ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Too little and too much: hypoactivation and disinhibition of medial prefrontal cortex cause attentional deficits.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 106 citations in OpenAlex.
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- Transcutaneous auricular vagus nerve stimulation as a potential therapy for attention deficit hyperactivity disorder: modulation of the noradrenergic pathway in the prefrontal lobe.Frontiers in neuroscience · 2024Review
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- EEG Neurofeedback for Anxiety Disorders and Post-Traumatic Stress Disorders: A Blueprint for a Promising Brain-Based Therapy.Current psychiatry reports · 2021Review
- Dissociable control of μ-opioid-driven hyperphagia vs. food impulsivity across subregions of medial prefrontal, orbitofrontal, and insular cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Reduced exploratory behavior in neuronal nucleoredoxin knockout mice.Redox biology · 2021Article
- The role of the medial prefrontal cortex in cognition, ageing and dementia.Brain communications · 2021Review
- Prefrontal corticotropin-releasing factor neurons impair sustained attention via distal transmitter release.The European journal of neuroscience · 2021Article
- Sex differences in dopamine innervation and microglia are altered by synthetic progestin in neonatal medial prefrontal cortex.Journal of neuroendocrinology · 2021Article
- Prevention of age-associated neuronal hyperexcitability with improved learning and attention upon knockout or antagonism of LPAR2.Cellular and molecular life sciences : CMLS · 2021Article
- Overexpression of neuregulin 1 in GABAergic interneurons results in reversible cortical disinhibition.Nature communications · 2021Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis-related dopamine hyperfunction.
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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.