Original Article

Nicotine induction of theta frequency oscillations in rodent medial septal diagonal band in vitro

Cheng-biao Lu, Cheng-zhang Li, Dong-liang Li, Zaineb Henderson
DOI: 10.1038/aps.2012.198


Cheng-biao LU1, *, Cheng-zhang LI1, Dong-liang LI1, Zaineb HENDERSON2
1Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, China; 2Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK

Aim: This study aimed to examine the role of the nicotinic receptor (nAChR) in the generation of theta oscillations (4–12 Hz) in vitro.
Methods: Electrophysiological studies were performed on medial septal diagonal band area (MSDB) slices to measure theta oscillation. Immunofluorescence and confocal microscopy studies were carried out to detect α4 nAChR and β2 nAChR subunits in perfused-fixed tissue from VGluT2-GFP and GAD67-GFP transgenic mice.

Results: Application of nicotine to MSDB slices produced persistent theta oscillations in which area power increased in a dose-responsive manner. This activity was inhibited by GABAA receptor antagonists and partially by ionotropic glutamate receptor antagonists, indicating the involvement of local GABAergic and glutamatergic neurons in the production of the rhythmic activity. The nicotine-induced theta activity was also inhibited selectively by non-α7*nAChR antagonists, suggesting the presence of these receptor types on GABAergic and glutamatergic neuron populations in the MSDB. This was confirmed by immunofluorescence and confocal microscopy studies in transgenic mice in which the GABAergic and glutamatergic neurons express green fluorescent protein (GFP), showing localisation of β2 nAChR and α4 nAChR subunits, the most common constituents of non-α7*nAChRs, in both cell types in the MSDB.

Conclusion: Theta activity in the MSDB may be generated by tonic stimulation of non-α7*nAChRs.

Keywords: nicotinic receptors; medial septal diagonal band; rhythmogenesis; hippocampal theta rhythm; learning and memory; Alzheimer’s disease

This work was supported by National Natural Science Foundation of China (grant No 31070938, No 81271422) and the UK Medical Research Council (grant No G0500823).

* To whom correspondence should be addressed.
E-mail johnlu9000@hotmail.com
Received 2012-08-10 Accepted 2012-12-20

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