Nicotinic Cholinergic Receptors in VTA Glutamate Neurons Modulate Excitatory Transmission

Yijin Yan, Can Peng, Matthew C. Arvin, Xiao Tao Jin, Veronica J. Kim, Matthew D. Ramsey, Yong Wang, Sambashiva Banala, David L. Wokosin, J. Michael McIntosh, Luke D. Lavis, Ryan M. Drenan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Ventral tegmental area (VTA) glutamate neurons are important components of reward circuitry, but whether they are subject to cholinergic modulation is unknown. To study this, we used molecular, physiological, and photostimulation techniques to examine nicotinic acetylcholine receptors (nAChRs) in VTA glutamate neurons. Cells in the medial VTA, where glutamate neurons are enriched, are responsive to acetylcholine (ACh) released from cholinergic axons. VTA VGLUT2+ neurons express mRNA and protein subunits known to comprise heteromeric nAChRs. Electrophysiology, coupled with two-photon microscopy and laser flash photolysis of photoactivatable nicotine, was used to demonstrate nAChR functional activity in the somatodendritic subcellular compartment of VTA VGLUT2+ neurons. Finally, optogenetic isolation of intrinsic VTA glutamatergic microcircuits along with gene-editing techniques demonstrated that nicotine potently modulates excitatory transmission within the VTA via heteromeric nAChRs. These results indicate that VTA glutamate neurons are modulated by cholinergic mechanisms and participate in the cascade of physiological responses to nicotine exposure. Yan et al. examine how functional activity of nicotinic cholinergic receptors is distributed in diverse VTA cell types, revealing nAChR activity in VTA glutamate neurons. These receptors modulate local glutamate transmission in VTA, suggesting mechanisms by which nicotine influences mesolimbic circuitry.

Original languageEnglish (US)
Pages (from-to)2236-2244
Number of pages9
JournalCell reports
Volume23
Issue number8
DOIs
StatePublished - May 22 2018

Keywords

  • acetylcholine
  • cholinergic
  • dopamine
  • electrophysiology
  • glutamate
  • nicotine
  • nicotinic
  • optogenetics
  • receptor
  • synapse

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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