Hardingham Neil, Wright Nick, Dachtler James, Fox Kevin
School of Bioscience, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK.
Neuron. 2008 Dec 10;60(5):861-74. doi: 10.1016/j.neuron.2008.10.018.
Calcium/calmodulin kinase II (CaMKII) is required for LTP and experience-dependent potentiation in the barrel cortex. Here, we find that whisker deprivation increases LTP in the layer IV to II/III pathway and that PKA antagonists block the additional LTP. No LTP was seen in undeprived CaMKII-T286A mice, but whisker deprivation again unmasked PKA-sensitive LTP. Infusion of a PKA agonist potentiated EPSPs in deprived wild-types and deprived CaMKII-T286A point mutants but not in undeprived animals of either genotype. The PKA-dependent potentiation mechanism was not present in GluR1 knockouts. Infusion of a PKA antagonist caused depression of EPSPs in undeprived but not deprived cortex. LTD was occluded by whisker deprivation and blocked by PKA manipulation, but not blocked by cannabinoid antagonists. NMDA receptor currents were unaffected by sensory deprivation. These results suggest that sensory deprivation causes synaptic depression by reversing a PKA-dependent process that may act via GluR1.
钙/钙调蛋白激酶II（CaMKII）是桶状皮层中长时程增强（LTP）和经验依赖性增强所必需的。在此，我们发现触须剥夺会增加IV层到II/III层通路中的LTP，并且蛋白激酶A（PKA）拮抗剂可阻断额外的LTP。在未剥夺触须的CaMKII-T286A小鼠中未观察到LTP，但触须剥夺再次揭示了PKA敏感的LTP。向剥夺触须的野生型和剥夺触须的CaMKII-T286A点突变体中注入PKA激动剂可增强兴奋性突触后电位（EPSP），但在两种基因型的未剥夺动物中则不然。PKA依赖性增强机制在谷氨酸受体1（GluR1）基因敲除小鼠中不存在。向未剥夺触须但非剥夺触须的皮层中注入PKA拮抗剂会导致EPSP降低。长时程抑制（LTD）被触须剥夺所阻断，并被PKA操作所阻断，但未被大麻素拮抗剂所阻断。N-甲基-D-天冬氨酸（NMDA）受体电流不受感觉剥夺的影响。这些结果表明，感觉剥夺通过逆转可能经由GluR1起作用且依赖PKA的过程导致突触抑制。
