Jedema Hank P, Grace Anthony A
Department of Neuroscience, University of Pittsburgh, PA 15260, USA.
Neuropsychopharmacology. 2003 Jan;28(1):63-72. doi: 10.1038/sj.npp.1300020.
Chronic stress exposure can alter central noradrenergic function. Previously, we reported that in chronically cold-exposed rats the release of norepinephrine and electrophysiological activation of locus coeruleus (LC) neurons is enhanced in response to multiple excitatory stimuli without alterations in basal activity. In the present studies, we used in vitro intracellular recording techniques to explore the effect of chronic cold exposure on the basal and evoked electrophysiological properties of LC neurons in horizontal slices of the rat brainstem. Consistent with our findings from in vivo experiments, chronic cold exposure did not affect basal firing rate. Furthermore, gross morphology of LC neurons and spike waveform characteristics were similar in slices from control and previously cold-exposed rats. However, excitability in response to intracellular current injection and input resistance were larger in slices from previously cold-exposed rats. In addition, the accommodation of spike firing in response to sustained current injection was smaller and the period of postactivation inhibition appeared to be less in LC neurons from cold-exposed rats. These data demonstrate that the stress-evoked sensitization of LC neurons observed in vivo is at least in part maintained in the slice preparation and suggest that alterations in electrophysiological properties of LC neurons contribute to the chronic stress-induced sensitization of central noradrenergic function observed in vivo. Furthermore, the present data suggest that an alteration in autoinhibitory control of LC activity is involved in the chronic stress-induced alterations. The enhanced functional capacity of LC neurons following cold exposure of rats may represent a unique model to study the mechanisms underlying the alterations in central noradrenergic function observed in humans afflicted with mood and anxiety disorders.
长期暴露于应激环境会改变中枢去甲肾上腺素能功能。此前，我们报道过，在长期处于寒冷环境的大鼠中，去甲肾上腺素的释放以及蓝斑（LC）神经元的电生理激活在受到多种兴奋性刺激时会增强，而基础活动并无改变。在本研究中，我们使用体外细胞内记录技术，探究长期寒冷暴露对大鼠脑干水平切片中LC神经元的基础电生理特性和诱发电生理特性的影响。与我们体内实验的结果一致，长期寒冷暴露并未影响基础放电频率。此外，对照大鼠和先前暴露于寒冷环境的大鼠的切片中，LC神经元的大体形态和动作电位波形特征相似。然而，先前暴露于寒冷环境的大鼠的切片中，对细胞内电流注入的兴奋性和输入电阻更大。此外，暴露于寒冷环境的大鼠的LC神经元对持续电流注入的动作电位发放适应性较小，激活后抑制期似乎也较短。这些数据表明，在体内观察到的LC神经元应激诱发的敏化现象至少部分在切片制备中得以维持，这表明LC神经元电生理特性的改变有助于体内观察到的慢性应激诱导的中枢去甲肾上腺素能功能敏化。此外，目前的数据表明，LC活动的自身抑制控制改变参与了慢性应激诱导的改变。大鼠寒冷暴露后LC神经元功能能力的增强可能代表了一个独特的模型，用于研究在患有情绪和焦虑障碍的人类中观察到的中枢去甲肾上腺素能功能改变的潜在机制。
