Background: Aluminum (Al) causes neurodegeneration and its toxic effects on cholinergic
system in the brain is well documented. However, it is unknown whether and how Al changes oscillation
patterns, driven by the cholinergic system, in the hippocampus.
Objective: We studied acute effects of Al on nicotinic acetylcholine receptors (nAChRs)-mediated
modulation of persistent gamma oscillations in the hippocampus.
Method: The field potential recording was done in CA3 area of acute hippocampal slices.
Results: Carbachol-induced gamma oscillation peak power increased (1.32±0.09mV2/Hz, P<0.01) in
control conditions (without Al) by application of 10µM nicotine as compared to baseline value normalized
to 1. This nicotine-induced facilitation of gamma oscillation peak power was found to depend
on non-α7 nAChRs. In slices with Al
pre-incubation for three to four hours, gamma oscillation peak
power was reduced (5.4±1.8mV2/Hz, P<0.05) and facilitatory effect of nicotine on gamma oscillation
peak power was blocked as compared to the control (18.06±2.1mV2/Hz) or one hour Al pre-incubated
slices (11.3±2.5mV2/Hz). Intriguingly wash-out, after three to four hours of Al incubation, failed to restore
baseline oscillation power and its facilitation by nicotine as no difference was observed in
gamma oscillation peak power between Al wash-out slices (3.4±1.1mV2/Hz) and slices without washout
Conclusion: This study shows that at cellular level, exposure of hippocampal tissue to Al compromised
nAChR-mediated facilitation of cholinergic hippocampal gamma oscillations. Longer in vitro
Al exposure caused permanent changes in hippocampal oscillogenic circuitry and changed its sensitivity
to nAChR-modulation. This study will help to understand the possible mechanism of cognitive decline
induced by Al.