The Emergence of a Stable Neuronal Ensemble from a Wider Pool of Activated Neurons in the Dorsal Medial Prefrontal Cortex during Appetitive Learning in Mice
The Emergence of a Stable Neuronal Ensemble from a Wider Pool of Activated Neurons in the Dorsal Medial Prefrontal Cortex during Appetitive Learning in Mice
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DOI：
10.1523/jneurosci.1496-19.2019
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发表时间：
2020-01-08
影响因子：
5.3
通讯作者：
Koya, Eisuke
中科院分区：
文献类型：
--
作者：
Brebner, Leonie S.;Ziminski, Joseph J.;Koya, Eisuke
动物选择性地对与食物奖励相关的环境线索作出反应，以优化营养摄入。这种食欲条件刺激-非条件刺激（CS-US）关联被认为是在选择性的、稳定的神经元群体或神经元群中编码的，它们在食欲条件作用期间经历生理修饰。内侧前额叶皮层（mPFC）中的这些集合控制着完善的、线索诱发的食物寻找，但这些集合的发生机制尚不清楚。在这里，我们使用在最近行为激活的神经元中表达绿色荧光蛋白（GFP）的雄性Fos-GFP小鼠，来揭示背侧mPFC神经元是如何通过食欲条件反射任务被招募和修饰来编码CS-US记忆表征的。在最初的条件反射中，动物没有表现出歧视性的、线索选择性的食物寻找，但在后来的条件反射中却出现了这种情况，这表明CS-US关联已经建立起来。利用基于微棱镜的体内2光子成像，我们发现只有少数在初始阶段激活的神经元在随后的条件反射阶段和线索诱发记忆回忆期间持续激活。值得注意的是，使用离体电生理学，我们发现在初始会话后激活的神经元表现出短暂的高兴奋性。在随后的条件反射过程中，从化学上增强这些神经元的兴奋性会干扰可靠的线索选择性食物寻找的发展，这表现为持久的、非歧视性的表现。我们展示了在CS-US关联形成过程中，食欲学习如何持续激活神经元子集以形成稳定的神经元集合。这种组合可能是由在初始条件作用过程中激活的过度兴奋神经元池引起的。
Animals selectively respond to environmental cues associated with food reward to optimize nutrient intake. Such appetitive conditioned stimulus- unconditioned stimulus (CS-US) associations are thought to be encoded in select, stable neuronal populations or neuronal ensembles, which undergo physiological modifications during appetitive conditioning. These ensembles in the medial prefrontal cortex (mPFC) control well-established, cue-evoked food seeking, but the mechanisms involved in the genesis of these ensembles are unclear. Here, we used male Fos-GFP mice that express green fluorescent protein (GFP) in recently behaviorally activated neurons, to reveal how dorsal mPFC neurons are recruited and modified to encode CS-US memory representations using an appetitive conditioning task. In the initial conditioning session, animals did not exhibit discriminated, cue-selective food seeking, but did so in later sessions indicating that a CS-US association was established. Using microprism-based in vivo 2-Photon imaging, we revealed that only a minority of neurons activated during the initial session was consistently activated throughout subsequent conditioning sessions and during cue-evoked memory recall. Notably, using ex vivo electrophysiology, we found that neurons activated following the initial session exhibited transient hyperexcitability. Chemogenetically enhancing the excitability of these neurons throughout subsequent conditioning sessions interfered with the development of reliable cue-selective food seeking, indicated by persistent, nondiscriminated performance. We demonstrate how appetitive learning consistently activates a subset of neurons to form a stable neuronal ensemble during the formation of a CS-US association. This ensemble may arise from a pool of hyperexcitable neurons activated during the initial conditioning session.