ArticleBiological psychiatry2018
Habits Are Negatively Regulated by Histone Deacetylase 3 in the Dorsal Striatum.
Article in Biological psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- Histone deacetylase inhibitor sodium butyrate increases risk-taking during acquisition of the rat gambling task.Psychopharmacology · 2026Article
- HDAC3 in Alzheimer's Disease: established evidence, unresolved questions, and translational priorities.Molecular biology reports · 2026Review
- Corticosterone accelerates behavioral inflexibility via plasticity-related gene expression in the dorsal striatum.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Goal-directed actions and habits in head-fixed mice.Frontiers in behavioral neuroscience · 2026Article
- Epigenetic manipulation of anterior insular cortex alters neural signals and cognitive control.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Escalated Oxycodone Self-Administration Is Associated with Activation of Specific Gene Networks in the Rat Dorsal Striatum.International journal of molecular sciences · 2025Article
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- Striatal cell-type specific stability and reorganization underlying agency and habit.bioRxiv : the preprint server for biology · 2025Article
- A dual-pathway architecture enables chronic stress to disrupt agency and promote habit formation.bioRxiv : the preprint server for biology · 2024Article
- Striatal insights: a cellular and molecular perspective on repetitive behaviors in pathology.Frontiers in cellular neuroscience · 2024Review
- Characterization of striatal dopamine projections across striatal subregions in behavioral flexibility.The European journal of neuroscience · 2023Article
- Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation.Biomedicines · 2023Review
- Epigenetic mechanisms regulate cue memory underlying discriminative behavior.Neuroscience and biobehavioral reviews · 2022Review
- Review
- Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.International journal of molecular sciences · 2022Review
- Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions.Frontiers in behavioral neuroscience · 2022Article
- Overexpressing Histone Deacetylase 5 in Rat Dorsal Striatum Alters Reward-Guided Decision-Making and Associated Neural Encoding.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Maintained goal-directed control with overtraining on ratio schedules.Learning & memory (Cold Spring Harbor, N.Y.) · 2021Article
- Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release.Scientific reports · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOptimal behavior and decision making result from a balance of control between two strategies, one cognitive/goal-directed and one habitual. These systems are known to rely on the anatomically distinct dorsomedial and dorsolateral striatum, respectively. However, the transcriptional regulatory mechanisms required to learn and transition between these strategies are unknown. Here we examined the role of one chromatin-based transcriptional regulator, histone modification via histone deacetylases (HDACs), in this process.
methodsWe combined procedures that diagnose behavioral strategy in rats with pharmacological and viral-mediated HDAC manipulations, chromatin immunoprecipitation, and messenger RNA quantification.
resultsThe results indicate that dorsal striatal HDAC3 activity constrains habit formation. Systemic HDAC inhibition following instrumental (lever press → reward) conditioning increased histone acetylation throughout the dorsal striatum and accelerated habitual control of behavior. HDAC3 was removed from the promoters of key learning-related genes in the dorsal striatum as habits formed with overtraining and with posttraining HDAC inhibition. Decreasing HDAC3 function, either by selective pharmacological inhibition or by expression of dominant-negative mutated HDAC3, in either the dorsolateral striatum or the dorsomedial striatum accelerated habit formation, while HDAC3 overexpression in either region prevented habit.
conclusionsThese results challenge the strict dissociation between dorsomedial striatum and dorsolateral striatum function in goal-directed versus habitual behavioral control and identify dorsostriatal HDAC3 as a critical molecular directive of the transition to habit. Because this transition is disrupted in many neurodegenerative and psychiatric diseases, these data suggest a potential molecular mechanism for the negative behavioral symptoms of these conditions and a target for therapeutic intervention.
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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.