force, increased with increasing frequency, due to reflex delays, with a 180 deg lag occurring between 12 and 18 Hz (tremor frequencies). The mean gain was significantly lower and the phase lag was significantly greater during locomotion than during tonic crossed extensor contractions, suggesting different reflex mechanisms. 5. In conclusion, during locomotion in spinal cats afferent feedback from low frequency ankle movements, similar to those occurring during the normal step cycle, reflexly produces a small but significant fraction of the extensor force (about a quarter of the stretch-related force modulation). This fraction is remarkably constant at the different contraction levels of the step cycle. Afferent feedback during higher frequency movement is less effective, minimizing the chance of instability and tremor. In contrast during tonic contractions afferent feedback produces half of the total muscle force during perturbations, clearly contributing to the maintenance of posture.

1. In order to study fusimotor control in reduced preparations, soleus muscle spindle afferents were recorded in premammillary decerebrate cats (n = 15) during crossed extensor reflexes and, after spinalization, during locomotion produced by either clonidine or L-beta-3,4-dihydroxyphenylalanine (L-DOPA). The soleus muscle was oscillated sinusoidally (0.25 mm, 4 Hz) and the afferent mean firing rate and modulation were calculated. An increase in firing rate was assumed to arise from activity in dynamic gamma-motoneurones (dynamic gamma-drive) when associated with an increase in modulation to stretching, and in static gamma-motoneurones (static gamma-drive) when modulation decreased. 2. At rest in all preparations the firing rate and modulation in primary muscle spindle afferents were generally much higher than after de-efferentation (ventral root section), suggesting a predominant dynamic gamma-drive. Clonidine decreased and even eliminated this presumed resting gamma-drive in many afferents, both in the decerebrate (7 of 8) and the spinal (6 of 18) state. This effect on gamma-drive may account, at least in part, for its suppressive effect on spasticity in humans. 3. When locomotion commenced in clonidine-treated spinal cats, primary afferents generally fired with much higher mean rates (+121%) and lower sensitivities (-32%), suggesting a large increase in static gamma-drive (possibly accompanied by a small decrease in dynamic gamma-drive). These high rates were usually maintained tonically throughout the step cycle. However, a third of the afferents were silenced during locomotor contractions, and de-efferentation had no significant effect on their firing rates. Thus, for some spindles alpha-activity can occur without significant gamma-drive. 4. During locomotion in L-DOPA-treated spinal cats the inferred static gamma-drive only occurred phasically, coactivated with the EMG, though it could precede the EMG by 100-500 ms. In the flexion phase both the afferent rate and modulation were lower than before locomotion, suggesting a lack of effective gamma-drive. 5. Crossed extensor reflexes in decerebrate cats also produced a substantial increase in primary afferent firing rate (+187%) and decrease in sensitivity (-37%), again suggesting increased static gamma-drive (n = 18). This gamma-drive was largely independent of EMG activity and often occurred without alpha-activity. The mean firing rate of secondary muscle spindle afferents increased significantly during locomotion (with L-DOPA) and crossed extensor reflexes, again indicating increased static gamma-drive. Clonidine reduced or eliminated the gamma-drive in seven of eight afferents during crossed extensor reflexes. 6. In conclusion, although there are some common features, such as a predominant static gamma-drive in all walking preparations, the pattern of static and dynamic gamma-drive is not closely linked to alpha-activity under the conditions studied. As well as gamma-drive without alpha-activity, we have shown for the first time that alpha-motoneurones can be activated without significant gamma-drive to many spindles during behavioural tasks.

In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we sought evidence for a similar role of constitutive monoamine receptor activity in the development of spasticity in human spinal cord injury. In chronically injured participants with partially preserved sensory and motor function, the serotonin reuptake inhibitor citalopram facilitated long-lasting reflex responses (spasms) previously shown to be mediated by CaPICs, suggesting that in incomplete spinal cord injury, functional descending sources of monoamines are present to activate monoamine receptors below the lesion. However, in participants with motor or motor/sensory complete injuries, the inverse agonist cyproheptadine, which blocks both ligand and constitutive 5-HT2/α1 receptor activity, decreased long-lasting reflexes, whereas the neutral antagonist chlorpromazine, which only blocks ligand activation of these receptors, had no effect. When tested in noninjured control participants having functional descending sources of monoamines, chlorpromazine was effective in reducing CaPIC-mediated motor unit activity. On the basis of these combined results, it appears that in severe spinal cord injury, facilitation of persistent inward currents and muscle spasms is mainly mediated by the activation of constitutive 5-HT2 and α1 receptor activity. Drugs that more selectively block these constitutively active monoamine receptors may provide better oral control of spasticity, especially in motor complete spinal cord injury where reducing motoneuron excitability is the primary goal.

Neurons of the dorsal spinocerebellar tracts (DSCT) have been described to be rhythmically active during walking on a treadmill in decerebrate cats, but this activity ceased following deafferentation of the hindlimb. This observation supported the hypothesis that DSCT neurons primarily relay the activity of hindlimb afferents during locomotion, but lack input from the spinal central pattern generator. The ventral spinocerebellar tract (VSCT) neurons, on the other hand, were found to be active during actual locomotion (on a treadmill) even after deafferentation, as well as during fictive locomotion (without phasic afferent feedback). In this study, we compared the activity of DSCT and VSCT neurons during fictive rhythmic motor behaviors. We used decerebrate cat preparations in which fictive motor tasks can be evoked while the animal is paralyzed and there is no rhythmic sensory input from hindlimb nerves. Spinocerebellar tract cells with cell bodies located in the lumbar segments were identified by electrophysiological techniques and examined by extra- and intracellular microelectrode recordings. During fictive locomotion, 57/81 DSCT and 30/30 VSCT neurons showed phasic, cycle-related activity. During fictive scratch, 19/29 DSCT neurons showed activity related to the scratch cycle. We provide evidence for the first time that locomotor and scratch drive potentials are present not only in VSCT, but also in the majority of DSCT neurons. These results demonstrate that both spinocerebellar tracts receive input from the central pattern generator circuitry, often sufficient to elicit firing in the absence of sensory input.

Van den Brand et al. (Reports, 1 June 2012, p. 1182) claim to have restored voluntary control of locomotion after paralyzing spinal cord injury. They have not considered recent findings that their upright posture paradigm contributes to locomotor capability after such injuries. We propose that postural adjustments that activate the locomotor central pattern generator in the upright posture, rather than direct voluntary control of locomotion, account for their results.

The locomotor system is one of the best-explored neuronal motor systems and has provided detailed insight into the function and organization of neuronal networks. The success of studies in the locomotor field are partly based on the finding that basic principles of these networks are very similar in vertebrates and invertebrates, allowing very in-depth studies at various physiological levels. In the following paragraphs we will discuss the neuronal control of locomotion and the organization of the underlying networks. This will involve how sensory signals and neuromodulatory input can change network properties, and how these networks can respond to injuries of the nervous systems. Keywords: walking; swimming flying; neuronal networks; central pattern generator; plasticity; neuromodulation

N-methyl-d-aspartate (NMDA) receptors are of critical importance for locomotion in the developing neonatal spinal cord in rats and mice. However, due to profound changes in the expression of NMDA receptors in development between the neonatal stages and adulthood, it is unclear whether NMDA receptors are still an important component of locomotion in the adult rodent spinal cord. To shed light on this issue, we have taken advantage of recently developed preparations allowing the intracellular recording of adult motoneurons that control the tail in the sacrocaudal spinal cord of adult mice and rats. We show that in the adult sacrocaudal spinal cord, NMDA induces rhythmic activity recorded on the ventral roots, often coordinated from left to right, as in swimming motions with the tail (fictive locomotion). The adult motoneurons themselves are intrinsically sensitive to NMDA application. That is, when motoneurons are synaptically isolated with TTX, NMDA still causes spontaneous bursts of rhythmic activity, depending on the membrane potential. We show that these bursts in motoneurons depend on an NMDA-mediated persistent inward current and are terminated by the progressive activation of a persistent outward current. These results indicate that motoneurons, along with the central pattern generator, can actively participate in the production of swimminglike locomotor activity in adult rodents.

Sensory afferent transmission and associated spinal reflexes are normally inhibited by serotonin (5-HT) derived from the brain stem. Spinal cord injury (SCI) that eliminates this 5-HT innervation leads to a disinhibition of sensory transmission and a consequent emergence of unusually long polysynaptic excitatory postsynaptic potentials (EPSPs) in motoneurons. These EPSPs play a critical role in triggering long polysynaptic reflexes (LPRs) that initiate muscles spasms. In the present study we examined which 5-HT receptors modulate the EPSPs and whether these receptors adapt to a loss of 5-HT after chronic spinal transection in rats. The EPSPs and associated LPRs recorded in vitro in spinal cords from chronic spinal rats were consistently inhibited by 5-HT1B or 5-HT1F receptor agonists, including zolmitriptan (5-HT1B/1D/1F) and LY344864 (5-HT1F), with a sigmoidal dose-response relation, from which we computed the 50% inhibition (EC50) and potency (−log EC50). The potencies of 5-HT receptor agonists were highly correlated with their binding affinity to 5-HT1B and 5-HT1F receptors, and not to other 5-HT receptors. Zolmitriptan also inhibited the LPRs and general muscle spasms recorded in vivo in the awake chronic spinal rat. The 5-HT1B receptor antagonists SB216641 and GR127935 and the inverse agonist SB224289 reduced the inhibition of LPRs by 5-HT1B agonists (zolmitriptan). However, when applied alone, SB224289, SB216641, and GR127935 had no effect on the LPRs, indicating that 5-HT1B receptors do not adapt to chronic injury, remaining silent, without constitutive activity. The reduction in EPSPs with zolmitriptan unmasked a large glycine-mediated inhibitory postsynaptic current (IPSC) after SCI. This IPSC and associated chloride current reversed at −73 mV, slightly below the resting membrane potential. Zolmitriptan did not change motoneuron properties. Our results demonstrate that 5-HT1B/1F agonists, such as zolmitriptan, can restore inhibition of sensory transmission after SCI without affecting general motoneuron function and thus may serve as a novel class of antispastic drugs.

The Gospels never mention Jesus laughing. Therefore, the inference some make is that if it does not specifically say that he did, then he must not have. Other scholars have argued that it is easy to see humor in the writings about Christ if you look for it (e.g., Buckner, The joy of Jesus, The Canterbury Press, 1993; Trueblood, The humor of Christ, Harper & Row Publishers, 1964; Wirt, Jesus man of joy, Harvest House Publishers, 1999). The goal of the present study is to examine how Christians describe the humorous (or not) behavior of Jesus Christ using the Humorous Behavior Q-Sort Deck (Craik, Lampert, and Nelson, Humor: International Journal of Humor Research 9: 273–302, 1996). This is a new application of an established methodological approach which should aid our thinking on the subject of humor and Christ. Thirty subjects sorted the 100 statements while reflecting on Jesus. The results are discussed within the humorous style framework of Craik and Ware (Humor and personality in everyday life, Mouton de Gruyter. 1998) and the larger research context.

A stable and high potency dry powder measles vaccine with a particle size distribution suitable for inhalation was manufactured by CO(2)-Assisted Nebulization with a Bubble Dryer(®) (CAN-BD) process from bulk liquid Edmonston-Zagreb live attenuated measles virus vaccine supplied by the Serum Institute of India. A novel dry powder inhaler, the PuffHaler(®) was adapted for use in evaluating the utility of cotton rats to study the vaccine deposition, vaccine virus replication, and immune response following inhalation of the dry powder measles vaccine. Vaccine deposition in the lungs of cotton rats and subsequent viral replication was detected by measles-specific RT-PCR, and viral replication was confined to the lungs. Inhalation delivery resulted in an immune response comparable to that following injection. The cotton rat model is useful for evaluating new measles vaccine formulations and delivery devices.

The objective of this study was to determine the extent to which subjects modulate their elbow joint mechanical properties during ongoing arm movement. Small pseudo-random force disturbances were applied to the wrist with an airjet actuator while subjects executed large (1 rad) elbow joint movements. Using a lumped parameter model of the muscle, tendon and proprioceptive feedback dynamics, a time-varying system identification technique was developed to analyze the phasic changes in the elbow joint's mechanical response. The mechanical properties were found to be time-varying, and well approximated by a quasi-linear second-order model. The stiffness of the arm was found to drop during movement. The arm was always underdamped, with the damping ratio changing during movement. Inertia estimates were constant and consistent with previous measurements. Overall, the moving arm was found to be very compliant, with a peak stiffness value less than the lowest value measured during posture, and a natural frequency of less than 3 Hz. Changing the speed of movement, or the load from gravity, changed the stiffness measured, but not in strict proportion to the change in net muscle torque.

Autonomous robot calibration is defined as the process of determining a robot's model by using only its internal sen sors. It is shown that autonomous calibration of a manip ulator and stereo camera system is possible. The pro posed autonomous calibration algorithm may obtain the manipulator kinematic parameters, external kinematic camera parameters, and internal camera parameters. To do this, only joint angle readings and camera image plane data are used. A condition for the identifiability of the manipulator/camera parameters is derived. The method is a generalization of a recently developed scheme for self- calibrating a manipulator by forming it into a mobile closed-loop kinematic chain.

The authors present a kinematic calibration method that does not require endpoint measurements or precision points. By forming manipulators into mobile closed kinematic chains, it is shown that consistency conditions in the kinematic loop closure equations are adequate to calibrate the manipulator from joint angle readings alone. This closed-loop kinematic calibration method is an adaptation of an iterative least-squares algorithm used in calibrating open-chain manipulators. Example tasks include a fixed endpoint (zero-degree-of-freedom (DOF) task), the opening of a door (one-DOF task), and point contact (three-DOF task). >

A system for determining the mechanical properties of the human arm during unconstrained posture and movement is described. An airjet perturbation device is attached to the wrist with a special cuff, providing high-frequency stochastic perturbations in three orthogonal directions. The airjet operations as a fluidic flip-flop utilizing the Coanda effect. The design greatly reduces the mass of mechanical moving parts and enhances the frequency bandwidth dramatically. This airjet is intrinsically a bistable device that can generate arbitrary binary force sequences, such as pseudorandom binary sequences, colored white noise, and Walsh functions. The force transmissibility is identified. Cuff design and data acquisition are discussed. >

Following spinal cord injury (SCI), prolonged muscle spasms are readily triggered by brief sensory stimuli. Animal and indirect human studies have shown that a substantial portion of the depolarization of motoneurons during a muscle spasm comes from the activation of persistent inward currents (PICs). The brief (single pulse) sensory stimuli that trigger the PICs and muscle spasms in chronically spinalized animals evoke excitatory post-synaptic potentials (EPSPs) that are broadened to more than 500 ms, the duration of depolarization required to activate a PIC in the motoneuron. Thus, in humans, we investigated if post-synaptic potentials (PSPs) evoked from brief (1 year), incomplete SCI. In non-injured controls, a single shock or brief (

The recovery of persistent inward currents (PICs) and motoneuron excitability after chronic spinal cord transection is mediated, in part, by the development of supersensitivity to residual serotonin (5HT) below the lesion. The purpose of this paper is to investigate if, like 5HT, endogenous sources of norepinephrine (NE) facilitate motoneuron PICs after chronic spinal transection. Cutaneous-evoked reflex responses in tail muscles of awake chronic spinal rats were measured after increasing presynaptic release of NE by administration of amphetamine. An increase in long-lasting reflexes, known to be mediated by the calcium component of the PIC (CaPIC), was observed even at low doses (0.1–0.2 mg/kg) of amphetamine. These findings were repeated in a reduced S2 in vitro preparation, demonstrating that the increased long-lasting reflexes by amphetamine were neural. Under intracellular voltage clamp, amphetamine application led to a large facilitation of the motoneuron CaPIC. This indicates that the increases in long-lasting reflexes induced by amphetamine in the awake animal were, in part, due to actions directly on the motoneuron. Reflex responses in acutely spinal animals were facilitated by amphetamine similar to chronic animals but only at doses that were ten times greater than that required in chronic animals (0.2 mg/kg chronic vs. 2.0 mg/kg acute), pointing to a development of supersensitivity to endogenous NE in chronic animals. In summary, the increases in long-lasting reflexes and associated motoneuron CaPICs by amphetamine are likely due to an increased release of endogenous NE, which motoneurons become supersensitive to in the chronic stages of spinal cord injury.

Low voltage–activated persistent inward calcium currents (Ca PICs) occur in rat motoneurons and are mediated by Cav1.3 L-type calcium channels (L-Ca current). The objectives of this paper were to determine whether this L-Ca current activates a sustained calcium-activated potassium current (SK current) and examine how such SK currents change with spinal injury. For comparison, the SK current that produces the postspike afterhyperpolarization (mAHP) was also quantified. Intracellular recordings were made from motoneurons of adult acute and chronic spinal rats while the whole sacrocaudal spinal cord was maintained in vitro. Spikes/AHPs were evoked with current injection or ventral root stimulation. Application of the SK channel blocker apamin completely eliminated the mAHP, which was not significantly different in chronic and acute spinal rats. The Ca PICs were measured with slow voltage ramps (or steps) with TTX to block sodium currents. In chronic spinal rats, the PICs were activated at –58.6 ± 6.0 mV and were 2.2 ± 1.2 nA in amplitude, significantly larger than in acute spinal rats. Apamin significantly increased the PIC, indicating that there was an SK current activated by L-Ca currents (SKLcurrent), which ultimately reduced the net PIC. This SKLcurrent was not different in acute and chronic spinal rats. The SKAHPand the SKLcurrents were activated by different calcium currents because the mAHP/SKAHPwas blocked by the N, P-type calcium channel blocker ω-conotoxin MVIIC and was resistant to the L-type calcium channel blocker nimodipine, whereas the L-Ca and SKLcurrents were blocked by nimodipine. Furthermore, the SKAHPcurrent activated within 10 ms of the spike, whereas the SKLcurrent was delayed ∼100 ms after the onset of the L-Ca current, suggesting that the SKLcurrents were not as spatially close to the L-Ca currents. Finally, the SKLand the L-Ca currents were poorly space clamped, with oscillations at their onset and hysteresis in their activation and deactivation voltages, consistent with currents of dendritic origin. The impact of these dendritic currents was especially pronounced in 15% of motoneurons, where apamin led to uncontrollable L-Ca currents that could not be deactivated, even with large hyperpolarizations of the soma. Thus, although the SKLcurrents are fairly small, they play a critical role in terminating the dendritic L-Ca currents.

Paralyzed skeletal muscle sometimes becomes faster and more fatigable after spinal cord injury (SCI) because of reduced activity. However, in some cases, pronounced muscle activity in the form of spasticity (hyperreflexia and hypertonus) occurs after long-term SCI. We hypothesized that this spastic activity may be associated with a reversal back to a slower, less fatigable muscle. In adult rats, a sacral (S2) spinal cord transection was performed, affecting only tail musculature and resulting in chronic tail spasticity beginning 2 wk later and lasting indefinitely. At 8 mo after injury, we examined the contractile properties of the segmental tail muscle in anesthetized spastic rats and in age-matched normal rats. The segmental tail muscle has only a few motor units (150%) in the fraction of the peak muscle twitch force remaining at 50 ms. With injury, the peak muscle twitch (evoked with supramaximal stimulation) also increased in its time to peak (+48.9%) and half-rise time (+150.0%), and decreased in its maximum rise (−35.0%) and decay rates (−40.1%). Likewise, after a tetanic stimulation, the tetanus half-fall time increased by 53.8%. Therefore the slow portion of the muscle was enhanced in spastic muscles. Consistent with slowing, posttetanic potentiation was 9.2% lower and the stimulation frequency required to produce half-maximal tetanus decreased 39.0% in chronic spinals. Interestingly, in spastic muscles compared with normal, whole muscle twitch force was 81.1% higher, whereas tetanic force production was 38.1% lower. Hence the twitch-to-tetanus ratio increased 104.0%. Inconsistent with overall slowing, whole spastic muscles were 61.5% more fatigable than normal muscles. Thus contrary to the classical slow-to-fast conversion that is seen after SCI without spasticity, SCI with spasticity is associated with a mixed effect, including a preservation/enhancement of slow properties, but a loss of fatigue resistance.

Although the spasticity that follows spinal cord injury in humans is common, it has been difficult to study experimentally because spinal cord injury in animals produces only comparatively mild spasticity. Spasticity occurs in humans without complete spinal cord transections, whereas in animals such as rats and cats, incomplete spinal cord injury only leads to mild hyperreflexia. However, these cats have inconvenient and traumatic functional impairments, requiring twice-daily bladder and bowel expression. Bladder infection, pressure sores, and impaired locomotion can lead to significant morbidity and mortality. Thus, the complete spinal cat is an impractical model, and many groups have used hemisections, partial transections, and contusions to study spinal cord injury, even though spasticity is not always prominent. By using sacral spinal cord lesions in rats, a model of spasticity that is convenient to study in the awake state and requires minimal care is developed. Furthermore, the small diameter of the spinal cord at this level allows for electrophysiological study of adult spastic motoneurons and reflexes in vitro. This preparation has been central to the understanding of how plateau potentials lead to the intense muscle spasms characteristic of spinal spasticity. Ongoing experiments are elucidating the underlying currents associated with plateaus and the neuromodulators that are involved in the development of these plateaus in the months following the injury.

In the months after spinal cord injury, motoneurons develop large voltage-dependent persistent inward currents (PICs) that cause sustained reflexes and associated muscle spasms. These muscle spasms are triggered by any excitatory postsynaptic potential (EPSP) that is long enough to activate the PICs, which take >100 ms to activate. The PICs are composed of a persistent sodium current (Na PIC) and a persistent calcium current (Ca PIC). Considering that Ca PICs have been shown in other neurons to be inhibited by baclofen, we tested whether part of the antispastic action of baclofen was to reduce the motoneuron PICs as opposed to EPSPs. The whole sacrocaudal spinal cord from acute spinal rats and spastic chronic spinal rats (with sacral spinal transection 2 mo previously) was studied in vitro. Ventral root reflexes were recorded in response to dorsal root stimulation. Intracellular recordings were made from motoneurons, and slow voltage ramps were used to measure PICs. Chronic spinal rats exhibited large monosynaptic and long-lasting polysynaptic ventral root reflexes, and motoneurons had associated large EPSPs and PICs. Baclofen inhibited these reflexes at very low doses with a 50% inhibition (EC50) of the mono- and polysynaptic reflexes at 0.26 ± 0.07and 0.25 ± 0.09 (SD) μM, respectively. Baclofen inhibited the monosynaptic reflex in acute spinal rats at even lower doses (EC50 = 0.18 ± 0.02 μM). In chronic (and acute) spinal rats, all reflexes and EPSPs were eliminated with 1 μM baclofen with little change in motoneuron properties (PICs, input resistance, etc), suggesting that baclofen's antispastic action is presynaptic to the motoneuron. Unexpectedly, in chronic spinal rats higher doses of baclofen (20–30 μM) significantly increased the total motoneuron PIC by 31.6 ± 12.4%. However, the Ca PIC component (measured in TTX to block the Na PIC) was significantly reduced by baclofen. Thus baclofen increased the Na PIC and decreased the Ca PIC with a net increase in total PIC. By contrast, when a PIC was induced by 5-HT (10–30 μM) in motoneurons of acute spinal rats, baclofen (20–30 μM) significantly decreased the PIC by 38.8 ± 25.8%, primarily due to a reduction in the Ca PIC (measured in TTX), which dominated the total PIC in these acute spinal neurons. In summary, baclofen does not exert its antispastic action postsynaptically at clinically achievable doses (

After chronic spinal injury, motoneurons spontaneously develop two persistent inward currents (PICs): a TTX-sensitive persistent sodium current (sodium PIC) and a nimodipine-sensitive persistent calcium current (calcium PIC). In the present paper, we examined how these PICs contributed to motoneuron firing. Adult rats were spinalized at the S2sacral level, and after 2 months intracellular recordings were made from sacrocaudal motoneurons in vitro. The PICs and repetitive firing were measured with slow triangular voltage and current ramps, respectively. The sodium PIC was examined after blocking the calcium PIC with nimodipine (20 μM; n = 12). It was always activated subthreshold, and during current ramps in nimodipine, it produced a sodium plateau that assisted in initiating and maintaining firing (self-sustained firing). The sodium PIC oscillated off and on during firing and helped initiate each spike, and near threshold this caused abnormally slow firing (2.82 ± 1.21 Hz). A low dose of TTX (0.5 μM) blocked the sodium PIC, sodium plateau, and very slow firing prior to affecting the spike itself. The calcium PIC was estimated as the current blocked by nimodipine or current remaining in TTX (2 μM; n = 13). In 59% of motoneurons, the calcium PIC was activated subthreshold to firing and produced a plateau that assisted in initiating and sustaining firing because nimodipine significantly increased the firing threshold current and decreased the self-sustained firing. In the remaining motoneurons (41%), the calcium PIC was activated suprathreshold to firing and during current ramps did not initially affect firing but eventually was activated and caused an acceleration in firing followed by self-sustained firing, which were blocked by nimodipine. The frequency-current ( F-I) slope was 3.0 ± 1.0 Hz/nA before the calcium PIC activation (primary range), 6.3 ± 3.6 Hz/nA during the calcium PIC onset (secondary range; acceleration), and 2.1 ± 1.3 Hz/nA with the calcium PIC steadily activated (tertiary range). Nimodipine eliminated the secondary and tertiary ranges, leaving a linear F-I slope of 3.7 ± 1.0 Hz/nA. A single low-threshold shock to the dorsal root evoked a many-second-long discharge, the counterpart of a muscle spasm in the awake chronic spinal rat. This long-lasting reflex was caused by the motoneuron PICs because when the activation of the voltage-dependent PICs was prevented by hyperpolarization, the same dorsal root stimulation only produced a brief excitatory postsynaptic potential (

An approach to identifying the kinematic models of manipulators and their task geometry is presented. Starting with the observation that in many tasks manipulators naturally form mobile closed kinematic chains, it is shown that these closed loops can be identified by an iterative least-squares algorithm similar to that used in calibrating open chain manipulators. By merely using joint angle readings and self motions, consistency conditions can be utilized to identify the kinematic parameters. While the task of a robot opening a door is studied in detail, the method readily generalizes to a large class of robot tasks. Simulations are presented to accompany the analysis. >

A novel approach to identifying the kinematic models of redundant or dual manipulators without end-point sensing is presented. Starting from the observation that such manipulators can be made to form mobile closed kinematic chains, it is shown that these closed loops can be identified by an iterative-least-squares algorithm similar to that used in calibrating open-chain manipulators. Simulations have demonstrated that this technique is viable. The issue of the identifiability of the kinematic parameters of the closed loop is addressed. >

A method for kinematic calibration is presented, which directly estimates the Jacobian matrix from measurements and extracts the kinematic parameters from the Jacobian exactly and without iteration. Two different experimental approaches are presented for measuring the Jacobian. In the first approach, a six degree-of-freedom manipulator is rigidly attached to the environmental at its endpoint, in one pose only. Joint torques are systematically exerted and the resulting endpoint forces and torques are measured. In the second approach, a manipulator attains different motions through the same endpoint location, and the joint velocities are related to measured endpoint linear and angular velocities. Simulations are presented to verify the method. >

The triceps surae (TS) stretch reflex was measured in decerebrate cats during crossed extensor stimulation (tonic contractions) and after spinalization during rhythmic locomotor activity. The TS reflex force in response to a short pulse stretch measured during tonic contractions at low level of background activity was greater than when more background activity was present at the time of application of stretch. In contrast, the reflex force measured during rhythmic contractions was very small at low level of background force (flexion phase) and increased at moderate and high levels of background activity (extension phase). Thus, even in reduced preparations, a task modulation of the stretch reflex occurs. Throughout the experimental procedure, the torque motor used to stretch the muscles behaved like a spring of a preset compliance (from isometric to very compliant). A reflex model was used to simulate the responses obtained experimentally. The gain of the stretch reflex loop was estimated for each load condition and both behavioural tasks. The reflex loop gain was significantly larger as the compliance of the external load increased for both tonic and rhythmic contractions, although to a lesser extent in the phasically activated muscles. During rhythmic locomotor contractions the gain was less than 1, assuring stability of the system. In contrast, during tonic contractions against a compliant load the gain exceeded 1, consistent with the instability (oscillations, clonus) seen at times under these load conditions. However, the high gain and instability was only transient, since repeated stretch reduced the gain. Thus, non-linearities in the system assured vigorous responses at the onset of perturbations, but then weaker responses to ongoing perturbations to reduce the chance of feedback instability (clonus).

The main purpose of this study was to examine whether facilitation of human motor unit recruitment by repeated voluntary contractions is mediated, in part, by time and activity-dependent increases in the intrinsic excitability of the parent motoneuron. To do this, pairs of tibialis anterior or soleus motor units were recorded during slowly increasing and then decreasing voluntary contractions. The firing rate of the lower-threshold motor unit of the pair (control unit) was used as a measure of effective synaptic excitation (i.e., drive) to the motoneurons. This rate was used to estimate the recruitment threshold of the higher-threshold unit of the pair (test unit). The test unit was repeatedly recruited and de-recruited in a series of contractions, and the interval between the de-recruitment and re-recruitment of the test unit (interactivation interval) was systematically varied between 0.6 and 60 s. An increase in intrinsic excitability of a unit was considered to have occurred if the level of estimated synaptic input (as measured by the firing rate of the control motor unit) needed to recruit a unit was reduced. At short interactivation intervals (1–2 s), the control unit firing frequency was significantly lower when the test unit was recruited on the second contraction, compared with the first (by 3.9 Hz or a 64% reduction). This suggested that the intrinsic excitability of the test motor unit had increased during the second contraction because it could be recruited at a much lower level of estimated synaptic drive. Longer interaction intervals (2–6 s) produced less recruitment facilitation. At even longer interactivation intervals (>6 s) there was no significant facilitation (time constant of effect was 4.8 s). In some motor units, the effect of this short-term facilitation appeared to be so pronounced that it resulted in reversing the order of de-recruitment with the other initially lower-threshold motor units. Such reversals were occasionally observed for orderly re-recruitment. The time course and behavior of the observed short-term facilitation of motor unit discharge was qualitatively similar to the warm-up phenomenon of plateau potentials seen in motoneurons of reduced preparations (e.g., 4–6 s). The possibility of warm-up contributing to the time and activity-dependent facilitation of human motor unit recruitment is discussed.

Motoneurones in reduced animal preparations can exhibit plateau potentials that amplify their response to synaptic inputs and can persist for prolonged periods in the absence of synaptic drive. There is mounting evidence that a similar mechanism may be an integral part of the normal activation of motoneurones. Some of the work describing plateau potentials in reduced animal preparations is reviewed and then evidence that similar properties contribute to the normal activation of motoneurones in rats and humans is presented. Recent data have shown that during high-frequency electrical stimulation over human muscle, large contractions can develop which originate within the central nervous system and are present in addition to the contraction due to the direct activation of motor axons. These “extra” contractions may in part be due to plateau potentials in spinal motoneurones. It is becoming clear that intrinsic properties of human motoneurones may make a large contribution to muscle contractions during normal movements. The extent to which the nervous system uses this as a gain control mechanism to tailor motor output for a given task needs to be further explored.

This paper compares the activity of hindlimb motor units from muscles mainly composed of fast-twitch muscle fibers (medial and lateral gastrocnemius: MG/LG, tibialis anterior: TA) to motor units from a muscle mainly composed of slow-twitch muscle fibers (soleus: SOL) during unrestrained walking in the conscious rat. Several differences in the activation profiles of motor units from these two groups of muscles were observed. For example, motor units from fast muscles (e.g., MG/LG and TA) fired at very high mean frequencies of discharge, ranging from 60 to 100 Hz, and almost always were recruited with initial doublets or triplets, i.e., initial frequencies ≥100 Hz. In contrast, the majority of SOL units fired at much lower mean rates of discharge, ≈30 Hz, and had initial frequencies of only 30–60 Hz (i.e., there were no initial doublets/triplets ≥100 Hz). Thus the presence of initial doublet or triplets was dependent on the intrinsic properties of the motor unit, i.e., faster units were recruited with a doublet/triplet more often than slower units. Moreover, in contrast to units from the slow SOL muscle, the activity of single motor units from the fast MG/LG muscle, especially units recruited midway or near the end of a locomotor burst, was unrelated to the activity of the remainder of the motoneuron pool, as measured by the corresponding gross-electromyographic (EMG) signal. This dissociation of activity was suggested to arise from a compartmentalized recruitment of the MG/LG motoneuron pool by the rhythm-generating networks of the spinal cord. In contrast, when comparing the rate modulation of simultaneously recorded motor units within a single LG muscle compartment, the frequency profiles of unit pairs were modulated in a parallel fashion. This suggested that the parent motoneurons were responsive to changes in synaptic inputs during unrestrained walking, unlike the poor rate modulation that occurs during locomotion induced from brain stem stimulation. In summary, data from this study provide evidence that the firing behavior of motor units during unrestrained walking is influenced by both the intrinsic properties of the parent motoneuron and by synaptic inputs from the locomotor networks of the spinal cord. In addition, it also provides the first extensive description of motor-unit activity from different muscles during unrestrained walking in the conscious rat.

In two experiments, we asked college students to judge the ease of learning word pairs known to differ reliably in actual ease of learning. The independent variable in both experiments was the rate of presentation (fast and slow) of to-be-judged items. The results of both experiments revealed only small differences in decision accuracy as a function of presentation rate. This suggests that metacognitive judgments of this kind rely on rather fundamental cognitive processes, which in our view are similar to those used to discover meaning in everyday verbal messages.

The activity of hindlimb motor units from the lateral gastrocnemius and tibialis anterior muscles in the awake rat was compared during locomotion and during slow, sinusoidal muscle stretch. The majority of units were activated with high initial frequencies and often commenced firing with an initial doublet or triplet, even when activated by slow muscle stretch. The high firing rates at recruitment occurred without jumps in the firing rates of other concurrently activated units, the firing rate profiles of which were used as a measure of the net synaptic drive onto the motoneuronal pool. This suggested that the sharp recruitment jumps were not due to an abrupt increase in synaptic drive but rather due to intrinsic properties of the motoneuron. In addition, motor units that were activated phasically by the muscle stretch fired more action potentials during muscle shortening than during muscle lengthening, resulting in rightwardly skewed, asymmetrical firing profiles. In contrast, when the same units fired tonically during the imposed muscle stretch, the frequency profiles were modulated symmetrically and no nonlinearities were observed. Tonically firing units were modulated symmetrically throughout a wide range of firing frequencies, and discrete jumps in rate (i.e., bistable firing) were not observed. The sharp recruitment jumps during locomotion and muscle stretch are proposed to have resulted from the additional depolarization produced by the activation of plateau potentials at recruitment. Likewise, the sustained activation of plateaus subsequent to recruitment may have produced the prolonged firing of the motor units during sinusoidal muscle stretch.

This paper reports the result of a lexical decision experiment in which the primes were either directly related to their targets, mediated, or unrelated. Mediated primes are indirectly related to their targets through a single connecting link (e.g., PASTURE-COW-MILK). Older and younger adult subjects responded to each letter string in a continuous lexical decision task, deciding whether each string was a word or a nonword. The results indicated that both younger and older subjects benefited from the mediated primes, as well as from the directly related primes. The results are discussed in relation to issues of age changes in processing speed.

Bennett, David J., Hans Hultborn, Brent Fedirchuk, and Monica Gorassini. Short-term plasticity in hindlimb motoneurons of decerebrate cats. J. Neurophysiol. 80: 2038–2045, 1998. Cat hindlimb motoneurons possess noninactivating voltage-gated inward currents that can, under appropriate conditions, regeneratively produce sustained increments in depolarization and firing of the cell (i.e., plateau potentials). Recent studies in turtle dorsal horn neurons and motoneurons indicate that facilitation of plateaus occurs with repeated plateau activation (decreased threshold and increased duration; this phenomenon is referred to as warm-up). The purpose of the present study was to study warm-up in cat motoneurons. Initially, cells were studied by injecting a slow triangular current ramp intracellularly to determine the threshold for activation of the plateau. In cells where the sodium spikes were blocked with intracellular QX314, plateau activation was readily seen as a sudden jump in membrane potential, which was not directly reversed as the current was decreased (cf. hysteresis). With normal spiking, the plateau activation (the noninactivating inward current) was reflected by a steep and sustained jump in firing rate, which was not directly reversed as the current was decreased (hysteresis). Repetitive plateau activation significantly lowered the plateau activation threshold in 83% of cells (by on average 5 mV and 11 Hz with and without QX314, respectively). This interaction between successive plateaus (warm-up) occurred when tested with 3- to 6-s intervals; no interaction occurred at times >20 s. Plateaus initiated by synaptic activation from muscle stretch were also facilitated by repetition. Repeated slow muscle stretches that produced small phasic responses when a cell was hyperpolarized with intracellular current bias produced a larger and more prolonged responses (plateau) when the bias was removed, and the amplitude and duration of this response grew with repetition. The effects of warm-up seen with intracellular recordings during muscle stretch could also be recorded extracellularly with gross electromyographic (EMG) recordings. That is, the same repetitive stretch as above produced a progressively larger and more prolonged EMG response. Warm-up may be a functionally important form of short-term plasticity in motoneurons that secures efficient motor output once a threshold level is reached for a significant period. Finally, the finding that warm-up can be readily observed with gross EMG recordings will be useful in future studies of plateaus in awake animals and humans.

Motoneurons of invertebrates and vertebrates can continue to fire repetitively after being activated by a brief, excitatory synaptic input (self-sustained firing). This firing behavior is due to the activation of intrinsic, voltage-gated currents which produce sustained regenerative depolarizations (plateau potentials) of the cell. Examination of these intrinsic cellular properties has been performed in reduced animal preparations and it is unknown if such self-sustained firing occurs in motoneurons of the intact human. In this paper, we present evidence of this in the human by using a technique of dual motor unit recordings. Subjects were instructed to maintain a constant dorsiflexion effort, and the common synaptic input (e.g. descending drive) onto the tibialis anterior (TA) motoneuron pool was monitored by recording the firing frequency of a low threshold 'control' unit. Once the firing rate of the control unit was constant, vibration of the TA tendon recruited a second 'test' unit which continued to fire after the vibration (i.e. synaptic input) was removed, even though the firing rate of the control unit (and thus, the common drive) remained the same or decreased. Self-sustained firing of motoneurons such as this may reduce the need for prolonged synaptic input when constant muscle activation is required (e.g. for postural tone).

We tested the hypothesis that the neural networks for walking in the mudpuppy can be divided into a flexor and an extensor center, each of which contains collections of interneurons localized in the vicinity of their motoneuron pools. Combining a battery of techniques, we identified and localized the elbow flexor center and its motoneuron pool in the C2 segment and the elbow extensor center and its motoneuron pool in the C3 segment. Rhythmic flexion or extension of the limb in isolation could be induced by continuous trains of current pulses of the C2 or C3 segments, respectively. Independent activation could also occur after application of glutamate receptor agonist NMDA. Part of segment C2 in isolation generated rhythmic elbow flexor bursts, whereas part of segment C3 in isolation generated rhythmic elbow extensor bursts. An isolated region spanning the C3 roots generated both flexor and extensor bursts. The step cycle was modulated in a phase-dependent manner by stimulation of the dorsal roots, the ventral roots, or either of the two centers. The effects of ventral root stimulation were removed by deafferentation to block reafferent input attributable to muscle contraction induced by the stimulation. We conclude that the neural networks for walking contain at least a flexor and an extensor generator that are localized in close apposition to the motoneuron pools, that the two centers can work independently despite the fact that there are reciprocal inhibitory interconnections between them, and that sensory input interacts with the spinal neural networks to reset the ongoing walking rhythm in a phase-dependent manner.

Clinical assessment of rigidity in parkinsonian patients is largely qualitative. The reliability and validity of the assessments are sometimes in doubt. Several "engineering" methods of quantifying rigidity have been described, but none has been adopted into general clinical practice. A possible reason is that these methods differ in crucial aspects from the clinical exam. We therefore tackled the problem by monitoring the clinical exam itself, using small sensors to measure the forces and displacements applied. Limb impedance (Z) was computed using parameter identification methods and compared to raters' verbalized ratings of rigidity based on a 5-point scale: the Unified Parkinson's Disease Rating System. The qualitative and quantitative estimates of impedance covaried over a fourfold range, depending on the forces imposed and the subject's motor set. Raters differed by up to 1 full point in their mean qualitative ratings and sometimes disagreed on whether levodopa reduced rigidity. This was not due to any significant differences in the overall range of rigidity they evoked, but rather to the way they scored this range [the ratio of mean rating to mean impedance (R/Z) varied between raters and subjects]. On the other hand, the R/Z ratio was reproducible over separate sets of ratings and may therefore serve to convert measured impedance into a standardized rating. Our results indicate that the current clinical exam may be too abbreviated to detect the sometimes quite small reductions in rigidity after levodopa. We conclude that a device that conveniently quantifies the clinical assessment of rigidity is now available and will lead to more standardized protocols for rating rigidity in the near future.

Van den Brand et al . (Reports, 1 June 2012, p. 1182) claim to have restored voluntary control of locomotion after paralyzing spinal cord injury. They have not considered recent findings that their upright posture paradigm contributes to locomotor capability after such injuries. We propose that postural adjustments that activate the locomotor central pattern generator in the upright posture, rather than direct voluntary control of locomotion, account for their results.

Recordings from awake behaving cats indicate that muscle spindle sensitivity is lower during walking than during postural tasks (Prochazka, 1989), due to a predominant static fusimotor drive. Thus, during walking the effectiveness of the stretch reflex should be relatively reduced by this static fusimotor drive. We investigated this possibility in acute locomoting spinal cats, where we could directly measure spindle sensitivity and reflex responsiveness. For comparison, measurements were also taken in the quiescent state (resting) and during tonic contractions. As tonic contractions are unusual in the spinal cat, we elicited them in the decerebrate cat prior to spinalisation.