Phylogenetic divergence of GABAB receptor signalling in neocortical networks over adult life.

Abstract

Cortical circuit activity is controlled by GABA-mediated inhibition in a spatiotemporally restricted manner. Much is known about fast GABA currents, GABAB receptor (GABABR) signalling exerts powerful slow inhibition that controls synaptic, dendritic and neuronal activity. However, little is known about how GABABRs contribute to circuit-level inhibition over the lifespan of rodents and humans. In this study, we quantitatively determine the functional contribution of GABABR signalling to pre- and postsynaptic domains in rat and human cortical principal cells (PC). We find that postsynaptic GABABR differentially control pyramidal cell activity within the cortical column as a function of age and species, and that these receptors contribute to co-ordination of local information processing in a layer- and species-dependent manner. 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. HighlightsO_LIGABAB receptor signalling displays age and species differences in cortex C_LIO_LIGABAB receptor presynaptic inhibition is stronger in humans than rodents C_LIO_LIIn vitro oscillations in human cortex are strongly regulated by GABABRs C_LIO_LILevetiracetam enhances endogenous GABABR signalling in human cortex C_LI