AI Article Synopsis
- Gephyrin is a key scaffolding protein at GABAergic synapses, but its specific role in synapse formation and maintenance is still being researched.
- Knocking down gephyrin in hippocampal neurons led to a reduction in both gephyrin and GABA(A) receptor clusters, indicating its importance in maintaining these structures.
- Disruption of gephyrin clusters resulted in fewer presynaptic GABAergic boutons and decreased inhibitory signals, confirming gephyrin’s critical role in the stability and functionality of GABAergic synapses.
Article Abstract
Although gephyrin is an important postsynaptic scaffolding protein at GABAergic synapses, the role of gephyrin for GABAergic synapse formation and/or maintenance is still under debate. We report here that knocking down gephyrin expression with small hairpin RNAs (shRNAs) in cultured hippocampal pyramidal cells decreased both the number of gephyrin and GABA(A) receptor clusters. Similar results were obtained by disrupting the clustering of endogenous gephyrin by overexpressing a gephyrin-EGFP fusion protein that formed aggregates with the endogenous gephyrin. Disrupting postsynaptic gephyrin clusters also had transsynaptic effects leading to a significant reduction of GABAergic presynaptic boutons contacting the transfected pyramidal cells. Consistent with the morphological decrease of GABAergic synapses, electrophysiological analysis revealed a significant reduction in both the amplitude and frequency of the spontaneous inhibitory postsynaptic currents (sIPSCs). However, no change in the whole-cell GABA currents was detected, suggesting a selective effect of gephyrin on GABA(A) receptor clustering at postsynaptic sites. It is concluded that gephyrin plays a critical role for the stability of GABAergic synapses.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464357 | PMC |
| http://dx.doi.org/10.1016/j.mcn.2007.08.008 | DOI Listing |
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