Gating of Hippocampal Rhythms and Memory by Synaptic Plasticity in Inhibitory Interneurons

Mental experiences can become long-term memories if the hippocampal activity patterns that encode them are broadcast during network oscillations. The activity of inhibitory neurons is essential for generating these neural oscillations, but molecular control of this process during learning remains unknown. Here we show that hippocampal oscillatory strength positively correlates with excitatory monosynaptic drive onto inhibitory neurons (E→I) in vivo. To establish direct causality between them, we identified γCaMKII as the long-sought mediator of long-term potentiation for E→I synapses (LTPE→I), which enabled the genetic manipulation of experience-dependent E→I synaptic input/plasticity. Deleting γCaMKII in parvalbumin interneurons not only selectively eliminated LTPE→I, but also disrupted experience-driven oscillation strengthening in theta and gamma rhythmicity. Consequently, this manipulation impaired long-term memory, for which the kinase activity of γCaMKII was required. Taken together, our data suggest that E→I synaptic plasticity, exemplified by LTPE→I, plays a gatekeeping role in tuning experience-dependent brain rhythms and mnemonic function.