SYNAPTIC TRANSMISSION BETWEEN VENTROLATERAL FUNICULUS AXONS AND LUMBAR MOTONEURONS IN THE ISOLATED SPINAL-CORD OF THE NEONATAL RAT

1. We studied the projections of ventrolateral funiculus (VLF) axons t o lumbar motoneurons in the in vitro spinal cord preparation of 1- to 6-day-old rats using extracellular and sharp-electrode intracellular r ecordings. 2. Ipsilateral and contralateral VLF projections to lumbar motoneurons (L(4)-L(5)) could be activated in the neonatal rat by stim ulation of the surgically peeled VLF at the rostral (L(1)-L(2)) and ca udal lumbar (L(6)) cord. Motoneurons were activated ipsilaterally thro ugh short- and long-latency projections in all cases and contralateral ly through long-latency projections in most cases. 3. Suppression of t he excitatory components of VLF postsynaptic potentials (PSPs) by appl ication of the specific antagonists of N-methyl D-aspartate (NMDA) and non-NMDA receptors, 2-amino-5-phosphonovaleric acid (APV) and 6-cyano -7-nitroquinoxaline-2,3-dione (CNQX), revealed depolarizing PSPs that could be reversed at -55 to -60 mV by injection of depolarizing curren t steps to the motoneurons. These depolarizing PSPs were blocked by ad dition of strychnine and bicuculline and are therefore suggested to be glycine and gamma-aminobutyric acid-A (GABA(A)) receptor-mediated inh ibitory PSPs. The identity of a small (less than or equal to 0.2 mV) r esidual depolarizing component that persisted in the presence of APV, CNQX, strychnine, and bicuculline remains to be determined. 4. Short-l atency excitatory PSPs (EPSPs) could be resolved from the ipsilaterall y elicited VLF PSPs after the reduction of the polysynaptic activity i n the preparation by administration of mephenesin, which was followed by suppression of the glycine and GABA(A) receptor-mediated components of the PSPs by bath application of strychnine and bicuculline. The la tencies of these EPSPs were similar to those of the monosynaptic dorsa l root afferent EPSPs recorded from the same motoneurons. These short- latency VLF EPSPs were shortened by the NMDA antagonist APV and reveal ed an NMDA receptor-mediated component after administration of the non -NMDA receptor antagonist CNQX. Addition of the GABA(B) receptor agoni st L-(-) baclofen or the glutamate analogue L-2-amino-4-phosphonobutyr ic acid (L-AP4) attenuated the pharmacologically resolved short-latenc y EPSPs.5. The amplitude of the short-latency EPSPs produced by low-fr equency (0.016-0.5 Hz) repetitive stimulation of the ipsilateral VLF d id not vary with the frequency of stimulation. Stimulation of dorsal r oot afferents at the same frequencies induced prolonged EPSP depressio n in the same motoneurons. 6. Double pulse (interpulse intervals 15 ms -1 s) and high-frequency (1-20 Hz) stimulation of the ipsilateral VLF revealed substantial facilitation and tetanic potentiation of the EPSP s. Stimulation of dorsal root afferents induced under the same conditi ons double pulse depression and severe tetanic depression of the EPSPs in the same motoneurons. Perfusion of the preparations with low-calci um, high-magnesium Krebs saline decreased the amplitude of the EPSPs p roduced by VLF and dorsal root stimulation, markedly increased the fac ilitation and frequency potentiation of VLF EPSPs, and decreased but d id not abolished the tetanic depression of dorsal root afferent EPSPs. 7. The frequency potentiation developed during high-frequency stimula tion of VLF was accompanied in many motoneurons by prolonged transmemb rane depolarization (tetanic depolarization). The depolarization incre ased with the frequency and the intensity of VLF stimulation and decre ased after shortening the duration of the EPSPs by application of the NMDA receptor blocker APV. Tetanic depolarization developed also on st imulation of the polysynaptic contralateral VLF. In this case, however , the depolarization decayed before the end of the stimulus train, wit h the appearance of intermittent polysynaptic transmission. These find ings suggest that the tetanic depolarization reflects temporal summati on of the VLF EPSPs. 8. We suggest that the combination of frequency p otentiation and temporal summation of the PSPs elicited by VLF stimula tion in the neonatal rat reflects early functional specialization of t he pathways traveling in VLF and is used to assure safe synaptic trans mission in these pathways. We discuss the relevance of these findings to the performance of the motor control functions in the developing ma mmalian spinal cord.