High-frequency oscillations and sequence generation in two-population models of hippocampal region CA1

Hippocampal sharp wave/ripple oscillations are a prominent pattern of collective activity, which consists of a strong overall increase of activity with superimposed (140 - 200 Hz) ripple oscillations. Despite its prominence and its experimentally demonstrated importance for memory consolidation, the mechanisms underlying its generation are to date not understood. Several models assume that recurrent networks of inhibitory cells alone can explain the generation and main characteristics of the ripple oscillations. Recent experiments, however, indicate that in addition to inhibitory basket cells, the pattern requires in vivo the activity of the local population of excitatory pyramidal cells. Here, we study a model for networks in the hippocampal region CA1 incorporating such a local excitatory population of pyramidal neurons. We start by investigating its ability to generate ripple oscillations using extensive simulations. Using biologically plausible parameters, we find that short pulses of external excitation triggering excitatory cell spiking are required for sharp/wave ripple generation with oscillation patterns similar to in vivo observations. Our model has plausible values for single neuron, synapse and connectivity parameters, random connectivity and no strong feedforward drive to the inhibitory population. Specifically, whereas temporally broad excitation can lead to high-frequency oscillations in the ripple range, sparse pyramidal cell activity is only obtained with pulse-like external CA3 excitation. Further simulations indicate that such short pulses could originate from dendritic spikes in the apical or basal dendrites of CA1 pyramidal cells, which are triggered by coincident spike arrivals from hippocampal region CA3. Finally we show that replay of sequences by pyramidal neurons and ripple oscillations can arise intrinsically in CA1 due to structured connectivity that gives rise to alternating excitatory pulse and inhibitory gap coding; the latter denotes phases of silence in specific basket cell groups, which induce selective disinhibition of groups of pyramidal neurons. This general mechanism for sequence generation leads to sparse pyramidal cell and dense basket cell spiking, does not rely on synfire chain-like feedforward excitation and may be relevant for other brain regions as well. Author summary During certain phases of sleep, rest and consummatory behavior the hippocampus brain area generates strong high frequency oscillations. These oscillations are important for memory formation and consolidation. To date, the mechanisms underlying their generation remain incompletely understood. We find that in unstructured networks, carefully designing how excitation is transmitted within the hippocampus is required for the generation of robust fast oscillations. Broad, temporally extended excitation of cells results in unrealistic single cell activity, whereas temporally narrow input that differs from cell to cell gives rise to oscillations with realistic single cell and network activity. We show that the biophysical mechanism to generate the required temporally narrow excitation may be related to spiking events in the dendrites, which are triggered by coincident input. Our results in structured networks suggest that the interplay of hippocampal excitation and inhibition can serve as a means to generate robust sequential activity, which is thought to be crucial for memory formation and recall. The sequence generation mechanism also leads to strong high frequency oscillations with sparse excitatory cell and frequent inhibitory cell spiking, as observed in the hippocampus.

Automated summary

Hippocampal sharp wave/ripple oscillations are important for memory consolidation, but the mechanisms underlying their generation are not fully understood. Recent experiments indicate that in addition to inhibitory cells, the activity of excitatory pyramidal cells is required for generating this pattern.