Removal of NMDA receptor Mg(2+) block extends the action of NT-3 on synaptic transmission in neonatal rat motoneurons.
NT-3 has previously been reported to enhance AMPA/kainate receptor-mediated synaptic responses in motoneurons via an effect on the N-methyl-D-aspartate (NMDA) receptor. To investigate neurotrophin-3 (NT-3) action further, we measured the NMDA receptor (NMDAR)-mediated synaptic response directly by intracellular recording in motoneurons after blocking AMPA/kainate, GABA(A), GABA(B) and glycine receptor-mediated responses pharmacologically. Two pathways were stimulated, the segmental dorsal root (DR) and the descending ventrolateral fasciculus (VLF). The DR-evoked NMDAR-mediated response in motoneurons of rats younger than 1 wk has two components, the initial one of which is generated monosynaptically. NT-3 strongly potentiated both NMDA components in a rapidly reversible manner. No NMDAR-mediated responses were present at VLF connections and at DR connections in older (1- to 2-wk-old) neonates. Bath-applied NT-3-induced potentiation of the AMPA/kainate receptor-mediated response occurred only at connections that exhibit a synaptic NMDA receptor-mediated response. Reducing Mg(2+) concentration in the bathing solution restored the NMDAR-mediated response elicited by DR stimulation in older neonates and by VLF throughout the neonatal period (0-2 wk). In low-Mg(2+), NT-3 enhanced AMPA/kainate receptor-mediated responses elicited by inputs normally not influenced by NT-3. Thus a major reason for the loss of NT-3 action on AMPA/kainate synaptic responses is the reduced activity of the NMDA receptor due to developing Mg(2+) block of NMDA receptor-channel complex as the animal matures, and both can be re-established by reducing Mg(2+) concentration in fluid bathing the spinal cord.
Arvanian
V L
VL
Department of Neurobiology and Behavior, SUNY at Stony Brook, Stony Brook, New York 11794-5230, USA.
Mendell
L M
LM
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D020933:Neurotrophin 3 / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D020933:Neurotrophin 3; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008274:Magnesium; D002118:Calcium