Significance Neurotransmitter switching generally involves replacement of an excitatory transmitter with an inhibitory transmitter or vice versa and has been linked to changes in animal behavior. There are corresponding switches in postsynaptic receptors that enable continued function of the circuit, but the mechanism by which receptor expression is regulated in this context was unknown. Sustained exposure to the neurotransmitter glutamate during development is both necessary and sufficient for the upregulation of ionotropic glutamate receptors in vertebrate striated skeletal muscle cells. This finding suggests a basis by which neurotransmitter release up-regulates expression of matching receptors at newly formed synapses during development of the nervous system and in response to neurotransmitter switching at established synapses.