Synaptic excitation of α-motoneurons by dorsal root afferents in the neonatal rat spinal cord

M. Pinco, A. Lev-Tov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

1. Excitatory synaptic transmission in mono- and polysynaptic pathways between dorsal root afferents and α-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 γ-aminobutyric acid A (GABA(A)) 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 α- 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 GABA(B) 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. These results are consistent with the hypothesis that the excitatory amino acid (EAA) transmitter activating the NMDA and non-NMDA receptor subtypes is released from the same set of presynaptic fibers. 6. Bath application of the glutamate analogue 2-amino-4-phosphonobutyric acid (AP4), reduced the amplitude of the non-NMDA- and NMDA-receptor-mediated components of monosynaptic EPSPs by a factor of 2 to 5. This reduction was not accompanied by changes in the time course of the EPSPs or in the passive properties of the motoneuron membrane. We suggest that AP4 reduces the EPSPs by a presynaptic mechanism. 7. Despite the two- to fivefold decrease in their amplitude, monosynaptic EPSPs recorded in the presence of AP4 were substantially depressed during low-frequency stimulation, exhibiting a prolonged synaptic depression that was similar to that of the untreated control preparations. Contrary to this, reduction of the EPSPs by lowering the Ca2+/Mg2+ ratio of the perfusate or by bath application of L-(-) baclofen has been shown to alleviate the prolonged synaptic depression. We therefore suggest that the action of AP4 may not be accomplished by a direct reduction of the presynaptic calcium influx and the EAA release probability. Alternative mechanisms involving branch point blockade of presynaptic afferents, partial depletion of releasable transmitter stores, or inactivation of presynaptic release sites are suggested to underlie the AP4 action.

Original languageEnglish
Pages (from-to)406-417
Number of pages12
JournalJournal of Neurophysiology
Volume70
Issue number1
DOIs
StatePublished - 1993

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