The modulation of nicotinic acetylcholine receptors on the neuronal network oscillations in rat hippocampal CA3 area.

Yang Wang,Xi Zhang,Jiangang Wang,Zhan Wang,Zaineb Henderson,Chengbiao Lu,Yali Wang,Xiaofang Wang,Jinggui Song

doi:10.1038/srep09493

Abstract

γ oscillations are associated with higher brain functions such as memory, perception and consciousness. Disruption of γ oscillations occur in various neuro-psychological disorders such as schizophrenia. Nicotinic acetylcholine receptors (nAChR) are highly expressed in the hippocampus, however, little is known about the role on hippocampal persistent γ oscillation. This study examined the effects of nicotine and selective nAChR agonists and antagonists on kainate-induced persistent γ oscillation in rat hippocampal slices. Nicotine enhanced γ oscillation at concentrations of 0.1–10 μM, but reduced it at a higher concentration of 100 μM. The enhancement on γ oscillation can be best mimicked by co-application of α4β2- and α7- nAChR agonist and reduced by a combination of nAChR antagonists, DhβE and MLA. However, these nAChR antagonists failed to block the suppressing role of nicotine on γ. Furthermore, we found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine. These results demonstrate that nicotine modulates γ oscillations via α7 and α4β2 nAChR as well as NMDA activation, suggesting that nAChR activation may have a therapeutic role for the clinical disorder such as schizophrenia, which is known to have impaired γ oscillation and hypo-NMDA receptor function.

Highlights

The modulation of nicotinic acetylcholine receptors on the neuronal network oscillations in rat hippocampal CA3 area
Kainate (KA, 200 nM) induced persistent c oscillation (20–60 Hz) in rat hippocampal CA3 area. c oscillation usually takes approximately 1 to 2 hours to achieve steady-state and would last for at least three hours (Fig. 1A1, B1, C1), which is in agreement with previous studies35–37. c oscillations can be blocked by the AMPA/kainate receptor antagonist, NBQX (20 mM), or the GABAA receptor antagonist, bicuculline (20 mM) (n 5 5, data not shown), confirming that these oscillations are mediated by excitatory and inhibitory neurotransmission
Our results demonstrated that nicotine enhanced persistent c oscillations at a relative low concentration but decreased it at a higher concentration in the hippocampal CA3 area

Summary

Introduction

The modulation of nicotinic acetylcholine receptors on the neuronal network oscillations in rat hippocampal CA3 area. Nicotinic acetylcholine receptors (nAChR) are highly expressed in the hippocampus, little is known about the role on hippocampal persistent c oscillation. The enhancement on c oscillation can be best mimicked by co-application of a4b2- and a7- nAChR agonist and reduced by a combination of nAChR antagonists, DhbE and MLA These nAChR antagonists failed to block the suppressing role of nicotine on c. We found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine These results demonstrate that nicotine modulates c oscillations via a7 and a4b2 nAChR as well as NMDA activation, suggesting that nAChR activation may have a therapeutic role for the clinical disorder such as schizophrenia, which is known to have impaired c oscillation and hypo-NMDA receptor function. Nicotine is not able to induce c oscillation, it appears to enhance auditory evoked c oscillations[14], but the mechanism of nicotinic modulation of c oscillations remains largely unknown

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