Abstracts

Neural activity has been reported to scale synaptic strength. To determine the effects of neural activity on GABAergic synapse strength, this study analyzed both the function and structure of GABAergic synapses in cultured hippocampal neurons, which provided the advantages of visibility of and accessibility to individual synapses. To measure synaptic strength, whole-cell patch clamp electrophysiology was performed to record miniature inhibitory postsynaptic currents (mIPSCs). To visualize synapses, immunocytochemistry was conducted for presynaptic GAD-65 and the [gamma]2 subunit of the GABA[sub]A[/sub] receptor. When neural activity was blocked with tetrodotoxin (TTX, 1 [mu]M) for 48 hours, the amplitude of mIPSCs was reduced. Also in activity-deprived neurons, the sizes of GAD-65 puncta and [gamma]2 clusters were diminished but their density was unchanged. Treatment with the NMDA receptor antagonist APV mimicked the reduction in size of GAD-65 puncta. An attractive candidate mediator of these actions is brain-derived neurotrophic factor (BDNF), whose expression is induced by activity. Application of BDNF (100 ng/mL) in activity-deprived neurons for 48 hours prevented both the decrease in mIPSC amplitude and GAD-65 puncta size. Moreover, when control neurons were treated with BDNF (100 ng/mL) alone for 48 hours, both mIPSC amplitude and GAD-65 puncta size were enhanced. Overall, these results suggest that neural activity modulates the strength of GABAergic synapses via NMDA receptor activation and BDNF-mediated signaling. (Supported by NINDS grants F31 NS 43831, RO1 NS 44370 and RO1 NS 43370.)