Spatiotemporal characteristics and pharmacological modulation of multiple gamma oscillations in the CA1 region of the hippocampus

Multiple components of “γ-oscillations” between 30–170 Hz in the CA1 region of the hippocampus have been described, based on their coherence with oscillations in other brain regions and on their cross-frequency coupling with local θ-oscillations. However, it remains unclear whether the different sub-bands are generated by a single broadband oscillator coupled to multiple external inputs, or by separate oscillators that incorporate distinct circuit elements. To distinguish between these possibilities, we used high-density linear array recording electrodes in awake behaving mice to examine the spatiotemporal characteristics of γ-oscillations and their responses to midazolam and atropine. We characterized oscillations using current source density (CSD) analysis, and measured θ-γ phase-amplitude coupling by cross frequency coupling (CFC) analysis. Prominent peaks were present in the CSD signal in the mid- and distal apical dendritic layers at all frequencies, and at stratum pyramidale for γ(slow) (30–45 Hz) and γ(mid) (50–90 Hz), but not γ(fast) (90–170 Hz) oscillations. Differences in the strength and timing of θ-γ(slow) and θ-γ(mid) cross frequency coupling, and a lack of coupling at the soma and mid-apical region for γ(fast) oscillations, indicated that separate circuit components generate the three sub-bands. Midazolam altered CSD amplitudes and cross-frequency coupling in a lamina- and frequency specific manner, providing further evidence for separate generator circuits. Atropine altered CSD amplitudes and θ-γ CFC uniformly at all locations. Simulations using a detailed compartmental model were consistent with γ(slow) and γ(mid) oscillations driven primarily by inputs at the mid-apical dendrites, and γ(fast) at the distal apical dendrite. Our results indicate that multiple distinct local circuits generate γ-oscillations in the CA1 region of the hippocampus, and provide detailed information about their spatiotemporal characteristics.