Shansky Rebecca M, Hamo Carine, Hof Patrick R, McEwen Bruce S, Morrison John H
Department of Neuroscience Mount Sinai School of Medicine, New York, NY 10029, USA.
Cereb Cortex. 2009 Oct;19(10):2479-84. doi: 10.1093/cercor/bhp003. Epub 2009 Feb 4.
Chronic stress exposure has been reported to induce dendritic remodeling in several brain regions, but it is not known whether individual neural circuits show distinct patterns of remodeling. The current study tested the hypothesis that the projections from the infralimbic (IL) area of the medial prefrontal cortex (mPFC) to the basolateral nucleus of the amygdala (BLA), a pathway relevant to stress-related mental illnesses like depression and post-traumatic stress disorder, would have a unique pattern of remodeling in response to chronic stress. The retrograde tracer FastBlue was injected into male rats' BLA or entorhinal cortex (EC) 1 week prior to 10 days of immobilization stress. After cessation of stress, FastBlue-labeled and unlabeled IL pyaramidal neurons were loaded with fluorescent dye Lucifer Yellow to visualize dendritic arborization and spine density. As has been previously reported, randomly selected (non-FastBlue-labeled) neurons showed stress-induced dendritic retraction in apical dendrites, an effect also seen in EC-projecting neurons. In contrast, BLA-projecting neurons showed no remodeling with stress, suggesting that this pathway may be particularly resilient against the effects of stress. No neurons showed stress-related changes in spine density, contrasting with reports that more dorsal areas of the mPFC show stress-induced decreases in spine density. Such region- and circuit-specificity in response to stress could contribute to the development of stress-related mental illnesses.
据报道,长期暴露于应激会在多个脑区诱导树突重塑,但尚不清楚单个神经回路是否呈现出不同的重塑模式。当前研究检验了以下假设:内侧前额叶皮质(mPFC)腹内侧前额叶(IL)区域向杏仁核基底外侧核(BLA)的投射,这一与抑郁症和创伤后应激障碍等应激相关精神疾病相关的通路,在应对慢性应激时会有独特的重塑模式。在对雄性大鼠进行为期10天的束缚应激前1周,将逆行示踪剂快蓝注入其BLA或内嗅皮质(EC)。应激停止后,用荧光染料路西法黄标记快蓝标记和未标记的IL锥体神经元,以观察树突分支和棘密度。如先前报道,随机选择的(非快蓝标记的)神经元在顶端树突中表现出应激诱导的树突回缩,在投射至EC的神经元中也观察到了这种效应。相比之下,投射至BLA的神经元在应激时未表现出重塑,这表明该通路可能对应激影响具有特别的抵抗力。没有神经元表现出与应激相关的棘密度变化,这与mPFC更多背侧区域应激诱导棘密度降低的报道形成对比。这种对应激的区域和回路特异性可能有助于应激相关精神疾病的发展。