Wilber A A, Wellman C L
Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, 1101 East 10th Street, Bloomington, IN 47405, United States.
Neurosci Lett. 2009 Sep 4;460(3):214-8. doi: 10.1016/j.neulet.2009.05.076. Epub 2009 Jun 7.
Neonatal maternal separation impairs adult eyeblink conditioning. This impairment is correlated with increases in adult glucocorticoid receptor (GR) expression in the posterior interpositus nucleus [A.A. Wilber, C. Southwood, G. Sokoloff, J.E. Steinmetz, C.L. Wellman, Neonatal maternal separation alters adult eyeblink conditioning and glucocorticoid receptor expression in the interpositus nucleus of the cerebellum, Developmental Neurobiology 67 (2007) 1751-1764], a key structure in the neural circuitry controlling eyeblink conditioning. To further localize this effect, we assessed adult eyeblink conditioning and GR expression in projection versus interneurons in the interpositus of rats that had undergone standard rearing or maternal separation (1h/day) on postnatal days 2-14. At 3 months of age, interpositus neurons were labeled with the retrograde tracer biotinylated dextran amine (BDA). After delay eyeblink conditioning, brains were processed immunohistochemically for GR and BDA labeling of interpositus neurons. GR expression was quantified in BDA-labeled and unlabeled neurons. Neonatal maternal separation impaired adult eyeblink conditioning. Control rats had significantly less GR expression in posterior interpositus BDA-unlabeled versus BDA-labeled neurons, but this difference was absent in maternally separated rats. While neonatal separation significantly increased GR expression in BDA-labeled and unlabeled posterior interpositus neurons, only GR expression in non-BDA-labeled neurons was associated with eyeblink conditioning. Thus, neonatal maternal separation may alter interneuronal modulation of interpositus output neurons, producing deficits in adult eyeblink conditioning.
新生期母婴分离会损害成年大鼠的眨眼条件反射。这种损害与成年大鼠小脑后间位核中糖皮质激素受体（GR）表达的增加相关[A.A.威尔伯、C.索思伍德、G.索科洛夫、J.E.斯坦梅茨、C.L.韦尔曼，《新生期母婴分离改变成年大鼠眨眼条件反射及小脑间位核中糖皮质激素受体表达》，《发育神经生物学》67（2007）1751 - 1764]，小脑后间位核是控制眨眼条件反射神经回路中的关键结构。为了进一步定位这种效应，我们评估了在出生后第2 - 14天经历标准饲养或母婴分离（每天1小时）的大鼠间位核中投射神经元与中间神经元的成年眨眼条件反射及GR表达情况。在3月龄时，用逆行示踪剂生物素化葡聚糖胺（BDA）标记间位核神经元。延迟眨眼条件反射后，对大脑进行免疫组织化学处理，以对间位核神经元进行GR和BDA标记。对BDA标记和未标记的神经元中的GR表达进行定量分析。新生期母婴分离损害成年大鼠眨眼条件反射。对照大鼠后间位核中BDA未标记的神经元与BDA标记的神经元相比，GR表达显著减少，但在母婴分离的大鼠中这种差异不存在。虽然新生期分离显著增加了BDA标记和未标记的后间位核神经元中的GR表达，但只有未被BDA标记的神经元中的GR表达与眨眼条件反射相关。因此，新生期母婴分离可能会改变间位核输出神经元的中间神经元调节，导致成年大鼠眨眼条件反射出现缺陷。
