Anacker Christoph, Scholz Jan, O'Donnell Kieran J, Allemang-Grand Rylan, Diorio Josie, Bagot Rosemary C, Nestler Eric J, Hen René, Lerch Jason P, Meaney Michael J
Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York; Columbia University, and Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York.
Mouse Imaging Centre, Hospital for Sick Children, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Biol Psychiatry. 2016 May 15;79(10):840-849. doi: 10.1016/j.biopsych.2015.08.009. Epub 2015 Aug 18.
We examined the neurobiological mechanisms underlying stress susceptibility using structural magnetic resonance imaging and diffusion tensor imaging to determine neuroanatomic differences between stress-susceptible and resilient mice. We also examined synchronized anatomic differences between brain regions to gain insight into the plasticity of neural networks underlying stress susceptibility.
C57BL/6 mice underwent 10 days of social defeat stress and were subsequently tested for social avoidance. For magnetic resonance imaging, brains of stressed (susceptible, n = 11; resilient, n = 8) and control (n = 12) mice were imaged ex vivo at 56 µm resolution using a T2-weighted sequence. We tested for behavior-structure correlations by regressing social avoidance z-scores against local brain volume. For diffusion tensor imaging, brains were scanned with a diffusion-weighted fast spin echo sequence at 78 μm isotropic voxels. Structural covariance was assessed by correlating local volume between brain regions.
Social avoidance correlated negatively with local volume of the cingulate cortex, nucleus accumbens, thalamus, raphe nuclei, and bed nucleus of the stria terminals. Social avoidance correlated positively with volume of the ventral tegmental area (VTA), habenula, periaqueductal gray, cerebellum, hypothalamus, and hippocampal CA3. Fractional anisotropy was increased in the hypothalamus and hippocampal CA3. We observed synchronized anatomic differences between the VTA and cingulate cortex, hippocampus and VTA, hippocampus and cingulate cortex, and hippocampus and hypothalamus. These correlations revealed different structural covariance between brain regions in susceptible and resilient mice.
Stress-integrative brain regions shape the neural architecture underlying individual differences in susceptibility and resilience to chronic stress.
我们使用结构磁共振成像和扩散张量成像来研究应激易感性背后的神经生物学机制，以确定应激易感小鼠和应激恢复力强的小鼠之间的神经解剖学差异。我们还研究了脑区之间同步的解剖学差异，以深入了解应激易感性背后神经网络的可塑性。
C57BL/6小鼠经历10天的社会挫败应激，随后进行社会回避测试。对于磁共振成像，使用T2加权序列以56微米分辨率对应激（易感，n = 11；恢复力强，n = 8）和对照（n = 12）小鼠的大脑进行离体成像。我们通过将社会回避z分数与局部脑体积进行回归来测试行为与结构的相关性。对于扩散张量成像，使用扩散加权快速自旋回波序列以78微米各向同性体素对大脑进行扫描。通过关联脑区之间的局部体积来评估结构协方差。
社会回避与扣带回皮质、伏隔核、丘脑、中缝核和终纹床核的局部体积呈负相关。社会回避与腹侧被盖区（VTA）、缰核、导水管周围灰质、小脑、下丘脑和海马CA3的体积呈正相关。下丘脑和海马CA3的分数各向异性增加。我们观察到VTA与扣带回皮质、海马与VTA、海马与扣带回皮质以及海马与下丘脑之间存在同步的解剖学差异。这些相关性揭示了易感小鼠和恢复力强的小鼠脑区之间不同的结构协方差。
应激整合脑区塑造了个体对慢性应激易感性和恢复力差异背后的神经结构。
