AKAP-CaN-NFATc3 signaling drives persistent inhibitory long-term potentiation

Activation of NFAT and anchoring of calcineurin to AKAP79/150 are required to sustain persistent inhibitory long-term potentiation (iLTP) in hippocampal synapses.

• Why it matters: Inhibitory iLTP depends on activity-driven gene expression, but the upstream signaling that coordinates new inhibitory protein synthesis and lasting synaptic strengthening is unclear.
• What they did: In hippocampus, shRNA knockdown of NFATc3 tests its role in iLTP-associated new GABAergic protein synthesis, synapse growth, and current strengthening; a knock-in AKAP CaN-binding-region mutant tests AKAP-CaN upstream control of NFATc3 via miRNA transcriptional activity and protein synthesis.
• The result: NFATc3 is required for persistent iLTP structural and functional strengthening, and AKAP-CaN signaling is upstream of NFATc3 activation, enabling increased inhibitory synapse clustering and synapse strengthening during iLTP.

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