Abstract

Hippocampal sharp wave (SW)/ripple complexes are thought to contribute to memory consolidation. Previous studies suggest that behavioral rewards facilitate SW occurrence in vivo. However, little is known about the precise mechanism underlying this enhancement. Here, we examined the effect of dopaminergic neuromodulation on spontaneously occurring SWs in acute hippocampal slices. Local field potentials were recorded from the CA1 region. A brief (1 min) treatment with dopamine led to a persistent increase in the event frequency and the magnitude of SWs. This effect lasted at least for our recording period of 45 min and did not occur in the presence of a dopamine D1/D5 receptor antagonist. Functional multineuron calcium imaging revealed that dopamine-induced SW augmentation was associated with an enriched repertoire of the firing patterns in SW events, whereas the overall tendency of individual neurons to participate in SWs and the mean number of cells participating in a single SW were maintained. Therefore, dopaminergic activation is likely to reorganize cell assemblies during SWs.

Highlights

  • Hippocampal sharp wave (SW)/ripples are a complex of relatively slow (10–30 Hz) field transients and fast (150–250 Hz) field oscillations and are observed in the hippocampus during slow wave sleep and quiet awake states [1,2,3]

  • We demonstrated that a brief bath-application of dopamine to hippocampal slices induced a long-lasting increase in the SW event frequency through dopamine D1/D5 receptor activation

  • The D1/D5 receptor activation did not largely change SW-participating neurons and the number of neurons involved in single SWs, but it reorganized combinations of neurons co-participating in SWs and thereby expanded the diversity of the internal structures of SWs

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Summary

Introduction

Hippocampal sharp wave (SW)/ripples are a complex of relatively slow (10–30 Hz) field transients and fast (150–250 Hz) field oscillations and are observed in the hippocampus during slow wave sleep and quiet awake states [1,2,3]. A current hypothesis on learning and memory implies that labile hippocampal memory traces are transferred to a more stable neocortical storage [5] through offline reverberatory replays of behavioral experiences during SW/ripples [6]. In support of this concept, selective suppression of SWs results in an impairment of long-term memory formation [7]. SW/ripples are reported to increase when a rat is rewarded or placed in a novel environment [8,9] Because both situations increase dopaminergic neuronal activities [10,11], dopamine is one of the candidate neuromodulators of the SWs/ripple facilitation, other modulators such as opioids [12] and orexin [13] are released during rewarding. Bilateral injection of a D1/D5 receptor agonist into the hippocampus enhances memory retention [17], whereas a D1/D5 receptor antagonist disturbs one-day memory without affecting shorter-term memory [18]

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