GABAergic synapses are formed without the involvement of dendritic protrusions.

Synaptogenesis and the role of dendritic protrusions in this process are well studied in glutamatergic synapses. Much less is known about the formation of GABAergic synapses, which are located predominantly on the dendritic shaft. We used genetically labeled interneurons in mature hippocampal slice cultures and two-photon laser-scanning microscopy to examine contact formation between GABAergic axons and the dendrites of CA1 pyramidal cells. Dendritic protrusions distinguished and selected between glutamatergic and GABAergic boutons. In contrast with contacts with glutamatergic boutons, which can be long lasting, the contacts of dendritic protrusions with GABAergic boutons were always short lived. Similarly, the contacts made by GABAergic axonal protrusions were always transient. New putative GABAergic synapses were formed exclusively by new boutons appearing at pre-existing axon-dendrite crossings without the involvement of any dendritic or axonal protrusions. These findings imply that fundamentally different mechanisms underlie the generation of GABAergic and glutamatergic synapses.