Atorvastatin enhances kainate-induced gamma oscillations in rat hippocampal slices

And why would studying oscillations of dead rat brain give any useful information? This should have been laughed out of existence. Or is the rat alive but able to virtually slice its' brain?
http://onlinelibrary.wiley.com/doi/10.1111/ejn.13322/abstract

1. ChengZhang Li^1,†,
2. JianGang Wang^1,†,
3. Jianhua Zhao²,
4. Yali Wang¹,
5. Zhihua Liu¹,
6. FangLi Guo¹,
7. XiaoFang Wang¹,
8. Martin Vreugdenhil^3,4 and
9. ChengBiao Lu^1,*

DOI: 10.1111/ejn.13322

This article is protected by copyright. All rights reserved.

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European Journal of Neuroscience

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

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1. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ejn.13322

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Keywords:

• Hippocampus;
• pyramidal neurons;
• interneurons;
• PKA ;
• ERK ;
• PI3K

Abstract

Atorvastatin has been shown to affect cognitive functions in rodents and humans. However, the underlying mechanism is not fully understood. Because hippocampal gamma oscillations (γ, 20-80 Hz) are associated with cognitive functions, we studied the effect of atorvastatin on persistent kainate-induced γ oscillation in the CA3 area of rat hippocampal slices. The involvement of NMDA receptors and multiple kinases was tested before and after administration of atorvastatin. Whole-cell current-clamp and voltage-clamp recordings were made from CA3 pyramidal neurons and interneurons before and after atorvastatin application. Atorvastatin increased γ power by ~50% in a concentration-dependent manner, without affecting dominant frequency. Whereas atorvastatin did not affect intrinsic properties of both pyramidal neurons and interneurons, it increased the firing frequency of interneurons but not that of pyramidal neurons. Furthermore, whereas atorvastatin did not affect synaptic current amplitude, it increased the frequency of spontaneous IPSCs, but did not affect the frequency of spontaneous EPSCs. The atorvastatin-induced enhancement of γ oscillations was prevented by pretreatment with the PKA inhibitor H89, the ERK inhibitor U0126, or the PI3K inhibitor wortmanin, but not by the NMDA receptor antagonist D-AP5. Taken together, these results demonstrate that atorvastatin enhanced the kainate-induced γ oscillation by increasing interneuron excitability, with an involvement of multiple intracellular kinase pathways. Our study suggests that the classical cholesterol-lowering agent atorvastatin may improve cognitive functions compromised in disease, via the enhancement of hippocampal γ oscillations.

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