Phylogenetic divergence of GABA<sub>B</sub> receptor signaling in neocortical networks over adult life.
basic_science · Level V
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- Record sourced from PubMed, PMID 40328769.
- Also identified by DOI 10.1038/s41467-025-59262-8 and PMC identifier 12056048.
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Abstract
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.
Medical subject headings
- Receptors, GABA-B
- Neocortex
- Signal Transduction