ArticlePloS one2018
Ketamine independently modulated power and phase-coupling of theta oscillations in Sp4 hypomorphic mice.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 8 citations in OpenAlex.
- Effects of Ketamine and Midazolam on Simultaneous EEG/fMRI Data During Working Memory Processes.Brain topography · 2021Trial
- Partial rescue of schizophrenia-related phenotypes in young adult Sp4 hypomorphic mice.Journal of psychiatric research · 2025Article
- Hippocampal-prefrontal coherence mediates working memory and selective attention at distinct frequency bands and provides a causal link between schizophrenia and its risk gene GRIA1.Translational psychiatry · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Reduced expression of Sp4, the murine homolog of human SP4, a risk gene of multiple psychiatric disorders, led to N-methyl-D-aspartate (NMDA) hypofunction in mice, producing behavioral phenotypes reminiscent of schizophrenia, including hypersensitivity to ketamine. As accumulating evidence on molecular mechanisms and behavioral phenotypes established Sp4 hypomorphism as a promising animal model, systems-level neural circuit mechanisms of Sp4 hypomorphism, especially network dynamics underlying cognitive functions, remain poorly understood. We attempted to close this gap in knowledge in the present study by recording multi-channel epidural electroencephalogram (EEG) from awake behaving wildtype and Sp4 hypomorphic mice. We characterized cortical theta-band power and phase-coupling phenotypes, a known neural circuit substrate underlying cognitive functions, and further studied the effects of a subanesthetic dosage of ketamine on theta abnormalities unique to Sp4 hypomorphism. Sp4 hypomorphic mice had markedly elevated theta power localized frontally and parietally, a more pronounced theta phase progression along the neuraxis, and a stronger frontal-parietal theta coupling. Acute subanesthetic ketamine did not affect theta power in wildtype animals but significantly reduced it in Sp4 hypomorphic mice, nearly completely neutralizing their excessive frontal/parietal theta power. Ketamine did not significantly alter cortical theta phase progression in either wildtype or Sp4 hypomorphic animals, but significantly strengthened cortical theta phase-coupling in wildtype, but not in Sp4 hypomorphic animals. Our results suggested that the resting-state phenotypes of cortical theta oscillations unique to Sp4 hypomorphic mice closely mimicked a schizophrenic endophenotype. Further, ketamine independently modulated Sp4 hypomorphic anomalies in theta power and phase-coupling, suggesting separate underlying neural circuit mechanisms.
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