Cholinergic Plasticity of Oscillating Neuronal Assemblies in Mouse Hippocampal Slices

Maura M Zylla,Martin Both,Andreas Draguhn,Susanne Reichinnek,Xiaomin Zhang,Gennady Cymbalyuk

doi:10.1371/journal.pone.0080718

Abstract

The mammalian hippocampus expresses several types of network oscillations which entrain neurons into transiently stable assemblies. These groups of co-active neurons are believed to support the formation, consolidation and recall of context-dependent memories. Formation of new assemblies occurs during theta- and gamma-oscillations under conditions of high cholinergic activity. Memory consolidation is linked to sharp wave-ripple oscillations (SPW-R) during decreased cholinergic tone. We hypothesized that increased cholinergic tone supports plastic changes of assemblies while low cholinergic tone favors their stability. Coherent spatiotemporal network patterns were measured during SPW-R activity in mouse hippocampal slices. We compared neuronal activity within the oscillating assemblies before and after a transient phase of carbachol-induced gamma oscillations. Single units maintained their coupling to SPW-R throughout the experiment and could be re-identified after the transient phase of gamma oscillations. However, the frequency of SPW-R-related unit firing was enhanced after muscarinic stimulation. At the network level, these changes resulted in altered patterns of extracellularly recorded SPW-R waveforms. In contrast, recording of ongoing SPW-R activity without intermittent cholinergic stimulation revealed remarkably stable repetitive activation of assemblies. These results show that activation of cholinergic receptors induces plasticity at the level of oscillating hippocampal assemblies, in line with the different role of gamma- and SPW-R network activity for memory formation and –consolidation, respectively.

Highlights

The mammalian hippocampus plays a crucial role in spatial and declarative memory formation
Disruption of sharp wave-ripple complexes (SPW-R) during slow-wave sleep (SWS) [28,29] or during waking states [30] impairs spatial memory performance in rodents. These findings suggest that cholinergicallydriven gamma oscillations support activity-dependent plasticity of assemblies whereas sharp waves (SPW)-R stabilize pre-existing groups of coactive neurons
[31] In accordance with their known propagation pattern in vivo, SPW-R in CA1 were regularly preceded by high-frequency network bursts in CA3 [32,38]

Summary

Introduction

The mammalian hippocampus plays a crucial role in spatial and declarative memory formation. The underlying neuronal mechanisms are likely to involve activity-dependent changes in coupling of local neurons, thereby forming transiently stable assemblies [1,2,3] According to this concept of plasticity, environmental cues result in co-activation of defined neurons, encoding for segments of episodic memory, which stabilize their connections [4,5,6]. Active exploratory behavior goes along with hippocampal theta rhythms (5–10 Hz) which are superimposed by gamma oscillations (30–100 Hz) [13,14,15]. During these activity patterns, afferent fibers from septal nuclei release acetylcholine [16]. Cholinergic activity may, thereby, contribute to assembly formation [4,22]

Methods

Results

Conclusion