This is to our knowledge the first demonstration that a few hours of anesthesia, can almost double the spine density on cortical neurons and thus the complexity of cortical synaptic networks. The magnitude of the effect, its persistence over several days and its restriction to critical periods of development certainly raises important questions as to the mechanisms involved,AP24534 but also regarding the possible functional consequences of such a massive synaptic reorganization. The fact that both anesthetics that enhance GABAA receptor-mediated inhibition and those blocking NMDA receptor-mediated excita-tion promoted spine growth suggests that the balance between excitation and inhibition was the major determinant of this synaptic growth process. This could be in line with previous results indicating changes in spine and synapse properties or number upon prolonged interference with excitatory or inhibitory receptors,. However neither the context, nor the dynamics of these previously reported changes makes them really compa-rable to our study, and clearly more experiments will be required to identify the signaling mechanisms implicated in these regulations. The increase in spine and synapse density reported here following reduction of excitation in the tissue points to similarities with the homeostatic scaling effect described for excitatory receptors where pharmacological blockade of excitation promotes expression of additional receptors at all synapses. In both cases the regulations involved tend to maintain neuronal activity,Axitinib either by increasing sensitivity to glutamate at existing synapses, or as shown here, by increasing synapse number. There are however also different specificities between these mechanisms. The synaptic changes reported here are surprisingly fast and predominantly observed during a critical period of development, unlike the receptor scaling effect and unlike the changes in spine density or properties reported following long-term, chronic blockade or genetic manipulation of NMDA or AMPA receptors.