Centre for Neuroendocrinology, Department of Physiology, University of Otago, Dunedin, New Zealand.
Centre for Neuroendocrinology, Department of Physiology, University of Otago, Dunedin, New Zealand.
Neuropharmacology. 2019 Aug;154:79-86. doi: 10.1016/j.neuropharm.2019.02.017. Epub 2019 Feb 13.
Corticosteroid stress hormones drive a multitude of adaptations in the brain. Hypothalamic corticotropin-releasing hormone (CRH) neurons control the circulating levels of corticosteroid stress hormones in the body and are themselves highly sensitive to corticosteroids. CRH neurons have been shown to undergo various adaptions in response to acute stress hormone elevations. However, their structural and physiological changes under chronically elevated corticosterone are less clear. To address this, we determined the structural and functional changes in CRH neurons in the paraventricular nucleus of the hypothalamus following 14 days of corticosterone treatment. We find that prolonged corticosterone elevation reduces CRH neuron intrinsic excitability as measured by summation of subthreshold postsynaptic depolarisations and spiking output. We find that under normal conditions, CRH neurons have a relatively compact and simple dendritic arbor, with a low density of somatic and dendritic spines. Interestingly, the axon originated from a proximal dendrite close to the soma in approximately half of the CRH neurons reconstructed. While prolonged elevation in corticosterone levels did not result in any changes to gross dendritic morphology, it induced a significant reduction in both somatic and dendritic spine density. Together these data reveal the morphological features of hypothalamic CRH neurons and highlight their capacity to undergo functional and morphological plasticity in response to chronic corticosterone elevations. This article is part of the Special Issue entitled 'Hypothalamic Control of Homeostasis'.
皮质甾类应激激素驱动大脑的多种适应性变化。下丘脑促肾上腺皮质激素释放激素（CRH）神经元控制着体内皮质甾类应激激素的循环水平，它们本身对皮质甾类物质高度敏感。已经证明，CRH 神经元会对急性应激激素升高做出各种适应。然而，它们在慢性升高的皮质酮下的结构和生理变化尚不清楚。为了解决这个问题，我们确定了下丘脑室旁核中 CRH 神经元在皮质酮处理 14 天后的结构和功能变化。我们发现，长期皮质酮升高会降低 CRH 神经元的内在兴奋性，这可以通过测量亚阈突触后去极化和尖峰输出的总和来衡量。我们发现，在正常情况下，CRH 神经元的树突具有相对紧凑和简单的形态，体细胞和树突棘的密度较低。有趣的是，在大约一半重建的 CRH 神经元中，轴突起源于靠近体的近端树突。虽然皮质酮水平的长期升高并没有导致树突形态的任何变化，但它导致体细胞和树突棘密度显著降低。这些数据共同揭示了下丘脑 CRH 神经元的形态特征，并强调了它们在应对慢性皮质酮升高时具有功能和形态可塑性的能力。本文是特刊“下丘脑对稳态的控制”的一部分。
