Cotella Evelin M, Nawreen Nawshaba, Moloney Rachel D, Martelle Susan E, Oshima Kristen M, Lemen Paige, NiBlack Jordan N, Julakanti Reetu R, Fitzgerald Maureen, Baccei Mark L, Herman James P
Department of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, Ohio.
Veterans Affairs Medical Center, Cincinnati, Ohio.
Biol Psychiatry Glob Open Sci. 2022 Mar 8;3(2):274-282. doi: 10.1016/j.bpsgos.2022.02.009. eCollection 2023 Apr.
Adolescent brains are sensitive to stressors. However, under certain circumstances, developmental stress can promote an adaptive phenotype, allowing individuals to cope better with adverse situations in adulthood, thereby contributing to resilience.
Sprague Dawley rats (50 males, 48 females) were subjected to adolescent chronic variable stress (adol CVS) for 2 weeks at postnatal day 45. At postnatal day 85, a group was subjected to single prolonged stress (SPS). After a week, animals were evaluated in an auditory-cued fear conditioning paradigm, and neuronal recruitment during reinstatement was assessed by Fos expression. Patch clamp electrophysiology (17-35 cells/group) was performed in male rats to examine physiological changes associated with resilience.
Adol CVS blocked fear potentiation evoked by SPS. We observed that SPS impaired extinction (males) and enhanced reinstatement (both sexes) of the conditioned freezing response. Prior adol CVS prevented both effects. SPS effects were associated with a reduction of infralimbic (IL) cortex neuronal recruitment after reinstatement in males and increased engagement of the central amygdala in females, both also prevented by adol CVS, suggesting different neurocircuits involved in generating resilience between sexes. We explored the mechanism behind reduced IL recruitment in males by studying the intrinsic excitability of IL pyramidal neurons. SPS reduced excitability of IL neurons, and prior adol CVS prevented this effect.
Our data indicate that adolescent stress can impart resilience to the effects of traumatic stress on neuroplasticity and behavior. Our data provide a mechanistic link behind developmental stress-induced behavioral resilience and prefrontal (IL) cortical excitability in males.
青少年的大脑对压力源敏感。然而，在某些情况下，发育性压力可促进适应性表型，使个体在成年后能更好地应对不利情况，从而有助于形成心理韧性。
将斯普拉格-道利大鼠（50只雄性，48只雌性）在出生后第45天接受为期2周的青少年慢性可变应激（青少年慢性可变应激）。在出生后第85天，一组大鼠接受单次长时间应激（SPS）。一周后，在听觉提示恐惧条件反射范式中对动物进行评估，并通过Fos表达评估恢复过程中的神经元募集情况。对雄性大鼠进行膜片钳电生理学研究（每组17 - 35个细胞），以检查与心理韧性相关的生理变化。
青少年慢性可变应激阻断了单次长时间应激诱发的恐惧增强。我们观察到，单次长时间应激损害了条件性僵住反应的消退（雄性）并增强了其恢复（两性）。先前的青少年慢性可变应激可预防这两种效应。单次长时间应激的效应与雄性恢复后边缘下皮质（IL）神经元募集减少以及雌性中央杏仁核参与增加有关，这两种情况也都被青少年慢性可变应激所预防，表明两性在产生心理韧性方面涉及不同的神经回路。我们通过研究IL锥体神经元的内在兴奋性来探索雄性中IL募集减少背后的机制。单次长时间应激降低了IL神经元的兴奋性，而先前接受青少年慢性可变应激可预防这种效应。
我们的数据表明，青少年期应激可使创伤性应激对神经可塑性和行为的影响产生心理韧性。我们的数据为发育性应激诱导的行为韧性与雄性前额叶（IL）皮质兴奋性之间提供了一个机制联系。
