AbstractThe early development of functionally active GABA and glutamate receptors on neurons from hippocampus, septal region, and neocortex of embrryonic rats were studied using primary dissociated serum‐free cell cultures. The responses to GABA and glutamate, applied to individual neurons by pressure ejection, were tested at different development stages, starting at 1 day in vitro (DIV) until 3 weeks. In all three types of neuronal cultures, the GABAA‐receptor developed prior to the glutamate receptros, and after 9 DIV most of the neurons were sensitive to both GABA and glutamate. N‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptor subtypes of the glutamate receptors could be distinguished in hippocampal cultures. The development of GABA and glutamate receptors on septal region neurons appeared to be delyed as compared to hippocampal neurons. In neucortical cultures the majority of nueorns was sensitive to GABA just after plating, whereas the sensitivity to glutamate was retarded. The differences in GABA and glutamate receptor development among these three neuronal cultures provide evidence that the apearance of tranmitter receptors on cultured neurons is predominantly determined by intrinsic mechanisms rather than by environmental coditions. The proportion of spontaneously active networks in these cultures increased with a time course very similar to the rise in glutamate‐sensitive neurons suggesting that functional active glutamate receptors may be involved in the generation of spontan