Barosensory cells in the nucleus tractus solitarius receive convergent input from group III muscle afferents and central command.

Some neural mechanism must prevent the full expression of the baroreceptor reflex during static exercise because arterial blood pressure increases even though the baroreceptors are functioning. Two likely candidates are central command and input from the thin fiber muscle afferents evoking the exercise pressor reflex. Recently, activation of the mesencephalic locomotor region, an anatomical locus for central command, was found to inhibit the discharge of nucleus tractus solitarius cells that were stimulated by arterial baroreceptors in decerebrated cats. In contrast, the effect of thin fiber muscle afferent input on the discharge of nucleus tractus solitarius cells stimulated by baroreceptors is not known. Consequently in decerebrated unanesthetized cats, we examined the responses of barosensory nucleus tractus solitarius cells to stimulation of thin fiber muscle afferents and to stimulation of the mesencephalic locomotor region, a maneuver which evoked fictive locomotion. We found that electrical stimulation of either the mesencephalic locomotor region or the gastrocnemius nerve at current intensities that recruited group III afferents inhibited the discharge of nucleus tractus solitarius cells receiving baroreceptor input. We also found that the inhibitory effects of both gastrocnemius nerve stimulation and mesencephalic locomotor region stimulation converged onto the same barosensory nucleus tractus solitarius cells. We conclude that the nucleus tractus solitarius is probably the site whereby input from both central command and thin fiber muscle afferents function to reset the baroreceptor reflex during exercise.

Bicuculline and strychnine suppress the mesencephalic locomotor region-induced inhibition of group III muscle afferent input to the dorsal horn.

We examined the effect of iontophoretic application of bicuculline methiodide and strychnine hydrochloride on the mesencephalic locomotor region (MLR)-induced inhibition of dorsal horn cells in paralyzed cats. The activity of 60 dorsal horn cells was recorded extracellularly in laminae I, II, V-VII of spinal segments L7-S1. Each of the cells was shown to receive group III muscle afferent input as demonstrated by their responses to electrical stimulation of the tibial nerve (mean latency and threshold of activation: 20.1+/-6.4 ms and 15.2+/-1.4 times motor threshold, respectively). Electrical stimulation of the MLR suppressed transmission in group III muscle afferent pathways to dorsal horn cells. Specifically the average number of impulses generated by the dorsal horn neurons in response to a single pulse applied to the tibial nerve was decreased by 78+/-2.8% (n=60) during the MLR stimulation. Iontophoretic application (10-50 nA) of bicuculline and strychnine (5-10 mM) suppressed the MLR-induced inhibition of transmission of group III afferent input to laminae I and II cells by 69+/-5% (n=10) and 29+/-7% (n=7), respectively. Likewise, bicuculline and strychnine suppressed the MLR-induced inhibition of transmission of group III afferent input to lamina V cells by 59+/-13% (n=14) and 39+/-11% (n=10), respectively. Our findings raise the possibility that GABA and glycine release onto dorsal horn neurons in the spinal cord may play an important role in the suppression by central motor command of thin fiber muscle afferent-reflex pathways.

Patterns of locomotor drive to motoneurons and last-order interneurons: clues to the structure of the CPG.

We have examined the linkage between patterns of activity in several hindlimb motor pools and the modulation of oligosynaptic cutaneous reflex pathways during fictive locomotion in decerebrate unanesthetized cats to assess the notion that such linkages can shed light on the structure of the central pattern generator (CPG) for locomotion. We have concentrated attention on the cutaneous reflex pathways that project to the flexor digitorum longus (FDL) motor pool because of that muscle's unique variable behavior during normal and fictive locomotion in the cat. Differential locomotor control of last-order excitatory interneurons in pathways from low-threshold cutaneous afferents in the superficial peroneal and medial plantar afferents to FDL motoneurons is fully documented for the first time. The qualitative patterns of differential control are shown to remain the same whether the FDL muscle is active in early flexion, as usually found, or during the extension phase of fictive locomotion, which is less common during fictive stepping. The patterns of motor pool activity and of reflex pathway modulation indicate that the flexion phase of fictive locomotion has distinct early versus late components. Observations during "normal" and unusual patterns of fictive stepping suggest that some aspects of locomotor pattern formation can be separated from rhythm generation, implying that these two CPG functions may be embodied, at least in part, in distinct neural organizations. The results are discussed in relation to a provisional circuit diagram that could explain the experimental findings.

Stimulation of the mesencephalic locomotor region inhibits the discharge of neurons in the superficial laminae of the dorsal horn of cats.

In decerebrate cats, we found that stimulation of the mesencephalic locomotor region (MLR) attenuated the responses of neurons in the superficial laminae of the dorsal horn to thin fiber muscle afferent input. The attenuation appeared to be more effective for group III afferent input than for group IV. These findings may shed light on the interaction between central command, (i.e. the MLR) and the muscle reflex, mechanisms which both contribute to the cardiovascular responses to exercise.

Stimulation of the MLR inhibits the discharge of dorsal horn neurons responsive to muscular contraction.

We found that electrical stimulation of the mesencephalic locomotor region (MLR) inhibited the discharge of deep dorsal horn neurons receiving group III afferent input from the triceps surae muscles. In contrast, contraction of these muscles induced by electrical stimulation of the tibial nerve activated these dorsal horn neurons. Our findings show that descending central motor commands can inhibit dorsal horn interneurons receiving input from group III afferents during exercise.

Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin fiber afferent input.

In decerebrate paralyzed cats, we examined the effects of two central motor commands (fictive locomotion and scratching) on the discharge of dorsal horn neurons receiving input from group III and IV tibial nerve afferents. We recorded the impulse activity of 74 dorsal horn neurons, each of which received group III input from the tibial nerve. Electrical stimulation of the mesencephalic locomotor region (MLR), which evoked fictive static contraction or fictive locomotion, inhibited the discharge of 44 of the 64 dorsal horn neurons tested. The mean depth from the dorsal surface of the spinal cord of the 44 neurons whose discharge was inhibited by MLR stimulation was 1.77 +/- 0.04 mm. Fictive scratching, evoked by topical application of bicuculline to the cervical spinal cord and irritation of the ear, inhibited the discharge of 22 of the 29 dorsal horn neurons tested. Fourteen of the twenty-two neurons whose discharge was inhibited by fictive scratching were found to be inhibited by MLR stimulation as well. The mean depth from the dorsal surface of the cord of the 22 neurons whose discharge was inhibited by fictive scratching was 1.77 +/- 0.06 mm. Stimulation of the MLR or the elicitation of fictive scratching had no effect on the activity of 22 dorsal horn neurons receiving input from group III and IV tibial nerve afferents. The mean depth from the dorsal surface of the cord was 1.17 +/- 0.07 mm, a value that was significantly (P < 0.05) less than that for the neurons whose discharge was inhibited by either MLR stimulation or fictive scratching. We conclude that centrally evoked motor commands can inhibit the discharge of dorsal horn neurons receiving thin fiber input from the periphery.

Locomotor modulation of disynaptic EPSPs from the mesencephalic locomotor region in cat motoneurons.

Locomotor modulation of disynaptic EPSPs from the mesencephalic locomotor region in cat motoneurons. J. Neurophysiol. 80: 3284-3296, 1998. When low-frequency tetanization of the mesencephalic locomotor region (MLR) produce fictive locomotion in unanesthetized, decerebrate cats, each MLR stimulus produces a distinctive cord dorsum potential (CDP) and oligosynaptic excitatory postsynaptic potentials (EPSPs) in many lumbosacral motoneurons. The average segmental latency from the initial CDP wave [mean delay from stimulus: 4.3 +/- 0.9 (SD) ms] to the onset of detectable MLR EPSPs was 1.6 +/- 0.4 ms, suggesting a disynaptic segmental connection. In gastrocnemius/soleus, flexor hallucis longus, flexor digitorum longus, tibialis anterior, and posterior biceps-semitendinosus motoneurons (35/38 cells), MLR EPSPs either appeared or were enhanced during the phase of fictive stepping in which the target motoneurons were depolarized and the motor pool was active (the phase), with parallel changes between EPSP amplitudes and membrane depolarization. In contrast, MLR stimulation produced small (1/10) or no EPSPs in extensor digitorum longus (EDL) motoneurons, with no phase enhancement (4/10) or oligosynaptic inhibitory postsynaptic potentials during the phase (5/10). Eight of 10 flexor digitorum longus (FDL) cells exhibited membrane depolarization in the early flexion phase of fictive stepping, and five of these showed parallel enhancement of disynaptic MLR EPSPs during early flexion. Three cases were studied when the FDL motor pool exhibited exclusively extensor phase firing. In these cases, the disynaptic MLR EPSPs were enhanced only during the extensor phase, accompanied by membrane depolarizations. We conclude that the last-order interneurons that produce disynaptic MLR EPSPs may well participate in producing the depolarizing locomotor drive potentials (LDPs) found in hindlimb motoneurons during fictive locomotion. However, the absence of linkage between MLR EPSP enhancement and LDP depolarizations in EDL motoneurons suggests that other types of excitatory interneurons also must be involved at least in some motor pools. We compared these patterns with the modulation of disynaptic EPSPs produced in FDL cells by stimulation of the medial longitudinal fasciculus (MLF). In all seven FDL motoneurons tested, disynaptic MLF EPSPs appeared only during the extension phase, regardless of when the FDL motoneurons were active. The fact that the modulation patterns of MLR and MLF disynaptic EPSPs is different in FDL motoneurons indicates that the two pathways do not converge on common last-order interneurons to that motor pool.

Modulation of oligosynaptic cutaneous and muscle afferent reflex pathways during fictive locomotion and scratching in the cat.

We have compared state-dependent transmission through oligosynaptic (minimally disynaptic) reflex pathways from low-threshold cutaneous and muscle afferents to some flexor and extensor lumbosacral motoneurons during fictive locomotion and scratching in decerebrate unanesthetized cats. As reported in earlier work, oligosynaptic cutaneous excitatory postsynaptic potentials (EPSPs) in flexor digitorum longus (FDL) and inhibitory postsynaptic potentials (IPSPs) in extensor digitorum (EDL) longus motoneurons were enhanced markedly during the early flexion phase of fictive locomotion. We show in this paper that, in contrast, these cutaneous reflex pathways were depressed markedly during all phases of fictive scratching. On the other hand, disynaptic EPSPs produced by homonymous and synergist group I muscle afferents in flexor (tibialis anterior and EDL) motoneurons were present and strongly modulated during both fictive locomotion and scratching. During both actions, these disynaptic group I EPSPs appeared or exhibited the largest amplitude when the motoneuron membrane potential was most depolarized and the parent motor pool was active. There was an interesting exception to the simple pattern of coincident group I EPSP enhancement and motoneuron depolarization. During locomotion, disynaptic group I EPSPs in both FDL and flexor hallucis longus (FHL) motoneurons cells were facilitated during the extension phase, although FDL motoneurons were relatively hyperpolarized whereas FHL cells were depolarized. The reverse situation was found during fictive scratching; group I EPSPs were facilitated in both FDL and FHL cells during the flexion phase when FDL motoneurons were depolarized and FHL cells were relatively hyperpolarized. These observations suggest that the disynaptic EPSPs in these two motor nuclei are produced by common interneurons. Reciprocal disynaptic inhibitory pathways from group Ia muscle afferents to antagonist motoneurons were also active and subject to phase-dependent modulation during both fictive locomotion and scratching. In all but one cell tested, reciprocal disynaptic group Ia IPSPs were largest during those phases in which the motoneuron membrane potential was relatively hyperpolarized and the parent motor pool was inactive. Oligosynaptic PSPs in motoneurons produced by stimulation of the mesencephalic locomotor region (MLR) were modulated strongly during fictive locomotion but were suppressed powerfully throughout fictive scratching. Large cord dorsum potentials generated by MLR stimuli also were suppressed markedly during fictive scratching. These results allow certain inferences about the organization of interneurons in the pathways examined. They also suggest that the central pattern generators that produce fictive locomotion and scratching are organized differently.

Differential modulation of disynaptic cutaneous inhibition and excitation in ankle flexor motoneurons during fictive locomotion.

1. Intracellular recording from extensor digitorum longus (EDL) and tibialis anterior (TA) alpha-motoneurons during fictive locomotion was used to examine patterns of modulation of oligosynaptic postsynaptic potentials (PSPs) produced by electrical stimulation of the cutaneous superficial peroneal (SP) and medial plantar (MPL) nerves in unanesthetized, decerebrate adult cats. 2. In all 20 EDL motoneurons studied, electrical stimulation of the SP nerve with single pulses at about twice threshold for the most excitable fibers in the nerve (2xT) produced either no synaptic potentials or relatively small oligosynaptic excitatory or inhibitory PSPs (EPSPs or IPSPs), both at rest and during the extension phase of fictive stepping. However, at the onset of the flexion phase large, presumably disynaptic IPSPs (central latencies 1.7-2.0 ms) appeared in the SP responses. These IPSPs usually decreased in amplitude later in the flexion phase despite maintained membrane depolarization. 3. In most (7/8) TA motoneurons, SP stimulation produced oligosynaptic EPSPs at rest and during the extension phase of fictive stepping. These EPSPs were suppressed during flexion in a majority of TA cells studied (5/8) but no clearly disynaptic IPSPs were found in any TA motoneuron. 4. In most EDL and TA motoneurons, stimulation of the MPL nerve produced oligosynaptic EPSPs at rest and during the extension phase, most with latencies in the presumably disynaptic range (< or = 2.0 ms). When present, these MPL EPSPs were suppressed throughout the flexion phase of stepping in almost all EDL (18/ 20) and TA (6/8) motoneurons examined. 5. The available evidence suggests that these modulation effects during fictive stepping are due primarily to convergence of control information from the spinal central pattern generator (CPG) for locomotion onto segmental interneurons in the oligosynaptic cutaneous pathways. 6. These observations extend the evidence for precise differential control of transmission through cutaneous reflex pathways in the cat hindlimb by the locomotor CPG. Taken together with earlier evidence about locomotor modulation of cutaneous PSPs in flexor digitorum longus (FDL) motoneurons, the data suggest that cutaneous information from the dorsal surface of the foot, carried in part by the SP nerve, projects to digit motoneurons (FDL and EDL) through discrete sets of last-order interneurons that also receive powerful excitation from the locomotor CPG during flexion. In contrast, the last-order interneurons that convey excitatory information from the SP nerve to at least some TA motoneurons are inhibited by the CPG during flexion. 7. Another contrast resides in the fact that oligosynaptic cutaneous excitation from the plantar surface of the foot, via the MPL nerve, is suppressed in FDL, EDL, and TA motoneurons during the flexion phase of locomotion. The available information is consistent with the possibility that MPL effects may be delivered to these motor nuclei by common interneurons. 8. We suggest an interneuronal circuitry that could account for these observations and discuss possible functional implications of modulation of these sensory pathways during locomotion.

Disynaptic vestibulospinal and reticulospinal excitation in cat lumbosacral motoneurons: modulation during fictive locomotion.

This study compares some characteristics of the disynaptic excitatory pathways from the lateral vestibular nucleus (LVN) and medial longitudinal fasciculus (MLF) to lumbosacral alpha-motoneurons in the decerebrate cat. We used the spatial facilitation technique to test whether disynaptic LVN and MLF excitatory postsynaptic potentials (EPSPs) are produced by common last-order interneurons in the lumbosacral segments of the spinal cord. Of 77 motoneurons examined, 26 exhibited disynaptic EPSPs from both supraspinal sources. No spatial facilitation was found between LVN and MLF EPSPs in 21 of 24 cells that were adequately tested. In 3 of 23 cells (all flexor motoneurons), some spatial facilitation was found in some but not all trials. These observations suggest that stimulation of the LVN and MLF produces disynaptic EPSPs in motoneurons through largely separate populations of last-order interneurons. Disynaptic MLF and LVN EPSPs showed parallel patterns of modulation during fictive locomotion. Maximal disynaptic EPSP amplitudes occurred during the phase of the step cycle when the recorded motoneuron, whether flexor or extensor, exhibited depolarizing locomotor drive potentials and the corresponding muscle nerve was active. These observations, taken together, suggest that disynaptic LVN and MLF EPSPs are produced in motoneurons by at least four separate populations of segmental last-order excitatory interneurons, with separate populations projecting to flexor versus extensor cells. The results also suggest that the modulation of the disynaptic EPSPs during fictive locomotion is mainly due to premotoneuronal convergence of input from the respective descending systems and from the segmental central pattern generator for locomotion onto common interneurons.

Mechanisms of supraspinal correction of locomotor activity generator.

In experiments on immobilized decerebrate cats, data about reorganization of efferent activity parameters of the forelimb and hindlimb locomotor generators evoked by electrical stimulation of descending systems were obtained. The generators controlling both forelimb and hindlimb locomotor movements were found to be characterized by the existence of stable states at which total influence of different descending systems on these generators was extremely limited. These data enable us to conclude that the sense of activity reorganization in locomotor generators of both forelimb and hindlimb under the influence of descending system signals is in bringing the motor program to a dynamic relation with supraspinal inflow, where a sufficient degree of limitation and balancing of the influences of corresponding descending systems on the interneuronal nets, determining time and phase characteristics of these generators, is ensured. Possible mechanisms of realization of this interaction between descending signals and locomotor activity generators are discussed.

Mechanisms of supraspinal correction of scratching generator.

The influences of signals in descending systems on the parameters of scratching generator activity were studied on decerebrate immobilized cats. It was shown that phasic electric stimulation of descending systems evoked certain phase-dependent reorganization of the parameters of scratching generator efferent activity. Maximum increase in scratching cycle duration during electric stimulation of Deiters' nucleus, red nucleus and pyramidal tract is observed during stimulation in the first half of aiming phase. Stimulation in the second half of aiming phase and at the beginning of scratching jerk phase virtually does not change the scratching cycle duration. Maximum increase in scratching cycle duration during electric stimulation of the nucleus reticularis gigantocellularis is observed in the second half of aiming phase. Electric activation of descending pathways during aiming phase increases its intensity and decreases the intensity of scratching jerk phase. Activation of descending pathways during scratching jerk phase increases its intensity and virtually does not change the aiming phase intensity. Influences of electric activation of descending systems on scratching generator work reveal dependence on limb position. They are increased when the limb is deflected to the rear and are decreased during over-aimed position. Decerebellation leads to a decrease of scratching generator activity parameters rearrangement under influence of electric stimulation of the red nucleus and nucleus reticularis gigantocellularis, and to its increase during Deiters' nucleus stimulation. On the basis of these results the principles of supraspinal correction of scratching generator work are discussed.