Depolarization of the terminals of different groups of afferent fibers of the lumbar region of the spinal cord during fictive scratching

Kinetics of lumbar primary afferent depolarization was investigated during fictitious scratching of decerebrated and decapitated cats. Fictitious scratching was accompanied by tonic and phasic primary afferent depolarization. Periodic depolarization of primary afferents was synphasic in different segments of the lumbosacral spinal cord. Tonic depolarization was observed in the terminals of all the investigated groups of fibres (low-threshold cutaneous and of groups 1a and 1b). Phasic changes took place in terminals of low-threshold cutaneous fibres and fibres of group 1b. Physiological significance of modulation of primary afferent depolarization by the spinal scratching generator is discussed on the basis of the data obtained.     

Presynaptic mechanisms of the change in segmental responses accompanying the formation of the spinal locomotor generator in the cat

It is shown on unanesthetized immobilized decorticated cats that spinalization of the animal leads to depolarization of the central afferent terminals, decrease of early polysynaptic responses in motoneurons and dorsal root potentials (DRP) evoked by stimulation of the low-threshold cutaneous and muscle afferents, increase of early polysynaptic responses and DRP evoked by stimulation of high-threshold muscle afferents, reduction in the activity of intermediate nucleus interneurons mono- and polysynaptically connected with primary afferents, rise of the activity of interneurons di- and oligosynaptically connected with primary afferents. Injection of DOPA into spinal animals leads to opposite changes. Dependence between changes in the state of segmental neuronal apparatus and the level of spinal locomotor generator activity are discussed on the basis of the data obtained.     

Late prolonged discharges in the motor nerves of the hindlimbs and their relationship to locomotor rhythmicity in thalamically immobilized cats]

Effects of flexor reflex afferents stimulation were investigated on high decerebrated curarized cats. Stimulation of ipsilateral flexor reflex afferents evoked late long-lasting discharges in flexor nerves. Contralateral flexor reflex afferents stimulation evoked late discharges both in extensor and flexor nerves. Transition from late discharges to rhythmic discharges was observed. Early segmental reflexes were tonically depressed in thalamic in comparison with acute spinal cats. A similar tonic depression of segmental reflexes took place in acute spinal cats after DOPA injection. Segmental reflexes were distinctly modulated during late and rhythmic discharges. On the basis of the data available possible central mechanisms of the observed changes of segmental reflexes are discussed.     

Synaptic effects from chemically activated fine muscle afferents upon α-motoneurones in decerebrate and spinal cats

In spinal and decerebrate cats fine muscle afferents (group III and IV) were selectively activated by intra-arterial injection of bradykinin and KCl into the gastrocnemius-soleus muscle. By this method the synaptic responses induced in lumbar α-motoneurones by fine muscle afferents could be examinedwithout interference of effect from large afferents. α-Motoneurones receiving EPSPs evoked by electrical stimulation of cutaneous and high threshold muscle afferents (mainly flexor motoneurones) responded to the activation of fine muscle afferents with a depolarization of their membrane and an increase in synaptic noise, while motoneurones in which IPSPs were evoked by electrical stimulation of cutaneous and high threshold muscle afferents (mainly extensor motoneurones), responded with hyperpolarization of their membrane. Cells with mixed excitatory-inhibitory electrically induced response characteristic responded with an increase in synaptic noise without substantial change in the level of their membrane potential to chemical stimulation of fine muscle afferents. The results indicate that one function of group IIIand IV muscle afferents is to participate in the complex reflex control performed by the flexor reflex system.     

Differential decerebrate control of depolarization in the central terminals of cutaneous afferents in the sacral cord

Presynaptic depolarization of cutaneous afferents has been investigated in the sacral cord of decerebrate cats before and after spinal cord transection. In the decerebrate state the central terminals of caudal femoral cutaneous nerve are depolarized by ipsilateral volleys entering the cord via sacral and lumbar dorsal roots. A significant increase of depolarization occurring after severing the cord indicates that there is tonic decerebrate inhibition of presynaptic depolarization in terminals of caudal femoral cutaneous nerve. In contrast to this finding, presynaptic depolarization evoked in the central terminals of the pudendal nerve by ipsilateral volleys entering the cord through sacral and lumbar dorsal roots is not subjected to decerebrate inhibitory control. It is suggested that differential inhibitory control of depolarization in the central terminals of cutaneous nerves in the sacral cord is related to the intraspinal course of their fibres, to differences in the receptor types involved, and to the location of their innervation fields. In more than half of the decerebrate preparations stimulation of the central terminals of cutaneous afferents through microelectrodes evokes antidromic spikes appearing simultaneously in ipsi- and contralateral nerves. The time course of bilateral excitability changes is similar on both sides of the cord. It is assumed that presynaptic effects are transmitted to the contralateral side by collaterals of ipsilateral cutaneous afferents.     

Inhibitory and facilitatory effects from the peroneal nerve onto the soleus H-reflex in normal and spinal man

The effects of conditioning stimulation of a mixed nerve in the leg, the common peroneal nerve (CPN), on the ipsilateral soleus H-reflex were compared with the effects of stimulating its cutaneous branch, the superficial peroneal nerve (SPN), in two groups of subjects--normals and patients with spinal spasticity subsequent to a clinically complete transection of the spinal cord. Condition-test delays of 20 msec to 2 sec, measured from the end of the 20 msec train (3 pulses at 100 Hz), were investigated. In normal subjects, CPN stimulation at 1.4 X MT profoundly depressed the soleus H-reflex. There was an initial depression (peak 40-90 msec) followed by a slow recovery which was incomplete at condition-test delays of 2 sec. One-half of the subjects showed a late facilitation, or disinhibition, peaking at 170-190 msec. The inhibitory effects were attributed to activation of low threshold, groups I and II, muscle afferents because stimulation of the SPN, at 1.5 X threshold for a compound action potential recorded from the CPN, had only facilitatory effects on the soleus H-reflex. Facilitation occurred at condition-test delays of 30-190 msec. The cutaneous stimulation was presumed to activate the largest, A beta, cutaneous afferents as it elicited a weak paraesthesia on the dorsum of the foot. The results suggested that cutaneous afferents may have contributed to the late facilitation seen with CPN conditioning stimulation. In spinal cord-lesioned subjects, CPN stimulation depressed the soleus H-reflex but the decrease was less and the recovery was faster and more complete than in normals. The magnitude of the initial depression at 20-100 msec varied with the severity of the spasticity, subjects with mild spasticity showing less of a depression. Weak cutaneous conditioning stimulation either had no effect or produced a slight depression of the soleus H-reflex, providing clear evidence that transmission in the pathways mediating the facilitatory effects of cutaneous afferents onto extensor motoneuronal pools is depressed in spinal spasticity. This may shift the balance of activity toward the flexor motoneurones, thus favouring the development of, for example, flexor spasms and flexor hypertonia. Since inhibitory effects from cutaneous stimulation are associated with activation of higher threshold afferents in normal man, the present results may reflect a decrease in the threshold for flexor withdrawal reflexes commonly associated with spasticity of spinal origin.     

Rapid modulation of cortical proprioceptive activity induced by transient cutaneous deafferentation: neurophysiological evidence of short-term plasticity across different somatosensory modalities in humans

Single cell recording in non-human primates shows plastic changes of cortical somatic representations across different types of somatic inputs originating from the same peripheral territory. In humans, muscle afferents from first dorsal interosseus are supplied by the ulnar nerve while the cutaneous territory overlying this muscle is supplied by the radial nerve. This peculiar anatomical nervous distribution allowed us to devise an experimental model which provided a unique opportunity to assess, in humans with a non-invasive technique, the functional relationships between cutaneous and muscle afferent inputs originating from the same peripheral territory. We recorded spinal, brainstem and cortical somatosensory potentials evoked by stimulation of muscle afferents of the right first dorsal interosseus before, during and after anaesthetic block of the sensitive branch of the ipsilateral radial nerve. Amplitude of parietal N20 and P27 and frontal N30 somatosensory evoked potential components showed an increase of amplitudes with more profound anaesthesia. Amplitudes returned to pre-anaesthetic values several minutes after anaesthesia. By contrast, spinal N13 and brainstem P14 potentials did not change throughout the experiment. Results show, for the first time in humans, that a transient cutaneous deafferentation may induce rapid modulation of cortical activity evoked by stimulation of muscle afferents originating in the anaesthetic territory.     

Specific and potassium components in the depolarization of the la afferents in the spinal cord of the cat

In the cat spinal cord, primary afferent depolarization (PAD) of group Ia fibers of extensor muscles is produced by high-frequency stimulation (100 Hz) of group I muscle flexor afferents without significant increases in extracellular potassium. On the other hand, the PAD produced by stimulation of mixed and pure cutaneous nerves correlates well with increases in potassium ions. We conclude that the PAD produced by group I muscle afferents results from the activation of specific pathways making axo-axonic synapses with the Ia fiber terminals. The PAD of Ia fibers resulting from activation of cutaneous nerves involves instead unspecific accumulation of potassium ions.     

Depolarization of primary afferents during real scratching in the cat

Changes in depolarization of primary afferents and their correlation with afferent impulsation and limb movement were studied in the lumbar spinal cord during real scratching of decerebrated cats. Two components in rhythmic dorsal root potential were observed. First--centrally evoked, retained during fictitive scratching after immobilization; second--evoked by afferent discharge, coming to the spinal cord during the scratching phase of the limb movement.     

Specific and potassium components in the depolarization of the Ia afferents in the spinal cord of the cat

In the cat spinal cord, primary afferent depolarization (PAD) of group Ia fibers of extensor muscles is produced by high-frequency stimulation (100 Hz) of group I muscle flexor afferents without significant increases in extracellular potassium. On the other hand, the PAD produced by stimulation of mixed and pure cutaneous nerves correlates well with increases in potassium ions. We conclude that the PAD produced by group I muscle afferents results from the activation of specific pathways making axo-axonic synapses with the Ia fiber terminals. The PAD of Ia fibers resulting from activation of cutaneous nerves involves instead unspecific accumulation of potassium ions.     

Inhibition of spinal nociceptive transmission accompanies cardiovascular changes from stimulation in diencephalic 'defence' regions of cats

In anaesthetized cats, diencephalic regions were electrically stimulated while recording evoked responses from lumbar dorsal horn neurones and cardiovascular parameters. Neuronal responses to impulses evoked electrically in unmyelinated primary afferents were inhibited by stimulation in many diencephalic regions. Responses to non-noxious cutaneous stimulation (hair deflection) were inhibited at relatively few sites. Indirect circulatory measurements showed that this selective spinal inhibition was accompanied by increases in cardiac output and muscle blood flow but reduced cutaneous perfusion. This association between selective inhibition of nociceptive spinal neuronal responses and a cardiovascular response pattern associated with the defence reaction supports the proposal that analgesia could be an important component of defensive behaviour.     

On the role of central program and afferent inflow in the control of scratching movements in the cat.

Rhythmical scratching movements of the hindlimb were evoked in decerebrate and decapitate cats by stimulation of C1-C2 segments of the spinal cord. Movements of the limb and electrical activity of its muscles were recorded. All muscles were divided into two groups according to their activity. Muscles of the first group supported the limb in a propriate position; they were active during most of the cycle and relaxed during small intervals when muscles of the second group contracted. A deafferented limb was also capable of rhythmical scratching movements with approximately the same cycle duration. However, after deafferentation, the mean position of the limb changed and the amplitude of oscillations increased. This is due mainly to decreased activity of the first group muscles. In curarized preparations, stimulation of C1-C2 segments evoked a rhythmical process within the lumbosacral spinal cord ('fictive' scratching) with a cycle duration nearly the same as in normal scratching. Electrical activity of the muscle nerves during 'fictive' scratching resembled that of corresponding muscles during normal movements. 'Fictive' scratching could be easily elicited provided that the limb was put in a position similar to that of normal scratching.     

Vibration-evoked startle behavior in larval lampreys

Larval lampreys (ammocoetes) exhibit a rapid vibration-evoked startle response involving a bilateral activation of musculature along the length of the body. The resulting movement is variable, contingent on the animal's prestimulus posture: lateral curves along the trunk and tail contract more on the inner side of the curve than on the outer side. Thus, the startle response increases preexisting body curvature. Because ammocoetes are burrowing filter feeders, this startle behavior results in rapid withdrawal of the head into the burrow. A vibratory pulse to the otic capsules in a semi-intact preparation evokes simultaneous action potentials in both primary Mauthner neurons. Vibration also excites several Müller cells. Intracellular stimulation of one primary Mauthner axon (eliciting one action potential) produces bilateral trunk electromyographic potentials that are smaller than those evoked by vibration; simultaneous stimulation of both Mauthner axons (one action potential each) reproduces the vibration-evoked electromyographic amplitudes. The Mauthner cell's sensitivity to vestibular input is centrally modulated during changes in behavioral state. Mauthner action potentials are most easily elicited by vibratory or electrical stimulation of vestibular afferents while an intact animal is at rest; the same stimuli become subthreshold for Mauthner activity while the animal is swimming. A similar depression of Mauthner excitability is observed in semi-intact preparations during arousal. 'Arousal' was defined by the occurrence of tonic, descending spinal cord discharge. Mauthner cells are tonically depolarized during arousal and exhibit an increased membrane conductance; excitatory postsynaptic potentials evoked by vibratory or electrical stimulation of vestibular afferents are greatly attenuated. Modulated sensory transmission to the Mauthner cell may help to prevent inappropriate activation of the startle circuit.     

Synaptic activation of the interneurons of the thoracic portion of the spinal cord by reticulospinal fibers of the lateral funiculus

Synaptic processes evoked in various functional groups of thoracic interneurons (Th10,11) by stimulation of ipsi- and contralateral bulbar reticular formation were studied in anesthetized cats with lesions of the spinal cord that remained intact only the ipsilateral funiculus. Activation of reticulospinal fibres of the lateral funiculus with conduction velocities of 30-100 m/s evoked monosynaptic EPSPs in the following types of cells tested: monosynaptically excited by group la muscle afferents; excited by flexor reflex afferents; excited mainly by descending systems; excited by low-threshold cutaneous afferents to a less extent. All these neurons with responses to reticular stimulation were located predominantly in the central and lateral regions of Rexed's lamina VII. Most of the cells in the dorsal horn were not affected by short-latency reticulofugal influences. The only exception were 6 neurons located in the horn most dorsal laminae. Functional organization of connections between the lateral reticulospinal pathways and spinal neurons is discussed as compared to that of medial reticulo-spinal pathways as well as to the organization of "lateral" descending systems: cortico- and rubro-spinal.     

Stabilization of the discharge rate of sympathetic preganglionic neurons

A characteristic feature of the sympathetic preganglionic neuron (SPN) is the low rate of firing during both tonic and evoked activity. Firing rates between 1 and 2 Hz are typical of tonic activity, and the rates increase only slightly during sustained reflex activation. The low mean firing rate of the SPN may result from mechanisms which depress the excitability of the neuron and /or from a very low synaptic efficacy of its excitatory inputs. In recent years depressant mechanisms, other than baroreceptor inhibition, have been identified which may be involved in the control of SPN firing rate. Some of these mechanisms are spinal. This paper reviews data on 3 depressant mechanisms, namely post-impulse depression, recurrent inhibition and inhibition by myelinated spinal afferents, which are operating within the spinal cord.     

Interfering cutaneous stimulation and the muscle afferent contribution to cortical potentials

Cerebral potentials were recorded in response to selective stimulation using microelectrodes of muscle afferents in motor fascicles innervating the intrinsic muscles of the foot or at the motor point of abductor hallucis. The early components of these potentials (P40, N50 and P60) were consistently attenuated by continuous tactile stimulation of related skin areas and by electrical stimulation of digital nerves, timed so that the digital volley reached cortex approximately 5 msec before the muscle afferent volley. The same conditioning cutaneous inputs also attenuated the cerebral potentials evoked by selective stimulation of cutaneous afferents. These findings confirm that there are intermodality and intramodality interactions between low-threshold cutaneous and muscle afferents and between cutaneous afferents, respectively. The findings indicate that 'interference phenomena' (Kakigi and Jones 1986) can occur between different afferent modalities, and within any one modality, and cannot be used to determine the afferent species responsible for the test evoked potential.     

Differential effects of plantar cutaneous afferent excitation on soleus stretch and H‐reflex

Previous studies have demonstrated that plantar cutaneous afferents can adjust motoneuron excitability, which may contribute significantly to the control of human posture and locomotion. However, the role of plantar cutaneous afferents in modulating the excitability of stretch and H‐reflex with respect to the location of their excitation remains unclear. In the present study, it was hypothesized that electrical stimulation delivered to the sole of the foot might be followed by modulation of spinal excitability that depends on: (1) the stimulation location and (2) the reflex studied. In these experiments, conditioned and unconditioned stretch and H‐reflexes were evoked in 16 healthy subjects in a seated position. Both reflexes were conditioned by non‐noxious electrical plantar cutaneous afferent stimulation at two different sites, the heel and metatarsal regions, at four different conditioning–test (CT) intervals. The conditioning stimulation delivered to the heel caused a significant facilitation of the soleus stretch reflex for all CT intervals, whereas the soleus H‐reflex had significant facilitation only at CT interval of 50 ms and significant inhibition at longer CT intervals. Stimulation delivered to the metatarsal region, however, resulted mainly in reduced stretch and H‐reflex sizes. This study extends the reported findings on the contribution of plantar cutaneous afferents within spinal interneuron reflex circuits as a function of their location and the reflex studied. Muscle Nerve, 2008     

Functional organization of the spinal reflex pathways from forelimb afferents to hindlimb motoneurons in the cat. II. Conditions of the interneuronal connections

The interneuronal conditionsof the descending pathways from forelimb afferents to hindlimb motoneurones were investigated by testing spatial interactions in these pathways and between these pathways and segmental lumbar reflex pathways. In high spinal unanaesthetized cats hindlimb motoneuroneswere intracellularly recorded and spatial interactions were tested between effects evoked by stimulation of pairs of ipsi- and contralateral forelimb nerves or pairs of a forelimb and an ipsilateral hindlimb nerve. The excitatory and late inhibitory pathways from forelimb afferents projecting to most of the hindlimb motoneurone pools, showed an interactive pattern which was distinctly different to the fast inhibitory pathway projecting specifically for ipsilateral forelimb afferents to flexor digitorum and hallucis longus (FDHL) motoneurones. Stimulation of homonymous or heteronymous pairs of two forelimb nerves of both sides evoked generally a distinct spatial facilitation of the excitatory and late inhibitory effects, while the specific early IPSPs to FDHL motoneurones were not facilitated. Paired stimulation of two forelimb nerves of one side only produced spatial facilitation of EPSPs or late IPSPs if low strength stimuli were used, using higher strength which induced larger effects, generally caused occlusion instead. In case of large IPSPs this may be due to the vicinity to the equilibrium potential. Except for an inhibition of cutaneous reflex pathways, the spatial interaction of the excitatory and late inhibitory pathways onto segmental lumbar reflex pathways was weak and variable. The fast inhibitory pathway to FDHL motoneurone showed a partial spatial facilitatory interaction with lumbar reflex pathways from cutaneous and group II muscle afferents. The second IPSP wave evoked by this pathway was inhibited by antidromic stimulation of the ventral root L7S1 and of the α-efferents of the antagonistic peroneal nerve. From the results conclusions are drawn on the interneuronal organization of the descending pathways from forelimb afferents to hindlimb motoneurones.     

Neurons in the caudal ventrolateral medulla mediate the somato-sympathetic inhibitory reflex response via GABA receptors in the rostral ventrolateral medulla.

In urethane-anesthetized rabbits, stimulation of the sural nerve, consisting of cutaneous afferents (A-fibers), evoked reflex responses consisting of an early small excitatory component followed by a prolonged inhibitory component in renal sympathetic nerve activity. Bilateral injections of GABA antagonist, bicuculline (4 nmol/site), into the rostral ventrolateral medulla (RVLM), where sympatho-excitatory reticulospinal neurons are located, attenuated the inhibitory component in a dose-dependent manner as well as the inhibition evoked by stimulation of the aortic nerve A-fibers (baroreceptor afferents). Bilateral injections of a neurotoxic agent, kainic acid (4 nmol/site, 3 sites/side), into the caudal ventrolateral medulla (CVLM), where sympatho-inhibitory neurons with axonal projection to the RVLM are located, diminished these sympatho-inhibitory responses. Therefore it is concluded that the sympatho-inhibition evoked by activation of somatic afferents was mediated by neurons in the CVLM and by GABA receptors in the RVLM, as was the sympatho-inhibition associated with the arterial baroreceptor reflex. Bilateral injections of kynurenic acid (4 nmol/site, 3 sites/side) into the CVLM did not affect the somato-sympathetic reflex response, but diminished the sympatho-inhibition produced by activation of the baroreceptor afferents. Sympatho-inhibitory neurons in the CVLM were activated by glutamate when baroreceptor afferents were activated, but another excitatory transmitter may participate in the somato-sympathetic reflex in the CVLM.