ArticleBiological psychiatry2017
Connections of the Mouse Orbitofrontal Cortex and Regulation of Goal-Directed Action Selection by Brain-Derived Neurotrophic Factor.
Article in Biological psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 85 citations in OpenAlex.
- Successful pharmacotherapy for the treatment of severe feeding aversion with mechanistic insights from cross-species neuronal remodeling.Translational psychiatry · 2017Trial
- Neuromodulators of orbitofrontal cortex function: A review of endocannabinoid, neurotrophin, and cell adhesion systems.Neurobiology of disease · 2026Review
- Parallel neuronal structural plasticity with memory trace formation in the orbitofrontal cortex.Nature communications · 2025Article
- Review
- Action inflexibility and compulsive-like behavior accompany neurobiological alterations in the anterior orbitofrontal cortex and associated striatal nuclei.Scientific reports · 2025Article
- Social experience in adolescence shapes prefrontal cortex structure and function in adulthood.Molecular psychiatry · 2024Article
- Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice.Current biology : CB · 2024Article
- Article
- A molecularly defined orbitofrontal cortical neuron population controls compulsive-like behavior, but not inflexible choice or habit.Progress in neurobiology · 2024Article
- Changes in dorsomedial striatum activity during expression of goal-directed vs. habit-like cue-induced cocaine seeking.Addiction neuroscience · 2024Article
- Homeostasis to Allostasis: Prefrontal Astrocyte Roles in Cognitive Flexibility and Stress Biology.Advances in neurobiology · 2024Review
- Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice.bioRxiv : the preprint server for biology · 2023Article
- Subunit-selective PI3-kinase control of action strategies in the medial prefrontal cortex.Neurobiology of learning and memory · 2023Article
- GluN2B inhibition confers resilience against long-term cocaine-induced neurocognitive sequelae.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Article
- Article
- 7,8-dihydroxyflavone enhances long-term spatial memory and alters brain volume in wildtype mice.Frontiers in systems neuroscience · 2023Article
- Review
- A molecularly integrated amygdalo-fronto-striatal network coordinates flexible learning and memory.Nature neuroscience · 2022Article
- Inter-individual variability amplified through breeding reveals control of reward-related action strategies by Melanocortin-4 Receptor in the dorsomedial striatum.Communications biology · 2022Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDistinguishing between actions that are more likely or less likely to be rewarded is a critical aspect of goal-directed decision making. However, neuroanatomic and molecular mechanisms are not fully understood.
methodsWe used anterograde tracing, viral-mediated gene silencing, functional disconnection strategies, pharmacologic rescue, and designer receptors exclusively activated by designer drugs (DREADDs) to determine the anatomic and functional connectivity between the orbitofrontal cortex (OFC) and the amygdala in mice. In particular, we knocked down brain-derived neurotrophic factor (Bdnf) bilaterally in the OFC or generated an OFC-amygdala "disconnection" by pairing unilateral OFC Bdnf knockdown with lesions of the contralateral amygdala. We characterized decision-making strategies using a task in which mice selected actions based on the likelihood that they would be reinforced. Additionally, we assessed the effects of DREADD-mediated OFC inhibition on the consolidation of action-outcome conditioning.
resultsAs in other species, the OFC projects to the basolateral amygdala and dorsal striatum in mice. Bilateral Bdnf knockdown within the ventrolateral OFC and unilateral Bdnf knockdown accompanied by lesions of the contralateral amygdala impede goal-directed response selection, implicating BDNF-expressing OFC projection neurons in selecting actions based on their consequences. The tyrosine receptor kinase B agonist 7,8-dihydroxyflavone rescues action selection and increases dendritic spine density on excitatory neurons in the OFC. Rho-kinase inhibition also rescues goal-directed response strategies, linking neural remodeling with outcome-based decision making. Finally, DREADD-mediated OFC inhibition weakens new action-outcome memory.
conclusionsActivity-dependent and BDNF-dependent neuroplasticity within the OFC coordinate outcome-based decision making through interactions with the amygdala. These interactions break reward-seeking habits, a putative factor in multiple psychopathologies.
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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.