Journal
CEREBRAL CORTEX
Volume 23, Issue 11, Pages 2700-2711Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhs260
Keywords
activity-dependent regulation; fluorescence recovery after photobleaching; organotypic slice culture; synaptic plasticity; whole-cell patch-clamp recording
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Funding
- Max-Planck Society
- Deutsche Forschungsgemeinschaft [EXC 115, DFG DE 551/10-1]
- Young Investigators Grant (Faculty of Medicine, Goethe-University Frankfurt)
- International Max-Planck Research School, Frankfurt
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Gephyrin is a scaffolding protein important for the postsynaptic clustering of inhibitory neurotransmitter receptors. Here, we investigated the properties of gephyrin scaffolds at gamma-aminobutyric acid- (GABA-)ergic synapses in organotypic entorhino-hippocampal cultures prepared from a transgenic mouse line, which expresses green fluorescent protein-tagged gephyrin under the control of the Thy1.2 promoter. Fluorescence recovery after photobleaching revealed a developmental stabilization of postsynaptic gephyrin clusters concomitant with an increase in cluster size and synaptic strength between 1 and 4 weeks in vitro. Prolonged treatment of the slice cultures with diazepam or a GABA(A) receptor antagonist disclosed a homeostatic regulation of both inhibitory synaptic strength and gephyrin cluster size and stability in 4-weeks-old cultures, whereas at 1 week in vitro, the same drug treatments modulated GABAergic postsynapse and gephyrin cluster properties following a Hebbian mode of synaptic plasticity. Our data are consistent with a model in which the postnatal maturation of the hippocampal network endows CA1 pyramidal neurons with the ability to homeostatically adjust the strength of their inhibitory postsynapses to afferent GABAergic drive by regulating gephyrin scaffold properties.
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