Introduction to synaptic circuits, Gordon M.Shepherd and Christof Koch membrane properties and neurotransmitter actions, David A.McCormick peripheral ganglia, Paul R.Adams and Christof Koch spinal cord - ventral horn, Robert E.Burke olfactory bulb, Gordon M.Shepherd, and Charles A.Greer retina, Peter Sterling cerebellum, Rodolfo R.Llinas and Kerry D.Walton thalamus, S.Murray Sherman and Christof Koch basal ganglia, Charles J.Wilson olfactory cortex, Lewis B.Haberly hippocampus, Thomas H.Brown and Anthony M.Zador neocortex, Rodney J.Douglas and Kevan A.C.Martin Gordon M.Shepherd. Appendix: Dendretic electrotonus and synaptic integration.

The synaptic organization of the brain

Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. It may arise not only because of peripheral changes at the level of the muscle, but also because the central nervous system fails to drive the motoneurons adequately. Evidence for “central” fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it. Much data suggest that voluntary activation of human motoneurons and muscle fibers is suboptimal and thus maximal voluntary force is commonly less than true maximal force. Hence, maximal voluntary strength can often be below true maximal muscle force. The technique of twitch interpolation has helped to reveal the changes in drive to motoneurons during fatigue. Voluntary activation usually diminishes during maximal voluntary isometric tasks, that is central fatigue develops, and motor unit firing rates decline. Transcranial magnetic stimulation over the motor cortex during fatiguing exercise has revealed focal cha...

Spinal and Supraspinal Factors in Human Muscle Fatigue

Calbindin D-28k and parvalbumin in the rat nervous system

It is generally accepted that human bipedal upright stance is achieved by feedback mechanisms that generate an appropriate corrective torque based on body-sway motion detected primarily by visual, vestibular, and proprioceptive sensory systems. Because orientation information from the various senses is not always available (eyes closed) or accurate (compliant support surface), the postural control system must somehow adjust to maintain stance in a wide variety of environmental conditions. This is the sensorimotor integration problem that we investigated by evoking anterior-posterior (AP) body sway using pseudorandom rotation of the visual surround and/or support surface (amplitudes 0.5-8 degrees ) in both normal subjects and subjects with severe bilateral vestibular loss (VL). AP rotation of body center-of-mass (COM) was measured in response to six conditions offering different combinations of available sensory information. Stimulus-response data were analyzed using spectral analysis to compute transfer functions and coherence functions over a frequency range from 0.017 to 2.23 Hz. Stimulus-response data were quite linear for any given condition and amplitude. However, overall behavior in normal subjects was nonlinear because gain decreased and phase functions sometimes changed with increasing stimulus amplitude. "Sensory channel reweighting" could account for this nonlinear behavior with subjects showing increasing reliance on vestibular cues as stimulus amplitudes increased. VL subjects could not perform this reweighting, and their stimulus-response behavior remained quite linear. Transfer function curve fits based on a simple feedback control model provided estimates of postural stiffness, damping, and feedback time delay. There were only small changes in these parameters with increasing visual stimulus amplitude. However, stiffness increased as much as 60% with increasing support surface amplitude. To maintain postural stability and avoid resonant behavior, an increase in stiffness should be accompanied by a corresponding increase in damping. Increased damping was achieved primarily by decreasing the apparent time delay of feedback control rather than by changing the damping coefficient (i.e., corrective torque related to body-sway velocity). In normal subjects, stiffness and damping were highly correlated with body mass and moment of inertia, with stiffness always about 1/3 larger than necessary to resist the destabilizing torque due to gravity. The stiffness parameter in some VL subjects was larger compared with normal subjects, suggesting that they may use increased stiffness to help compensate for their loss. Overall results show that the simple act of standing quietly depends on a remarkably complex sensorimotor control system.

Sensorimotor integration in human postural control

Muscle fatigue encompasses a class of acute effects that impair motor performance. The mechanisms that can produce fatigue involve all elements of the motor system, from a failure of the formulation of the descending drive provided by suprasegmental centers to a reduction in the activity of the contractile proteins. We propose four themes that provide a basis for the systematic evaluation of the neural and neuromuscular fatigue mechanisms: 1) task dependency to identify the conditions that activate the various mechanisms; 2) force-fatigability relationship to explore the interaction between the mechanisms that results in a hyperbolic relationship between force and endurance time; 3) muscle wisdom to examine the association among a concurrent decline in force, relaxation rate, and motor neuron discharge that results in an optimization of force; and 4) sense of effort to determine the role of effort in the impairment of performance. On the basis of this perspective with an emphasis on neural mechanisms, we suggest a number of experiments to advance our understanding of the neurobiology of muscle fatigue.

Neurobiology of muscle fatigue.

1. In the preceding paper (Crone, Hultborn, Kiehn, Mazieres & Wigstrom, 1988) it was shown that a short-lasting synaptic excitation ('on' stimulus) of extensor motoneurones (primarily triceps surae) in the decerebrate cat often resulted in a maintained excitability increase, which could be reset by a short-lasting inhibitory stimulus train ('off' stimulus). In the present experiments intracellular recording from triceps surae motoneurones and the electroneurogram (ENG activity) from triceps surae nerve branches were performed in parallel. 2. Sustained firing of individual triceps surae motoneurones was most often recorded in parallel with the maintained ENG activity following a synaptic 'on' stimulus. When the motoneurone was silenced, by a hyperpolarizing current through the microelectrode, there was no sign of on-going synaptic excitation during the maintained ENG activity following an 'on' stimulus. It was therefore suggested that voltage-dependent intrinsic properties of the motoneurones themselves could be responsible for the maintained firing. 3. In confirmation of this hypothesis it was found that short-lasting depolarizing current pulses through the recording microelectrode could trigger a self-sustained firing in the motoneurone provided that the bias current (i.e. the holding potential) was kept within certain limits. Hyperpolarizing current pulses terminated the firing. When the spike-generating mechanism was inactivated (by long-lasting excessive depolarization) similar depolarizing and hyperpolarizing current pulses could initiate and terminate plateau potentials in the motoneurones. By grading the depolarizing current pulses it was found that the plateau potentials were of all-or-none character, typically around 10 mV in amplitude. The two levels of excitability which can be triggered by short-lasting excitation and inhibition of the motoneurones is referred to as 'bistable' behaviour of the motoneurones. 4. After an acute spinal transection, in the unanaesthetized cat, the bistable behaviour of the motoneurones disappeared. However, it reappears following intravenous injection of the serotonin precursor 5-hydroxytryptophan (50-120 mg/kg). 5. Individual triceps surae motor units were recorded by selective EMG electrodes during tonic stretch reflexes in the decerebrate preparations. Based on an analysis of their firing pattern during lengthening and shortening (or vibration) of the muscle it is suggested that plateau potentials in motoneurones are recruited during the tonic stretch reflex. Furthermore, it is argued that a quantitatively important part of the depolarization of motoneurones during the tonic stretch reflex indeed originates from these plateau potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Bistability of alpha-motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5-hydroxytryptophan.

The sections in this article are:


1
Methodological Considerations
1.1
Selective Stimulation of Primary Afferents

1.2
Stimulation of Central Motor Systems

1.3
Methods for Investigation of Convergence at Interneuronal Level




2
Spinal Neuronal Circuits Used in Common by Segmental Afferents and Supraspinal Motor Centers
2.1
Recurrent Inhibition

2.2
Pathways From Ia-Afferents and Their Control by γ-Motoneurons

2.3
Reflex Pathways From Group Ib Tendon Organ Afferents

2.4
Reflex Pathways From Cutaneous and Joint Afferents and From Groups II and III Muscle Afferents

2.5
Propriospinal Neurons

2.6
Presynaptic Inhibition of Transmission From Primary Afferents




3
Reticulospinal Inhibition of Segmental Reflex Transmission
3.1
Dorsal Reticulospinal System

3.2
Ventral Reticulospinal Pathways

3.3
Monoaminergic Reticulospinal Pathways

3.4
Decerebrate Preparation




4
Direct Projections of Descending Pathways to α-Motoneurons

5
Ascending Pathways that Monitor Segmental Interneuronal Activity
5.1
Evidence That Ascending FRA Pathways Monitor Activity in Interneurons of Reflex Pathways

5.2
Information Via Ascending Collaterals of Interneurons

5.3
Ventral Flexor Reflex Tracts

5.4
Ventral Spinocerebellar Tract




6
General Summary and Epilogue
6.1
General Summary

6.2
Epilogue

Integration in Spinal Neuronal Systems

1. Two independent methods were used, in man, to assess changes in presynaptic inhibition of I a terminals at the onset of selective voluntary contractions: (1) measurement of the amount of heteronymous monosynaptic I a facilitation (from the quadriceps muscle to soleus motoneurones) to provide an assessment of the amount of ongoing presynaptic inhibition exerted on the I a fibres responsible for the facilitation; (2) measurement of the inhibition of H reflexes 40-60 ms after a short vibration to the tibialis anterior tendon to estimate the excitability of the interneurones mediating presynaptic inhibition from tibialis anterior I a afferents to the I a afferents of the test H reflex (soleus or quadriceps). 2. At the onset of an isolated voluntary plantar flexion of the foot (gastrocnemius-soleus contraction) the heteronymous facilitation from quadriceps to soleus was increased, reflecting a decreased presynaptic inhibition of the quadriceps I a terminals on soleus motoneurones. Vibratory inhibition of the soleus H reflex was decreased, reflecting an inhibition of transmission of presynaptic inhibition to homonymous soleus I a afferent terminals. 3. At the onset of the same gastrocnemius-soleus contraction there was, on the contrary, an increased vibratory inhibition of the quadriceps H reflex indicating a facilitation of transmission of presynaptic inhibition to homonymous quadriceps I a afferent terminals. 4. At the onset of an isolated voluntary knee extension (quadriceps contraction) the opposite pattern was seen: the heteronymous facilitation from quadriceps to soleus was decreased and the vibratory inhibition of a soleus H reflex was increased, whereas the vibratory inhibition of the quadriceps H reflex was decreased. 5. These results indicate that presynaptic inhibition of I a afferent terminals on motoneurones of contracting muscles is decreased, permitting I a activity to contribute to excitation of voluntarily activated motoneurones. On the contrary, presynaptic inhibition of I a fibres to motoneurones of muscles not involved in the contraction is increased. It is argued that the former must be supraspinal in origin. 6. It is concluded that the control of presynaptic inhibition of I a fibres at the onset of movement may be organized so as to aid in achieving selectivity of muscle activation, i.e. so as to increase motor contrast.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1987.sp016681

Changes in presynaptic inhibition of Ia fibres at the onset of voluntary contraction in man.

The reflex regulation of stepping is an important factor in adapting the step cycle to changes in the environment. The present experiments have examined the influence of muscle proprioceptors on centrally generated rhythmic locomotor activity in decerebrate unanesthetized cats with a spinal transection at Th12. Fictive locomotion, recorded as alternating activity in hindlimb flexor and extensor nerves, was induced by administration of nialamide (a monoamine oxidase inhibitor) and L-DOPA. Brief electrical stimulation of group I afferents from knee and ankle extensors were effective in resetting fictive locomotion in a coordinated fashion. An extensor group I volley delivered during a flexor burst would abruptly terminate the flexor activity and initiate an extensor burst. The same stimulus given during an extensor burst prolonged the extensor activity while delaying the appearance of the following flexor burst. Intracellular recordings from motoneurones revealed that these actions were mediated at premotoneuronal levels resulting from a distribution of inhibition to centres generating flexor bursts and excitation of centres generating extensor bursts. These results indicate that extensor group I afferents have access to central rhythm generators and suggest that this may be of importance in the reflex regulation of stepping. Experiments utilizing natural stimulation of muscle receptors demonstrate that the group I input to the rhythm generators arises mainly from Golgi tendon organ Ib afferents. Thus an increased load of limb extensors during the stance phase would enhance and prolong extensor activity while simultaneously delaying the transition to the swing phase of the step cycle.

Proprioceptive input resets central locomotor rhythm in the spinal cat.

In parallel experiments on humans and in the cat it was investigated how the sensitivity of monosynaptic test reflexes to facilitation and inhibition varies as a function of the size of the control test reflex itself. In man the monosynaptic reflex (the Hoffmann reflex) was evoked in either the soleus muscle (by stimulation of the tibial nerve) or the quadriceps muscle (by stimulation of the femoral nerve). In the decerebrate cat monosynaptic reflexes were recorded from the nerves to soleus and medial gastrocnemius muscles; they were evoked by stimulation of the proximal ends of the sectioned L7 and S1 dorsal roots. Various excitatory and inhibitory spinal reflex pathways were used for conditioning the test reflexes (e.g. monosynaptic Ia excitation, disynaptic reciprocal inhibition, cutaneous inhibition, recurrent inhibition, presynaptic inhibition of the Ia fibres mediating the test reflex). It was shown that the additional number of motoneurones recruited in a monosynaptic test reflex by a constant excitatory conditioning stimulus was very much dependent on the size of the test reflex itself. This dependency had the same characteristic pattern whatever the conditioning stimulus. With increasing size of the test reflex the number of additionally recruited motoneurones first increased, then reached a peak (or plateau) and finally decreased. A similar relation was also seen with inhibitory conditioning stimuli. The basic physiological factors responsible for these findings are discussed. Finally, the implications for the interpretation of experiments in man with the H-reflex technique are considered.

Hans Hultborn

Papers

Bistability of alpha-motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5-hydroxytryptophan.

Integration in Spinal Neuronal Systems

Changes in presynaptic inhibition of Ia fibres at the onset of voluntary contraction in man.

Proprioceptive input resets central locomotor rhythm in the spinal cat.

Sensitivity of monosynaptic test reflexes to facilitation and inhibition as a function of the test reflex size: a study in man and the cat.