Section Neurophysiology and Neuroinformatics, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, 6500 HB, Netherlands.
Exp Brain Res. 2010 Jan;200(2):151-9. doi: 10.1007/s00221-009-1955-6. Epub 2009 Jul 31.
Norepinephrine has been hypothesized to provide a learning and memory signal. Norepinephrine long-term potentiation of perforant path input to the dentate gyrus of the hippocampus provides a model for norepinephrine initiated memory processes. However, in vitro, the pairing of perforant path stimulation and norepinephrine is not required for the occurrence of norepinephrine-dependent long-term potentiation. Since bath application of norepinephrine induces long-term changes in 2nd messenger signalling and differs in a number of ways from physiological norepinephrine release, the present study is an in vivo test of the associative requirement for the pairing of perforant path input with norepinephrine to induce long-term potentiation. Phasic activation of the locus coeruleus is provided by glutamate infusion into the locus coeruleus to initiate transient norepinephrine release in the hippocampus of urethane-anesthetized Sprague-Dawley rats. Perforant path stimulation (0.067 Hz) was given throughout the experiment in the paired condition. In the unpaired condition perforant path stimulation was interrupted 10 min prior to locus coeruleus activation and resumed 10 min after locus coeruleus activation. Locus coeruleus-induced long-term potentiation of both EPSP slope and population spike only occurred in the pairing condition. This result argues that, in vivo, temporal proximity of locus coeruleus-associated norepinephrine release and perforant path stimulation are required to induce long-term plasticity. The associativity requirement for locus coeruleus activation and perforant path stimulation in vivo is consistent with the hypothesis that norepinephrine can initiate circuit changes supporting learning and memory.
去甲肾上腺素被假设为提供学习和记忆信号。海马齿状回的穿通纤维输入的去甲肾上腺素长时程增强提供了去甲肾上腺素引发的记忆过程的模型。然而，在体外，穿通纤维刺激和去甲肾上腺素的配对对于发生去甲肾上腺素依赖性长时程增强不是必需的。由于去甲肾上腺素的浴内应用诱导第二信使信号的长期变化，并且在许多方面与生理去甲肾上腺素释放不同，因此本研究是对穿通纤维输入与去甲肾上腺素配对以诱导长时程增强的关联要求的体内测试。通过将谷氨酸注入蓝斑核来短暂激活蓝斑核，以在乌拉坦麻醉的 Sprague-Dawley 大鼠的海马中引发短暂的去甲肾上腺素释放。在配对条件下，整个实验过程中都给予穿通纤维刺激（0.067 Hz）。在未配对条件下，在蓝斑核激活前 10 分钟中断穿通纤维刺激，并在蓝斑核激活后 10 分钟恢复。只有在配对条件下，才会发生蓝斑核诱导的 EPSP 斜率和群体峰长时程增强。这一结果表明，在体内，蓝斑核相关去甲肾上腺素释放和穿通纤维刺激的时间接近是诱导长时可塑性所必需的。体内蓝斑核激活和穿通纤维刺激的关联性要求与去甲肾上腺素可以引发支持学习和记忆的电路变化的假设一致。
