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

Summary Cortical circuit activity is controlled by GABA-mediated inhibition in a spatiotemporally restricted manner. Much is known about fast GABA currents, GABA B receptor (GABA B R) signalling exerts powerful slow inhibition that controls synaptic, dendritic and neuronal activity. However, little is known about how GABA B Rs contribute to circuit-level inhibition over the lifespan of rodents and humans. In this study, we quantitatively determine the functional contribution of GABA B R signalling to pre- and postsynaptic domains in rat and human cortical principal cells (PC). We find that postsynaptic GABA B R 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 GABA B Rs in the treatment of seizure disorders. Highlights GABA B receptor signalling displays age and species differences in cortex GABA B receptor presynaptic inhibition is stronger in humans than rodents In vitro oscillations in human cortex are strongly regulated by GABA B Rs Levetiracetam enhances endogenous GABA B R signalling in human cortex