Homeostatic plasticity induced by chronic block of AMPA/kainate receptors modulates the generation of rhythmic bursting in rat spinal cord organotypic cultures

Generation of spontaneous rhythmic activity is a distinct feature of develo ping spinal networks. We report that rat embryo organotypic spinal cultures contain the basic circuits responsible for pattern generation. In this pre paration rhythmic activity can be recorded from ventral interneurons and is developmentally regulated. When chronically grown in the presence of an AM PA/kainate receptor blocker, this circuit expresses long-term plasticity co nsisting largely of increased frequency of fast synaptic activity and reduc tion in slow GABAergic events, We examined whether, once this form of homeo static plasticity is established, the network could still exhibit rhythmici ty with properties similar to controls. Control or chronically treated vent ral interneurons spontaneously generated (with similar probability) irregul ar, network-driven bursts over a background of ongoing synaptic activity. I n control cultures increasing network excitability by strychnine plus bicuc ulline, or by raising [K+](o), induced rapid-onset, regular rhythmic bursts . In treated cultures the same pharmacological block of Cl--mediated transm ission or high-K+ application also induced regular patterned activity, alth ough significantly faster and, in the case of high K+, characterized by slo w onset due to postsynaptic current summation. Enhancing GABAergic transmis sion by pentobarbital surprisingly accelerated the high-K+ rhythm of contro l cells (though depressing background activity), whereas it slowed it down in chronically treated cells. This contrasting effect of pentobarbital sugg ests that, to preserve bursting ability, chronic slices developed a distinc t GABAergic inhibitory control on over-expressed bursting circuits. Convers ely, in control slices GABAergic transmission depressed spontaneous activit y but it facilitated bursting frequency. Thus, even after homeostatic rearr angement, developing mammalian spinal networks still generate rhythmic acti vity.