|M.Sc Student||Rubinski Anna|
|Subject||Remodeling of Inhibitory Synapses: Relationships with|
Network Activity and Neighboring Excitatory
|Department||Department of Medicine||Supervisor||Professor Noam Ziv|
|Full Thesis text|
Activity-dependent modification of synaptic connections - synaptic plasticity - is widely believed to represent a fundamental mechanism for altering network function. This belief also implies, however, that synapses, when not driven to change their properties by physiologically relevant stimuli, should retain these properties over time. We refer to the expected tendency of synapses to hold on to their properties as "synaptic tenacity". Whereas most studies on relationships between activity, synaptic plasticity and tenacity have focused on excitatory glutamatergic synapses, less attention has been given to inhibitory synapses in this regard.
Here we used long-term imaging combined with multielectrode array recordings to examine 1) how the remodeling of individual GABAergic synapses and the properties of GABAergic synapse populations are affected by network activity and 2) examine relationships between the remodeling of neighboring inhibitory and excitatory synapses. To that end we expressed the GABAergic scaffold molecule Gephyrin tagged with mTurquoise2 (mTurq2:Gephyrin) in rat cortical neurons. When individual mTurq2:Gephyrin puncta were followed over time, significant fluctuations in their fluorescence were observed whose extent was only minimally affected by suppressing spontaneous activity. In active networks, large synapses tended to grow smaller whereas small synapses tended to grow larger. Interestingly, these tendencies were mostly lost when activity was suppressed. Coexpressing PSD-95:EGFP allowed us to compare inhibitory and excitatory remodeling in the same neurons. The extent of inhibitory and excitatory synapse remodeling was very similar. However, no obvious relationships between the remodeling of neighboring inhibitory and excitatory synapses were observed. These findings indicate that in common with what has been reported for glutamatergic synapses, the tenacity of GABAergic synapses is inherently limited. Furthermore, these findings point to similarities in the rules that govern the remodeling of both excitatory and inhibitory synapses.