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The role of filopodia in synapse formation in absence of dendritic spines

Final Activity Report Summary - SYNAPSE FORMATION (The role of filopodia in synapse formation in absence of dendritic spines)

Chemical synapses are the key connective elements in neuronal networks. They are not only crucial for information processing but their plasticity also endows the brain with its outstanding capacity for adaptation to the environment. Understanding synapses, and how they are formed, is therefore a fundamentally important task in neuroscience. So far, most studies have focused on the formation of glutamatergic synapses while the formation of the other major type of synapses in the brain, which use the inhibitory transmitter GABA, remains less examined, in spite of the fact that GABAergic synapses form 10-20 % of all synapses in the brain and are indispensable for proper and stable functioning of in the brain.

Glutamatergic synapses on excitatory neurons in the hippocampus are almost exclusively located on dendritic spines. It has been shown that dendrites play an active role in the formation of new glutamatergic synapses by growing out small protrusions which make contact with presynaptic axons and boutons. In contrast to glutamatergic synapses, GABAergic synapses are usually not located on spines, but directly on the dendritic shaft.

We used high-resolution two-photon imaging to examine the formation of GABAergic synapses in the CA1 area of organotypical hippocampal cultures. We made use of GAD65-GFP mice, in which a subset of GABAergic interneurons expresses GFP. CA1 pyramidal neurons were filled with Alexa Fluor 594 through a patch pipette.

We found that GABAergic synapses are formed via a fundamentally different process than glutamatergic spine synapses. Outgrowing dendritic protrusions can distinguish between potential presynaptic partners. Whereas contacts with glutamatergic boutons could be long-lasting, contacts with GABAergic boutons were always short-lived and resulted in retraction of the dendritic protrusions. Similarly, contacts made by GABAergic axonal protrusions were always transient. This strongly suggests that axonal and dendritic protrusions do not mediate the formation of GABAergic synapses. New GABAergic contacts were formed exclusively at locations where GABAergic axons and postsynaptic dendrite are already in close proximity: by the appearance of new boutons at preexisting axon-dendrite crossings.

These findings imply that GABAergic axons in a mature network can make new synapses only with postsynaptic partners that are in their immediate neighborhood, which is in marked contrast to the way glutamatergic synapses are made. This puts significant structural constraints on the generation and plasticity of GABAergic and glutamatergic synapses which will be important to be kept in mind when trying to understand development and plasticity of the intricate neural networks of the brain.