Duffy S N, Craddock K J, Abel T, Nguyen P V
Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta T6G 2H7, Canada.
Learn Mem. 2001 Jan-Feb;8(1):26-34. doi: 10.1101/lm.36301.
cAMP-dependent protein kinase (PKA) is critical for the expression of some forms of long-term potentiation (LTP) in area CA1 of the mouse hippocampus and for hippocampus-dependent memory. Exposure to spatially enriched environments can modify LTP and improve behavioral memory in rodents, but the molecular bases for the enhanced memory performance seen in enriched animals are undefined. We tested the hypothesis that exposure to a spatially enriched environment may alter the PKA dependence of hippocampal LTP. Hippocampal slices from enriched mice showed enhanced LTP following a single burst of 100-Hz stimulation in the Schaffer collateral pathway of area CA1. In slices from nonenriched mice, this single-burst form of LTP was less robust and was unaffected by Rp-cAMPS, an inhibitor of PKA. In contrast, the enhanced LTP in enriched mice was attenuated by Rp-cAMPS. Enriched slices expressed greater forskolin-induced, cAMP-dependent synaptic facilitation than did slices from nonenriched mice. Enriched mice showed improved memory for contextual fear conditioning, whereas memory for cued fear conditioning was unaffected following enrichment. Our data indicate that exposure of mice to spatial enrichment alters the PKA dependence of LTP and enhances one type of hippocampus-dependent memory. Environmental enrichment can transform the pharmacological profile of hippocampal LTP, possibly by altering the threshold for activity-dependent recruitment of the cAMP-PKA signaling pathway following electrical and chemical stimulation. We suggest that experience-dependent plasticity of the PKA dependence of hippocampal LTP may be important for regulating the efficacy of hippocampus-based memory.
环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）对于小鼠海马体CA1区某些形式的长时程增强（LTP）的表达以及海马体依赖性记忆至关重要。暴露于空间丰富的环境中可改变啮齿动物的LTP并改善其行为记忆，但丰富环境下动物记忆增强的分子基础尚不清楚。我们检验了以下假设：暴露于空间丰富的环境可能会改变海马体LTP对PKA的依赖性。来自丰富环境饲养小鼠的海马切片在CA1区的Schaffer侧支通路接受单次100赫兹刺激后显示出增强的LTP。在来自非丰富环境饲养小鼠的切片中，这种单次爆发形式的LTP较弱，且不受PKA抑制剂Rp-cAMPS的影响。相比之下，丰富环境饲养小鼠中增强的LTP被Rp-cAMPS减弱。丰富环境饲养的切片比非丰富环境饲养的切片表现出更强的福斯可林诱导的、cAMP依赖性突触易化。丰富环境饲养的小鼠在情境恐惧条件反射方面表现出更好的记忆，而线索恐惧条件反射的记忆在丰富环境饲养后未受影响。我们的数据表明，小鼠暴露于空间丰富环境会改变LTP对PKA的依赖性，并增强一种海马体依赖性记忆。环境丰富可能通过改变电刺激和化学刺激后cAMP-PKA信号通路的活性依赖性募集阈值来改变海马体LTP的药理学特征。我们认为，海马体LTP对PKA依赖性的经验依赖性可塑性可能对调节基于海马体的记忆的效能很重要。
