Interdisciplinary Program in Neuroscience, Florida Atlantic University, Boca Raton, FL 33431-0991, USA.
Neuropharmacology. 2010 Mar;58(3):650-9. doi: 10.1016/j.neuropharm.2009.11.008. Epub 2009 Nov 24.
Small conductance Ca(2+)-activated K(+) channels (SK, K(Ca2.1), K(Ca2.2), K(Ca2.3)) are expressed at high levels in brain regions critical for learning and memory. The activation of dendritic SK channels limits the induction of synaptic plasticity that may underlie hippocampal and amygdala dependent memory. EBIO facilitates SK channel activation by increasing their sensitivity to calcium. The compound CyPPA selectively activates SK2 and SK3 channels in a similar manner. To date there has been no report of the effects of SK channel activators on memory. Therefore, the present study examined the effects of systemic EBIO on mice in a behavioral task battery. Significant effects of EBIO on memory and motor activity were validated and extended by examining the effects of systemic CyPPA. Systemic EBIO and CyPPA both produced a transient decline in locomotor behavior. Neither SK channel activator affected anxiety. EBIO (17.5 mg/kg) impaired the encoding, but not retrieval, of object memory in a spontaneous object recognition task. A similar impairment of object memory encoding was observed in CyPPA (15 mg/kg)-treated mice. These memory-impairing effects were not due to changes in motivation, attention or movement. Systemic EBIO did not affect contextual or cued fear memory after conditioning with a 3 tone (CS)-footshock (US) pairing protocol or a 1 CS-US pairing protocol. Interestingly, apamin (0.4 mg/kg) enhanced contextual fear memory in mice conditioned with a 1 CS-US pairing protocol. These results suggest that SK channel activation impairs the encoding of non-aversive memory but not memory for aversive events. These data support converging evidence that SK channels regulate cellular mechanisms of memory encoding.
小电导钙激活钾通道（SK，K（Ca2.1），K（Ca2.2），K（Ca2.3））在学习和记忆关键脑区高表达。树突 SK 通道的激活限制了突触可塑性的诱导，而突触可塑性可能是海马和杏仁核依赖记忆的基础。EBIO 通过增加其对钙的敏感性来促进 SK 通道的激活。化合物 CyPPA 以类似的方式选择性地激活 SK2 和 SK3 通道。迄今为止，尚无关于 SK 通道激活剂对记忆影响的报道。因此，本研究在行为任务组中检查了全身给予 EBIO 对小鼠的影响。通过检查全身给予 CyPPA 的影响，验证并扩展了 EBIO 对记忆和运动活动的影响。全身给予 EBIO 和 CyPPA 都会导致运动行为短暂下降。两种 SK 通道激活剂均不影响焦虑。EBIO（17.5mg/kg）在自发物体识别任务中损害了物体记忆的编码，但不损害其检索。在 CyPPA（15mg/kg）处理的小鼠中也观察到了类似的物体记忆编码损伤。这些记忆损伤效应不是由于动机、注意力或运动的变化引起的。在使用 3 个音调（CS）-电击（US）配对方案或 1 个 CS-US 配对方案进行条件作用后，全身给予 EBIO 不会影响上下文或线索恐惧记忆。有趣的是，在使用 1 个 CS-US 配对方案进行条件作用后，apamin（0.4mg/kg）增强了小鼠的上下文恐惧记忆。这些结果表明，SK 通道的激活会损害非厌恶记忆的编码，但不会损害对厌恶事件的记忆。这些数据支持了 SK 通道调节记忆编码细胞机制的证据。
