Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits

Daniel Dautan, Albert S. Souza, Icnelia Huerta-Ocampo, Miguel Valencia, Maxime Assous, Ilana B. Witten, Karl Deisseroth, James M. Tepper, J. Paul Bolam, Todor V. Gerdjikov, Juan Mena-Segovia

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT cholinergic axons selectively enhanced the bursting activity of mesolimbic dopamine neurons that were excited by aversive stimulation. In contrast, PPN cholinergic axons activated and changed the discharge properties of VTA neurons that were integrated in distinct functional circuits and were inhibited by aversive stimulation. Although both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of cholinergic transmission operate in the VTA and segregate the neurons involved in different reward circuits.

Original languageEnglish (US)
Pages (from-to)1025-1033
Number of pages9
JournalNature neuroscience
Issue number8
StatePublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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