Abstract
In the earliest days of neuroscience, it was thought that a neuron made and released only a single chemical, known as a neurotransmitter, to send a signal across a synapse to an adjacent neuron (1). At the same time, it was deeply mysterious why so many signaling molecules were used in nervous systems. Subsequently, it became clear that many, if not most, neurons (including those in mammals) make and release two or more neurotransmitters including small-molecules and neuropeptides (2–4). As the list of these potential cotransmitters and their receptors has increased, we are faced with understanding the functional relevance of this embarrassment of riches for neural circuits and behavior. Neurotransmitters and neuromodulators (substances often released with small-molecule neurotransmitters) can elicit a variety of different actions on their neuron targets, including directly opening ion channels or acting through signal transduction pathways to alter neuronal excitability or synaptic transmission. Thus, characterizing the mixture of cotransmitters released by a neuron is important for understanding how neuronal circuits operate. The mechanisms that change the profile of neurotransmitter release provide opportunities for plastic changes in circuit function, and consequently in organism behavior. On page 449 of this issue, Dulcis et al. (5) report changes in the neurotransmitter profile of neurons that underlie photoperiod-triggered changes in animal behavior. The findings argue that neurotransmitter switching is a new mechanism for neuroplasticity (6) in adult nervous systems.