- Complex olfactory-discrimination (OD) learning results in a series of intrinsic and excitatory synaptic modifications in piriform cortex pyramidal neurons that enhance the circuit excitability. Such over-excitation must be balanced to prevent runway activity while maintaining the efficient ability to store memories. We showed previously that OD learning is accompanied by enhancement of the GABAA -mediated inhibition. Here we show that GABAB-mediated inhibition is also enhanced after learning, study the mechanism underlying such enhancement and explore its functional role. We show that pre-synaptic, GABAB-mediated synaptic inhibition is enhanced after learning. In contrast, the population-average post-synaptic GABAB-mediated synaptic inhibition is unchanged, but its standard deviation is enhanced. Learning-induced reduction in paired pulse facilitation (PPF) in the glutamatergic synapses interconnecting pyramidal neurons was abolished by application of the GABAB antagonist CGP55845 but not by blocking GIRK channels only, indicating enhanced suppression of excitatory synaptic release via pre-synaptic GABAB-receptors activation. In addition, the correlation between the strengths of the early (GABAA-mediated) and late (GABAB-mediated) synaptic inhibition was much stronger for each particular neuron after learning. Consequently, GABAB-mediated inhibition was also more efficient in controlling epileptic-like activity induced by blocking GABAA receptors. We suggest that complex OD learning is accompanied by enhancement of the GABAB-mediated inhibition that enables the cortical network to store memories while preventing uncontrolled activity.