For a long time, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors permeable to calcium have been considered to be either non-existent or as "atypical". There is now ample evidence that these receptors exist in numerous regions of the nervous system and in many neuronal as well as non-neuronal cell populations. This evidence has been accumulated by several methods, including electrophysiological recording, calcium imaging and cobalt-loading. Functional AMPA receptors permeable to calcium are already expressed at very early stages of embryonic development, well before the onset of synaptogenesis. They are probably involved in the paracrine signaling necessary for construction of the nervous system before becoming involved in synaptic transmission. In immature cells, cyclothiazide strongly increases the steady-state level of responses not only to AMPA, but also to kainate. Ingestion, during pregnancy, of food or drug substances that can cross the placental barrier and act upon the embryonic receptors may constitute a risk for normal development. In the adult nervous system, synaptic as well as non-synaptic (paracrine) AMPA receptors permeable to calcium are probably widely expressed in both glial and neuronal cells. They may also participate in controlling some aspects related to adult neurogenesis, in particular the migration of newly formed neurons.