Gustatory cortex and reward-based, taste-action associations

项目总结 味觉系统根据特定的感官和享乐类别处理味觉。天真的 对于动物，味觉刺激代表它们所唤起的味道质量--即甜、咸、鲜味、苦、酸 -以及它们的享乐价值(可口的或令人厌恶的)。然而，味觉回路是高度可塑性的 表示法可以通过学习进行修改。味觉可塑性的最好例子来自于对 条件性味觉厌恶(CTA)-一种学习范式，在这种学习范式中，天生可口的味觉变得厌恶 曾经伴随着胃病。电生理记录和成像实验表明，CTA 导致了对味觉的皮质表达的持续重新映射。虽然这些研究是有用的 在证明味觉皮质(GC)可以重塑其代表味觉的方式时，他们并没有澄清 持久的重新映射是特定于厌恶学习和享乐维度的，或者如果它也可以发生在其他 味觉体验的形式。 这项拨款中的实验将通过调查奖励驱动的 味觉-行为关联可以修改和重新映射感觉表征。为此，我们修改了一个经典的 二选一选择程序。在这项任务中，小鼠从四种口味中挑选一种(两种糖果：蔗糖[S1]) 和麦芽糖[S2]；两种苦味物质：奎宁[B1]和放线菌亚胺[B2]) 舔着两个侧面喷嘴中的一个。在这个任务的主要版本中，老鼠将产生相同的反应 不一致的口味对(例如，蔗糖或奎宁舔侧面喷嘴1与麦芽糖或环己亚胺舔 侧向喷口2)。这一版本的范例要求小鼠忽略先天的味道相似，并产生i) 对于不同品质和相反享乐的品尝者有相似的反应；ii)对品尝者有不同的反应 有着相似的品质和享乐主义。一些额外的行为范例将被用作对照。 这项拨款中的实验将检验GC允许小鼠形成味觉动作这一重要假设。 这种行为与任务相关的活动和味觉诱发的可塑性有关 回应。拟议的研究主要集中在以下目标：目标1将开发一种受控良好的 训练小鼠形成新的味觉-动作联想的行为范式。此外，这些实验将依赖于 关于GC的化学发生和光发生失活，以确定其参与味觉的表现- 操作关联任务。目标2将使用电生理方法揭示单个单元的可塑性变化 警觉小鼠学习和执行味觉-动作联想任务的GC中的刺激性活动。波形分析 这将使我们能够分离假定的兴奋性和抑制性神经元，并跟踪它们在几天内的活动。最后， 目标3将依靠GAD2-T2a-NLS-mCherry小鼠的双光子钙成像来跟踪联想学习 改变兴奋性神经元和GABA能神经元大型集合的活动空间模式。 这些实验将使我们能够研究抑制在GC可塑性中的可能作用。此外， 通过比较清醒小鼠和麻醉小鼠的活动模式，我们可以了解到 重新映射。 总之，拟议的实验将开辟一条研究GC功能的新途径，并建立一个 研究基于奖励的味觉学习和GC可塑性的实验管道。如果成功，这些研究 将证明味觉的GC表示解释了味觉与动作的联系。证明这一原则将会 对我们理解GC在进食行为和决策中的作用有重要的影响。

PROJECT SUMMARY The gustatory system processes tastants according to specific sensory and hedonic categories. In naïve animals, gustatory stimuli are represented for the taste quality they evoke – i.e., sweet, salty, umami, bitter, sour – and for their hedonic value (palatable or aversive). However, gustatory circuits are highly plastic and representations can be modified by learning. The best example of gustatory plasticity comes from studies on conditioned taste aversion (CTA) - a learning paradigm in which an innately palatable tastant becomes aversive once paired with gastric illness. Electrophysiological recordings and imaging experiments demonstrate that CTA leads to a persistent remapping of cortical representations of taste. While these studies have been instrumental in demonstrating that the gustatory cortex (GC) can reshape how it represents taste, they do not clarify whether persistent remapping is specific to aversive learning and to the hedonic dimension, or if it can occur also for other forms of taste experience. The experiments in this grant will address this unanswered question by investigating whether reward-driven, taste-action associations can modify and remap sensory representations. To this purpose, we modified a classic two-alternative choice procedure. In this task, mice sample one out of four tastants (two sweets: sucrose [S1] and maltose [S2]; two bitters: quinine [B1] and cycloheximide [B2]) from a central licking spout and respond by licking one of two lateral spouts. In the main version of this task, mice will produce the same response to incongruent pairs of tastants (i.e., sucrose or quinine -> lick lateral spout 1 vs maltose or cycloheximide -> lick lateral spout 2). This version of the paradigm requires mice to ignore innate taste similarities and produce i) similar responses for tastants with different qualities and opposite hedonics; ii) different responses for tastants with similar qualities and hedonics. A number of additional behavioral paradigms will be used as controls. The experiments in this grant will test the overarching hypothesis that GC allows mice to form taste-action associations and that this behavior is associated with task-related activity and plasticity of taste-evoked responses. The proposed research focuses on the following aims: Aim #1 will develop a well-controlled behavioral paradigm for training mice to form new taste-action associations. In addition, the experiments will rely on chemogenetic and optogenetic inactivation of GC to determine its involvement in the performance of a taste- action association task. Aim #2 will use electrophysiological methods to unveil plastic changes of single unit spiking activity in GC of alert mice learning and performing a taste-action association task. Waveform analyses will allow us to separate putative excitatory and inhibitory neurons and to follow their activity across days. Finally, Aim #3 will rely on 2-photon calcium imaging in Gad2-T2a-NLS-mCherry mice to track how associative learning changes the spatial patterns of activity in large ensembles of excitatory and GABAergic neurons across days. These experiments will allow us to investigate the possible role of inhibition in GC plasticity. Furthermore, comparing patterns of activity in alert and anesthetized mice will inform us on the state-dependency of remapping. Altogether, the proposed experiments will open a new alley of research on the function of GC and establish an experimental pipeline to investigate reward-based taste learning and GC plasticity. If successful, these studies will demonstrate that GC representation of taste accounts for taste-action associations. Proving this principle will have important consequences for our understanding of the role of GC in ingestive behaviors and decisions.