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

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

doi:10.1038/s41467-025-59262-8

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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-59262-8
Publication status	Published - 6 May 2025

Access to Document

10.1038/s41467-025-59262-8Licence: Creative Commons: Attribution (CC-BY)

https://www.nature.com/articles/s41467-025-59262-8

Cite this

Wilson, M. A., Sumera, A., Taylor, L. W., Meftah, S., McGeachan, R. I., Modebadze, T., Jayasekera, B. A. P., Cowie, C. J. A., LeBeau, F. E. N., Liaquat, I., Durrant, C. S., Brennan, P. M., & Booker, S. A. (2025). Phylogenetic divergence of GABAB receptor signaling in neocortical networks over adult life. Nature Communications, 16(1). https://doi.org/10.1038/s41467-025-59262-8

@article{db5fbb51fc9743cb9052a1e80663ae0b,

title = "Phylogenetic divergence of GABAB receptor signaling in neocortical networks over adult life",

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.",

author = "Wilson, \{Max A.\} and Anna Sumera and Taylor, \{Lewis W.\} and Soraya Meftah and McGeachan, \{Robert I.\} and Tamara Modebadze and Jayasekera, \{B. Ashan P.\} and Cowie, \{Christopher J. A.\} and LeBeau, \{Fiona E. N.\} and Imran Liaquat and Durrant, \{Claire S.\} and Brennan, \{Paul M.\} and Booker, \{Sam A.\}",

year = "2025",

month = may,

day = "6",

doi = "10.1038/s41467-025-59262-8",

language = "English",

volume = "16",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Phylogenetic divergence of GABAB receptor signaling in neocortical networks over adult life

AU - Wilson, Max A.

AU - Sumera, Anna

AU - Taylor, Lewis W.

AU - Meftah, Soraya

AU - McGeachan, Robert I.

AU - Modebadze, Tamara

AU - Jayasekera, B. Ashan P.

AU - Cowie, Christopher J. A.

AU - LeBeau, Fiona E. N.

AU - Liaquat, Imran

AU - Durrant, Claire S.

AU - Brennan, Paul M.

AU - Booker, Sam A.

PY - 2025/5/6

Y1 - 2025/5/6

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-025-59262-8

DO - 10.1038/s41467-025-59262-8

M3 - Article

SN - 2041-1723

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Access to Document

Fingerprint

Cite this