ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2025
Abnormal Local Cortical Functional Connectivity due to Interneuron Dysmaturation after Neonatal Intermittent Hypoxia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Heterogeneity, Measurement, and Clinical Implications of Oxygenation, Cell Signaling, and Redox Biology in Glioblastoma and Adult Diffuse Gliomas, with Context from Other Brain Tumors.Antioxidants (Basel, Switzerland) · 2026Review
- Hypoxia-inducible factor signaling regulates embryonic interneuron development, GRIN2B expression and adult cortical function.Developmental cell · 2026Article
- Cognitive impairment after cerebral ischemia-reperfusion injury: a neuroecosystem perspective.Frontiers in neurology · 2026Review
- Aberrant brain functional network in COPD patients with cognitive impairment: clinical manifestations, mechanisms and therapeutic strategies.Journal of neuroinflammation · 2025Review
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Abstract
Prematurely born infants often experience frequent hypoxic episodes due to immaturity of respiratory control resulting in disturbances of cortical development and long-term cognitive and behavioral abnormalities. We hypothesize that neonatal intermittent hypoxia alters maturation of cortical excitatory and inhibitory circuits that can be detected early with functional MRI. C57BL/6 mouse male and female pups were exposed to an intermittent hypoxia (IH) regimen from P3 to P7, corresponding to preterm humans. Adult mice after neonatal IH exhibited motor hyperactivity and impaired motor learning in complex wheel tests. Patch-clamp and evoked field potential recordings revealed increased glutamatergic synaptic transmission. To investigate the role of GABAergic inhibition on glutamatergic transmission during the developmental, we applied a selective GABAA receptor inhibitor picrotoxin. A decreased synaptic inhibitory drive in the motor cortex was evidenced by miniature IPSC frequency on pyramidal cells, multi-unit activity recording in vivo with picrotoxin injection, and decreased interneuron density. There was also an increased tonic depolarizing effect of picrotoxin after IH on Betz cells' membrane potential on patch-clamp and direct current potential in extracellular recordings. The amplitude of low-frequency fluctuation on resting-state fMRI was larger, with a larger increase in regional homogeneity index after picrotoxin injection in the IH group. The increased glutamatergic transmission, decreased numbers, and activity of inhibitory interneurons after neonatal IH may affect the maturation of connectivity in cortical networks, resulting in long-term cognitive and behavioral changes. Functional MRI reveals increased intrinsic connectivity in the sensorimotor cortex, suggesting neuronal dysfunction in cortical maturation after neonatal IH.
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