Acta Pharmacologica Sinica (2009) 30: 859-867; doi: 10.1038/aps.2009. 66

Aim: Hippocampal neuronal network and synaptic impairment underlie learning and memory deficit in Alzheimer’s disease (AD) patients and animal models.  In this paper, we analyzed the dynamics and complexity of hippocampal neuronal network synchronization induced by acute exposure to carbachol, a nicotinic and muscarinic receptor co-agonist, using the nonlinear dynamical model based on the Lempel-Ziv estimator.  We compared the dynamics of hippocampal oscillations between wild-type (WT) and triple-transgenic (3xTg) mice, as an AD animal model.  We also compared these dynamic alterations between different age groups (5 and 10 months).  We hypothesize that there is an impairment of complexity of CCh-induced hippocampal oscillations in 3xTg AD mice compared to WT mice, and that this impairment is age-dependent.

Methods: To test this hypothesis, we used electrophysiological recordings (field potential) in hippocampal slices.

Results: Acute exposure to 100 µmol/L CCh induced field potential oscillations in hippocampal CA1 region, which exhibited three distinct patterns: (1) continuous neural firing, (2) repeated burst neural firing and (3) the mixed (continuous and burst) pattern in both WT and 3xTg AD mice.  Based on Lempel-Ziv estimator, pattern (2) was significantly lower than patterns (1) and (3) in 3xTg AD mice compared to WT mice (P<0.001), and also in 10-month old WT mice compared to those in 5-month old WT mice (P<0.01).

Conclusion: These results suggest that the burst pattern (theta oscillation) of hippocampal network is selectively impaired in 3xTg AD mouse model, which may reflect a learning and memory deficit in the AD patients.

Keywords: hippocampus; oscillations; carbachol; Lempel-Ziv complexity; 3xTg AD mice; electrophysiology