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

Abstract

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.

Interneuronal network model of theta-nested fast oscillations predicts differential effects of heterogeneity, gap junctions and short term depression for hyperpolarizing versus shunting inhibition

“…Such high firing rates are clearly not consistent [ 8 ] with a stochastic population oscillator [ 82 ], and our model in this study of theta-nested fast oscillations is clearly a coupled oscillator model. A recent computational study [ 86 ] on ripple generation in area CA1 found that, in some cases, an inhibitory interneuronal population can exhibit strong synchrony, while the excitatory neuron population simultaneously exhibits weak stochastic synchrony. That study modeled single neurons as conductance-based leaky integrate-and-fire neurons and assumed that fast oscillations are a network dynamical pattern that does not crucially depend on the details of subthreshold dynamics and spike generation.…”

Ultrafast (400 Hz) network oscillations induced in mouse barrel cortex by optogenetic activation of thalamocortical axons

“…Although widely studied, the mechanisms pacing hippocampal ripples are still under debate (reviewed in Buzsáki, 2015 ). Several competing models are proposed in the literature, assigning different weights to pyramidal–pyramidal (PYR-PYR), pyramidal–interneuron (PYR-INT), and interneuron–interneuron (INT-INT) connections ( Traub and Bibbig, 2000 ; Taxidis et al, 2012 ; Traub et al, 2012 ; Malerba et al, 2016 ; Donoso et al, 2018 ; Braun and Memmesheimer, 2022 ). Recent experimental and computational studies lean in favor of a ‘hybrid’ PYR-INT-INT model, suggesting that FS interneurons act as the central pacemakers of the ripple oscillation, and that tonic excitation from pyramidal neurons is needed only to keep interneurons sufficiently depolarized ( Schlingloff et al, 2014 ; Stark et al, 2014 ; Gan et al, 2017 ; Ramirez-Villegas et al, 2018 ).…”

Interneuronal network model of theta-nested fast oscillations predicts differential effects of heterogeneity, gap junctions and short term depression for hyperpolarizing versus shunting inhibition

“…Such high firing rates are clearly not consistent [8] with a stochastic population oscillator [67], and our model in this study of theta-nested fast oscillations is clearly a coupled oscillator model. A recent computational study [71] on ripple generation in area CA1 found that, in some cases, an inhibitory interneuronal population can exhibit strong synchrony, while the excitatory neuron population simultaneously exhibits weak stochastic synchrony. That study modeled single neurons as conductance-based leaky integrate-and-fire neurons and assumed that fast oscillations are a network dynamical pattern that does not crucially depend on the details of subthreshold dynamics and spike generation.…”