Gustatory cortex and reward-based, taste-action associations

味觉皮层和基于奖励的味觉-动作关联

• 批准号: 10410396
• 负责人: Alfredo Fontanini
• 金额: $ 41.2万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10410396
• 关键词: Address; Animals; Aversive Stimulus; Behavior; Behavioral; Behavioral Paradigm; Calcium; Categories; Cognitive; Cycloheximide; Dependence; Development; Diet Habits; Dimensions; Disinhibition; Eating Disorders; Electrophysiology (science); Event; Feeding behaviors; Glutamates; Goals; Grant; Hyperphagia; Image; Implant; In Vitro; Ingestion; Interneurons; Lateral; Lead; Learning; Left; Life; Maltose; Mediating; Methods; Modification; Monitor; Mus; Neurons; Operant Conditioning; Palate; Pattern; Performance; Procedures; Process; Protocols documentation; Quinine; Research; Rewards; Rodent; Role; Sampling; Savory; Sensory; Stimulus; Stomach; Sucrose; Synapses; Task Performances; Taste Perception; Taste aversion; Testing; Training; Variant; base; behavior change; classical conditioning; cognitive process; cohort; designer receptors exclusively activated by designer drugs; excitatory neuron; experience; experimental study; hedonic; inhibitory neuron; neural patterning; optogenetics; relating to nervous system; response; sensory cortex; sweet taste perception; taste system; transmission process; two-photon

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.

项目摘要 味觉系统根据特定的感觉和享乐类别处理味剂。天真地 动物，味觉刺激被表示为它们唤起的味觉质量-即，甜，咸，鲜，苦，酸 - 和他们的享乐价值（可口或厌恶）。然而，味觉回路是高度可塑的， 表示可以通过学习来修改。味觉可塑性最好的例子来自于 条件性味觉厌恶（CTA）-一种学习范式，其中天生的美味味觉变得厌恶 一旦与胃病相结合。电生理记录和成像实验表明，CTA 导致了味觉皮质表征的持续重新映射。虽然这些研究对 在证明味觉皮层（GC）可以重塑其代表味觉的方式时，他们没有澄清是否 持续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学习者身上， 品味体验的形式。 这项资助的实验将通过调查奖励驱动， 味觉-动作关联可以改变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，小鼠从四种促味剂中选择一种（两种甜食：蔗糖[S1]） 和麦芽糖[S2];两种苦味：奎宁[B1]和放线菌酮[B2]），并通过 舔着两个侧喷口之一在这个任务的主要版本中，小鼠将产生相同的反应， 不一致的促味剂对（即，蔗糖或奎宁->舔侧喷口1 vs麦芽糖或放线菌酮->舔 侧喷口2）。这个版本的范例要求小鼠忽略先天的味觉相似性，并产生i） 对具有不同性质和相反的享乐主义的味剂的类似反应; ii）对味剂的不同反应 有着相似的品质和快乐。一些额外的行为范例将被用作对照。 这项资助的实验将验证GC允许小鼠形成味觉-动作的总体假设 这种行为与任务相关的活动和味觉诱发的可塑性有关。 应答拟议的研究集中在以下目标：目标#1将开发一个控制良好的 行为模式，用于训练小鼠形成新的味觉-动作关联。此外，实验将依赖于 对GC的化学遗传学和光遗传学失活进行研究，以确定其参与味觉的表现- 动作关联任务。目标2将使用电生理学方法揭示单个单位的塑性变化 警觉小鼠学习和执行味觉-动作关联任务的GC中的尖峰活动。波形分析 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将依赖于Gad 2-T2 a-NLS-mCherry小鼠中的双光子钙成像来跟踪联想学习如何 改变了兴奋性和GABA能神经元的大集合在几天内的活动空间模式。 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，委员会认为， 比较警觉和麻醉小鼠的活动模式将告诉我们， 重新映射 总之，本实验为GC功能的研究开辟了一条新的途径，并建立了一种新的GC功能研究方法。 实验管道，以研究基于奖励的味觉学习和GC可塑性。如果成功，这些研究 将证明GC代表的味道帐户的味道行动协会。证明这一原则将 对我们理解GC在摄食行为和决策中的作用具有重要意义。