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

Abstract

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. Immunofl uorescence and confocal microscopy studies were carried out to detect α4 nAChR and β2 nAChR subunits in perfused-fi xed 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 doseresponsive manner. This activity was inhibited by GABA A 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 nicotineinduced 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 confi rmed by immunofl uorescence and confocal microscopy studies in transgenic mice in which the GABAergic and glutamatergic neurons express green fl uorescent 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.

Co-activation of nAChR and mGluR induces γ oscillation in rat medial septum diagonal band of Broca slices

“…Our results indicate that in the presence of DhβE but not MLA, nicotine+DHPG failed to induce γ oscillation, suggesting that α4β2 nAChR plays a more important role than α7 nAChR in mediating the oscillatory activity of MSDB, which is in line with our previous observation that α4β2 nAChR mediated nicotine-induced θ activity in the MSDB [24] . Our results further demonstrated that the induced γ oscillation is dependent on excitatory and inhibitory neurotransmission based on the roles of AMPA receptor and GABA A receptor blockers, which is in agreement with previous reports [26,27] .…”

“…The present study extends our previous investigations [15,16,22] on the contribution of nAChR and mGluR1 to the control of θ and γ oscillations in the MSDB. Specifically, we demonstrated that co-activation of mGluR1 and nAChR can control the pattern of network oscillation in MSDB through the combination of various concentrations of two receptor agonists, DHPG and nicotine.…”

“…The enhancement of evoked hippocampal γ oscillations by nicotine can be reduced by α7 nAChR antagonists, which is in agreement with our observation in the hippocampus that nicotine-induced θ oscillations can be reduced by α7 nAChRs antagonists [16] . In the MSDB, nicotine-induced θ oscillation can be reduced by α4 but not α7 nAChR antagonists [24] . Thus, it appears that α7 nAChRs play a role in nicotine-mediated enhancement of hippocampal-related functions and that non-α7 nAChRs are involved in the modulation of MSDB-related functions.…”

“…Previous studies demonstrate that nAChR is expressed in both glutamatergic and GABAergic neurons within the local network circuit of MSDB [23,24] , suggesting that activation of these receptors may alter MSDB function.…”

“…Nicotine induced θ oscillations in the MSDB and in the hippocampus [15][16][17] , suggesting that nAChR activation modulates septal-hippocampal function [18] .…”