Start/stop signals emerge in nigrostriatal circuits during sequence learning

Nature. 2010 Jul 22;466(7305):457-62. doi: 10.1038/nature09263.


Learning new action sequences subserves a plethora of different abilities such as escaping a predator, playing the piano, or producing fluent speech. Proper initiation and termination of each action sequence is critical for the organization of behaviour, and is compromised in nigrostriatal disorders like Parkinson's and Huntington's diseases. Using a self-paced operant task in which mice learn to perform a particular sequence of actions to obtain an outcome, we found neural activity in nigrostriatal circuits specifically signalling the initiation or the termination of each action sequence. This start/stop activity emerged during sequence learning, was specific for particular actions, and did not reflect interval timing, movement speed or action value. Furthermore, genetically altering the function of striatal circuits disrupted the development of start/stop activity and selectively impaired sequence learning. These results have important implications for understanding the functional organization of actions and the sequence initiation and termination impairments observed in basal ganglia disorders.

Publication types

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

MeSH terms

  • Action Potentials
  • Animals
  • Behavior, Animal / physiology
  • Dopamine / metabolism
  • Glutamic Acid / metabolism
  • Learning / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Neurological
  • Neostriatum / physiology*
  • Neural Pathways / physiology*
  • Receptors, N-Methyl-D-Aspartate / deficiency
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Substantia Nigra / physiology*


  • NR1 NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Dopamine