State-dependent modulation of positive and negative affective valences by a parabrachial nucleus-to-ventral tegmental area pathway in mice

Front Neural Circuits. 2023 Nov 29:17:1273322. doi: 10.3389/fncir.2023.1273322. eCollection 2023.

Abstract

Appropriately responding to various sensory signals in the environment is essential for animal survival. Accordingly, animal behaviors are closely related to external and internal states, which include the positive and negative emotional values of sensory signals triggered by environmental factors. While the lateral parabrachial nucleus (LPB) plays a key role in nociception and supports negative valences, it also transmits signals including positive valences. However, the downstream neuronal mechanisms of positive and negative valences have not been fully explored. In the present study, we investigated the ventral tegmental area (VTA) as a projection target for LPB neurons. Optogenetic activation of LPB-VTA terminals in male mice elicits positive reinforcement in an operant task and induces both avoidance and attraction in a place-conditioning task. Inhibition of glutamic acid decarboxylase (GAD) 65-expressing cells in the VTA promotes avoidance behavior induced by photoactivation of the LPB-VTA pathway. These findings indicate that the LPB-VTA pathway is one of the LPB outputs for the transmission of positive and negative valence signals, at least in part, with GABAergic modification in VTA.

Keywords: aversive memory; avoidance; glutamic acid decarboxylase 65; mice; operant task; optogenetics; parabrachial nucleus; ventral tegmental area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Male
  • Mice
  • Neurons / physiology
  • Parabrachial Nucleus*
  • Reinforcement, Psychology
  • Ventral Tegmental Area* / physiology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported in part by Japan Agency for Medical Research and Development (AMED) Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) (Grant number: JP19dm0207081 to AMW; JP21dm0207111 to HH), JSPS Grants-in-Aid for Scientific Research (Grant number: 19H04062, 21K18564, and 22H03542 to AMW), Core Research for Evolutional Science and Technology Japan Science and Technology Agency (CREST-JST) (Grant number: JPMJCR1751 to AMW), JST (Moonshot R and D) (Grant number: JPMJMS2024 to AMW), and Early-Career Scientists (Grant numbers: JP21K16374 to TN and JP22K15231 to ST). Production of AAV vectors was partly supported by the Brain/MINDS, AMED (JP21dm0207113).