Spyrka Jadwiga, Gugula Anna, Rak Agnieszka, Tylko Grzegorz, Hess Grzegorz, Blasiak Anna
Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, 30-387, Krakow, Poland.
Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, 30-387, Krakow, Poland.
Neurobiol Stress. 2020 Sep 3;13:100250. doi: 10.1016/j.ynstr.2020.100250. eCollection 2020 Nov.
Childhood maltreatment, which can take the form of physical or psychological abuse, is experienced by more than a quarter of all children. Early life stress has substantial and long-term consequences, including an increased risk of drug abuse and psychiatric disorders in adolescence and adulthood, and this risk is higher in women than in men. The neuronal mechanisms underlying the influence of early life adversities on brain functioning remain poorly understood; therefore, in the current study, we used maternal separation (MS), a rodent model of early-life neglect, to verify its influence on the properties of neurons in the ventral tegmental area (VTA), a brain area critically involved in reward and motivation processing. Using whole-cell patch-clamp recordings in brain slices from adolescent female Sprague-Dawley rats, we found an MS-induced increase in the excitability of putative dopaminergic (DAergic) neurons selectively in the medial part of the VTA. We also showed an enhancement of excitatory synaptic transmission in VTA putative DAergic neurons. MS-induced alterations in electrophysiology were accompanied by an increase in the diameter of dendritic spine heads on lateral VTA DAergic neurons, although the overall dendritic spine density remained unchanged. Finally, we reported MS-related increases in basal plasma ACTH and corticosterone levels. These results show the long-term consequences of early life stress and indicate the possible neuronal mechanisms of behavioral disturbances in individuals who experience early life neglect.
超过四分之一的儿童经历过童年期虐待,其形式可能为身体虐待或心理虐待。早年生活压力会产生重大的长期后果,包括在青少年期和成年期药物滥用和精神疾病风险增加,且女性的这种风险高于男性。早年逆境对大脑功能影响的神经机制仍知之甚少;因此,在本研究中,我们采用母婴分离(MS)这一早年忽视的啮齿动物模型,来验证其对腹侧被盖区(VTA)神经元特性的影响,VTA是一个在奖赏和动机处理中起关键作用的脑区。通过对青春期雌性斯普拉格-道利大鼠脑片进行全细胞膜片钳记录,我们发现MS选择性地增加了VTA内侧部分假定多巴胺能(DAergic)神经元的兴奋性。我们还表明VTA假定DAergic神经元的兴奋性突触传递增强。MS诱导的电生理改变伴随着VTA外侧DAergic神经元树突棘头部直径增加,尽管总体树突棘密度保持不变。最后,我们报告了MS导致基础血浆促肾上腺皮质激素(ACTH)和皮质酮水平升高。这些结果显示了早年生活压力的长期后果,并指出了经历早年忽视个体行为障碍可能的神经机制。