Gamma oscillation plasticity is mediated via parvalbumin interneurons

Michael D. Hadler, Alexandra Tzilivaki, Dietmar Schmitz, Henrik Alle, Jörg R. P. Geiger

Understanding the plasticity of neuronal networks is an emerging field of (patho-)physiological research, yet little is known about the underlying cellular mechanisms. Gamma-oscillations (30-80 Hz), a biomarker of cognitive performance, require and potentiate glutamatergic transmission onto parvalbumin-positive interneurons (PVIs), suggesting an interface for cell-to-network plasticity. In ex vivo local field potential recordings, we demonstrate long-term potentiation of hippocampal gamma-power. Gamma-potentiation obeys established rules of PVI plasticity, requiring calcium-permeable AMPA receptors (CP-AMPARs) and metabotropic glutamate receptors (mGluRs). A microcircuit model of CA3 gamma-oscillations predicts CP-AMPAR plasticity onto PVIs critically outperforms pyramidal cell plasticity in increasing gamma-power and completely accounts for gamma-potentiation. We re-affirm this ex vivo in three PVI-targeting animal models, demonstrating that gamma-potentiation requires PVI-specific metabotropic signaling via a Gq/PKC-pathway comprising mGluR5 and a Gi-sensitive, PKA-dependent pathway. Gamma-activity dependent, metabotropically mediated CP-AMPAR plasticity on PVIs may serve as a guiding principle in understanding network plasticity in health and disease.

Sci. Adv. 10,eadj7427(2024)


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