Valence-encoding in the lateral habenula arises from the entopeduncular region

Hao Li, Dominika Pullmann, Thomas C. Jhou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Lateral habenula (LHb) neurons are activated by negative motivational stimuli and play key roles in the pathophysiology of depression. Prior reports suggested that rostral entopeduncular nucleus (rEPN) neurons drive these responses in the LHb and rostromedial tegmental nucleus (RMTg), but these influences remain untested. Using rabies viral tracers, we demonstrate disynaptic projections from the rEPN to RMTg, but not VTA, via the LHb in rats. Using in vivo electrophysiology, we find that rEPN or LHb subpopulations exhibit activation/inhibition patterns after negative/positive motivational stimuli, similar to the RMTg, while temporary inactivation of a region centered on the rEPN decreases LHb basal and burst firing, and reduces valence-related signals in LHb neurons. Additionally, excitotoxic rEPN lesions partly diminish footshock-induced cFos in the LHb and RMTg. Together, our findings indicate an important role of the rEPN, and possibly immediately adjacent hypothalamus, in driving basal activities and valence processing in LHb and RMTg neurons.

Original languageEnglish (US)
Article numbere41223
StatePublished - Mar 2019

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)


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