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

Science. 2014 Sep 26;345(6204):1616-20. doi: 10.1126/science.1255514.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dendritic Spines / drug effects*
  • Dendritic Spines / physiology
  • Dopamine / pharmacology*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Electrical Synapses / drug effects
  • Electrical Synapses / physiology
  • Glutamic Acid / physiology*
  • Learning / drug effects
  • Learning / physiology*
  • Mice
  • Neuronal Plasticity / drug effects*
  • Phosphoric Diester Hydrolases / metabolism
  • Reward*
  • Time Factors


  • Dopamine Plasma Membrane Transport Proteins
  • Glutamic Acid
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Phosphoric Diester Hydrolases
  • Dopamine