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.
Objective To determine whether the convergences of tactile information also occur at thalamic ventroposterolateral nucleus in rats, we investigated the properties of tactile responses of the thalamic ventroposterolateral nucleus in rats. Methods Unit responses were recorded extracellularly from thalamic ventroposterolateral nucleus in anesthetized rats. Results Among 156 neurons examined, 140 neurons （89.7%） had the single, continual and small receptive fields, and 16 neurons （10.3%） had two discrete receptive fields. Some neurons exhibited different responses to the same intensity stimulation which delivered to different points in their receptive fields. In addition, 4.5% neurons （n -- 7） responded only to locomotive stimulation but not to a punctiform tactile stimulation. Conclusion The majority of neurons in ventroposterolateral nucleus of rats have the spatial, temporal and submodal characteristics of cutaneous receptors, while the minority of neurons exhibit the responses of interaction of different peripheral receptors. Therefore, it is con- cluded that there are convergences of tactile information at the ventroposterolateral nucleus of rats.
