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首页> 外文期刊>The European Journal of Neuroscience >Axonal projection-specific differences in somatodendritic alpha 2 autoreceptor function in locus coeruleus neurons
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Axonal projection-specific differences in somatodendritic alpha 2 autoreceptor function in locus coeruleus neurons

机译：在洛杉矶植物群神经元的索马托替塞alpha 2自身反应功能的轴突投射特异性差异

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The locus coeruleus (LC) contains the majority of central noradrenergic neurons sending wide projections throughout the entire CNS. The LC is considered to be essential for multiple key brain functions including arousal, attention and adaptive stress responses as well as higher cognitive functions and memory. Electrophysiological studies of LC neurons have identified several characteristic functional features such as low-frequency pacemaker activity with broad action potentials, transient high-frequency burst discharges in response to salient stimuli and an apparently homogeneous inhibition of firing by activation of somatodendritic alpha 2 autoreceptors (alpha 2AR). While stress-mediated plasticity of the alpha 2AR response has been described, it is currently unclear whether different LC neurons projecting to distinct axonal targets display differences in alpha 2AR function. Using fluorescent beads-mediated retrograde tracing in adult C57Bl6/N mice, we compared the anatomical distributions and functional in vitro properties of identified LC neurons projecting either to medial prefrontal cortex, hippocampus or cerebellum. The functional in vitro analysis of LC neurons confirmed their mostly uniform functional properties regarding action potential generation and pacemaker firing. However, we identified significant differences in tonic and evoked alpha 2AR-mediated responses. While hippocampal-projecting LC neurons were partially inhibited by endogenous levels of norepinephrine and almost completely silenced by application of saturating concentrations of the alpha 2 agonist clonidine, prefrontal-projecting LC neurons were not affected by endogenous levels of norepinephrine and only partially inhibited by saturating concentrations of clonidine. Thus, we identified a limited alpha 2AR control of electrical activity for prefrontal-projecting LC neurons indicative of functional heterogeneity in the LC-noradrenergic system.
机译：基因座Coeruleus（LC）含有大多数中部的诺肾肾上腺素神经元，在整个CNS中发送宽的投影。 LC被认为对于多个关键大脑功能至关重要，包括唤醒，关注和自适应应力响应以及更高的认知功能和记忆。 LC神经元的电生理学研究已经确定了几种特征功能特征，例如具有广泛动作电位的低频起搏器活动，瞬态高频爆发响应于突出刺激和通过激活Sematodendriticα吸腹剂的显然均匀抑制（Alpha 2ar）。虽然已经描述了α2AR反应的应激介导的可塑性，但目前目前不清楚不同的LC神经元是否突出到不同的轴突靶标在α2AR功能中显示差异。在成人C57BL6 / n小鼠中使用荧光珠介导的逆行跟踪，我们将鉴定的LC神经元的解剖分布和功能性的体外特性进行了比较，该鉴定的LC神经元突出为内侧前额叶皮质，海马或小脑。 LC神经元的功能性体外分析证实了关于作用潜在发电和起搏器烧制的主要功能性质。然而，我们确定了滋补和诱发α2AR介导的反应的显着差异。虽然通过施加饱和浓度的α2激动剂克拿尼金属的内源性水平的内源性水平而部分地抑制了海马突出的LC神经元，但突出的突出的LC神经元不受脱甲肾上腺素的内源性水平的影响，并且仅通过饱和浓度部分抑制Clonidine。因此，我们鉴定了对LC-丙肾上腺素能系统中功能异质性的前额相突出的LC神经元的有限α2AR控制。

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