1. The effects of stimulating hindlimb extensor nerves (100‐200 ms trains, 100 Hz, < or = 2 times threshold) during the flexor and extensor phases of the locomotor step cycle were analysed in the decerebrate, paralysed cat during fictive locomotion evoked by stimulation of the mesencephalic locomotor region. 2. Stimulation during extension of either the medial gastrocnemius (MG), lateral gastrocnemius‐soleus (LGS) or plantaris (Pl) nerves was equally effective in increasing the duration and amplitude of electroneurogram (ENG) activity recorded in ipsilateral ankle, knee and hip extensor nerves. Enhancement of extensor ENG activity could be evoked with near threshold stimulation intensity and appeared within 10‐40 ms of the onset of ankle extensor nerve stimulation. Stimulation of anterior biceps during extension occasionally evoked a modest increase in the duration of activity of hip, knee and ankle extensors. Stimulation of quadriceps during extension enhanced the activity of proximal extensors and soleus, but inhibited other ankle extensors. 3. Selective activation of ankle extensor Ia spindle afferents by muscle stretch also enhanced ipsilateral extension. It is argued that both muscle spindle and tendon organ afferents can contribute to the increase in extensor nerve activity evoked by group I stimulation intensity during fictive locomotion. 4. During flexion, stimulation of either the MG, Pl or LGS nerves at group I strength terminated on‐going activity in ipsilateral flexors and initiated a burst of activity in ipsilateral hip, knee and ankle extensors, i.e. reset the step cycle to extension. 5. Low strength stimulation of the mixed muscle and cutaneous nerve innervating the plantar aspect of the foot produced extension enhancement and resetting similar to that evoked by group I muscle afferent stimulation. Stimulation of the cutaneous nerve supplying the dorsal aspect of the foot during extension enhanced extensor activity, and during flexion, enhanced the activity of flexors. 6. The effects reported here during fictive locomotion may also occur during overground locomotion with natural activation of group I muscle spindle and tendon organ afferents. Extensor spindle and tendon organ afferents may thus serve as an excitatory reflex system helping to shape the amplitude, duration and timing of ipsilateral extensor activity. Increased or unexpected activation of group I ankle extensor afferents or plantar foot afferents during locomotion could also compensate for increased loading of the limb.

1. This study examines the effects of electrical stimulation of hindlimb flexor nerves on the fictive locomotion pattern. Locomotion was initiated by stimulation of the mesencephalic locomotor region in the decerebrate paralysed cat and monitored by recording the electroneurogram from selected hindlimb flexor and extensor muscle nerves. Flexor nerves were stimulated using short trains (20-50 stimuli at 100 Hz) during either the flexor or the extensor phase of the fictive locomotor cycle. 2. Stimulation of tibialis anterior (TA), posterior biceps and semitendinosus (PBSt) or sartorius (Sart) nerves at 5 times threshold (T) during the flexor phase of the fictive locomotor cycle terminated on-going activity in flexor nerves and initiated activity in extensors. Thus, flexor nerve stimulation during flexion shortened the locomotor cycle by resetting to extension. The failure of lower intensity (2T) stimulation of PBSt or Sart nerves to reset the step cycle to extension suggests that group II afferents are responsible for these actions.Resetting evoked by 2 T stimulation of the TA nerve may be due to a high proportion of group II afferents with low electrical threshold. 3. During extension, stimulation of TA and PBSt nerves at 5Tdid not perturb the locomotor rhythm whereas Sart stimulation prolonged the locomotor cycle. 4. Stimulation of cutaneous or knee joint afferents failed to produce effects similar to those evoked by stimulation of flexor muscle nerves at group II strength. These findings are at odds with those obtained elsewhere in the acute spinal, DOPA fictive locomotion preparation. The possibility that group II resetting during fictive locomotion is not mediated by flexion reflex pathways but by previously unknown pathways released in the present preparation is discussed. 5. Since many of the flexor afferents recruited by 5T electrical stimulation are the lengthsensitive group II fibres, spindle secondaries may act to regulate the duration and onset of flexor and extensor activity during real locomotion. The resetting from flexion to extension also suggests that unexpected or enhanced activity of flexor secondaries during swing would promote a switch of the step cycle to stance.

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Hematopoietic stem cells (HSCs) have been proposed as a potential source of neural cells for use in repairing brain lesions, but previous studies indicate a low rate of neuronal differentiation and have not provided definite evidence of neuronal phenotype. To test the neurogenic potential of human HSCs, we implanted CD34؉ HSCs from adult human bone marrow into lesions of the developing spinal cord in the chicken embryo and followed their differentiation by using immunohistochemistry, retrograde labeling, and electrophysiology. We find that human cells derived from the implanted population express the neuronal markers NeuN and MAP2 at substantially higher rates than previously reported. We also find that these cells exhibit neuronal cytoarchitecture, extend axons into the ventral roots or several segments in length within the spinal white matter, are decorated with synaptotagmin؉ and GABA؉ synaptic terminals, and exhibit active membrane properties and spontaneous synaptic potentials characteristic of functionally integrated neurons. Neuronal differentiation is accompanied by loss of CD34 expression. Careful examination with confocal microscopy reveals no signs of heterokaryons, and human cells never express a chicken-specific antigen, suggesting that fusion with host chicken cells is unlikely. We conclude that the microenvironment in the regenerating spinal cord of the chicken embryo stimulates substantial proportions of adult human HSCs to differentiate into full-fledged neurons. This may open new possibilities for a high-yield production of neurons from a patient's own bone marrow.bone marrow ͉ neurogenesis ͉ stem cell therapy

For a large number of vertebrate species it is now indisputable that spinal networks have the capability of generating the basic locomotor rhythm. However, because of technical difficulties, the rate of progress in defining the intrinsic properties of mammalian locomotor rhythm generators has been slow in comparison to that made in the study of such networks in lower vertebrates. Investigations on afferent and descending control of locomotor activity in mammals have demonstrated that many of these pathways interact with the rhythm generator. In this review we discuss how these interactions (resetting) can be used for outlining relevant spinal circuits as a basis for a future identification of individual neurons of the spinal locomotor networks. In this overview we have given particular emphasis to selected afferent systems to illustrate the possibilities and problems with this approach.

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1. The pattern of discharge of medullary reticulospinal neurons, identified by antidromic stimulation applied at the L1-L2 segment of the spinal cord, was studied during fictive locomotion, occurring spontaneously, or evoked by stimulation of the mesencephalic locomotor region in high-decerebrate, paralyzed cats. Unitary recordings were made in the medial reticular formation (P5.0-14.0 mm; L0.5-2.0 mm), and the fictive locomotor pattern was monitored by recording the electroneurogram (ENG) of representative flexor and extensor muscle nerves from each of the four limbs. 2. In total, 117 reticulospinal neurons were recorded in 15 cats. Among these, 73.5% (86/117) modified their discharge at the onset of locomotion. These cells were divided into three subpopulations: 34/86 of the cells always maintained a fixed temporal relationship with the activity of one of the recorded nerves (ENG-related = 39.6%); the pattern of discharge of 42/86 cells was related to the locomotor rhythm [(LR-related-48%)] but was not temporally correlated with any of the recorded nerves; and the remaining 10 cells increased their firing frequency at the onset of locomotion but remained tonic (TONIC-11.6%). 3. Of the ENG-related neurons, 64.8% were temporally correlated to extensor nerve activity, whereas the remaining 35.2% were correlated to flexor nerves. These neurons were either related to forelimb (55.9%) or hindlimb (44.1%) nerves lying either ipsilateral (38.2%) or contralateral (61.8%) to the recording site. A few neurons (n = 3; 8.8%) were related to nerve activity of more than one limb. 4. The pattern of discharge of the LR-related neurons, although not correlated to the activity of any one recorded nerve, could be preferentially related to the locomotor rhythm in either the forelimbs (12/23) or hindlimbs (11/23). 5. ENG- and LR-related reticulospinal neurons were intermingled in the medial reticular formation. In both cases, cells related to the forelimbs were located more dorsally than those related to the hindlimbs. It is suggested that both the ENG- and LR-related neurons represent a single functional population of reticulospinal neurons that is part of an intrinsically organized reticulospinal system that functions to coordinate the activity of the skeletal musculature. 6. The present results show that the majority of reticular neurons projecting as far as the lumbar spinal cord are phasically modulated during locomotion, even in the absence of phasic peripheral afferent inputs. Moreover, the complexity of the discharge patterns in paralyzed animals was found to be similar to that observed in the intact cat.(ABSTRACT TRUNCATED AT 400 WORDS)

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