Intrinsic NMDA-Induced Oscillations in Motoneurons of an Adult Vertebrate Spinal Cord Are Masked by Inhibition

Rioult-Pedotti, Mengia-Seraina. Intrinsic NMDA induced oscilto generate rhythmic motor behavior in spinal cords of the lations in motoneurons of an adult vertebrate spinal cord are lamprey (Sigvardt et al. 1985; Wallén and Grillner 1985, masked by inhibition. J. Neurophysiol. 77: 717–730, 1997. Low1987), tadpoles (Sillar and Simmers 1994), and neonatal frequency membrane potential oscillations were induced in motorats (Hochman et al. 1994), and in brain stem neurons of neurons (MNs) of isolated hemisected frog spinal cords during Nvarious vertebrates (swallowing: Tell and Jean 1991, 1993; methyl-D-aspartate (NMDA) application. Oscillations required the respiration: Dekin and Haddad 1990; Funk et al. 1993; locopresence of physiological Mg and preincubation with strychnine, motion: Durand 1993; Orlovsky 1972; Serafin et al. 1992). whereas incubation with bicuculline or phaclofen was not effective. Natural rhythmic motor output can be initiated by sensory Oscillations were evident in intracellular recordings from single afferents (e.g., Alford and Williams 1989; Soffe and Roberts MNs and simultaneous extracellular recordings from lumbar ventral roots. In Mg-free solution, MNs exhibited irregular transient 1982a,b) but can also be mimicked by pharmacological membrane potential depolarizations that were blocked by D,L-2treatment with excitatory amino acid agonists. In particular, amino-5-phosphonopentanoic acid (APV) but not by 6-cyano-7specific activation of the N-methyl-D-aspartate (NMDA) nitroquinoxaline-2,3-dione (CNQX). Generation and maintenance subtype of glutamate receptors has been shown to induce of membrane potential oscillations required specific NMDA recepboth rhythmic motor activity (Cazalets et al. 1992, 1994; tor activation. Oscillations were antagonized by APV but not by Dale and Roberts 1984; Hernández et al. 1991; Kudo and CNQX. Strychnine preincubation was required for NMDA to inYamada 1987; Roberts et al. 1986; Smith et al. 1988) and duce oscillations, but was not critical in maintaining them, because membrane potential oscillations in individual neurons (Duroscillations persisted after removal of strychnine. Therefore oscillaand 1991, 1993; Hochman et al. 1994; Serafin et al. 1992; tions are suggested to be an inherent property of the spinal neuronal Sillar and Simmers 1994; Tell and Jean 1991, 1993; Wallén circuitry. Tetrodotoxin (TTX) blocked spike activity and had a bimodal effect on membrane potential oscillations. Oscillations and Grillner 1987). In the isolated lamprey spinal cord, bath initially were blocked by TTX, but reappeared spontaneously after application of NMDA induces fictive locomotion (Brodin et 10–40 min. This suggests that maintenance of oscillations, once al. 1985; Grillner et al. 1981; Wallén and Grillner 1987) as evoked, does not involve MN firing. Na entry through TTXwell as inherent oscillatory activity in synaptically isolated insensitive Na channels and/or NMDA receptor channels, transneurons within the locomotor central pattern generator (Walmembrane Ca flux, Ca release from intracellular stores, and lén and Grillner 1987). Moreover, NMDA receptor antagoCa activated K channels were critical in controlling the amplinists are able to block naturally induced locomotor activity, tude and frequency of membrane potential oscillations. It is hypothindicating that NMDA receptors may play an important role esized that these unmasked intrinsic oscillations in adult frog spinal in rhythmic activities underlying naturally occurring lococord MNs may represent a premetamorphic spinal oscillator inmotion (Alford and Williams 1989; Wallén and Grillner volved in tadpole swimming that becomes suppressed during meta1987). morphosis as strychnine-sensitive inhibition becomes more pronounced. The voltage dependence of the NMDA receptor in the presence of physiological levels of Mg causes a negative slope conductance in the current-voltage relationship (Mayer