Francis T C, Chandra R, Gaynor A, Konkalmatt P, Metzbower S R, Evans B, Engeln M, Blanpied T A, Lobo M K
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA.
Division of Renal Diseases and Hypertension, The George Washington University, Washington, DC, USA.
Mol Psychiatry. 2017 Nov;22(11):1512-1519. doi: 10.1038/mp.2017.178. Epub 2017 Sep 12.
Molecular and cellular adaptations in nucleus accumbens (NAc) medium spiny neurons (MSNs) underlie stress-induced depression-like behavior, but the molecular substrates mediating cellular plasticity and activity in MSN subtypes in stress susceptibility are poorly understood. We find the transcription factor early growth response 3 (EGR3) is increased in D1 receptor containing MSNs of mice susceptible to social defeat stress. Genetic reduction of Egr3 levels in D1-MSNs prevented depression-like outcomes in stress susceptible mice by preventing D1-MSN dendritic atrophy, reduced frequency of excitatory input and altered in vivo activity. Overall, we identify NAc neuronal-subtype molecular control of dendritic morphology and related functional adaptations, which underlie susceptibility to stress.
伏隔核（NAc）中等多棘神经元（MSNs）的分子和细胞适应性是应激诱导的抑郁样行为的基础，但介导应激易感性中MSN亚型细胞可塑性和活性的分子底物尚不清楚。我们发现，在易受社会挫败应激影响的小鼠的含D1受体的MSNs中，转录因子早期生长反应3（EGR3）增加。通过防止D1-MSN树突萎缩、降低兴奋性输入频率和改变体内活性，降低D1-MSNs中Egr3水平可预防应激易感小鼠出现抑郁样结果。总体而言，我们确定了NAc神经元亚型对树突形态和相关功能适应性的分子控制，这是应激易感性的基础。
