Investigation of the development of neuronal excitability led to the discovery that calcium-dependent embryonic electrical activity rapidly and reversibly reconfigures the transmitters and matching postsynaptic transmitter receptors that neurons express. Activity modulates the transcriptional code for transmitter specification. Both sensory and motor stimuli reprogram neurotransmitter identity, resulting in transmitter switches in young and adult nervous systems. Transmitter switching often converts excitatory neurons to inhibitory ones, or vice versa – a form of plasticity that is distinct from changes in synaptic weights and synapse number. The changes in brain biochemistry during transmitter switching cause changes in behavior that can be beneficial, enhancing learning, or detrimental, contributing to neurological and psychiatric disorders.