ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2023
Involvement of cortical input to the rostromedial tegmental nucleus in aversion to foot shock.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- VTA-forebrain connectivity moderates adaptive behavior.Brain structure & function · 2026Review
- The prelimbic prefrontal cortex mediates the development of lasting social avoidance as a consequence of social threat conditioning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Activation of the tail of the ventral tegmental area in response to pup predicting cues in maternal rats.Brain structure & function · 2025Article
- Chronic ethanol exposure produces long-lasting, subregion-specific physiological adaptations in RMTg-projecting mPFC neurons.Neuropharmacology · 2024Article
- The imprint of dissociative seizures on the brain.NeuroImage. Clinical · 2024Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The rostromedial tegmental nucleus (RMTg) encodes negative reward prediction error (RPE) and plays an important role in guiding behavioral responding to aversive stimuli. Previous research has focused on regulation of RMTg activity by the lateral habenula despite studies revealing RMTg afferents from other regions including the frontal cortex. The current study provides a detailed anatomical and functional analysis of cortical input to the RMTg of male rats. Retrograde tracing uncovered dense cortical input to the RMTg spanning the medial prefrontal cortex, the orbitofrontal cortex and anterior insular cortex. Afferents were most dense in the dorsomedial subregion of the PFC (dmPFC), an area that is also implicated in both RPE signaling and aversive responding. RMTg-projecting dmPFC neurons originate in layer V, are glutamatergic, and collateralize to select brain regions. In-situ mRNA hybridization revealed that neurons in this circuit are predominantly D1 receptor-expressing with a high degree of D2 receptor colocalization. Consistent with cFos induction in this neural circuit during exposure to foot shock and shock-predictive cues, optogenetic stimulation of dmPFC terminals in the RMTg drove avoidance. Lastly, acute slice electrophysiology and morphological studies revealed that exposure to repeated foot shock resulted in significant physiological and structural changes consistent with a loss of top-down modulation of RMTg-mediated signaling. Altogether, these data reveal the presence of a prominent cortico-subcortical projection involved in adaptive behavioral responding to aversive stimuli such as foot shock and provide a foundation for future work aimed at exploring alterations in circuit function in diseases characterized by deficits in cognitive control over reward and aversion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.