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

Balakrishnan S, Pearce RA - Front Neural Circuits (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Training Program, University of Wisconsin-Madison Madison, WI, USA ; Department of Anesthesiology, University of Wisconsin-Madison Madison, WI, USA.

ABSTRACT
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.

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Example of comodulogram and phase amplitude coupling at somatic, mid-apical and distal apical dendrite recording sites, for a single animal. (A–C) Comodulogram showing the modulation Index (MI) plotted as a function of phase-frequency and amplitude-frequency from a single animal. Hotter colors indicate larger amplitude modulation. (D,G,J) γslow (30–45 Hz)/γmid(50–90 Hz) /γfast (90–170 Hz) amplitude modulation by θ (6–10 Hz) phase, binned into 18 subdivisions of 20° each at the somatic recording site. (E,H,K) The γslow, γmid, and γfast amplitudes from the recording site at the mid-apical dendrite (M-AD) shows relative amplitude modulation by θ similar to that seen at the somatic site; however the phase of θ at which gamma amplitude was maximum were offset by 120° for γslow and 20° for γmid. (F,I,L) At the distal apical dendrite (D-AD) the amplitude coupling was anti-phasic (offset by 180°) for γslow and γmid with respect to soma. In addition the θ-γfast coupling was visible primarily only at D-AD [Phase amplitude coupling measurements shown in this figure were obtained from pre-injection baseline data in an exploring animal using the method described by Tort et al. (2010)].
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Figure 5: Example of comodulogram and phase amplitude coupling at somatic, mid-apical and distal apical dendrite recording sites, for a single animal. (A–C) Comodulogram showing the modulation Index (MI) plotted as a function of phase-frequency and amplitude-frequency from a single animal. Hotter colors indicate larger amplitude modulation. (D,G,J) γslow (30–45 Hz)/γmid(50–90 Hz) /γfast (90–170 Hz) amplitude modulation by θ (6–10 Hz) phase, binned into 18 subdivisions of 20° each at the somatic recording site. (E,H,K) The γslow, γmid, and γfast amplitudes from the recording site at the mid-apical dendrite (M-AD) shows relative amplitude modulation by θ similar to that seen at the somatic site; however the phase of θ at which gamma amplitude was maximum were offset by 120° for γslow and 20° for γmid. (F,I,L) At the distal apical dendrite (D-AD) the amplitude coupling was anti-phasic (offset by 180°) for γslow and γmid with respect to soma. In addition the θ-γfast coupling was visible primarily only at D-AD [Phase amplitude coupling measurements shown in this figure were obtained from pre-injection baseline data in an exploring animal using the method described by Tort et al. (2010)].

Mentions: Previous studies have found that the different sub-bands differ in cross-frequency coupling with the θ-oscillation (Tort et al., 2008, 2012; Colgin et al., 2009; Belluscio et al., 2012; Scheffer-Teixeira et al., 2012). We explored layer-specific characteristics of CFC by measuring the amplitude of γ-oscillations as a function of the phase of the local θ-oscillation. Figure 5 shows an example from one animal during the baseline-recording period, prior to injecting a drug or saline. Here, the amplitude of the γ-oscillation is plotted as a function of the phase of the θ-oscillation, for all three sub-bands at each of three recording sites (Figures 5A,D,G,J: recording site at soma, Figures 5B,E,H,K: M-AD, Figures 5C,F,I,L: D-AD), where the top panel (Figures 5A–C) shows the comodulogram of the modulation index (MI) that quantifies the modulation of gamma at each of the sites. It is apparent that modulation was greater for γmid than for γslow or γfast oscillations at all locations. This pattern was observed consistently across animals; on average, the amplitude modulation of γmid was ~6 times that of γslow and ~4 times that of the γfast oscillation, as assessed by comparing the modulation index (MI) for each of the sub-bands at D-AD. Although the rmsCSD amplitudes of γslow and γmid were higher in the M-AD than at the soma (Figures 2D,E), the phase-amplitude coupling was lowest in the M-AD, confirming that MI values are independent of CSD amplitude (Tort et al., 2010).


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

Balakrishnan S, Pearce RA - Front Neural Circuits (2015)

Example of comodulogram and phase amplitude coupling at somatic, mid-apical and distal apical dendrite recording sites, for a single animal. (A–C) Comodulogram showing the modulation Index (MI) plotted as a function of phase-frequency and amplitude-frequency from a single animal. Hotter colors indicate larger amplitude modulation. (D,G,J) γslow (30–45 Hz)/γmid(50–90 Hz) /γfast (90–170 Hz) amplitude modulation by θ (6–10 Hz) phase, binned into 18 subdivisions of 20° each at the somatic recording site. (E,H,K) The γslow, γmid, and γfast amplitudes from the recording site at the mid-apical dendrite (M-AD) shows relative amplitude modulation by θ similar to that seen at the somatic site; however the phase of θ at which gamma amplitude was maximum were offset by 120° for γslow and 20° for γmid. (F,I,L) At the distal apical dendrite (D-AD) the amplitude coupling was anti-phasic (offset by 180°) for γslow and γmid with respect to soma. In addition the θ-γfast coupling was visible primarily only at D-AD [Phase amplitude coupling measurements shown in this figure were obtained from pre-injection baseline data in an exploring animal using the method described by Tort et al. (2010)].
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 5: Example of comodulogram and phase amplitude coupling at somatic, mid-apical and distal apical dendrite recording sites, for a single animal. (A–C) Comodulogram showing the modulation Index (MI) plotted as a function of phase-frequency and amplitude-frequency from a single animal. Hotter colors indicate larger amplitude modulation. (D,G,J) γslow (30–45 Hz)/γmid(50–90 Hz) /γfast (90–170 Hz) amplitude modulation by θ (6–10 Hz) phase, binned into 18 subdivisions of 20° each at the somatic recording site. (E,H,K) The γslow, γmid, and γfast amplitudes from the recording site at the mid-apical dendrite (M-AD) shows relative amplitude modulation by θ similar to that seen at the somatic site; however the phase of θ at which gamma amplitude was maximum were offset by 120° for γslow and 20° for γmid. (F,I,L) At the distal apical dendrite (D-AD) the amplitude coupling was anti-phasic (offset by 180°) for γslow and γmid with respect to soma. In addition the θ-γfast coupling was visible primarily only at D-AD [Phase amplitude coupling measurements shown in this figure were obtained from pre-injection baseline data in an exploring animal using the method described by Tort et al. (2010)].
Mentions: Previous studies have found that the different sub-bands differ in cross-frequency coupling with the θ-oscillation (Tort et al., 2008, 2012; Colgin et al., 2009; Belluscio et al., 2012; Scheffer-Teixeira et al., 2012). We explored layer-specific characteristics of CFC by measuring the amplitude of γ-oscillations as a function of the phase of the local θ-oscillation. Figure 5 shows an example from one animal during the baseline-recording period, prior to injecting a drug or saline. Here, the amplitude of the γ-oscillation is plotted as a function of the phase of the θ-oscillation, for all three sub-bands at each of three recording sites (Figures 5A,D,G,J: recording site at soma, Figures 5B,E,H,K: M-AD, Figures 5C,F,I,L: D-AD), where the top panel (Figures 5A–C) shows the comodulogram of the modulation index (MI) that quantifies the modulation of gamma at each of the sites. It is apparent that modulation was greater for γmid than for γslow or γfast oscillations at all locations. This pattern was observed consistently across animals; on average, the amplitude modulation of γmid was ~6 times that of γslow and ~4 times that of the γfast oscillation, as assessed by comparing the modulation index (MI) for each of the sub-bands at D-AD. Although the rmsCSD amplitudes of γslow and γmid were higher in the M-AD than at the soma (Figures 2D,E), the phase-amplitude coupling was lowest in the M-AD, confirming that MI values are independent of CSD amplitude (Tort et al., 2010).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Training Program, University of Wisconsin-Madison Madison, WI, USA ; Department of Anesthesiology, University of Wisconsin-Madison Madison, WI, USA.

ABSTRACT
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.

Show MeSH