ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Prefrontal correlates of fear generalization during endocannabinoid depletion.The Journal of clinical investigation · 2025Article
- Amygdala intercalated cells form an evolutionarily conserved system orchestrating brain networks.Nature neuroscience · 2025Review
- Distinct roles of monkey OFC-subcortical pathways in adaptive behavior.Nature communications · 2024Article
- Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.Human brain mapping · 2024Article
- Longitudinal microstructural changes in 18 amygdala nuclei resonate with cortical circuits and phenomics.Communications biology · 2024Article
- PREFRONTAL CORRELATES OF FEAR GENERALIZATION DURING ENDOCANNABINOID DEPLETION.bioRxiv : the preprint server for biology · 2024Article
- Gene expression in the primate orbitofrontal cortex related to anxious temperament.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion.Neuroscience and biobehavioral reviews · 2023Review
- Connectivity-based parcellation of the amygdala and identification of its main white matter connections.Scientific reports · 2023Article
- DREADD-mediated amygdala activation is sufficient to induce anxiety-like responses in young nonhuman primates.Current research in neurobiology · 2023Article
- The neural circuits and molecular mechanisms underlying fear dysregulation in posttraumatic stress disorder.Frontiers in neuroscience · 2023Review
- Multiple routes of communication within the amygdala-mPFC network: A comparative approach in humans and macaques.Current research in neurobiology · 2023Review
- Functional connectivity of intercalated nucleus with medial amygdala: A circuit relevant for chemosignal processing.IBRO neuroscience reports · 2022Article
- The prefrontal cortex, pathological anxiety, and anxiety disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
- Prefrontal cortex interactions with the amygdala in primates.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
- Prefrontal-hippocampal interactions supporting the extinction of emotional memories: the retrieval stopping model.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
- Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder.Molecular psychiatry · 2021Article
- Evolution, Emotion, and Episodic Engagement.The American journal of psychiatry · 2021Review
- The longitudinal association between externalizing behavior and frontoamygdalar resting-state functional connectivity in late adolescence and young adulthood.Journal of child psychology and psychiatry, and allied disciplines · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 5 countries.
Funding
Abstract
The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons expressing dopamine- and cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and inhibition of CeM, resulting in modulated autonomic function. By contrast, inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and triggers autonomic arousal. The findings provide a mechanism to help explain how a strong pOFC pathway, which is poised to moderate activity of CeM, through IM, can be undermined by the high level of dopamine during stress, resulting in collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic drive, as seen in chronic anxiety disorders.
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Registered trials
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.