Release of the neuromodulator noradrenaline signals salience during wakefulness, flagging novel or important experiences to reconfigure information processing and memory representations in the hippocampus. Noradrenaline is therefore expected to enhance hippocampal responses to synaptic input; however, noradrenergic agonists have been found to have mixed and sometimes contradictory effects on Schaffer collateral synapses and the resulting CA1 output. Here, we examine the effects of endogenous, optogenetically driven noradrenaline release on synaptic transmission and spike output in mouse hippocampal CA1 pyramidal neurons. We show that endogenous noradrenaline release enhances the probability of CA1 pyramidal neuron spiking without altering feedforward excitatory or inhibitory synaptic inputs in the Schaffer collateral pathway. β-adrenoceptors mediate this enhancement of excitation-spike coupling by reducing the charge required to initiate action potentials, consistent with noradrenergic modulation of voltage-gated potassium channels. Furthermore, we find the likely effective concentration of endogenously released noradrenaline is sub-micromolar. Surprisingly, although comparable concentrations of exogenous noradrenaline cause robust depression of slow afterhyperpolarization currents, endogenous release of noradrenaline does not, indicating that endogenous noradrenaline release is targeted to specific cellular locations. These findings provide a mechanism by which targeted endogenous release of noradrenaline can enhance information transfer in the hippocampus in response to salient events.

中文翻译：

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从海马蓝斑终端释放去甲肾上腺素通过 β-肾上腺素能受体增强 CA1 锥体神经元的兴奋-尖峰耦合。

神经调节剂去甲肾上腺素的释放在清醒期间发出显着信号，标记新的或重要的经验，以重新配置海马体中的信息处理和记忆表征。因此，去甲肾上腺素有望增强海马对突触输入的反应；然而，已发现去甲肾上腺素能激动剂对 Schaffer 侧支突触和由此产生的 CA1 输出具有混合且有时相互矛盾的影响。在这里，我们研究了内源性、光遗传学驱动的去甲肾上腺素释放对小鼠海马 CA1 锥体神经元突触传递和尖峰输出的影响。我们表明内源性去甲肾上腺素释放增加了 CA1 锥体神经元尖峰的可能性，而不会改变 Schaffer 侧支通路中的前馈兴奋性或抑制性突触输入。β-肾上腺素能受体通过减少启动动作电位所需的电荷来介导这种激发-尖峰耦合的增强，这与电压门控钾通道的去甲肾上腺素能调节一致。此外，我们发现内源性释放的去甲肾上腺素的可能有效浓度为亚微摩尔。令人惊讶的是，虽然相当浓度的外源性去甲肾上腺素会导致缓慢后超极化电流的强烈抑制，但去甲肾上腺素的内源性释放不会，这表明内源性去甲肾上腺素释放针对特定的细胞位置。这些发现提供了一种机制，通过该机制，去甲肾上腺素的靶向内源性释放可以增强海马中响应显着事件的信息传递。