Original Article

Effects of nicotine stimulation on spikes, theta frequency oscillations, and spike-theta oscillation relationship in rat medial septum diagonal band Broca slices

Dong Wen, Ce Peng, Gao-xiang Ou-yang, Zainab Henderson, Xiao-li Li, Cheng-biao Lu
DOI: 10.1038/aps.2012.180


Dong WEN1, #, Ce PENG2, #, Gao-xiang OU-YANG2, Zainab HENDERSON3, Xiao-li LI2, Cheng-biao LU1, 2, *
1The Key Laboratory for Computer Virtual Technology and System Integration of Hebei Province, Yanshan University, Qinhuangdao 066004, China; 2School of Electrical Engineering, Yanshan University, Qinhuangdao 066004, China; 3Institute of Membrane Biology, Leeds, University of Leeds, United Kingdom

Aim: Spiking activities and neuronal network oscillations in the theta frequency range have been found in many cortical areas during information processing. The aim of this study is to determine whether nicotinic acetylcholine receptors (nAChRs) mediate neuronal network activity in rat medial septum diagonal band Broca (MSDB) slices.
Methods: Extracellular field potentials were recorded in the slices using an Axoprobe 1A amplifier. Data analysis was performed off-line. Spike sorting and local field potential (LFP) analyses were performed using Spike2 software. The role of spiking activity in the generation of LFP oscillations in the slices was determined by analyzing the phase-time relationship between the spikes and LFP oscillations. Circular statistic analysis based on the Rayleigh test was used to determine the significance of phase relationships between the spikes and LFP oscillations. The timing relationship was examined by quantifying the spike-field coherence (SFC).

Results: Application of nicotine (250 nmol/L) induced prominent LFP oscillations in the theta frequency band and both small- and large-amplitude population spiking activity in the slices. These spikes were phase-locked to theta oscillations at specific phases. The Rayleigh test showed a statistically significant relationship in phase-locking between the spikes and theta oscillations. Larger changes in the SFC were observed for large-amplitude spikes, indicating an accurate timing relationship between this type of spike and LFP oscillations. The nicotine-induced spiking activity (large-amplitude population spikes) was suppressed by the nAChR antagonist dihydro-β-erythroidine (0.3 μmol/L).

Conclusion: The results demonstrate that large-amplitude spikes are phase-locked to theta oscillations and have a high spike-timing accuracy, which are likely a main contributor to the theta oscillations generated in MSDB during nicotine receptor activation.

Keywords: medial septum diagonal band of Broca; theta oscillations; spike; LFP; nicotinic acetylcholine receptor; nicotine; dihydro-β-erythroidine; brain slice; electrophysiology

This work was supported by the National Natural Science Foundation of China (grant No 31070938 and No 81271422), the open project of the State Key Laboratory of Cognitive Neuroscience and Learning in Beijing Normal University (time periods: form 2012 to 2013), Hebei applied basic research plan key program for basic research of China (grant No 12966119D), Natural Science Foundation of Hebei Province of China (grant No H2012203067), Specialized Research Fund for the Doctoral Program of Higher Education of China (grant No 20101333110006), Hebei Province Department of Education Fund (grant No 2010285) and UK Medical Research Council (grant No G0500823).
# These authors contributed equally to this paper.
* To whom correspondence should be addressed.
E-mail cblu@ysu.edu.cn
Received 2012-08-02 Accepted 2012-12-05

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