D'Amore Drew E, Tracy Brittany A, Parikh Vinay
Department of Psychology and Neuroscience Program, Temple University, 1701 N. 13th Street, Weiss Hall, Philadelphia, PA 19122, USA.
Department of Psychology and Neuroscience Program, Temple University, 1701 N. 13th Street, Weiss Hall, Philadelphia, PA 19122, USA.
Neuropharmacology. 2013 Dec;75:312-23. doi: 10.1016/j.neuropharm.2013.07.033. Epub 2013 Aug 16.
Brain-derived neurotrophic factor (BDNF) signaling via tropomyosin-related kinase B (trkB) receptors exerts modulatory effects on glutamatergic transmission, learning, memory and reward processing. Although the role of BDNF in the regulation of mnemonic and affective/motivational processes is well studied, whether this neurotrophin could also regulate executive functions is not known. In the present study, we assessed the effects of intrastriatal infusions on BDNF (1-100 ng/hemisphere) in mice performing an operant strategy set-shifting task that required the animals to eliminate a visual cue-based strategy and adopt a new egocentric spatial response strategy to achieve rewards. Exogenous BDNF administration facilitated the acquisition of strategy shifting by minimizing response perseveration to the previously acquired strategy and this effect resemble an inverted-U shaped dose-response pattern. Faster acquisition of strategy switching in BDNF-infused animals was dependent upon the activation of striatal trkB receptors. Moreover, activation of mGluR2/3 receptors by the selective group II metabotropic receptor agonist LY379268 abolished BDNF-induced cognitive enhancement suggesting the involvement of presynaptic glutamatergic activity. Assessment of striatal glutamate dynamics using electrochemical recordings indicated that local application of BDNF directly induces glutamate release by activating presynaptic trkB receptors on glutamatergic terminals, and this effect followed a bell-shaped dose-response pattern similar to strategy shifting performance. These data suggest that activation of BDNF-trkB signaling in the dorsal striatum improves strategy switching by effectively minimizing response conflicts, and this effect primarily involves facilitation of glutamatergic transmission.
脑源性神经营养因子（BDNF）通过原肌球蛋白相关激酶B（trkB）受体发出信号，对谷氨酸能传递、学习、记忆和奖赏处理发挥调节作用。尽管BDNF在调节记忆和情感/动机过程中的作用已得到充分研究，但这种神经营养因子是否也能调节执行功能尚不清楚。在本研究中，我们评估了向纹状体内注射BDNF（1-100 ng/半球）对执行操作性策略转换任务的小鼠的影响，该任务要求动物消除基于视觉线索的策略，并采用新的以自我为中心的空间反应策略以获得奖赏。外源性给予BDNF通过最小化对先前习得策略的反应持续性，促进了策略转换的获得，且这种效应呈现倒U形剂量反应模式。BDNF注射组动物更快获得策略转换依赖于纹状体trkB受体的激活。此外，选择性II组代谢型受体激动剂LY379268激活mGluR2/3受体，消除了BDNF诱导的认知增强，提示突触前谷氨酸能活性的参与。用电化学记录评估纹状体谷氨酸动力学表明，局部应用BDNF通过激活谷氨酸能终末上的突触前trkB受体直接诱导谷氨酸释放，且这种效应遵循与策略转换表现相似的钟形剂量反应模式。这些数据表明，背侧纹状体内BDNF-trkB信号的激活通过有效减少反应冲突来改善策略转换，且这种效应主要涉及促进谷氨酸能传递。
