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

Wilhelm Braun,Raoul-Martin Memmesheimer,Daniel Bush

doi:10.1371/journal.pcbi.1009891

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.

Highlights

Hippocampal sharp wave/ripples (SPW/Rs) are remarkable both from a neurophysiological viewpoint and in their behavioral impact: On the one hand, they consist of strong increases of spiking activity in large parts of local neuron populations together with oscillatory, extraordinarily coherent neuronal discharges
It was proposed that interactions between E and I cell populations after external excitation of E cells are both necessary and sufficient to generate ripple oscillations in vivo [19]. (In contrast, ref. [25] found in CA3 slices that GABAergic interneurons are both necessary and sufficient to generate ripple oscillations in the local field potential (LFP), even when excitation is blocked.) These results suggest for CA1 a second class of models, which are the focus of the present article and which may be called pyramidal interneuron ripples
We show that the generation of high-frequency oscillations in the right frequency range with realistic single-neuron dynamics is possible with random two-population models if excitation to CA1 pyramidal cells is delivered in an inhomogeneous, temporally narrow, fashion

Summary

Introduction

Hippocampal sharp wave/ripples (SPW/Rs) are remarkable both from a neurophysiological viewpoint and in their behavioral impact: On the one hand, they consist of strong increases of spiking activity in large parts of local neuron populations (the sharp wave) together with oscillatory, extraordinarily coherent neuronal discharges (ripples). During replay events co-occurring with SPW/R complexes, sequences of pyramidal cell action potentials encoding location, so-called place cells [9], are repeated on a faster timescale. The main source of external excitation arriving in CA1 during a SPW/R event is a sharp, wave-like depolarization from area CA3 delivered via the Schaffer collaterals (SCs) to the basal and proximal apical dendrites of CA1 pyramidal cells [1, 10,11,12]. This input likely generates the sharp wave of spiking activity in CA1. Direct measurements of spiking activity and modeling studies show that these LFP ripples are mainly caused by the temporally precise, sparse firing of excitatory pyramidal cells [17,18,19], possibly with a smaller contribution from interneuronal activity [1, 19]

Methods

Results

Discussion

Conclusion