Both observations are in agreement with a spread of SWR activity from proximal to distal sites in CA1 with respect to CA3. In addition, we found that ripple-associated cPSCs in pairs of pyramidal neurons were phase coherent, as demonstrated by coherence maxima in the ripple frequency range (Figure 3F). Cell-to-cell coherence maxima of cPSCs insignificantly decreased with increased spatial C59 purchase separation between cells (Figure 3G; R = −0.26, p = 0.26). In
line, comparison of cPSC coherence in close (<100 μm apart) versus distant (450–580 μm) neuron pairs revealed no significant difference ( Figure 3H; p = 0.39; rank-sum test). Together, these results on dual principal cell recordings confirm that ripple-locked cPSCs are indeed signatures of population oscillations. From the above experiments, MAPK Inhibitor Library it is not clear whether the observed synchrony is mediated by excitation, inhibition, or both (Figure S3B). To differentiate, we recorded from principal neurons at −66 mV, close to the reversal potential of Cl− (−67 mV in our conditions). By choosing this holding potential, we considerably reduced the driving force for Cl− and hence Cl−-driven GABAAR-mediated inhibition (see Figure S4A for the experimental confirmation of the Nernst potential). The kinetics derived
from spontaneous EPSCs (not associated with ripples) were fast enough to account for excitatory currents in ripple-associated cPSCs (Figure 4A). To corroborate this hypothesis, we quantified the temporal structure of ripple-coherent cPSCs. The underlying assumption was that rise times of synaptic currents are faster than their decays. At potentials below the reversal potential of excitatory synaptic transmission, excitatory currents within cPSCs are inward and should thus display downward slopes (rises) steeper than their upward slopes
(decays). In addition, at the potential we have chosen, putative inhibitory outward currents should display only small amplitudes, due to the small driving force for Cl−. We analyzed the slopes within Histone demethylase cPSCs in eight cells recorded at −66 mV (1,085 cPSCs in total). In line with EPSC kinetics, we found that downward slopes were indeed steeper than upward slopes ( Figure 4B): The analysis revealed slope values of 35.7 ± 0.5 pA/ms versus 18.9 ± 0.2 pA/ms for the populations of 10% strongest downward and upward slopes in individual cPSCs (p = 1.6·10−178; Kolmogorov-Smirnov test [K-S test]; n = 8 cells). We further checked whether the interval distribution of strong downward slopes can be related to ripples. Indeed, the incidence of strong downward slopes was in the range of ripple frequency as demonstrated by a peak at ∼5 ms in interdownward slope-interval histograms ( Figure 4C; see Figure S4B for single-cell analysis). Based on these findings, we hypothesized that the putatively excitatory PSCs are locked to the LFP.