Factors regulating AMPA-type glutamate receptor subunit changes induced bysciatic nerve injury in rats

Excitatory glutamatergic neurotransmission at Ia afferent-motoneuron synaps es is enhanced shortly after physically severing or blocking impulse propag ation of the afferent and/or motoneuron axons. We considered the possibilit y that these synaptic changes occur because of alterations in the number or properties of motoneuron alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propio nate (AMPA) receptors. Therefore, we quantitatively analyzed glutamate rece ptor (GluR)1, GluR2/3, and GluR4 AMPA subunit immunoreactivity (ir) in moto neurons 3, 7, or 14 days after axotomy or continuous tetrodotoxin (TTX) blo ck of the sciatic nerve. GluR1-ir remained low in experimental and control motoneurons with either treatment; and at any date. However, there was a la rge reduction of GluR2/3-ir (peak at 7 days >60% reduced) and a smaller, bu t statistically significant, reduction of GluR4-ir (around 10% reduction at days 3, 7, and 14) in axotomized motoneurons. TTX sciatic blockade did not affect AMPA subunit immunostainings. Axonal injury or interruption of the trophic interaction between muscle and spinal cord, but not activity disrup tion, appears therefore more likely responsible for altering AMPA subunit i mmunoreactivity in motoneurons. These findings also suggest that synaptic p lasticity induced by axotomy or TTX block, although similar in the first we ek, could be related to different mechanisms. The effects of axotomy or TTX block on motoneuron expression of the metabotropic glutamate receptor mGlu R1a were also studied. mGluR1a-ir was also strongly decreased after axotomy but not after TTX treatment. The time course of the known stripping of syn apses from the cell somas of axotomized motoneurons was studied by using sy naptophysin antibodies and compared with AMPA and mGluR1a receptor changes. Coverage by synaptophysin-ir boutons was only clearly decreased 14 days po st axotomy and not at shorter intervals or after TTX block. (C) 2000 Wiley- Liss, Inc.