Department of Biological Science, Program in Neuroscience, The Florida State University, Tallahassee, FL 32306, USA.
Brain Res. 2010 Aug 12;1348:84-94. doi: 10.1016/j.brainres.2010.06.029. Epub 2010 Jun 17.
Protein phosphatases (PPs) regulate many substrates implicated in learning and memory. Conditioned taste aversion (CTA) learning, in which animals associate a novel taste paired with a toxin and subsequently avoid the taste, is dependent on several serine/threonine phosphatase substrates and the PP1-binding protein spinophilin. In order to examine the effects of PP1/2A blockade on CTA acquisition and extinction, rats received bilateral infusions of okadaic acid (OA) (100nM, 1microl/hemisphere) or vehicle (0.15M NaCl) into the amygdala either 5min prior to, or 5min after, a single pairing of sodium saccharin (0.125%, 10-min access) and LiCl or NaCl (0.15M, 3ml/kg i.p.). Two-bottle, 24-h preference tests were conducted for 13days to measure CTA expression and extinction. Rats conditioned with saccharin and LiCl showed a decreased preference for saccharin, and OA administered before (but not after) the pairing of saccharin and LiCl resulted in a significantly stronger CTA that did not extinguish over 13days. The enhancement of the CTA was not due to aversive effects of OA, because rats given OA and a pairing of saccharin and NaCl did not acquire a CTA. Finally, OA administration increased levels of phosphorylated CREB immunoreactivity following a CTA trial. Together, these results suggest a critical role for PP1/2A during normal CTA learning. Because CTA learning was enhanced only when OA was given prior to conditioning, phosphatase activity may be a constraint on learning during the taste-toxin interval but not during acquisition and consolidation processes that occur after toxin administration.
蛋白磷酸酶（PPs）调节许多与学习和记忆有关的底物。条件性味觉厌恶（CTA）学习，即动物将一种新的味觉与毒素配对，并随后避免该味觉，依赖于几种丝氨酸/苏氨酸磷酸酶底物和 PP1 结合蛋白 spinophilin。为了研究 PP1/2A 阻断对 CTA 获得和消退的影响，大鼠在单次蔗糖（0.125%，10 分钟）与 LiCl 或 NaCl（0.15M，3ml/kg ip）配对之前或之后 5 分钟，将 okadaic acid（OA）（100nM，1μl/半脑）或载体（0.15M NaCl）双侧注入杏仁核。进行了为期 13 天的双瓶 24 小时偏好测试，以测量 CTA 表达和消退。用蔗糖和 LiCl 条件化的大鼠对蔗糖的偏好降低，而 OA 在前（而不是配对后）给予蔗糖和 LiCl 导致 CTA 明显增强，在 13 天内未消退。CTA 的增强不是由于 OA 的厌恶作用，因为给予 OA 和蔗糖与 NaCl 的配对不会产生 CTA。最后，OA 给药在 CTA 试验后增加了磷酸化 CREB 免疫反应性的水平。总之，这些结果表明 PP1/2A 在正常 CTA 学习中起着关键作用。因为只有在 OA 给予条件化之前给予 OA 时才增强 CTA 学习，所以磷酸酶活性可能是在味觉 - 毒素间隔期间学习的限制，但不是在毒素给药后发生的获得和巩固过程中。
