PHARMACOLOGIC ANALYSIS OF INHIBITION PRODUCED BY LAST-ORDER INTERMEDIATE NUCLEUS INTERNEURONS MEDIATING NONRECIPROCAL INHIBITION OF MOTONEURONS IN CAT SPINAL-CORD

The aim of this study was to investigate the effects of drugs blocking glycinergic and GABAergic transmission on the postsynaptic inhibition of hindlimb motoneurons produced by activation of last-order laminae V-VI interneuons, which are coexcited by muscle and cutaneous afferents and have axonal branches projecting to the Clarke's column. In anesthetized cats with right spinal cord hemisected and both dorsal columns cut between L4 and L5 segments, stimulation of the Clarke's column (CC) at L3-L4 level produced a short-latency, presumably monosynaptic, inhibitory potential that could be recorded either from L7 or S1 ventral rootlets by means of the sucrose-gap technique (iVRP) or intracellularly from hindlimb motoneurons (IPSP). These potentials have been attributed to antidromic activation of a population of last-order interneurons mediating nonreciprocal inhibition of motoneurons. The early iVRP and IPSP produced by CC stimulation was practically abolished 10-20 s after the intravenous injection of strychnine (0.1 mg/kg) and replaced by an excitatory synaptic potential followed by delayed, slow, strychnine-resistant inhibitory potential. Monosynaptic reflexes (MSR) elicited by stimulation of group I gastrocnemius (GS) afferents were inhibited during the occurrence of the CC-iVRP. This inhibition was significantly reduced after intravenous strychnine. On the other hand, the inhibition of the GS-MSR, produced by conditioning stimulation of the posterior biceps and semitendinosus (PBSt) nerve with trains of pulses applied 25-35 ms before the test stimulus, was practically unchanged after the intravenous injection of strychnine. The CC-iVRP and the associated inhibition of GS-MSRs were not significantly affected after the intravenous injection of 0.1 mg/kg of picrotoxin, which clearly reduced the dorsal root potentials (DRP), the late component of the iVRP, and the inhibition of MSRs produced by PBSt volleys. The effect of strychnine and picrotoxin was tested on the monosynaptic iVRP elicited by single intermediate nucleus interneurons that were antidromically activated from the CC and responded both to low-threshold cutaneous fibers and to group I or group II afferents. In three experiments where the interneuronal activity could be kept after the drug injection, it was possible to show that strychnine abolished the interneuronally elicited iVRP, which was replaced by an excitatory synaptic potential with onset preceding the interneural activity. In another experiment, it was possible to show that the interneuronally elicited iVRP was not affected by an intra-aortic injection of picrotoxin (0.5 mg/kg) that reduced to one-half the DRP and the iVRP produced by group I PBSt volleys. It is concluded that last-order interneurons that mediate nonreciprocal postsynaptic inhibition of motoneurons that are mono- or disynaptically activated by group I or group II inputs, and that give axon collaterals to the CC, are glycinergic. Because stimulation of group I flexor afferents produced iVRPs and DRPs that were reduced by picrotoxin but not by strychnine, it is suggested that the postsynaptic inhibition produced by group I volleys has, in addition, a GABAergic component mediated by interneurons that are shared with pathways producing presynaptic inhibition. The functional implications of these findings are discussed.