Theta oscillations decrease spike synchrony in the hippocampus and entorhinal cortex

Abstract

Oscillations and synchrony are often used synonymously. However, oscillatory mechanisms involving both excitation and inhibition can generate non-synchronous yet coordinated firing patterns. Using simultaneous recordings from multiple layers of the entorhinal-hippocampal loop, we found that coactivation of principal cell pairs (synchrony) was lowest during exploration and rapid-eye-movement (REM) sleep, associated with theta oscillations, and highest in slow wave sleep. Individual principal neurons had a wide range of theta phase preference. Thus, while theta oscillations reduce population synchrony, they nevertheless coordinate the phase (temporal) distribution of neurons. As a result, multiple cell assemblies can nest within the period of the theta cycle.

Keywords: brain states; cell assemblies; place cells; synchrony; temporal coordination; theta oscillations.

Figure 1.

Neuronal synchrony is brain state-dependent. Distribution of the pairwise correlation coefficient values of spike counts in CA1 pyramidal neuron–pyramidal neuron (a), interneuron–interneuron (b) and pyramidal neuron–interneuron pairs (c) in different brain states. Insets: cross-correlograms of example pairs with significant negative (r = −0.030) and positive (r = 0.058) correlation coefficient values during RUN. The time window for the correlation coefficient was 50 ms, but essentially similar patterns were observed at 10, 20, 100 ms windows. (Online version in colour.)

Figure 2.

Theta oscillations decorrelate spiking between neuron pairs. (a) Distribution of pairwise correlation values of spikes in principal neuron–principal neuron (left), interneuron–interneuron (middle) and principal neuron–interneuron pairs (right) in different brain states (calculated using 50 ms time windows). Only neuron pairs with significant cross-correlograms are shown. Note a fraction of significantly negatively correlated pairs in several regions, mainly during RUN. Note also much stronger correlation between putative interneurons. (b) Fraction of significantly correlated pairs (±95% Clopper–Pearson confidence intervals) in different regions, layers and brain states. Positively and negatively correlated pairs are shown upward and downward, respectively. Note largest positive correlations during SWS and IMM (non-theta) states. See also the electronic supplementary material, figure S5. (Online version in colour.)

Figure 3.

Negative correlations reflect phase-distributed cell assemblies in the theta cycle. (a) Top: normalized firing rates of five place cells, with neuron 3 as a reference (black trace with peak firing at 0 cm). Middle: normalized cross-correlations between the reference neuron and other place cells (colours) and the autocorrelogram of the reference neuron (black). Temporal offsets between the peaks represent the time needed for the rat to run between the place fields of the neurons. Bottom: Time-expanded versions of the normalized cross-correlograms shown in the middle (theta timescale). Note that maximum firing of the neurons is distributed within the theta cycle and that the order of peak activity of place cells 1–5 within the theta cycle is the same as the order of position representation on the track. The dip around time 0 in the autocorrelogram of the reference cell is due to refractory period of spikes. Auto- and cross-correlograms in the middle and bottom are plotted in 10 ms time bins without further smoothing. (b) Cross-correlograms of CA1 pyramidal cells in different brain states. Each row corresponds to a normalized cross-correlogram of a cell pair. Bin size, 1 ms; Gaussian kernel smoothing (s.d. = 10 ms) was applied, and height of cross-correlogram was z-scored and colour coded for each cell pair. Neuron pairs were sorted by the timing of the peak of the cross-correlogram. (c) Distribution of synchrony index of principal neuron–principal neuron pairs in 50 ms time windows in different states. Synchrony index was calculated as the difference between the mean spike counts across bins in [−25, +25] ms and that in [−500, −25] and [+25, +500] ms in cross-correlograms divided by the sum (see Material and methods). Only three regions are shown but similar patterns were observed in the dentate gyrus, EC3 and EC5. See also the electronic supplementary material, figure S6–S9. (Online version in colour.)