ArticleThe Journal of physiology2016
Aberrant regulation of synchronous network activity by the attention-deficit/hyperactivity disorder-associated human dopamine D4 receptor variant D4.7 in the prefrontal cortex.
Article in The Journal of physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 21 citations in OpenAlex.
- Dorsal-to-ventral imbalance in the superior longitudinal fasciculus mediates methylphenidate's effect on beta oscillations in ADHD.Psychophysiology · 2022Trial
- Behavioral and Prefrontal Circuit Deficits in a Newly DevelopedBiological psychiatry global open science · 2026Article
- Molecular Mechanisms Underlying NMDARs Dysfunction and Their Role in ADHD Pathogenesis.International journal of molecular sciences · 2023Review
- Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications.Molecular psychiatry · 2022Review
- Functional and pharmacological role of the dopamine DFrontiers in endocrinology · 2022Review
- Heteromerization between αPharmacological research · 2021Article
- Stress Exposure in Dopamine D4 Receptor Knockout Mice Induces Schizophrenia-Like Behaviors via Disruption of GABAergic Transmission.Schizophrenia bulletin · 2019Article
- Dopamine D4 Receptor Gene Associated with the Frontal-Striatal-Cerebellar Loop in Children with ADHD: A Resting-State fMRI Study.Neuroscience bulletin · 2018Article
- The Mechanism of Cortico-Striato-Thalamo-Cortical Neurocircuitry in Response Inhibition and Emotional Responding in Attention Deficit Hyperactivity Disorder with Comorbid Disruptive Behavior Disorder.Neuroscience bulletin · 2018Review
- Effects of the 2-Repeat Allele of the DRD4 Gene on Neural Networks Associated With the Prefrontal Cortex in Children With ADHD.Frontiers in human neuroscience · 2018Article
- Genetically-Driven Enhancement of Dopaminergic Transmission Affects Moral Acceptability in Females but Not in Males: A Pilot Study.Frontiers in behavioral neuroscience · 2017Article
- Key role of the dopamine DScience advances · 2017Article
- The ADHD-linked human dopamine D4 receptor variant D4.7 induces over-suppression of NMDA receptor function in prefrontal cortex.Neurobiology of disease · 2016Article
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Authors and funding
3 authors at 3 institutions in 2 countries.
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Abstract
key pointsThe hD4.7 variant has been linked to attention-deficit/hyperactivity disorder (ADHD); however, the underlying mechanism is unknown. We found that activation of hD4.7 induced over-suppression of glutamatergic excitatory network bursts and under-suppression of GABAergic inhibitory network bursts in the prefrontal cortex (PFC) circuitry. Methylphenidate, a psychostimulant drug used to treat ADHD, normalized the effects of hD4.7 on synchronous network bursts in PFC pyramidal neurons. The findings of the present study suggest that the aberrant regulation of PFC synchronous network activity by hD4.7 may underlie its involvement in ADHD. A unique feature of the human D4 receptor (hD4 R) gene is the existence of a large number of polymorphisms in exon 3 coding for the third intracellular loop, which consists of a variable number of tandem repeats. The hD4 R variants with long repeats have been linked to attention-deficit/hyperactivity disorder (ADHD); however, the underlying mechanism is unknown. Emerging evidence suggests that selective attention is controlled by the rhythmic synchronization in the prefrontal cortex (PFC) and its connected networks. In the present study, we examined the role of hD4 R variants in regulating PFC synchronous network activity. D4 R knockout mice with viral infection of hD4.4 or hD4.7 in the medial PFC were used. Whole-cell patch-clamp recordings were performed to examine the effects of activating hD4.x on the spontaneous large scale correlated activity in PFC pyramidal neurons. We found that, compared to the normal four-repeat variant hD4.4, the ADHD-linked variant hD4.7 induces more suppression of glutamatergic excitatory network bursts and less suppression of GABAergic inhibitory network bursts in the PFC circuitry. Methylphenidate, a psychostimulant drug used to treat ADHD, normalized the effects of hD4.7 on synchronous network bursts in PFC pyramidal neurons. These results reveal the differential effects of hD4 R variants on the integrated excitability of PFC circuits. It is suggested that the aberrant regulation of PFC network activity by hD4.7 may underlie its involvement in ADHD. The methylphenidate-induced normalization of synaptic circuitry regulation may contribute to its effectiveness in ADHD treatment.
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