Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission

Nat Neurosci. 2003 Sep;6(9):968-73. doi: 10.1038/nn1103.


The mesolimbic dopamine system is centrally involved in reward and goal-directed behavior, and it has been implicated in multiple psychiatric disorders. Understanding the mechanism by which dopamine participates in these activities requires comprehension of the dynamics of dopamine release. Here we report dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing. Only the increase in population activity increased ventral striatal dopamine efflux. After blockade of dopamine reuptake, however, enhanced bursting increased dopamine efflux three times more than did enhanced population activity. These results provide insight into multiple regulatory systems that modulate dopamine system function: burst firing induces massive synaptic dopamine release, which is rapidly removed by reuptake before escaping the synaptic cleft, whereas increased population activity modulates tonic extrasynaptic dopamine levels that are less influenced by reuptake.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology
  • Animals
  • Dopamine / physiology*
  • GABA Antagonists / pharmacology
  • Male
  • Mesencephalon / drug effects
  • Mesencephalon / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology


  • GABA Antagonists
  • Dopamine