Coupling between feline cerebellum (fastigial neurons) and motoneurons innervating hindlimb muscles

The aims of the study were twofold: (1) to verify the hypothesis that neurons in the fastigial nucleus excite and inhibit hindlimb alpha-motoneurons and (2) to determine both the supraspinal and spinal relays of these actions. Axons of fastigial neurons were stimulated at the level of their decussation in the cerebellum, within the hook bundle of Russell, in deeply anesthetized cats with only the right side of the spinal cord intact. The resulting excitatory postsynaptic potentials and inhibitory postsynaptic potentials were analyzed in motoneurons on the left side of the lumbar enlargement. Postsynaptic potentials evoked by the first effective stimulus were induced at latencies <2 ms from descending volleys and <1 ms from interneuronally relayed volleys, indicating a trisynaptic coupling between the fastigial neurons and alpha-motoneurons, via commissural interneurons on the right side. Cerebellar stimulation facilitated the synaptic actions of both vestibulospinal and reticulospinal tract fibers. However, the study leads to the conclusion that trisynaptic fastigial actions are mediated via vestibulospinal rather than reticulospinal tract fibers [stimulated within the lateral vestibular nucleus (LVN) and the medial longitudinal fascicle (MLF), respectively]. This is indicated firstly by collision between descending volleys induced by cerebellar stimulation and volleys evoked by LVN stimuli but not by MLF stimuli. Second, similar cerebellar actions were evoked before and after a transection of MLF. Mutual facilitation between the fastigial and reticulospinal, as well as between the fastigial and vestibulospinal actions, could be due to the previously reported integration of descending vestibulospinal and reticulospinal commands by spinal commissural interneurons.     

Responses in human pretibial muscles to sudden stretch and to nerve stimulation

Summary Electromyograms have been recorded from the human tibialis anterior muscle during voluntary contraction. The accessibility of the nerve to this muscle (common peroneal) has permitted a comparison of reflex responses to low threshold electrical stimulation of the nerve with those to stretch of the muscle itself. Nerve stimulation elicited a reflex at monosynaptic latency (V₁ at 28–29 ms) and a second response (V₂ at 50–52 ms). A tendon tap induced two responses (m₁ at 29 ms and M₂ at 50 ms). The responses to a ramp stretch were similar. The homology of V₁ with M₁, and of V₂ with M₂ is discussed. V₂ and M₂ probably correspond to the transcortical reflexes described from other muscles.Neither V₁ V₂, M₁ nor M₂ were influenced by anaesthesia of the foot. m₁ and M₂ were both reduced in amplitude by a selective -efferent block produced by local anaesthetic in the common peroneal nerve. It is concluded, that muscle spindles are the receptors predominantly responsible for M₂ (transcortical) responses.The amplitudes of M₁ and M₂, but not V₁ and V₂ were augmented by prior instruction to resist the stimulus. This is interpreted as evidence for voluntary modulation of -efferent activity at a constant force of contraction.Beit Memorial Research Fellow     

Responses of primate visual cortical V4 neurons to simultaneously presented stimuli

We report here results from 45 primate V4 visual cortical neurons to the preattentive presentations of seven different patterns located in two separate areas of the same receptive field and to combinations of the patterns in the two locations. For many neurons, we could not determine any clear relationship for the responses to two simultaneous stimuli. However, for a substantial fraction of the neurons we found that the firing rate was well modeled as the maximum firing rate of each stimulus presented separately. It has previously been proposed that taking the maximum of the inputs ("MAX" operator) could be a useful operation for neurons in visual cortex, although there has until now been little direct physiological evidence for this hypothesis. Our results here provide direct support for the hypothesis that the MAX operator plays a significant (although certainly not exclusive) role in generating the receptive field properties of visual cortical neurons.     

Responses of primate spinothalamic tract neurons to electrical stimulation of hindlimb peripheral nerves.

The responses of spinothalamic tract neurons were studied by extra- and intracellular recordings from the lumbosacral spinal cord in anesthetized rhesus monkeys (Macaca mulatta). The neurons were identified by antidromic activation from the contralateral diencephalon. They were then classified by the mildest form of mechanical stimulation applied to the ipsilateral hindlimb. The effects of electrical stimulation of the nerve(s) supplying the receptive field were investigated. Graded electrical stimulation revealed that the threshold responses of spinothalamic tract neurons excited by weak mechanical stimuli occurred when the largest afferent fibers were activated. On the other hand, neurons that required intense mechanical stimulation for their excitation tended to have higher thresholds to electrical stimulation. Some spinothalamic tract cells were shown to receive monosynaptic excitatory connections from peripheral nerve fibers, although polysynaptic connections may generally be more important. An input from unmyelinated afferent fibers was demonstrated. It is concluded the primate spinothalamic tract neurons receive a rich convergent input from a variety of cutaneous receptors. The experiments provide some evidence for the most likely types of receptors.     

Responses of spinal cord neurons to systematic changes in hindlimb skin temperatures in cats and primates.

Single-neuron recordings were made from the lumbar spinal cords of cats and squirrel monkeys. Recording sites were distributed throughout the dorsal horn and included Rexed's laminae I and III-VI in both species and laminae VII-VIII in cats. Activity was studied during systematic changes in skin temperature over the range of 15-49 degress C; this encompasses the perceptions of innocuous cooling and warming plus the initial stages of noxious heating. The experiment included studies in which the thermal stimulus was changed from various preadapting temperatures. In all cases, the sensitivity of an individual neuron to changes in skin temperature was associated with responses to various intensities of tactile stimulation which, for some neurons, could range from low to painful pressures. More than two-thirds of the neurons excited by innocuous temperature changes discharged to both cooling and warming, although the thresholds were much lower for cold temperature differecnes (less than or equal to 2 degrees C for cold steps as compared with more than 6 degrees C for warm steps). However, many neurons only responded to extreme cooling or, more frequently, noxious heating. The temperature response relationships of many neurons during cooling was best described in reference to specific cold-receptor activity because the discharge rates declined at extremely cold temperatures and because the slopes of the temperature-response functions were nearly identical when studied with different adapting temperatures. The responses of certain slowly adapting mechanoreceptors was considered in describing some of the spinal cord activity during extreme cooling. The responses to hot temperatures were attributed to activity in various receptors, including especially polymodal receptors. Activity during innocuous warming was ascribed to one population of peripheral warm receptors that do not show maximal static activity during innocuous warm stimuli. The significance of the extensive convergence in the spinal cord from mechanoreceptors and thermoreceptors was discussed in relation to thermal perception and the complexity of the information transmitted by the spinothalamic tract.     

Kinematic representation of imposed forearm movements by pericruciate neurons (areas 4 and 3a) in the awake cat

In eight awake cats, elbow flexion movements were imposed by a computer-controlled torque motor using three different classes of angular displacement inputs: force step-load displacements; sinusoidal displacements; and constant-velocity ramp displacements. Microelectrode recordings were obtained from 309 pericruciate neurons in areas 4 and 3a. Average response histograms for single-unit activity coupled with computer simulation of the imposed movements have shown in a neuronal population (n = 81), selected for receptive fields that were directly related to elbow movements, that both the magnitude and temporal features of the responses can be characterized by the coefficients of a third-order differential equation describing the movement's angular kinematics (i.e., position, velocity, acceleration, and jerk). To compare the responses of different neurons the coefficients were normalized to the angular velocity coefficient, which was assigned a weighted value of 1.0. The neurons' average responses were "predictable" by the normalized coefficients regardless of the imposed movements' temporal characteristics. Two distinct and spatially separate pericruciate areas containing neurons that responded to the imposed forearm movements were located: 1) one within area 4 at the lateral extent of the cruciate sulcus, which contained neurons that responded with predominant jerk and acceleration coefficients, exhibited either cutaneous or deep receptive fields, and demonstrated low microstimulation current thresholds to activate forelimb muscles; 2) a second, more laterally located area near the 3a/4 border in the postsygmoid gyrus, which contained neurons that responded with predominant velocity coefficients, and comparatively small jerk acceleration, and position coefficients, exhibited either cutaneous or deep receptive fields, and demonstrated high microstimulation thresholds (greater than 20 microA). Due to the sensitivity of the higher derivatives to changes in motion, the relative magnitude and time course of the average firing probability of area 4 neurons with prominent acceleration and jerk coefficients were dominated by these kinematic features during the more rapidly imposed movements. The findings are in accord with a hypothesis proposing that motor cortical neurons in area 4 form a sufficient substrate for a "predictive" feedback organization, and may constitute an essential component of a system capable of regulating errors in angular joint movements despite the relatively long conduction delays and the slow time course of muscle tension production inherent to mammalian neuromuscular systems.     

Intracellularly labeled pyramidal neurons in the cortical areas projecting to the spinal cord. II. Intra- and juxta-columnar projection of pyramidal neurons to corticospinal neurons

Intra- or juxta-columnar connections of pyramidal neurons to corticospinal neurons in rat motorsensory cortices were examined with brain slices by combining intracellular staining with Golgi-like retrograde labeling of corticospinal neurons. Of 108 intracellularly labeled pyramidal neurons, 27 neurons were selected for morphological analysis by successful staining of their axonal arborizations and sufficient retrograde labeling of corticospinal neurons. Many varicosities of local axon collaterals of each pyramidal neuron were closely apposed to the dendrites of corticospinal neurons, suggesting the convergent projections of layer II–VI pyramidal neurons to corticospinal neurons. Particularly, the varicosities of a layer IV star-pyramidal neuron made two- to three-fold more appositions to the dendrites of corticospinal neurons than those of a pyramidal neuron in the other layers. Fifteen appositions were examined electron-microscopically and 60% of them made asymmetric axospinous synapses. The present results together with those of the preceding report suggest that thalamic inputs are conveyed to corticospinal neurons preferentially via layer IV star-pyramidal neurons with phasic response properties, and thereby might contribute to the initiation or switching of movement. In contrast, inputs with tonic response properties from the other layers seem to be integrated in corticospinal neurons, and might be useful in maintaining the activity of corticospinal neurons.     

Responses of cortical neurons to stimulation of corpus callosum in vitro

1. An in vitro slice preparation of rat cingulate cortex was used to analyze the responses of layer V neurons to electrical stimulation of the corpus callosum (CC). In addition, synaptic termination of callosal afferents with layer V neurons was evaluated electron microscopically to provide a structural basis for interpreting some of the observed response sequences. 2. Layer V neurons had a resting membrane potential (RMP) of 60 +/- 0.68 (SE) mV, an input resistance of 47 +/- 4.74 M omega, a membrane time constant of 4.37 +/- 0.51 ms, an electrotonic length constant of 1.38 +/- 0.25, and produced spontaneous action potentials that were 50 +/- 0.3 mV in amplitude. Intracellular depolarizing current pulses evoked spikes that were sometimes associated with low-amplitude (2-5 mV) depolarizing (5-10 ms in duration) and hyperpolarizing (10-20 ms in duration) afterpotentials. 3. A single stimulus of increasing intensities to the CC produced one of the following response sequences: a) antidromic spike and an excitatory postsynaptic potential (EPSP), which initiated one or more spikes; b) antidromic spike, EPSP-evoked action potentials, and a hyperpolarization, which may have represented an intrinsic cell property or inhibitory synaptic activity; c) EPSP and evoked spikes only; d) high-amplitude EPSP with an all-or-none burst of action potentials. 4. Antidromically activated (AA) neurons always produced EPSPs in response to CC stimulation. When compared with nonantidromically activated neurons, AA cells had a more negative RMP, greater electrotonic length constant (LN), higher ratio of dendritic to somatic conductance (rho), and formed shorter duration, callosal-evoked EPSPs. 5. Neurons in anterior cingulate cortex produced EPSPs of longer duration than did those in posterior cortex (50 +/- 3.57 versus 26 +/- 1.56 ms, respectively). EPSPs in anterior neurons also had a higher maximum amplitude (20.5 +/- 1.0 versus 11.5 +/- 0.79 mV) and longer time to peak (11.6 +/- 2.2 versus 8.2 +/- 0.8 ms). 6. Electron microscopy of Golgi-impregnated neurons following contralateral lesions demonstrated that both pyramidal and nonpyramidal neurons received direct callosal afferents. Synaptic termination of callosal axons with the apical dendritic trees of anterior pyramidal cells was 6 times greater than it was with posterior pyramidal neurons. 7. EPSP shape differences in anterior and posterior neurons may be partially accounted for by the density and distribution of callosal afferents to these two cortices.     

Intracellularly labeled pyramidal neurons in the cortical areas projecting to the spinal cord. I. Electrophysiological properties of pyramidal neurons

To study cortical motor control, we examined electrical characteristics of pyramidal neurons in the present report, and intra- or juxta-columnar connections of the pyramidal neurons to corticospinal neurons in the accompanying report. Pyramidal neurons were intracellularly recorded and stained in slices of rat motorsensory cortices (areas FL, HL and M1) where many corticospinal neurons were labeled retrogradely. They were morphologically classified into classical, star and other modified pyramidal neurons, and electrophysiologically into regular-spiking (RS), intrinsic bursting (IB) and irregular-spiking (IS) neurons on the basis of spiking pattern in response to 500 ms depolarizing current pulses. RS responses were further divided into RS with slow adaptation (RS-SA) and RS with fast adaptation (RS-FA). The electrical properties were associated with the laminar location of the neurons; RS-SA responses were observed frequently in layer II/III and less frequently in layers IV–VI, and IB and IS responses were exclusively found in layers V and VI, respectively. Interestingly, all layer IV neurons in area FL/HL were RS-FA star-pyramidal neurons, whereas layer IV neurons in area M1 were RS-SA classical pyramidal neurons. Although weak stimulation of areas FL/HL and M1 is known to elicit movement, these results suggest different information processings between the two areas.     

Renal and hindlimb vascular control during acute emotion in the baboon.

Blood pressure, heart rate, oxygen consumption, and blood flow to the renal and hind-limb vasculatures were measured in healthy, unanesthetized baboons (Papio cynocephalus) in a controlled environment. Appropriate behavioral techniques were applied to allow the reproducible elicitation of a conditional emotional response (CER). Section of renal nerves and autonomic pharmacologic interventions were used to determine the mechanisms for the cardiovascular responses accompanying the CER. The resistance changes in the renal and hind-limb vascular beds were generated by rapid, neurally mediated vasoconstriction of the renal vasculature and by a slower acting, circulating vasoactive agent, most probably epinephrine, which causes a delayed second constriction in the renal bed and a net dilation in the hind limbs.     

The scaling of postcranial muscles in cats (Felidae) II: hindlimb and lumbosacral muscles

In quadrupeds the musculature of the hindlimbs is expected to be responsible for generating most of the propulsive locomotory forces, as well as contributing to body support by generating vertical forces. In supporting the body, postural changes from crouched to upright limbs are often associated with an increase of body mass in terrestrial tetrapods. However, felids do not change their crouched limb posture despite undergoing a 300‐fold size increase between the smallest and largest extant species. Here, we test how changes in the muscle architecture (masses and lengths of components of the muscle‐tendon units) of the hindlimbs and lumbosacral region are related to body mass, to assess whether there are muscular compensations for the maintenance of a crouched limb posture at larger body sizes. We use regression and principal component analyses to detect allometries in muscle architecture, with and without phylogenetic correction. Of the muscle lengths that scale allometrically, all scale with negative allometry (i.e. relative shortening with increasing body mass), whereas all tendon lengths scale isometrically. Only two muscles' belly masses and two tendons' masses scale with positive allometry (i.e. relatively more massive with increasing body mass). Of the muscles that scale allometrically for physiological cross‐sectional area, all scale positively (i.e. relatively greater area with increasing body mass). These muscles are mostly linked to control of hip and thigh movements. When the architecture data are phylogenetically corrected, there are few significant results, and only the strongest signals remain. None of the vertebral muscles scaled significantly differently from isometry. Principal component analysis and manova s showed that neither body size nor locomotor mode separate the felid species in morphospace. Our results support the inference that, despite some positively allometric trends in muscle areas related to thigh movement, larger cats have relatively weaker hindlimb and lumbosacral muscles in general. This decrease in power may be reflected in relative decreases in running speeds and is consistent with prevailing evidence that behavioural changes may be the primary mode of compensation for a consistently crouched limb posture in larger cats.     

Fiber-type composition of selected hindlimb muscles of a primate (cynomolgus monkey)

The distribution of fiber types in selected leg and thigh muscles of three male Cynomolgus monkeys were determined. Almost all fibers could be classified as fast-glycolytic (FG), fast-oxidative glycolytic (FOG), or slow-oxidative (SO) according to the qualitative histochemical staining scheme described by Peter et al. (1972). Most muscles showed regional variations in fiber-type distributions, i.e., the percent SO was higher and the percent FG was lower in the deep, compared to the superficial, regions of the muscle. Exceptions were the soleus and plantaris muscles, which contained similar distributions of fiber types throughout their cross sections. In the extensor compartment of the leg, a layering of fiber types from deep to superficial were evident in the triceps surae and plantaris complex with the deepest muscle, the soleus, having primarily SO fibers. A similar layering arrangement was observed in the extensor compartment of the thigh, with the deepest muscle, the vastus intermedius, having a much larger proportion of SO fibers than the other muscles in the quadriceps complex. These results indicate that Cynomolgus monkey hindlimb muscles, unlike human leg muscles (Saltin and Gollnick: Handbook of Physiology, L.D. Peachey, ed. American Physiological Society, MD, pp. 55-631, 1983) have a regional distribution of fiber types similar to that observed in many subprimate mammals. Further, the presence of compartmentalization of fiber types within the cross section of several of the muscles studied is suggestive of structure-function interrelationships related to motor control.     

Recurrent collaterals of motoneurons projecting to distal muscles in the cat hindlimb.

1. Recurrent collaterals of motoneurons innervating muscles that have a role in control of the hindlimb digits were studied with neuroanatomic tracing methods to determine whether these motoneurons have simple recurrent collateral arbors in comparison with those of hip, knee, and ankle muscles. 2. Motoneurons innervating the hindlimb muscles plantaris (Pln), flexor hallucis longus (FHL), or flexor digitorum longus (FDL) were injected with 10% horseradish peroxidase. Recurrent collaterals were reconstructed from serial transverse sections. 3. No recurrent collaterals were observed in a sample of 10 FDL motoneurons. 4. FHL motoneurons had simple recurrent collateral arbors as assessed by number of first-order collaterals, number of collateral swellings, number of end branches, and the highest-order branch of individual collateral trees. Recurrent collateral arbors of Pln motoneurons were more complex than those of FHL motoneurons. Pln and FHL recurrent collateral arbors were less complex than those described for gastrocnemius-soleus, anterior tibial, and posterior biceps motoneurons. 5. These anatomic findings correspond well with electrophysiological results indicating that the recurrent inhibition produced by FHL motoneurons is weak and that FDL motoneurons do not produce recurrent inhibition. In addition, Pln motoneurons are reported to produce stronger recurrent inhibition than FHL motoneurons in many motor pools. 6. Consideration of these results with respect to the mechanical actions and patterns of motor activity observed in FDL, FHL, and Pln suggests that the complexity of recurrent collaterals of a motoneuron pool and the extent of its contribution to recurrent inhibition diminish with its involvement in the individualized control of the digits.     

Directional asymmetry of neurons in cortical areas MT and MST projecting to the NOT-DTN in macaques

The cortical projection to the subcortical pathway underlying the optokinetic reflex was studied using antidromic electrical stimulation in the midbrain structures nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) while simultaneously recording from cortical neurons in the superior temporal sulcus (STS) of macaque monkeys. Projection neurons were found in all subregions of the middle temporal area (MT) as well as in the medial superior temporal area (MST). Antidromic latencies ranged from 0.9 to 6 ms with a median of 1.8 ms. There was a strong bias in the population of cortical neurons projecting to the NOT-DTN for ipsiversive stimulus movement (towards the recording side), whereas in the population of cortical neurons not projecting to the NOT-DTN a more or less equal distribution of stimulus directions was evident. Our data indicate that there is no special area in the posterior STS coding for ipsiversive horizontal stimulus movement. Instead, a specific selection of cortical neurons from areas MT and MST forms the projection to the NOT-DTN and as a subpopulation has the same directional bias as their subcortical target neurons. These findings are discussed in relation to the functional grouping of cortical output as an organizational principle for specific motor responses.