Harden Scott W, Frazier Charles J
Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida.
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida.
Hippocampus. 2016 Sep;26(9):1124-39. doi: 10.1002/hipo.22595. Epub 2016 May 2.
Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT-Rs) is currently being investigated as a potential treatment for conditions such as post-traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT-R but lie outside of the hypothalamus (where OXT-synthesizing neurons reside). We report that bath application of low concentrations of the selective OXT-R agonist Thr4,Gly7-OXT (TGOT) reliably and robustly drives GABA release in the dentate gyrus in an action potential dependent manner. Additional experiments led to identification of a small subset of small hilar interneurons that are directly depolarized by acute application of TGOT. From a physiological perspective, TGOT-responsive hilar interneurons have high input resistance, rapid repolarization velocity during an action potential, and a robust afterhyperpolarization. Further, they fire irregularly (or stutter) in response to moderate depolarization, and fire quickly with minimal spike frequency accommodation in response to large current injections. From an anatomical perspective, TGOT responsive hilar interneurons have dense axonal arborizations in the hilus that were found in close proximity with mossy cell somata and/or proximal dendrites, and also invade the granule cell layer. Further, they have primary dendrites that always extend into the granule cell layer, and sometimes have clear arborizations in the molecular layer. Overall, these data reveal a novel site of action for OXT in an important limbic circuit, and represent a significant step towards better understanding how endogenous OXT may modulate flow of information in hippocampal networks. © 2016 Wiley Periodicals, Inc.
目前，将外源性催产素（OXT）输送至中枢催产素受体（OXT-Rs）正作为创伤后应激障碍（PTSD）、抑郁症、社交焦虑症和自闭症谱系障碍（ASD）等疾病的一种潜在治疗方法进行研究。尽管有大量研究表明中枢OXT信号传导参与情绪、情感、社会行为和应激反应的调节，但对于这些复杂行为背后的细胞和突触机制，尤其是在表达OXT-R但位于下丘脑之外（OXT合成神经元所在部位）的脑区，人们了解相对较少。我们报告称，在齿状回中，浴用低浓度的选择性OXT-R激动剂Thr4,Gly7-OXT（TGOT）以动作电位依赖的方式可靠且强劲地驱动GABA释放。进一步的实验确定了一小部分小的海马门区中间神经元，它们在急性应用TGOT时会直接去极化。从生理学角度来看，对TGOT有反应的海马门区中间神经元具有高输入电阻、动作电位期间快速复极化速度以及强劲的超极化后电位。此外，它们在中等程度去极化时不规则放电（或结巴放电），在大电流注入时以最小的放电频率适应快速放电。从解剖学角度来看，对TGOT有反应的海马门区中间神经元在海马门区有密集的轴突分支，这些分支与苔藓细胞胞体和/或近端树突紧密相邻，并且还侵入颗粒细胞层。此外，它们的初级树突总是延伸到颗粒细胞层，有时在分子层有清晰的分支。总体而言，这些数据揭示了OXT在一个重要边缘回路中的新作用位点，代表了朝着更好地理解内源性OXT如何调节海马网络中信息流迈出的重要一步。© 2016威利期刊公司
