NAChR Activation-Induced Long Term Oscillation In Hippocampus

Objective To explore the mechanism of nAChR activation induced long term oscillation for the better understanding of its contribution to learning and memory functions and for the building a basis of possible clinical application of nAChR agonists.Methods Recording of neural network oscillation:(1) In vitro brain slices were perfused with the artificial cerebrospinal fluid bubbled with a gas mixture containing95%O2+5%CO2and (flow rate:1.5ml/min, pH:7.35-7.45) in the interface perfusion system (30℃-32℃).(2) SD rats,3-4weeks, was anesthetized by0.3%chloral hydrate i.p.. cerebrospinal fluid containing cold sucrose (1-4℃) was perfused in the interior of the heart until the limbs become white. The brain was removed quickly and the horizontal hippocampal slices (350μm-450μm) were cut using LEICA VT1000S vibrating slicer.(3) Hippocampal slices were put in an interface perfused bath-style groove for one hour and the extracellular field potentials were recorded. KA(200nM)was used to induce Gamma (30-80Hz) frequency oscillations and the effects of nAChR agonists and antagonists on y oscillations were studied.(4) Data analysis:Off-line data analysis using Spike2software was performed. Statistical software SigmaStat was used for Statistical analysis. Statistical methods of paired t-test before and after treatment (paired t-test or signed rank test) or repeated measures analysis of variance (Repeated measures, One-way ANOVA or Repeated measures on ranks). Results presented as mean±standard deviation. If P value≤0.05, the measurement is considered to be statistically significant.Result1.nAChR activation induced LTO in rat hippocampal slices;2. Glutamate ionotropic NMDA receptor is involved in the nicotine-induced LTO;3. Nicotine-induced LTO can be regulated by excitatory and inhibitory neurotransmis-sion; 4. The selective α4β2nAChR agonist mimics nicotine induction of LTO;5. Nicotine-pretreatment enhanced KA-induced γ oscillations with a two-step increase, but failed to induce LTO.Conclusion1. nAChR activation induced LTO representing a form of synaptic plasticity;2. LTO is mainly caused by the selective α4β2nAChR activation.