N-METHYL-D-ASPARTATE RECEPTOR-MEDIATED VOLTAGE OSCILLATIONS IN NEURONS SURROUNDING THE CENTRAL CANAL IN SLICES OF RAT SPINAL-CORD

1. The present study used the whole-cell patch-clamp technique to reco rd from visually identified neurons surrounding the central canal in 3 00-mu m transverse slices of lumbosacral spinal cord from 7- to 14-day -old rats. Neurons in this location are implicated in rhythmical activ ity during locomotion. We assessed whether similarly located neurons c ould produce voltage oscillations by local perfusion of neuroactive su bstances known to initiate locomotor activity. 2. The sample populatio n had mean values for cell resistance and membrane time constant of 1, 020 M Ohm and 61.5 ms, respec tively. Three general categories of osci llatory behavior were observed; spontaneous low-frequency voltage osci llations in the absence of an applied agonist, N-methyl-D-aspartate (N MDA)-induced rhythmic low-frequency voltage oscillations in the presen ce of tetrodotoxin (TTX), and NMDA-induced ''unpatterned'' low-frequen cy voltage oscillations in TTX. 3. Three of 42 neurons exhibited spont aneous low-frequency voltage oscillations and one continued to oscilla te in the presence of TTX. In 34 other neurons, manual adjustments of membrane voltage in 10 mV increments between -60 and -20 mV failed to elicit voltage oscillations (in TTX). 4. Five of 42 neurons produced r hythmic low-frequency voltage oscillations in the presence of TTX duri ng applications of NMDA (20-100 mu M). Oscillation frequency ranged fr om 0.09 to 1.45 Hz. These neurons were located in a similar region, ve ntrolateral to the central canal. 5. Thirteen of 42 neurons underwent NMDA-evoked ''unpatterned'' low-frequency voltage oscillations (in TTX ) characterized by great variability in depolarized and baseline membr ane potential durations. Three neurons produced single depolarizing ph ases only. Oscillation frequency ranged from 0.03 to 0.47 Hz. These ne urons were located predominantly in the dorsal region surrounding the central canal with two others located just ventral to the canal. 6. Lo w-frequency voltage oscillations demonstrated a dependence on voltage, applied agonist, and agonist concentration. Rhythmic and unpatterned oscillatory events typically arose from membrane voltages ranging from -70 to -55 mV with plateau peaks from -40 to -30 mV. Although NMDA (2 0-100 mu m) evoked voltage oscillations in neurons, kainate (10-50 mu m), serotonin (10-200 mu m), and noradrenaline (50-100 mu m) failed to evoke voltage oscillations in all neurons tested, including those whe re NMDA induced voltage oscillations. NMDA and L-glutamate (100-1,000 mu m) demonstrated a negative-slope conductance region on the current- voltage relation under voltage-clamp recording conditions. 7. High-fre quency membrane voltage oscillations (in TTX) appeared during depolari zations evoked by perfusion with NMDA or L-glutamate. These oscillatio ns were not evoked by similar depolarizations of membrane voltage with current injection or kainate application. High-frequency voltage osci llations often appeared in neurons independent of low-frequency oscill ations and required a threshold concentration of agonist. Although osc illation frequency was variable between cells, within individual cells oscillation frequency increased with membrane depolarization (range 2 -26 Hz). 8. We conclude that activation of the NMDA receptor is respon sible both for the genesis of low- and high-frequency membrane voltage oscillations. A group of neurons ventrolateral to the central canal d isplay pacemaker-like activity during NMDA receptor activation and are thus defined as neurons that undergo conditional bursting. These neur ons may be involved in the central pattern generator controlling locom otion.