NMDA receptor-dependent periodic oscillations in cultured spinal cord networks

Cultured spinal cord networks grown on microelectrode arrays display comple x patterns of spontaneous burst and spike activity. During disinhibition wi th bicuculline and strychnine, synchronized burst patterns routinely emerge . However, the variability of both intra- and interculture burst periods an d durations are typically large under these conditions. As a further step i n simplification of synaptic interactions, we blocked excitatory AMPA synap ses with 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzoquinoxaline-7-sulphonamid e (NBQX), resulting in network activity mediated through the N-methyl-D-asp artate (NMDA) receptor (NMDA(ONLY)). This activity was APV sensitive. The o scillation under NMDA(ONLY) conditions at 37 degreesC was characterized by a period of 2.9 +/-0.3 s (16 separate cultures). More than 98% of all neuro ns recorded participated in this highly rhythmic activity. The temporal coe fficients of variation, reflecting the rhythmic nature of the oscillation, were 3.7, 4.7, and 4.9% for burst rate, burst duration, and interburst inte rval, respectively [mean coefficients of variation (CVs) for 16 cultures]. The oscillation persisted for at least 12 h without change (maximum observa tion time). Once established, it was not perturbed by agents that block mGl u receptors, GABA(B) receptors, cholinergic receptors, purinergic receptors , tachykinin receptors, serotonin (5-HT) receptors, dopamine receptors, ele ctrical synapses, burst afterhyperpolarization, NMDA receptor desensitizati on, or the hyperpolarization-activated current. However, the oscillation wa s destroyed by bath application of NMDA (20-50 muM). These results suggest a presynaptic mechanism underlying this periodic rhythm that is solely depe ndent on the NMDA synapse. When the AMPA/kainate synapse was the sole drivi ng force (n=6), the resulting burst patterns showed much higher variability and did not develop the highly periodic, synchronized nature of the NMDA(O NLY) activity. Network size or age did not appear to influence the reliabil ity of expression of the NMDA(ONLY) activity pattern. For this reason, we s uggest that the NMDA(ONLY) condition unmasks a fundamental rhythmogenic mec hanism of possible functional importance during periods of NMDA receptor-do minated activity, such as embryonic and early postnatal development.