Objective To characterize the function of a new xanomeline-derived M 1 agonist, 3-[3-（3-florophenyl-2-propyn- 1- ylthio）-1,2,5-thiadiazol-4-yl]-1,2,5,6- tetrahydro-1-methylpyridine Oxalate （EUK1001）, the acute toxicity and the effects on synaptic plasticity and cognition of EUK1001 were evaluated. Methods To examine the median lethal dose （LD50） of EUK1001, a wide dose range of EUK1001 was administered by p.o. and i.p. in aged mice. Furthermore, novel object recognition task and in vitro electrophysiological technique were utilized to investigate the effects of EUK1001 on recognition memory and hippocampal synaptic plasticity in aged mice. Results EUK1001 exhibited lower toxicity than xanomeline, and improved the performance of aged mice in the novel object recognition test. In addition, bath application of 1 μmol/L EUK1001 directly induced long-term potentiation in the hippocampus slices. Conclusion We conclude that EUK1001 can improve the agerelated cognitive deficits.
目的:探讨触觉刺激对触觉注意的影响,以揭示选择性注意的机制。方法:利用在体电生理记录技术,记录了288个丘脑腹侧基底核(ventrobasal nuleus of thalamus,VB)神经元放电活动,并着重考察了不同强度触觉刺激对丘脑神经元细胞自发放电活动的影响。结果发现:触觉刺激对大部分的触觉神经元的自发放电活动均有抑制性影响。提示触觉刺激降低背景噪声可能是触发选择性触觉注意的神经机制。
