ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
GABAAα1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 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
- β1-Integrins in the Developing Orbitofrontal Cortex Are Necessary for Expectancy Updating in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Reward-Related Expectations Trigger Dendritic Spine Plasticity in the Mouse Ventrolateral Orbitofrontal Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- The Glutamatergic Postrhinal Cortex-Ventrolateral Orbitofrontal Cortex Pathway Regulates Spatial Memory Retrieval.Neuroscience bulletin · 2019Article
- Anatomical specialties for value information.Nature neuroscience · 2019Article
- Bidirectional coordination of actions and habits by TrkB in mice.Scientific reports · 2018Article
- Memory Retention Involves the Ventrolateral Orbitofrontal Cortex: Comparison with the Basolateral Amygdala.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Solving the Credit Assignment Problem With the Prefrontal Cortex.Frontiers in neuroscience · 2018Review
- Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure.PLoS biology · 2017Article
- Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors.Neurobiology of disease · 2016Review
- Strain commonalities and differences in response-outcome decision making in mice.Neurobiology of learning and memory · 2016Article
- Going and stopping: Dichotomies in behavioral control by the prefrontal cortex.Nature neuroscience · 2016Article
- Synaptic Cytoskeletal Plasticity in the Prefrontal Cortex Following Psychostimulant Exposure.Traffic (Copenhagen, Denmark) · 2015Review
- Adolescent-onset GABAA α1 silencing regulates reward-related decision making.The European journal of neuroscience · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
An essential aspect of goal-directed action selection is differentiating between behaviors that are more, or less, likely to be reinforced. Habits, by contrast, are stimulus-elicited behaviors insensitive to action-outcome contingencies and are considered an etiological factor in several neuropsychiatric disorders. Thus, isolating the neuroanatomy and neurobiology of goal-directed action selection on the one hand, and habit formation on the other, is critical. Using in vivo viral-mediated gene silencing, we knocked down Gabra1 in the orbitofrontal prefrontal cortex (oPFC) in mice, decreasing oPFC GABAAα1 expression, as well as expression of the synaptic marker PSD-95. Mice expressing Green Fluorescent Protein or Gabra1 knockdown in the adjacent M2 motor cortex served as comparison groups. Using instrumental response training followed by action-outcome contingency degradation, we then found that oPFC GABAAα1 deficiency impaired animals' ability to differentiate between actions that were more or less likely to be reinforced, though sensitivity to outcome devaluation and extinction were intact. Meanwhile, M2 GABAAα1 deficiency enhanced sensitivity to action-outcome relationships. Behavioral abnormalities following oPFC GABAAα1 knockdown were rescued by testing mice in a distinct context relative to that in which they had been initially trained. Together, our findings corroborate evidence that chronic GABAAα1 deficiency remodels cortical synapses and suggest that neuroplasticity within the healthy oPFC gates the influence of reward-related contextual stimuli. These stimuli might otherwise promote maladaptive habit-based behavioral response strategies that contribute to-or exacerbate-neuropsychiatric illness.
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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.