Can neurons induce surrounding glia to provide a more favorable microenvironment? Synapses and nerve growth cones have been shown to release neurotransmitters (Hume et al. Nature 1983;305:632-634; Kater et al. Trends Neurosci. 1988;11:315-321; Young and Poo Nature 1983;305:634-637) providing a possible mechanism for this type of control. The excitatory neurotransmitter glutamate induces an increase in the number of filopodia on the surface of astrocytes cultured from the neonatal rat hippocampus. This seems to be associated with a receptor-mediated event that is activated to a lesser degree by the quisqualate and kainate, but not NMDA receptors. In addition, time-lapse video recordings have revealed a rapid extension of filopodia from the apical margins of cells treated with glutamate. The apical margins of glutamate-treated cells studied with electron microscopy contained dense cortical actin networks that are devoid of microtubules. Coated pits are often seen to invaginate from the apical membrane in the vicinity of filopodia. A receptor-binding step may be followed by a rapid reorganization of cortical actin resulting in actin-containing filopodia. This process may be mediated by inositol lipid hydrolysis. Pyramidal neurons settled on glial cultures induced filopodia to form around the entire margin of growth cones and neurite tips suggesting that these events might occur in situ.