Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons

Neuron. 2006 May 4;50(3):443-52. doi: 10.1016/j.neuron.2006.04.010.

Abstract

Long-term depression (LTD) of the synapse formed between cortical pyramidal neurons and striatal medium spiny neurons is central to many theories of motor plasticity and associative learning. The induction of LTD at this synapse is thought to depend upon D(2) dopamine receptors localized in the postsynaptic membrane. If this were true, LTD should be inducible in neurons from only one of the two projection systems of the striatum. Using transgenic mice in which neurons that contribute to these two systems are labeled, we show that this is not the case. Rather, in both cell types, the D(2) receptor dependence of LTD induction reflects the need to lower M(1) muscarinic receptor activity-a goal accomplished by D(2) receptors on cholinergic interneurons. In addition to reconciling discordant tracts of the striatal literature, these findings point to cholinergic interneurons as key mediators of dopamine-dependent striatal plasticity and learning.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism
  • Calcium Signaling / physiology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism*
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Excitatory Amino Acid Antagonists
  • Interneurons / drug effects
  • Interneurons / metabolism*
  • Learning / physiology
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Organ Culture Techniques
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Receptor, Muscarinic M1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Cacna1d protein, mouse
  • Calcium Channels, L-Type
  • Excitatory Amino Acid Antagonists
  • Receptor, Muscarinic M1
  • Receptors, Dopamine D2
  • Acetylcholine
  • Dopamine