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<p>Cortical circuit activity is controlled by GABA-mediated inhibition in a spatiotemporally restricted manner. GABA<sub>B</sub> receptor (GABA<sub>B</sub>R) signalling exerts powerful slow inhibition that controls synaptic, dendritic and neuronal activity. But, how GABA<sub>B</sub>Rs 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 GABA<sub>B</sub>R signalling to pre- and postsynaptic domains in rat and human cortical principal cells. We find that postsynaptic GABA<sub>B</sub>R 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 GABA<sub>B</sub>Rs exert stronger inhibition in humans than rodents. Pre- and postsynaptic GABA<sub>B</sub>Rs contribute to co-ordination of local information processing in a layer- and species-dependent manner. Finally, we show that GABA<sub>B</sub>R 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 GABA<sub>B</sub>Rs in the treatment of seizure disorders.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月6日

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  • 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 S. Durrant,
  • Paul M. Brennan,
  • Sam A. Booker

摘要

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.