Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology.

Fertilization is well correlated with sperm concentration, rate of forward motility, and percentage of live, uncapacitated ejaculated spermatozoa, which is regulated in part by cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to their corresponding monophosphates, thereby counterbalancing the activities of cAMP and cGMP, and PDE11 is highly expressed in the testis, prostate, and developing spermatozoa. However, a physiological role of PDE11 is not known. We generated PDE11 knockout (PDE11-/-) mice to investigate the role of PDE11 in spermatozoa physiology. Ejaculated sperm from PDE11-/- mice displayed reduced sperm concentration, rate of forward progression, and percentage of live spermatozoa. Pre-ejaculated sperm from PDE11-/- mice displayed increased premature/spontaneous capacitance. These data are consistent with human data and suggest a role for PDE11 in spermatogenesis and fertilization potential. This is the first phenotype described for the PDE11-/- mouse and the first report of a physiological role for PDE11.

Discharge characteristics of the elbow joint nerve of the cat.

Direct recordings were made from intact elbow joint nerves (EJN) in decerebrate cats. These multiunit recordings indicate that the EJN is a relatively pure articular nerve and does not contain significant numbers of muscle afferent fibres. In every cat the EJN exhibited a tonic discharge throughout a full range of elbow joint positions. The discharge was most intense when the elbow was extended to 165 degrees and least intense when the joint was held in midrange positions between 90 degrees and 120 degrees. There was a modest increase in discharge as the elbow was held in more flexed positions and activity at 30 degrees was about half of that at 165 degrees. Alterations in the tone of muscles around the joint did not affect the adapted EJN discharge at any angle.

Modulation of transmission in flexion reflex pathways by knee joint afferent discharge in the decerebrate cat.

In the intact hindlimb, flexion reflexes are most easily obtained when the knee is extended. Movement of the knee joint after the muscles have been tenotomized and held at fixed lengths still modulates flexion reflex excitability. After anaesthesia of the joint capsule movement of the limb no longer affects flexion reflex excitability.

The effect of elbow joint afferent discharge on transmission in forelimb flexion reflex pathways to biceps and triceps brachii in decerebrate cats.

The present experiments were performed to investigate the influence of elbow joint afferent discharge on the excitability of reflex arcs mediating flexion withdrawal and crossed extensor reflexes in the forelimb muscles of decerebrate cats. The excitability of flexion withdrawal and crossed extensor reflexes in forelimb muscles was shown to be modulated by elbow joint position. Flexion withdrawal reflexes were most easily elicited when the elbow was extended and crossed extensor reflexes were most easily elicited when the elbow was flexed. This modulation of transmission was not confined to reflex pathways projecting to muscles acting at the elbow but also included pathways to muscles acting at the wrist and shoulder in addition to muscles in the contralateral forelimb. The changing excitability of reflex pathways caused by elbow movement was unaltered by degloving the skin covering the joint and tenotomy of the medial head of triceps and the long head of biceps. However, modulation of reflex excitability by joint movement was totally abolished by local anaesthesia of the joint in an otherwise intact limb. Thus, the present experiments indicate that transmission in forelimb flexion reflex pathways can be powerfully influenced by elbow joint afferent discharge.

Modulation of transmission in forelimb flexion reflex pathways by elbow joint afferent discharge in decerebrate cats.

In intact forelimbs in decerebrate cats, flexion reflexes are most easily elicited when the elbow joint is extended and extension reflexes are most easily elicited when the elbow joint is flexed. Abolition of sensory discharge arising from the elbow joint by intra-articular injection of local anaesthetic eliminates this modulation of reflex excitability. We conclude that elbow joint afferent discharge modulates the transmission in flexion reflex pathways to forelimb motoneurones.

Ascending and descending effects of joint afferent discharge on forelimb and hindlimb flexion reflex excitability in decerebrate cats.

In decerebrate cats with intact innervation of the fore- and hindlimbs, flexion reflexes are most easily elicited in forelimb muscles when the hindlimb is extended, and hindlimb flexion reflexes are most easily elicited when the forelimbs are extended. After intra-articular injection of local anaesthetic, this modulation of reflex excitability is abolished. Thus, in addition to their known segmental effects, joint afferents also exert significant ascending and descending effects on motoneurone excitability.

The effect of mechanical stimulation of knee joint afferents on quadriceps motor unit activity in the decerebrate cat.

The present experiments demonstrate that repetitive activation of as few as two joint afferents by an imposed mechanical stimulus results in entrainment of stretch-induced firing of quadriceps motor units. There is no significant input from extracapsular receptors as the effect is abolished during local anaesthetic block of the joint nerve. These results indicate that joint receptors can exert potent effects on motoneurone excitability which may be of considerable functional significance.

Responses of quadriceps motor units to mechanical stimulation of knee joint receptors in the decerebrate cat.

Recordings were obtained from single quadriceps motor units in decerebrate cats. Tonic discharges were induced in these units by stretch applied to the patellar tendon. The activity of these motor units was examined during repetitive mechanical indentation of the posterior aspect of the knee joint capsule. The amplitude of indentation could be graded to regularly elicit a volley of one or more action potentials from afferents travelling in the posterior articular nerve (PAN). Either repetitive indentation at a fixed frequency or random indentation resulted in entrainment of motor unit discharge with a latency of 6.5-17 ms from the onset of the first PAN spike. This effect was achieved in one case by a single joint afferent. Usually two or more afferents were required to produce entrainment. This effect was mediated by joint receptors as its reversibly abolished by application of lignocaine to the joint nerve. The modal reflex latency suggests that group II joint afferents were responsible for this effect. Stimulation of some areas of the joint capsule readily produced motor unit entrainment whereas other areas did not although PAN afferents were also activated at the latter sites, suggesting inhomogeneity in the synaptic actions of joint afferents.

Conditioning of crossed extensor reflex pathways by independent natural stimulation of labyrinth, neck and elbow joint afferents.

The present experiments demonstrated that labyrinth, neck and elbow joint afferents interact to influence the excitability of crossed extensor reflex pathways projecting to triceps brachii in decerebrate cats. Reflex excitability was dependent on head, neck and elbow position such that it was increased when the elbow was held at full flexion and either the head maintained side down or the neck rotated side up. Such interaction between these afferents is likely to be important in postural control.

The influence of joint afferent discharge on locomotion, proprioception and activity in conscious cats.

Injection of local anaesthetic into the knee joint cavity in a series of 14 cats produced obvious abnormalities of posture and gait in half the animals. However, on employing a more sensitive testing procedure, 7 out of 8 animals exhibited reduced proprioceptive acuity after knee joint anaesthesia, and all animals tested showed marked reduction in motor activity after this procedure. Control procedures revealed that these effects were due to the local anaesthetic agent, and that this remained localized to the knee joint and did not diffuse out to block cutaneous and muscle afferents. Thus, joint afferents would appear to play a significant role in the regulation of posture and movement.

Dishabituation of the flexion reflex in spinal cord-injured man and its application in the restoration of gait.

The flexion withdrawal reflex, evoked by surface electrical stimulation, has been used to provide hip flexion for the restoration of gait in paraplegics. A major limitation to its use has been the decrease in the magnitude of the response to repeated stimulation (habituation). In this study it was found that by using high intensity stimulation the response could be dishabituated. It was demonstrated that sufficient hip flexion for functional electrical stimulation-assisted gait was maintained using high intensity pulses in a one-step-ahead controller.

Evidence for a human spinal stepping generator.

Flexion reflexes elicited by surface stimulation in spinal cord-injured man have been used to provide limb flexion in gait restoration. In this study, the pattern of the flexion reflexes observed in one subject supports the theory that a spinal stepping generator exists in man.

Twitch interpolation in the assessment of the maximum force-generating capacity of the jaw-closing muscles in man.

The method of twitch interpolation was employed to study the maximum potential bite forces of humans. Transcutaneous electrical stimuli were applied to parts of one or both masseter muscles in eight volunteers while they bit with a variable but controlled isometric force on a unidirectional force transducer held between the anterior teeth. In all participants the twitch force produced by a single 1-ms pulse, of 25 50 mA intensity, was inversely and linearly related to the voluntary bite force. For each participant the slope of the regression between twitch force and bite force depended on the stimulus intensity and not on whether the stimulus was applied to one or both masseters. Extrapolation of the regression lines to zero twitch force showed that they converged towards a bite-force value that, for any given participant varied only a small amount between different stimulus intensities. For most participants this bite force lay above the maximum that they produced voluntarily: voluntary maximum bites ranged from 153 to 593 N, while the extrapolations predicted a narrower and higher potential range of 282-629 N. It was concluded that, for the masseters at least, there is often spare force-generating capacity which individuals are either unable or not prepared to utilize. This method is non-invasive and may help to define better the maximum bite-force potential of humans.

Variability of the dishabituation of flexion reflexes for FES assisted gait in spinal injured man.

Flexion reflexes, elicited by surface stimulation, can be used to produce a simple form of stepping in spinal cord injured (SCI) humans. A drawback of this approach is a decreasing magnitude of flexion reflex to repeated presentations of the stimuli (habituation). Pilot data indicated that high intensity stimulation could produce dishabituation of the reflex. The aim of this study was to examine and quantify the inter- and intra-subject variability of the short and long term conditioning effect of high intensity stimulation on the magnitude of flexion reflexes in a larger number of SCI subjects. Dishabituation was observed in all subjects, however the amount of dishabituation observed was small and highly variable. However the use of high intensity conditioning stimulation may offer a means of coping with habituation in a small number of subjects.

Masseter muscle relaxation rate in volunteers with a myogenous craniomandibular disorder.

Twelve volunteers were investigated to determine their masseter muscle relaxation rate following voluntary contractions. Four of these volunteers were patients diagnosed as having a myogenous craniomandibular disorder. Electromyograms were recorded from the left and right masseter muscles and maximum bite force was recorded in the midline between the incisor teeth. A sustained contraction was maintained at 50% maximum voluntary bite force for 90 s, during which there was a brief relaxation every 10 s. Recordings were continued for a 3 min recovery period. This sequence was then repeated at 25% of maximum bite force. Median power frequencies were calculated from the power spectra for the first and last 3 s of the sustained contractions. Relaxation rates were measured for each brief relaxation during the sustained contraction and for the relaxation from each brief clench during the recovery period. It was found that maximum bite force values were very similar for volunteers in both the patient and control groups. Relaxation rates slowed more and percentage changes in median frequency were greater in the controls than in the patients during the sustained contractions. However, relaxation rates returned to initial levels more quickly in the controls than in the patients.

The effect of knee joint afferent discharge on transmission in flexion reflex pathways in decerebrate cats.

1. Changes in excitability of reflex arcs mediating flexion withdrawal ad crossed extensor reflexes have been examined in decerebrate cats. 2. The excitability of flexion withdrawal and crossed extensor reflexes was shown to be modulated by knee joint position. Flexion withdrawal reflexes were most easily elicited when the knee was extended and crossed extensor reflexes were most easily elicited when the knee was flexed. 3. The modulation of transmission was not confined to reflex pathways to muscles acting at the knee but also included pathways to muscles acting at the hip and ankle, as well as pathways to muscles in the contralateral limb. 4. The changing excitability of reflex pathways caused by movement of the knee joint was unrelated to the stretch applied to muscles acting at the knee and to cutaneous afferent discharge. Modulation of reflex excitability by joint movement was totally abolished by local anaesthesia of the knee joint in an otherwise intact limb. 5. The results of the present experiments indicate that transmission in flexion reflex pathways can be inhibited by knee joint afferent discharge.

A preliminary electromyographic study of bite force and jaw-closing muscle fatigue in human subjects with advanced tooth wear.

The maximum bite force was recorded in five experimental volunteers with advanced tooth wear and five control volunteers who showed no abnormal wear. All subjects were then asked to maintain a force of 50% of the maximum for as long as possible while surface electromyograms from the masseter and temporalis muscles were recorded. The bite force and endurance time were found to be slightly increased in the experimental group, but no conclusions could be drawn regarding the state of fatigue. Two significant problems with regard to fatigue studies of the jaw-closing muscles emerged from the study, namely the use of the canine position for recording of the force, and the thickness of the force meter.

Fatigue and EMG changes in the masseter and temporalis muscles during sustained contractions.

Local muscle fatigue was investigated in the anterior temporal and masseter muscles during sustained isometric contractions. The volunteers' subjective perception of fatigue or pain was recorded at intervals during the sustained contractions, and this level was then compared to objective measures of fatigue. These objective measures included shift in median frequency of the power spectrum of the surface-detected EMG signal, and change in signal amplitude. The relationship was investigated while closing on a bite force meter placed between the second premolars and first molars unilaterally, and while simply clenching with the teeth together without the bite force meter. It was found that the subjective perception of fatigue, as measured on a visual analogue scale (VAS), had a nearly linear relationship with time, and that the relationship between the VAS score and median frequency shift was rather closer than the relationship with amplitude change.