EN
About 10% of neocortical pyramidal neurons in layer 2/3 are connected to each other with strong and reliable synapses, displaying near-zero failure rates under the condition of very low network activity. However, in vivo many cells, including inhibitory neurons, exhibit elevated spontaneous firing activity. Here we investigated the effect of network activity on connection probability, strength, and synapse reliability between layer 2/3 pyramidal neurons. Under the condition of network activity, failure rates are two-fold higher. We find that GABAB receptors are tonically active during spontaneous network activity and that these receptors profoundly influence release probability. Using optogenetic tools we examined what type of inhibitory neurons is responsible for GABAB inhibition. Our data suggest that neocortical networks may be dynamically rewired based upon presynaptic GABAB activation, and that this phenomenon may be state-dependent.