ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Optogenetic Activation of Adenosine A2A Receptor Signaling in the Dorsomedial Striatopallidal Neurons Suppresses Goal-Directed Behavior.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 76 citations in OpenAlex.
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- Neurodegenerative Disease Movement Disorders and Dorsal Striatum-Mediated Imbalance of Habitual Motor Sequences.Molecular neurobiology · 2025Review
- Direct and indirect striatal projecting neurons exert strategy-dependent effects on decision-making.Science advances · 2025Article
- Striatal cell-type specific stability and reorganization underlying agency and habit.bioRxiv : the preprint server for biology · 2025Article
- Hippocampal P2X7 and A2A purinoceptors mediate cognitive impairment caused by long-lasting epileptic seizures.Theranostics · 2025Article
- Targeting the adenosine AChinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- Neuronal and astrocytic CB1R signaling differentially modulates goal-directed behavior and working memory by distinct temporal mechanisms.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Towards translational optogenetics.Nature biomedical engineering · 2023Review
- Striatopallidal adenosine ANeuropharmacology · 2023Review
- α-Synuclein Aggregates in the Nigro-Striatal Dopaminergic Pathway Impair Fine Movement: Partial Reversal by the Adenosine AInternational journal of molecular sciences · 2023Article
- DNA methylation and hydroxymethylation characterize the identity of D1 and D2 striatal projection neurons.Communications biology · 2022Article
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update.Pharmacological reviews · 2022Review
- Genetic tagging of the adenosine A2A receptor reveals its heterogeneous expression in brain regions.Frontiers in neuroanatomy · 2022Article
- Retrosplenial Cortical Connectivity with Frontal Basal Ganglia Networks.Journal of cognitive neuroscience · 2021Article
- Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction.Molecular autism · 2020Review
- Activation of Astrocytes in the Dorsomedial Striatum Facilitates Transition From Habitual to Goal-Directed Reward-Seeking Behavior.Biological psychiatry · 2020Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The striatum has an essential role in neural control of instrumental behaviors by reinforcement learning. Adenosine A(2A) receptors (A(2A)Rs) are highly enriched in the striatopallidal neurons and are implicated in instrumental behavior control. However, the temporal importance of the A(2A)R signaling in relation to the reward and specific contributions of the striatopallidal A(2A)Rs in the dorsolateral striatum (DLS) and the dorsomedial striatum (DMS) to the control of instrumental learning are not defined. Here, we addressed temporal relationship and sufficiency of transient activation of optoA(2A)R signaling precisely at the time of the reward to the control of instrumental learning, using our newly developed rhodopsin-A2AR chimeras (optoA(2A)R). We demonstrated that transient light activation of optoA(2A)R signaling in the striatopallidal neurons in 'time-locked' manner with the reward delivery (but not random optoA(2A)R activation) was sufficient to change the animal's sensitivity to outcome devaluation without affecting the acquisition or extinction phases of instrumental learning. We further demonstrated that optogenetic activation of striatopallidal A(2A)R signaling in the DMS suppressed goal-directed behaviors, as focally genetic knockdown of striatopallidal A(2A)Rs in the DMS enhanced goal-directed behavior by the devaluation test. By contrast, optogenetic activation or focal AAV-Cre-mediated knockdown of striatopallidal A(2A)R in the DLS had relatively limited effects on instrumental learning. Thus, the striatopallidal A(2A)R signaling in the DMS exerts inhibitory and predominant control of goal-directed behavior by acting precisely at the time of reward, and may represent a therapeutic target to reverse abnormal habit formation that is associated with compulsive obsessive disorder and drug addiction.
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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.