Activation of pedunculopontine glutamate neurons is reinforcing

Ji Hoon Yoo, Vivien Zell, Johnathan Wu, Cindy Punta, Nivedita Ramajayam, Xinyi Shen, Lauren Faget, Varoth Lilascharoen, Byung Kook Lim, Thomas S. Hnasko

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Dopamine transmission from midbrain ventral tegmental area (VTA) neurons underlies behavioral processes related to motivation and drug addiction. The pedunculopontine tegmental nucleus (PPTg) is a brainstem nucleus containing glutamate-, acetylcholine-, and GABA-releasing neurons with connections to basal ganglia and limbic brain regions. Here we investigated the role of PPTg glutamate neurons in reinforcement, with an emphasis on their projections to VTA dopamine neurons. We used cell-type-specific anterograde tracing and optogenetic methods to selectively label and manipulate glutamate projections from PPTg neurons in mice. We used anatomical, electrophysiological, and behavioral assays to determine their patterns of connectivity and ascribe functional roles in reinforcement. We found that photoactivation of PPTg glutamate cell bodies could serve as a direct positive reinforcer on intracranial selfphotostimulation assays. Further, PPTg glutamate neurons directly innervate VTA; photostimulation of this pathway preferentially excites VTA dopamine neurons and is sufficient to induce behavioral reinforcement. These results demonstrate that ascending PPTg glutamate projections can drive motivated behavior, and PPTg to VTA synapses may represent an important target relevant to drug addiction and other mental health disorders.

Original languageEnglish
Pages (from-to)38-46
Number of pages9
JournalJournal of Neuroscience
Volume37
Issue number1
DOIs
StatePublished - 4 Jan 2017

Keywords

  • Dopamine
  • Glutamate
  • Optogenetics
  • Pedunculopontine
  • Reward
  • Ventral tegmental area

EGS Disciplines

  • Biology

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