ArticleThe Journal of pharmacology and experimental therapeutics2012
Regulation of GABAergic inputs to CA1 pyramidal neurons by nicotinic receptors and kynurenic acid.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The tryptophan catabolite or kynurenine pathway in schizophrenia: meta-analysis reveals dissociations between central, serum, and plasma compartments.Molecular psychiatry · 2022Pooled it
- Navigating the nano-bio immune interface: advancements and challenges in CNS nanotherapeutics.Frontiers in immunology · 2024Review
- Kynurenine, Kynurenic Acid, Quinolinic Acid and Interleukin-6 Levels in the Serum of Patients with Autism Spectrum Disorder.Medicina (Kaunas, Lithuania) · 2023Article
- Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain.Molecules (Basel, Switzerland) · 2023Review
- Kynurenine pathway abnormalities are state-specific but not diagnosis-specific in schizophrenia and bipolar disorder.Brain, behavior, & immunity - health · 2023Article
- Review
- Morphological and biochemical repercussions ofBrain, behavior, & immunity - health · 2021Article
- The role of anthranilic acid in the increase of depressive symptoms and major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a and oral ribavirin.Journal of psychiatry & neuroscience : JPN · 2021Article
- Neuromodulation of Glial Function During Neurodegeneration.Frontiers in cellular neuroscience · 2020Article
- Peripheral Biomarkers for First-Episode Psychosis-Opportunities from the Neuroinflammatory Hypothesis of Schizophrenia.Psychiatry investigation · 2019Article
- Astrocytic and microglial nicotinic acetylcholine receptors: an overlooked issue in Alzheimer's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2016Review
- Neonatal nicotine exposure increases excitatory synaptic transmission and attenuates nicotine-stimulated GABA release in the adult rat hippocampus.Neuropharmacology · 2015Article
- Localization and function of dopamine receptors in the subthalamic nucleus of normal and parkinsonian monkeys.Journal of neurophysiology · 2014Article
- Inflammation and the two-hit hypothesis of schizophrenia.Neuroscience and biobehavioral reviews · 2014Review
- Contribution of CA3 and CA1 pyramidal neurons to the tonic α7 nAChR-dependent glutamatergic input to CA1 pyramidal neurons.Neuroscience letters · 2013Article
- Acetylcholinesterase inhibition reveals endogenous nicotinic modulation of glutamate inputs to CA1 stratum radiatum interneurons in hippocampal slices.Neurotoxicology · 2013Article
- Kynurenic acid as an antagonist of α7 nicotinic acetylcholine receptors in the brain: facts and challenges.Biochemical pharmacology · 2013Review
- Lack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons.PloS one · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Impaired α7 nicotinic acetylcholine receptor (nAChR) function and GABAergic transmission in the hippocampus and elevated brain levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the kynurenine pathway, are key features of schizophrenia. KYNA acts as a noncompetitive antagonist with respect to agonists at both α7 nAChRs and N-methyl-D-aspartate receptors. Here, we tested the hypothesis that in hippocampal slices tonically active α7 nAChRs control GABAergic transmission to CA1 pyramidal neurons and are sensitive to inhibition by rising levels of KYNA. The α7 nAChR-selective antagonist α-bungarotoxin (α-BGT; 100 nM) and methyllycaconitine (MLA; 10 nM), an antagonist at α7 and other nAChRs, reduced by 51.3 ± 1.3 and 65.2 ± 1.5%, respectively, the frequency of GABAergic postsynaptic currents (PSCs) recorded from CA1 pyramidal neurons. MLA had no effect on miniature GABAergic PSCs. Thus, GABAergic synaptic activity in CA1 pyramidal neurons is maintained, in part, by tonically active α7 nAChRs located on the preterminal region of axons and/or the somatodendritic region of interneurons that synapse onto the neurons under study. L-Kynurenine (20 or 200 μM) or KYNA (20-200 μM) suppressed concentration-dependently the frequency of GABAergic PSCs; the inhibitory effect of 20 μM L-kynurenine had an onset time of approximately 35 min and could not be detected in the presence of 100 nM α-BGT. These results suggest that KYNA levels generated from 20 μM kynurenine inhibit tonically active α7 nAChR-dependent GABAergic transmission to the pyramidal neurons. Disruption of nAChR-dependent GABAergic transmission by mildly elevated levels of KYNA can be an important determinant of the cognitive deficits presented by patients with schizophrenia.
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Registered trials
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