Spontaneous Synaptic Activation of Muscarinic Receptors by Striatal Cholinergic Neuron Firing

Neuron. 2016 Aug 3;91(3):574-86. doi: 10.1016/j.neuron.2016.06.021. Epub 2016 Jun 30.


Cholinergic interneurons (CHIs) play a major role in motor and learning functions of the striatum. As acetylcholine does not directly evoke postsynaptic events at most striatal synapses, it remains unclear how postsynaptic cholinergic receptors encode the firing patterns of CHIs in the striatum. To examine the dynamics of acetylcholine release, we used optogenetics and paired recordings from CHIs and medium spiny neurons (MSNs) virally overexpressing G-protein-activated inwardly rectifying potassium (GIRK) channels. Due to the efficient coupling between endogenous muscarinic receptors and GIRK channels, we found that firing of individual CHIs resulted in monosynaptic spontaneous inhibitory post-synaptic currents (IPSCs) in MSNs. Paired CHI-MSN recordings revealed that the high probability of acetylcholine release at these synapses allowed muscarinic receptors to faithfully encode physiological activity patterns from individual CHIs without failure. These results indicate that muscarinic receptors in striatal output neurons reliably decode CHI firing.

MeSH terms

  • Acetylcholine / metabolism
  • Ambenonium Chloride / pharmacology
  • Animals
  • Cholinergic Neurons / metabolism
  • Cholinergic Neurons / physiology*
  • Cholinesterase Inhibitors / pharmacology
  • Corpus Striatum / cytology*
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiology*
  • Female
  • Humans
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Interneurons / physiology
  • Male
  • Mice
  • Receptor, Muscarinic M4 / physiology*
  • Synapses / metabolism*


  • Cholinesterase Inhibitors
  • Receptor, Muscarinic M4
  • Ambenonium Chloride
  • Acetylcholine