Biomedical Sciences Department, Quinnipiac University Hamden, CT, USA ; Cold Spring Harbor Laboratory, Neuroscience Cold Spring Harbor, NY, USA ; Brookhaven National Laboratory, Medical Department Upton, NY, USA.
Brookhaven National Laboratory, Medical Department Upton, NY, USA ; Department of Neurobiology and Behavior, Stony Brook University Stony Brook, NY, USA.
Front Hum Neurosci. 2014 Feb 3;8:29. doi: 10.3389/fnhum.2014.00029. eCollection 2014.
Uncontrollable stress can have a profound effect on an organism's ability to respond effectively to future stressful situations. Behavior subsequent to uncontrollable stress can vary greatly between individuals, falling on a spectrum between healthy resilience and maladaptive learned helplessness. It is unclear whether dysfunctional brain activity during uncontrollable stress is associated with vulnerability to learned helplessness; therefore, we measured metabolic activity during uncontrollable stress that correlated with ensuing inability to escape future stressors. We took advantage of small animal positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose ((18)FDG) to probe in vivo metabolic activity in wild type Sprague Dawley rats during uncontrollable, inescapable, unpredictable foot-shock stress, and subsequently tested the animals response to controllable, escapable, predictable foot-shock stress. When we correlated metabolic activity during the uncontrollable stress with consequent behavioral outcomes, we found that the degree to which animals failed to escape the foot-shock correlated with increased metabolic activity in the lateral septum and habenula. When used a seed region, metabolic activity in the habenula correlated with activity in the lateral septum, hypothalamus, medial thalamus, mammillary nuclei, ventral tegmental area, central gray, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and rostromedial tegmental nucleus, caudal linear raphe, and subiculum transition area. Furthermore, the lateral septum correlated with metabolic activity in the preoptic area, medial thalamus, habenula, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and caudal linear raphe. Together, our data suggest a group of brain regions involved in sensitivity to uncontrollable stress involving the lateral septum and habenula.
无法控制的压力会对生物体有效应对未来压力情况的能力产生深远影响。在不可控压力后，个体的行为可能会有很大差异，从健康的适应力到适应不良的习得性无助。目前尚不清楚不可控压力期间大脑活动的功能障碍是否与易患习得性无助有关；因此，我们测量了不可控压力期间与随后无法逃避未来压力源相关的代谢活性。我们利用小动物正电子发射断层扫描 (PET) 和 2-脱氧-2-[(18)F]氟-D-葡萄糖 ((18)FDG) 来探测野生型 Sprague Dawley 大鼠在不可控、不可逃避、不可预测的足底电击应激期间的体内代谢活性，然后测试动物对可控、可逃避、可预测的足底电击应激的反应。当我们将不可控压力期间的代谢活性与随后的行为结果相关联时，我们发现动物未能逃脱足底电击的程度与外侧隔核和缰核的代谢活性增加相关。当使用种子区域时，缰核的代谢活性与外侧隔核、下丘脑、内侧丘脑、乳头体、腹侧被盖区、中央灰色、脚间核、导水管周围灰质、中缝背核、中缝背核和 rostromedial 中脑核、尾侧线性中脑核以及 subiculum 过渡区相关。此外，外侧隔核与视前区、内侧丘脑、缰核、脚间核、导水管周围灰质、中缝背核和尾侧线性中脑核的代谢活性相关。总的来说，我们的数据表明，一组涉及外侧隔核和缰核的大脑区域参与了对不可控压力的敏感性。
