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Phylogenetic divergence of GABAB receptor signaling in neocortical networks over adult life

Author

Listed:
  • Max A. Wilson

    (University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Anna Sumera

    (University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Lewis W. Taylor

    (University of Edinburgh
    UK Dementia Research Institute at the University of Edinburgh)

  • Soraya Meftah

    (University of Edinburgh
    UK Dementia Research Institute at the University of Edinburgh)

  • Robert I. McGeachan

    (University of Edinburgh
    UK Dementia Research Institute at the University of Edinburgh)

  • Tamara Modebadze

    (Newcastle University)

  • B. Ashan P. Jayasekera

    (Newcastle University)

  • Christopher J. A. Cowie

    (Royal Victoria Infirmary)

  • Fiona E. N. LeBeau

    (Newcastle University)

  • Imran Liaquat

    (Royal Infirmary Edinburgh)

  • Claire S. Durrant

    (University of Edinburgh
    UK Dementia Research Institute at the University of Edinburgh)

  • Paul M. Brennan

    (Royal Infirmary Edinburgh
    University of Edinburgh)

  • Sam A. Booker

    (University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

Abstract

Cortical circuit activity is controlled by GABA-mediated inhibition in a spatiotemporally restricted manner. GABAB receptor (GABABR) signalling exerts powerful slow inhibition that controls synaptic, dendritic and neuronal activity. But, how GABABRs contribute to circuit-level inhibition over the lifespan of rodents and humans is poorly understood. In this study, we quantitatively determined the functional contribution of GABABR signalling to pre- and postsynaptic domains in rat and human cortical principal cells. We find that postsynaptic GABABR differentially control pyramidal cell activity within the cortical column as a function of age in rodents, but minimally change over adult life in humans. Presynaptic GABABRs exert stronger inhibition in humans than rodents. Pre- and postsynaptic GABABRs contribute to co-ordination of local information processing in a layer- and species-dependent manner. Finally, we show that GABABR signalling is elevated in patients that have received the anti-seizure medication Levetiracetam. These data directly increase our knowledge of translationally relevant local circuit dynamics, with direct impact on understanding the role of GABABRs in the treatment of seizure disorders.

Suggested Citation

  • Max A. Wilson & Anna Sumera & Lewis W. Taylor & Soraya Meftah & Robert I. McGeachan & Tamara Modebadze & B. Ashan P. Jayasekera & Christopher J. A. Cowie & Fiona E. N. LeBeau & Imran Liaquat & Claire , 2025. "Phylogenetic divergence of GABAB receptor signaling in neocortical networks over adult life," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59262-8
    DOI: 10.1038/s41467-025-59262-8
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