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bioRxiv · 10.1101/2023.06.21.545901

Gamma-Oscillation Plasticity Is Mediated by Parvalbumin Interneurons

Hadler, M. D.·Tzilivaki, A.·Schmitz, D.·Alle, H.·Geiger, J. R.
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Abstract

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.

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Hadler, M. D., Tzilivaki, A., Schmitz, D., Alle, H., Geiger, J. R.. 2023-06-21. Gamma-Oscillation Plasticity Is Mediated by Parvalbumin Interneurons. https://doi.org/10.1101/2023.06.21.545901

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