Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses
Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses
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DOI：
10.1523/jneurosci.3821-16.2017
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发表时间：
2017-06-21
影响因子：
5.3
通讯作者：
LaLumiere, Ryan T.
中科院分区：
文献类型：
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作者：
Gutman, Andrea L.;Nett, Kelle E.;LaLumiere, Ryan T.
边缘下皮质（IL）介导消退学习和主动抑制可卡因寻求行为。然而，IL 活动、杠杆按压和消退学习之间的精确时间关系尚不清楚。为了解决这个问题，我们在雄性 Sprague Dawley 大鼠中使用活动引导光遗传学，在可卡因自我给药后的早期灭绝训练期间，在无强化的杠杆按压后立即以光学方式使 IL 锥体神经元沉默 20 秒。 IL 的光学抑制在缩短的消退过程中增加了主动杠杆按压，但没有改变消退学习的保留，正如在随后的无光学抑制的消退过程中所评估的那样。在随后的提示恢复过程中，先前在灭绝过程中接受过光学抑制的老鼠表现出增加的可卡因寻求行为。这些发现似乎特定于杠杆按下后期间的抑制，因为在消退过程中以非偶然、伪随机方式给予 IL 抑制不会产生相同的效果。单独的照明（即没有视蛋白表达）和寻求食物的对照实验也未能产生相同的效果。在另一项实验中，在提示恢复过程中按下杠杆后，IL 抑制会增加这些过程中对可卡因的寻求。最后，在缩短的灭绝过程中，在未强化的杠杆按压后立即抑制前边缘皮层，减少了这些过程中的杠杆按压，但对随后的恢复没有影响。这些结果表明，在未加强的杠杆按压后立即产生的 IL 活性对于可卡因寻求的正常消除是必要的，这表明在杠杆按压和可卡因奖励之间的新意外事件的关键编码发生在该时期。
The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period.