Synaptic excitation of alpha-motoneurons by dorsal root afferents in the neonatal rat spinal cord.
1. Excitatory synaptic transmission in mono- and polysynaptic pathways between dorsal root afferents and alpha-motoneurons was studied in the spinal cord preparation of the neonatal rat isolated in vitro, using sharp-electrode intracellular recordings. 2. The duration of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited in lumbar motoneurons were shortened after addition of the specific N-methyl-D-aspartate (NMDA) receptor blocker 2-amino-5-phosphonovaleric acid (APV) to the perfusate. The EPSPs were then completely blocked by the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. A robust NMDA-receptor-mediated component of monosynaptic EPSPs was revealed by addition of CNQX to the bathing medium. This component reached as much as 30% of the EPSP amplitude, was evident at resting potential level in both low and normal Mg2+ Krebs saline, and could be completely abolished by addition of APV. These findings suggest that the NMDA-receptor-mediated component may contribute to monosynaptic excitation under normal conditions. 4. Polysynaptic EPSPs evoked in motoneurons in the fifth lumbar segment by stimulation of the fourth lumbar dorsal root in the presence of the glycine and gamma-aminobutyric acid A (GABAA) receptor blockers strychnine and bicuculline could be completely or partially blocked by application of either APV or CNQX. Suprathreshold activity could be then elicited in these motoneurons by increasing the stimulation intensity by a factor of 2 to 3. A complete blockade of polysynaptic excitation at these stimulation intensities was obtained only in the presence of both APV and CNQX. These results suggest that both receptor subtypes make a significant contribution to polysynaptic excitation of alpha-motoneurons by dorsal root afferents. 5. Analysis of variation in the amplitudes of the non-NMDA-receptor-mediated component of the monosynaptic EPSP and of the estimated (occurring 25 ms after the EPSP initiation) and the pharmacologically resolved NMDA component was done during low-frequency repetitive stimulation of the dorsal root. The kinetics of the initial decrease in EPSP amplitude during repetitive stimulation and the dependence of the EPSP amplitude on the stimulation frequency was similar for the NMDA- and non-NMDA-receptor-mediated components of the EPSPs. Addition of the GABAB receptor agonist L-(-) baclofen to the perfusate decreased the EPSP amplitude and reduced the frequency-dependent synaptic depression of both the NMDA- and non-NMDA-receptor-mediated components of monosynaptic EPSPs to the same level.(ABSTRACT TRUNCATED AT 400 WORDS)
Pinco
M
M
Department of Anatomy, Hebrew University Medical School, Jerusalem, Israel.
Lev-Tov
A
A
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D011810:Quinoxalines; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D015761:4-Aminopyridine