Science Topics - 97

Over a century ago Thorndike and Pavlov discovered that rewards need to follow the behaviors for conditioning. Recent studies indicate that dopamine release in the striatum serves as a reward signal and reinforces the preceding behaviors. However, the timing detection mechanisms of dopamine remains unknown. Using optical stimulation of glutamate and dopamine, we examined how dopamine affected the spike-timing plasticity (STDP) of single dendritic spines in the medium spiny neurons of the nucleus accumbens, a key brain area for reinforcement learning, and found that spine enlargement, representing long-term potentiation, was markedly enhanced only when dopamine was released within a very narrow time window (0.3-2 s) following the onset of STDP, consistent with the behavioral conditioning. We then performed imaging of Ca2+, CaMKII and PKA, and found that the sequence detection involved a process upstream of PKA activation: Sufficient generation of cAMP occurred only when spikes preceded dopamine to prime adenylyl-cyclase (AC1), otherwise cAMP was effectively removed by a potent phosphodiesterase (PDE) activity in thin distal dendrites of MSNs. Thus, PKA was activated only when spikes preceded dopamine, and promoted spine enlargement via CaMKII. Thus, we have clarified the cellular and molecular basis of reinforcement plasticity which is induced at the level of single dendritic spines.

Yagishita, S. et. al. A critical time window for dopamine actions on the structural plasticity of dendritic spines. Science 345:1616-1620, 2014. 

Yagishita, S. et. al. A critical time window for dopamine actions on the structural plasticity of dendritic spines. Science 345:1616-1620. 2014

Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo