Properties of rhythmic activity generated by the isolated spinal cord of the neonatal mouse

We examined the ability of the isolated lumbosacral spinal cord of the neon atal mouse (P0-7) to generate rhythmic motor activity under several differe nt conditions. In the absence of electrical or pharmacological stimulation, we recorded several patterns of spontaneous ventral root depolarization an d discharge. Spontaneous, alternating discharge between contralateral ventr al roots could occur two to three times over a 10-min interval. We also obs erved other patterns, including left-right synchrony and rhythmic activity restricted to one side of the cord. Trains of stimuli delivered to the lumb ar/coccygeal dorsal roots or the sural nerve reliably evoked episodes of rh ythmic activity. During these evoked episodes, rhythmic ventral root discha rges could occur on one side of the cord or could alternate from side to si de. Bath application of a combination of N-methyl-D,L-aspartate (NMA), sero tonin, and dopamine produced rhythmic activity that could last for several hours. Under these conditions, the discharge recorded from the left and rig ht L-1-L-3 ventral roots alternated. In the L-4-L-5 segments, the discharge had two peaks in each cycle, coincident with discharge of the ipsilateral and contralateral L-1-L-3 roots. The L-6 ventral root discharge alternated with that recorded from the ipsilateral L-1-L-3 roots. We established that the drug-induced rhythm was locomotor-like by recording an alternating patt ern of discharge between ipsilateral flexor and extensor hindlimb muscle ne rves. In addition, by recording simultaneously from ventral roots and muscl e nerves, we established that ankle flexor discharge was in phase with ipsi lateral L-1/L-2 ventral root discharge, while extensor discharge was in pha se with ipsilateral L6 ventral root discharge. Rhythmic patterns of ventral root discharge were preserved following mid-sagittal section of the spinal cord, demonstrating that reciprocal inhibitory connections between the lef t and right sides of the cord are not essential for rhythmogenesis in the n eonatal mouse cord. Blocking N-methyl-D-aspartate receptors, in both the in tact and the hemisected preparation, revealed that these receptors contribu te to but are not essential for rhythmogenesis. In contrast, the rhythm was abolished following blockade of kainate/AMPA receptors with 6-cyano-7-nitr oquinoxalene-2,3- dione. These findings demonstrate that the isolated mouse spinal cord can produce a variety of coordinated activities, including loc omotor-like activity. The ability to study these behaviors under a variety of different conditions offers promise for future studies of rhythmogenic m echanisms in this preparation.