INVOLVEMENT OF AMPA RECEPTORS IN POSTERIOR LOCOMOTOR-ACTIVITY IN THE RABBIT - AN IN-VIVO STUDY

Although AMPA receptors are known to be widely involved in excitatory synaptic neurotransmission at the spinal level, very little is known a bout their role in modulating motor activity In mammals. In curarized decerebrate or spinalized rabbit preparations, fictive locomotion was monitored on hindlimb nerves after either activation or blockade of AM PA receptors. In decerebrate preparations, the administration of the a ntagonist, NBQX (3.5 mg/kg i.p.) or the agonist, AMPA (0.5 mg/kg i.v.) produced, in both cases, a depression of locomotor activities induced by stimulation of cutaneous afferents (evoked locomotor activity). Th is potent effect was transient with AMPA (recovery after 20 min) and f ollowed by the occurrence of spontaneous locomotor sequences, while no recovery was observed with NBQX treatment. In spinal preparations whe re a continuous 'spontaneous' locomotor activity resulted from the pha rmacological activation of noradrenergic descending pathways (nialamid e-DOPA pretreatment), the same drugs injected at higher doses (5 mg/kg NBQX i.p. and 1 mg/kg AMPA i.v.) only weakly affected the frequency o f 'spontaneous' and evoked locomotor bursts while they exerted inhibit ory and facilitatory effects on the burst amplitude respectively. The results suggest that AMPA receptors are involved at spinal level: 1) i n direct mediation of cutaneous afferent excitatory effects on the pos terior locomotor generators (pLG); 2) in indirect mediation of a supra spinal descending inhibition controlling, likely presynaptically, the cutaneous afferent activation; and 3) in transmission to motoneurons o f the output signals from the pLG. Finally, tight spinal interactions between potent descending noradrenergic pathways and spinal AMPA neuro transmission were disclosed. (C) Elsevier, Paris.