Cholinergic control of striatal GABAergic microcircuits

Samet Kocaturk, Elif Beyza Guven, Fulva Shah, James M. Tepper, Maxime Assous

Research output: Contribution to journalArticlepeer-review


Cholinergic interneurons (CINs) are essential elements of striatal circuits and functions. Although acetylcholine signaling via muscarinic receptors (mAChRs) has been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on striatal GABAergic interneurons (GINs) are equally critical. One example is that CIN stimulation induces large disynaptic inhibition of striatal projection neurons (SPNs) mediated by nAChR activation of GINs. Although these circuits are ideally positioned to modulate striatal output, the neurons involved are not definitively identified because of an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs modulate four GINs populations via an intricate mechanism involving co-activation of presynaptic and postsynaptic mAChRs and nAChRs. Using optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.

Original languageEnglish (US)
Article number111531
JournalCell Reports
Issue number4
StatePublished - Oct 25 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


  • CP: Neuroscience
  • acetylcholine
  • electrical coupling
  • gap junction
  • interneurons
  • muscarinic
  • neurogliaform
  • nicotinic
  • optogenetic
  • projection neurons
  • striatum
  • tyrosine hydroxylase


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