A critical time window for dopamine actions on the structural plasticity of dendritic spines

Animal behavior follows rewards Animal behavior is learned and reinforced by rewards. On a molecular level, the reward comes in the form of the neurotransmitter, dopamine, which modulates synapses. The exact timing and mechanism of this process remain unknown. Using optical stimulation, Yagishita et al. found that dopaminergic modulation involved dendritic spine enlargement only during an extremely narrow time window. Known as reinforcement plasticity, this cellular basis for learning could provide insight into psychiatric disorders involving dopaminergic regulation, such as depression, drug addiction, and schizophrenia. Science, this issue p. 1616 Dopamine promotes spine structural plasticity during a narrow time window in mouse neuron distal dendrites. Animal behaviors are reinforced by subsequent rewards following within a narrow time window. Such reward signals are primarily coded by dopamine, which modulates the synaptic connections of medium spiny neurons in the striatum. The mechanisms of the narrow timing detection, however, remain unknown. Here, we optically stimulated dopaminergic and glutamatergic inputs separately and found that dopamine promoted spine enlargement only during a narrow time window (0.3 to 2 seconds) after the glutamatergic inputs. The temporal contingency was detected by rapid regulation of adenosine 3′,5′-cyclic monophosphate in thin distal dendrites, in which protein-kinase A was activated only within the time window because of a high phosphodiesterase activity. Thus, we describe a molecular basis of reinforcement plasticity at the level of single dendritic spines.