Noradrenaline, a potent activator of rhythmogenic networks in adult mammals has not been reported to produce functional rhythmic patterns in isolated spinal cords of newborn rats. We now show that a "fast" (cycle time: 1-4 s) transient rhythm was induced in sacrococcygeal (SC) and rostral-lumbar spinal segments of the neonatal rat by bath-applied noradrenaline. The fast rhythm was blocked by 1 microM of the alpha1-adrenoceptor antagonist prazosin but not by 1-20 microM of the alpha2-adrenoceptor blocker yohimbine, it could be initiated and maintained by alpha1-adrenoceptor agonists, and it was accompanied by a slow nonlocomotor rhythm. Transection at the lumbosacral junction abolished the fast-thoracolumbar (TL) rhythm while the fast-SC and slow-TL rhythms were unaffected. The N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) abolished the slow- and did not interrupt the fast rhythm. Thus alpha1-adrenoceptor agonists induce an NMDA receptor-independent rhythm in the SC cord and modulate NMDA receptor-dependent rhythmicity in TL segments. Injection of current steps into S(2) and flexor-dominated L(2) motoneurons during the fast rhythm revealed a 20-30% decrease in input-resistance (R(N)), coinciding with contralateral bursting. The R(N) of extensor-dominated L(5) motoneurons did not vary with the fast rhythm. The rhythmic fluctuations of R(N) in L(2) motoneurons were abolished, but the alternating left-right pattern of the fast rhythm was unchanged in midsagittally split TL cords. We suggest that the locomotor generators were not activated during the fast rhythm, that crossed-inhibitory pathways activated by SC projections controlled the rhythmic decrease in R(N) in L(2) motoneurons, and that the alternating pattern of the split TL cord was maintained by excitatory SC projections.

The rhythmogenic capacity of the tail-innervating segments (L4-Co3) of the spinal cord was studied in isolated spinal cord and tail-spinal cord preparations of neonatal rats. Bath-applied serotonin/N-methyl-D-aspartate (NMDA) failed to produce a robust sacrococcygeal rhythmicity following midlumbar transection of the spinal cord. By contrast, a regular alternating left-right rhythm could be induced in the sacrococcygeal segments by application of noradrenaline (NA) or NA and NMDA before and after midlumbar transection of the cord. This rhythm was accelerated with the concentration of NMDA and was blocked by alpha1 or alpha2 adrenoceptor antagonists. The efferent bursts induced by NA/NMDA were accompanied by rhythmic tail movements produced by alternating activation of the left and right tail muscles and by coactivation of flexors, extensors, and abductors on a given side of the tail. This coactivation implies that reciprocal inhibitory pathways were not activated during the rhythm. Lesion experiments revealed that the rhythmogenic circuitry is distributed along all or most of the sacrococcygeal segments. The NA/NMDA-induced rhythm persisted in the isolated sacrococcygeal (S1-Co3), sacral (S1-S4), coccygeal (Co1-Co3), and smaller isolated regions of the sacrococcygeal cord. The rhythm also could be maintained in longitudinally split sacrococcygeal hemicords in which flexor, extensor, and abductor motoneurons are coactivated. This finding indicates that neither left/right nor flexor/extensor inhibitory interactions are required for rhythmogenesis in the sacrococcygeal cord. A slow rhythm lacking the alternating left-right pattern was induced by NA/NMDA in tail-innervating caudal lumbar segments of isolated L4-Co3 preparations. This rhythm was independent of the concurrent sacrococcygeal rhythm and the activity pattern of the tail musculature and it does not seem to contribute to rhythmic tail movements under these conditions. Comparative studies of the rhythm produced in the isolated caudal lumbar, sacrococcygeal cord, and caudal thoracic-rostral lumbar segments revealed that the S1-Co3 rhythm was faster than the L4-L6 pattern and slower than the T6-L3 rhythm. It is suggested that the caudal lumbar and sacrococcygeal segments of the cord are normally driven by the faster rostral lumbar central pattern generators. The relevance of the findings described above to pattern generation in the mammalian spinal cord is discussed.

The characteristics of the rhythmic motor output and behavior produced by intrinsic sacrocaudal networks were studied in isolated tail-spinal cord preparations of neonatal rats. An alternating left-right rhythm could be induced in the sacral cord by stimulus trains applied to sacrocaudal afferents at various intensities. Strengthening the stimulation intensity enhanced the rhythmic efferent firing and accelerated the rhythm by < or =30%. High stimulation intensities induced tonic excitation or inhibition and thereby perturbed the rhythm. Increasing the stimulation frequency from 1 to 10 Hz decreased the cycle time of the rhythm by 36%. The rhythm was blocked during prolonged afferent stimulation but could be restored by stimulation of contralateral afferents. Sacrocaudal afferent activation produced ventroflexion accompanied by either low- or high-amplitude rhythmic abduction of the tail. The low-amplitude abductions were produced by alternating flexor bursts during long stimulus trains. The activity of abductors and extensors was substantially reduced during these trains, their recruitment lagged after that of the flexors, and their activity bursts were much shorter. It is suggested that tail extensor/abductor motoneurons were suppressed during the stimulus train by inhibitory afferent projections. The high-amplitude abductions appeared after cessation of stimulus trains. Alternating left-right activation of the tail muscles, and coactivation of the principal muscles on each side of the tail were observed during these abductions. It is suggested that flexors and extensors assist the abductors to produce the high-amplitude abductions. This suggestion is supported by the finding that tail abduction could be produced by direct unilateral stimulation of any of the principal tail muscles. The relevance of the findings described in the preceding text to the use of regional sacral circuits in generation of stereotypic motor behaviors and to future studies of rhythmogenic sacrocaudal networks is discussed.

The external segment of the globus pallidus (GPe) is one of the core nuclei of the basal ganglia, playing a major role in normal control of behavior and in the pathophysiology of basal ganglia-related disorders such as Parkinson's disease. In vivo, most neurons in the GPe are characterized by high firing rates (50 -100 spikes/s), interspersed with long periods (ϳ0.6 s) of complete silence, which are termed GPe pauses. Previous physiological studies of single and pairs of GPe neurons have failed to fully disclose the physiological process by which these pauses originate. We examined 1001 simultaneously recorded pairs of high-frequency discharge GPe cells recorded from four monkeys during task-irrelevant periods, considering the activity in one cell while the other is pausing. We found that pauses (n ϭ 137,278 pauses) coincide with a small yet significant reduction in firing rate (0.78 Ϯ 0.136 spikes/s) in other GPe cells. Additionally, we found an increase in the probability of the simultaneously recorded cell to pause during the pause period of the "trigger" cell. Importantly, this increase in the probability to pause at the same time does not account for the reduction in firing rate by itself. Modeling of GPe cells as class 2 excitability neurons (Hodgkin, 1948) with common external inputs can explain our results. We suggest that common inputs decrease the GPe discharge rate and lead to a bifurcation phenomenon (pause) in some of the GPe neurons.