PLoS ONE (Apr 2011)

Cholinergic interneurons mediate fast VGluT3-dependent glutamatergic transmission in the striatum.

  • Michael J Higley,
  • Aryn H Gittis,
  • Ian A Oldenburg,
  • Nina Balthasar,
  • Rebecca P Seal,
  • Robert H Edwards,
  • Bradford B Lowell,
  • Anatol C Kreitzer,
  • Bernardo L Sabatini

DOI
https://doi.org/10.1371/journal.pone.0019155
Journal volume & issue
Vol. 6, no. 4
p. e19155

Abstract

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The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that suggest that they are also capable of vesicular glutamate release. Striatal cholinergic interneurons (CINs) express the Type-3 vesicular glutamate transporter (VGluT3), although whether they form functional glutamatergic synapses is unclear. To examine this possibility, we utilized mice expressing Cre-recombinase under control of the endogenous choline acetyltransferase locus and conditionally expressed light-activated Channelrhodopsin2 in CINs. Optical stimulation evoked action potentials in CINs and produced postsynaptic responses in medium spiny neurons that were blocked by glutamate receptor antagonists. CIN-mediated glutamatergic responses exhibited a large contribution of NMDA-type glutamate receptors, distinguishing them from corticostriatal inputs. CIN-mediated glutamatergic responses were insensitive to antagonists of acetylcholine receptors and were not seen in mice lacking VGluT3. Our results indicate that CINs are capable of mediating fast glutamatergic transmission, suggesting a new role for these cells in regulating striatal activity.