Distinct gamma oscillations in the distal dendritic fields of the dentate gyrus and the CA1 area of mouse hippocampus

Abstract

The molecular layer of the dentate gyrus and the anatomically adjacent stratum lacunosum-moleculare of CA1 area, represent afferent areas at distinct levels of the hippocampal trisynaptic loop. Afferents to the dentate gyrus and CA1 area originate from different cell populations, including projection cells in entorhinal cortex layers two and three, respectively. To determine the organization of oscillatory activities along these terminal fields, we recorded local field potentials from multiple sites in the dentate gyrus and CA1 area of the awake mice, and localized gamma frequency (30-150 Hz) oscillations in different layers by means of current source density analysis. During theta oscillations, we observed different temporal and spectral organization of gamma oscillations in the dendritic layers of the dentate gyrus and CA1 area, with a sharp transition across the hippocampal fissure. In CA1 stratum lacunosum-moleculare, transient mid-frequency gamma oscillations (CA1-gamma_M; 80 Hz) occurred on theta cycle peaks, while in the dentate gyrus, fast (DG-gamma_F; 110 Hz), and slow (DG-gamma_S; 40 Hz) gamma oscillations preferentially occurred on troughs of theta waves. Units in dentate gyrus, in contrast to units in CA1 pyramidal layer, phase-coupled to DG-gamma_F, which was largely independent from CA1 fast gamma oscillations (CA1-gamma_F) of similar frequency and timing. Spike timing of units recorded in either CA1 area or dentate gyrus were modulated by CA1-gamma_M. Our experiments disclosed a set of gamma oscillations that differentially regulate neuronal activity in the dentate gyrus and CA1 area, and may allow flexible segregation and integration of information across different levels of hippocampal circuitry.

Keywords: CA1; Dentate gyrus; Entorhinal cortex; Gamma oscillations; Hippocampus.

Fig. 1

Gamma oscillations in the dentate gyrus and CA1 area of the hippocampus. a High-pass filtered (at 25 Hz) CSD traces calculated for silicon probe contacts located in different hippocampal input layers (source is upwards) and the corresponding LFP trace recorded from the CA1 pyramidal layer (bottom trace), during theta oscillations. Layers are indicated on the left. Theta troughs from the CA1 pyramidal layer LFP are marked by vertical dotted lines, for reference. Coloured arrowheads indicate instances of distinct gamma oscillations, as indicated. Dentate gyrus, and CA1 area are indicated by red and green background colours, respectively. b Left, mean amplitude of gamma oscillations (Z-score of CSD wavelet amplitude), plotted for each contact as a function of theta phase in CA1 pyramidal layer (18° bins, the theta cycle is duplicated for visualization), and gamma frequency (53 logarithmically equidistant wavelet scales between 20 and 150 Hz). Right, mean amplitude spectra (grey), and phase–amplitude modulation index spectra (black), of CSD from individual contacts. Coloured arrowheads indicate peak modulation index positions for various gamma oscillations in the most relevant contacts. Note the markedly different oscillatory dynamics across the fissure. s. gran. granule cell layer, s.mol. molecular layer, s. l-m. stratum lacunosum-moleculare, s.rad. stratum radiatum, s. pyr. stratum pyramidale, CSD current source density, LFP local field potential, DG dentate gyrus, CA1 cornu ammonis area 1

Fig. 2

Co-occurrence and coherence of gamma oscillations in the dentate gyrus and CA1 area. a Frequency distribution (upper plot) and theta phase-amplitude modulation of different gamma oscillations. Theta phase here, and throughout the manuscript, was measured in the pyramidal cell layer of CA1 area. b Overlap in the occurrence (defined as a positive mean Z score) of different gamma oscillation pairs during the theta cycle. Note that the DG gamma_F–CA1 gamma_F and DG gamma_S–CA1 gamma_S oscillation pairs show substantial overlap in their frequency and theta phase distributions. c Phase coherence (measured as phase locking value; PLV) between oscillatory activities in contact pairs, displayed as a function of theta phase, and frequency. In the top row, and the left column, mean CSD oscillation amplitude Z-scores are plotted for selected contacts in stratum moleculare, stratum lacunosum-moleculare, stratum radiatum, and stratum pyramidale, as indicated. At the intercept of these, phase coherence between pairs of contacts (displayed as colour-coded phase locking value) is plotted as a function of theta phase (18° bins, the theta cycle is duplicated for visualization), and gamma frequency (53 logarithmically equidistant wavelet scales between 20 and 150 Hz). In plots at the intercept of a contact with itself, the theta phase and frequency ranges of different gamma oscillations prominent in the particular contact are displayed, for reference (also plotted as black dotted lines on the left column amplitude plots). White dotted lines indicate these same ranges on coherence plots, to indicate overlaps in frequency and theta phase ranges of different gamma oscillations

Fig. 3

Phase modulation of spike-timing of units in the dentate gyrus and area CA1 by theta and different gamma oscillations. a Left, theta phase histogram of firing of one unclassified unit, recorded from the dentate gyrus. Right, mean theta phase of firing (abscissa), and modulation strength (mean r value, ordinate) of all significantly modulated putative principal cells (green), putative interneurons (red), and unclassified units (black), recorded from the dentate gyrus. b Spike-timing modulation by gamma oscillations during theta oscillations of one unit, recorded from the dentate gyrus (same unit as in a). Left, amplitude modulation of gamma oscillations by theta oscillations, in CSD traces from selected contacts in stratum moleculare of the dentate gyrus, and stratum lacunosum-moleculare, stratum radiatum, and stratum pyramidale of the CA1 area, as indicated. Middle, spike density (greyscale-coded) of the unit, plotted as a function of CSD gamma phase and frequency for the same contacts. The mean phase values for the frequencies significantly phase-modulating the spike timing are plotted in black. Right, modulation strength spectra (mean r values) for the unit, relative to gamma oscillations in different contacts (values at frequencies significantly modulating the spike-timing are plotted in black). Frequency ranges of the different gamma oscillations are displayed by colour-coded bars at the plots of most relevant contacts. c Same as in A for units recorded from the CA1 area. d Same as in b, for one unit recorded in the CA1 area (the same putative interneuron as in c). e Spike-timing modulation strength (mean r values) of units recorded in the dentate gyrus (DG) and the CA1 area, by different gamma oscillations. Only units with significantly non-uniform phase distribution are shown. Putative principal cells, interneurons, and unclassified units are plotted in green, red, and black, respectively. Asterisks denote significant differences by Mann-Whitney U test with Holm-Bonferroni correction procedure for multiple comparisons at a general α = 0.05. Note that CA1 units do not phase couple to DG-gamma_F and DG units are only weakly phase modulated by CA1-gamma_F. f Percentage of DG and CA1 units with spike-timing significantly modulated by different gamma oscillations. Asterisks denote significant differences by the χ ² test with Holm-Bonferroni correction procedure for multiple comparisons at a general α = 0.05