Received for publication July 29, 2004.
Revised September 20, 2004.
Accepted for publication September 21, 2004.

Comparison of metabotropic glutamate receptor responses at segmental and descending inputs to motoneurons in neonatal rat spinal cord

Abstract

We compared the contribution of mGluRs to the generation and modulation of synaptic responses elicited in intracellularly recorded L5 motoneurons from neonatal rats by segmental and descending fibers. Dorsal root (DR) stimulation at high intensity (C-fiber strength) evoked long latency (2-5 s) depolarization in addition to early monosynaptic and polysynaptic responses. Stimulation of the descending ventrolateral funiculus (VLF) failed to evoke a late response in the same motoneuron. The mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; 0.4 mM) selectively blocked the long latency DR-response. This mGluR- mediated response persisted in a cocktail of AMPA/kainate, GABA and glycine antagonists or NMDA antagonists, but not both, suggesting that glutamate transmission (either AMPA/kainate or NMDA) is required for mGluR- mediated inputs from small diameter sensory afferents to affect the motoneuron. Although MCPG inhibited the long latency DR-response, it induced moderate facilitation of monosynaptic DR and VLF responses. The mGluR agonist 1s3r-ACPD induced motoneuron depolarization and depressed the monosynaptic DR and VLF responses. MCPG also facilitated the neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF) induced strengthening of the monosynaptic DR-responses (but only before P6, since neurotrophins are ineffective later at DR synapses and never at VLF synapses after birth). Our results suggest that mGluRs are involved in synaptic pathways to motoneurons made by DR but not VLF fibers. MCPG-induced facilitation of monosynaptic AMPA/kainate DR and VLF responses suggest the possibility of tonic mGluR-mediated inhibition of DR and VLF responses. We speculate that MCPG facilitates neurotrophin-induced strengthening of monosynaptic DR-responses by reducing this tonic inhibition.

Key words: BDNF, metabotropic glutamate receptor, modulation, motoneuron, neurotrophin-3, rat spinal cord