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光遗传激活边缘下皮质可抑制消退后奖赏性条件反射反应的重现。

Optogenetic Activation of the Infralimbic Cortex Suppresses the Return of Appetitive Pavlovian-Conditioned Responding Following Extinction.

机构信息

Center for Studies in Behavioral Neurobiology/FRQS Groupe de Recherche en Neurobiologie Comportementale, Department of Psychology, Concordia University, Montreal, Quebec, Canada.

出版信息

Cereb Cortex. 2018 Dec 1;28(12):4210-4221. doi: 10.1093/cercor/bhx275.

DOI:10.1093/cercor/bhx275
PMID:29045570
Abstract

The infralimbic medial prefrontal cortex (IL) is important for suppressing learned behavior after extinction, but whether this function extends to responses acquired through appetitive Pavlovian conditioning is unclear. We trained male, Long-Evans rats to associate a white-noise conditional stimulus (CS; 10 s; 14 presentations per session) with 10% liquid sucrose (0.2 mL per CS presentation), and recorded entries into the fluid port during the CS. The CS was presented without sucrose in subsequent extinction and test sessions. Increasing IL activity with pretest microinfusions of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 0, 0.3 nmol; 0.3 μl/side) reduced the reinstatement of CS-elicited port entries. The same result was obtained when IL neurons that expressed Channelrhodopsin-2 (ChR2) were optically stimulated during CS presentations at test (473 nm, 5 ms pulses at 20 Hz for 10.2 s, unilateral). Optical stimulation of ChR2-expressing IL neurons during CS presentations also reduced spontaneous recovery and context-induced renewal. Furthermore, optical stimulation (1) during intertrial intervals had no impact on renewal, (2) depolarized ChR2-expressing IL pyramidal neurons in vitro, and (3) preferentially increased Fos in ChR2-expressing neurons. These novel converging data highlight a critical role for the IL in suppressing the return of appetitive Pavlovian-conditioned responding following extinction.

摘要

扣带皮层下边缘区(IL)对于抑制消退后习得行为很重要,但它在多大程度上扩展到通过奖赏性巴甫洛夫条件反射获得的反应尚不清楚。我们训练雄性长耳大白鼠将白噪声条件刺激(CS;10 秒;每节 14 次呈现)与 10%的液体蔗糖(每次 CS 呈现 0.2 毫升)相关联,并记录 CS 期间进入液体端口的次数。在随后的消退和测试阶段,CS 呈现时没有蔗糖。在测试前微注射α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA;0、0.3 nmol;0.3 μl/侧)增加 IL 活性会减少 CS 诱发的端口进入的重新出现。当在测试期间(473nm,5ms 脉冲,20Hz,持续 10.2s,单侧)用光刺激表达 Channelrhodopsin-2(ChR2)的 IL 神经元时,也得到了相同的结果。在 CS 呈现期间用光刺激表达 ChR2 的 IL 神经元也减少了自发恢复和上下文诱导的更新。此外,(1)光刺激在试验间间隔内对更新没有影响,(2)在体外使表达 ChR2 的 IL 锥体神经元去极化,(3)优先增加表达 ChR2 的神经元中的 Fos。这些新的趋同数据强调了 IL 在抑制消退后奖赏性巴甫洛夫条件反射反应重新出现方面的关键作用。

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