Janke Kellie L, Cominski Tara P, Kuzhikandathil Eldo V, Servatius Richard J, Pang Kevin C H
Research Service, Neurobehavioral Research Laboratory, VA New Jersey Heath Care System , East Orange, NJ , USA ; Graduate School of Biomedical Sciences, New Jersey Medical School, Rutgers Biomedical and Health Sciences , Newark, NJ , USA.
Research Service, Neurobehavioral Research Laboratory, VA New Jersey Heath Care System , East Orange, NJ , USA ; Veterans Biomedical Research Institute , East Orange, NJ , USA.
Front Psychiatry. 2015 Jul 24;6:106. doi: 10.3389/fpsyt.2015.00106. eCollection 2015.
Dysregulation of brain-derived neurotrophic factor (BDNF), behavioral inhibition temperament (BI), and small hippocampal volume have been linked to anxiety disorders. Individuals with BI show facilitated acquisition of the classically conditioned eyeblink response (CCER) as compared to non-BI individuals, and a similar pattern is seen in an animal model of BI, the Wistar-Kyoto (WKY) rat. The present study examined the role of hippocampal BDNF in the facilitated delay CCER of WKY rats. Consistent with earlier work, acquisition was facilitated in WKY rats compared to the Sprague Dawley (SD) rats. Facilitated acquisition was associated with increased BDNF, TrkB, and Arc mRNA in the dentate gyrus of SD rats, but learning-induced increases in BDNF and Arc mRNA were significantly smaller in WKY rats. To determine whether reduced hippocampal BDNF in WKY rats was a contributing factor for their facilitated CCER, BDNF or saline infusions were given bilaterally into the dentate gyrus region 1 h prior to training. BDNF infusion did not alter the acquisition of SD rats, but significantly dampened the acquisition of CCER in the WKY rats, such that acquisition was similar to SD rats. Together, these results suggest that inherent differences in the BDNF system play a critical role in the facilitated associative learning exhibited by WKY rats, and potentially individuals with BI. Facilitated associative learning may represent a vulnerability factor in the development of anxiety disorders.
脑源性神经营养因子（BDNF）失调、行为抑制气质（BI）和海马体体积减小与焦虑症有关。与非BI个体相比，BI个体表现出经典条件性眨眼反应（CCER）的习得更容易，在BI的动物模型——Wistar-Kyoto（WKY）大鼠中也观察到类似模式。本研究考察了海马体BDNF在WKY大鼠延迟CCER易化中的作用。与早期研究一致，与Sprague Dawley（SD）大鼠相比，WKY大鼠的习得更容易。SD大鼠齿状回中BDNF、TrkB和Arc mRNA增加与习得易化有关，但WKY大鼠中学习诱导的BDNF和Arc mRNA增加明显较小。为了确定WKY大鼠海马体BDNF减少是否是其CCER易化的一个促成因素，在训练前1小时双侧齿状回区域注射BDNF或生理盐水。注射BDNF并未改变SD大鼠的习得，但显著抑制了WKY大鼠CCER的习得，使其习得与SD大鼠相似。总之，这些结果表明BDNF系统的内在差异在WKY大鼠以及可能在BI个体所表现出的易化联想学习中起关键作用。易化联想学习可能是焦虑症发展中的一个易患因素。
