Activation of Pyramidal Neurons in Mouse Medial Prefrontal Cortex Enhances Food-Seeking Behavior While Reducing Impulsivity in the Absence of an Effect on Food Intake.
Activation of Pyramidal Neurons in Mouse Medial Prefrontal Cortex Enhances Food-Seeking Behavior While Reducing Impulsivity in the Absence of an Effect on Food Intake.
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DOI：
10.3389/fnbeh.2016.00063
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发表时间：
2016
影响因子：
3
通讯作者：
Scott MM
中科院分区：
文献类型：
--
作者：
Warthen DM;Lambeth PS;Ottolini M;Shi Y;Barker BS;Gaykema RP;Newmyer BA;Joy-Gaba J;Ohmura Y;Perez-Reyes E;Güler AD;Patel MK;Scott MM
内侧前额叶皮层（mPFC）参与了广泛的执行认知功能，包括奖励评估、决策、记忆消退、情绪和任务转换。操纵mPFC已被证明可以改变食物摄入和食物奖励评估，但是否单独刺激mPFC锥体神经元（PN） （mPFC的主要输出）足以介导食物奖励的工具行为尚不清楚。我们试图通过在一系列行为测试中刺激小鼠mPFC中的PN来确定操纵mPFC输出的行为后果，重点是食物奖励。我们发现，使用设计药物（DREADD）激活的设计受体增加mPFC锥体细胞输出，可以提高评估食物寻找行为的工具食物奖励测试的性能，同时保留对情绪和食物摄入的影响。具体而言，mPFC PN的激活增强了对食物奖励的操作性反应，恢复了对美味食物的寻找，并抑制了对食物奖励的冲动反应。相反，mPFC PN的激活对无条件的食物摄入、社会互动或开放领域的行为没有影响。此外，我们发现行为结果受mPFC激活程度的影响，低驱动足以增强操作反应，而高驱动则需要改变冲动性。此外，我们提供的数据表明，DREADD刺激涉及一氧化氮（NO）合成酶依赖途径，类似于内源性毒蕈碱M3受体刺激，这一发现为日益广泛的远程神经元控制方法提供了新的机制见解。
The medial prefrontal cortex (mPFC) is involved in a wide range of executive cognitive functions, including reward evaluation, decision-making, memory extinction, mood, and task switching. Manipulation of the mPFC has been shown to alter food intake and food reward valuation, but whether exclusive stimulation of mPFC pyramidal neurons (PN), which form the principle output of the mPFC, is sufficient to mediate food rewarded instrumental behavior is unknown. We sought to determine the behavioral consequences of manipulating mPFC output by exciting PN in mouse mPFC during performance of a panel of behavioral assays, focusing on food reward. We found that increasing mPFC pyramidal cell output using designer receptors exclusively activated by designer drugs (DREADD) enhanced performance in instrumental food reward assays that assess food seeking behavior, while sparing effects on affect and food intake. Specifically, activation of mPFC PN enhanced operant responding for food reward, reinstatement of palatable food seeking, and suppression of impulsive responding for food reward. Conversely, activation of mPFC PN had no effect on unconditioned food intake, social interaction, or behavior in an open field. Furthermore, we found that behavioral outcome is influenced by the degree of mPFC activation, with a low drive sufficient to enhance operant responding and a higher drive required to alter impulsivity. Additionally, we provide data demonstrating that DREADD stimulation involves a nitric oxide (NO) synthase dependent pathway, similar to endogenous muscarinic M3 receptor stimulation, a finding that provides novel mechanistic insight into an increasingly widespread method of remote neuronal control.