Sagol Department of Neuroscience, and.
Sagol Department of Neuroscience, and
J Neurosci. 2019 Nov 20;39(47):9369-9382. doi: 10.1523/JNEUROSCI.0752-19.2019. Epub 2019 Oct 9.
Conditioned taste aversion (CTA) is an associative learning paradigm, wherein consumption of an appetitive tastant (e.g., saccharin) is paired to the administration of a malaise-inducing agent, such as intraperitoneal injection of LiCl. Aversive taste learning and retrieval require neuronal activity within the anterior insula (aIC) and the basolateral amygdala (BLA). Here, we labeled neurons of the aIC projecting to the BLA in adult male mice using a retro-AAV construct and assessed their necessity in aversive and appetitive taste learning. By restricting the expression of chemogenetic receptors in aIC-to-BLA neurons, we demonstrate that activity within the aIC-to-BLA projection is necessary for both aversive taste memory acquisition and retrieval, but not for its maintenance, nor its extinction. Moreover, inhibition of the projection did not affect incidental taste learning per se, but effectively suppressed aversive taste memory retrieval when applied either during or before the encoding of the unconditioned stimulus for CTA (i.e., malaise). Remarkably, activation of the projection after novel taste consumption, without experiencing any internal discomfort, was sufficient to form an artificial aversive taste memory, resulting in strong aversive behavior upon retrieval. Our results indicate that aIC-to-BLA projecting neurons are an essential component in the ability of the brain to associate taste sensory stimuli with body states of negative valence and guide the expression of valence-specific behavior upon taste memory retrieval. In the present study we subjected mice to the conditioned taste aversion paradigm, where animals learn to associate novel taste with malaise (i.e., assign it negative valence). We show that activation of neurons in the anterior insular cortex (aIC) that project into the basolateral amygdala (BLA) in response to conditioned taste aversion is necessary to form a memory for a taste of negative valence. Moreover, artificial activation of this pathway (without any feeling of pain) after the sampling of a taste can also lead to such associative memory. Thus, activation of aIC-to-BLA projecting neurons is necessary and sufficient to form and retrieve aversive taste memory.
条件性味觉厌恶（CTA）是一种联想学习范式，在此范式中，可口味的味觉刺激物（例如，糖精）的消耗与引起不适的药剂（例如，腹膜内注射氯化锂）的给药相关联。厌恶味觉学习和检索需要在前脑岛（aIC）和基底外侧杏仁核（BLA）内的神经元活动。在这里，我们使用逆行 AAV 构建物标记成年雄性小鼠投射到 BLA 的 aIC 神经元，并评估了它们在厌恶和食欲味觉学习中的必要性。通过限制 aIC 到 BLA 神经元中的化学遗传受体的表达，我们证明了 aIC 到 BLA 投射内的活动对于厌恶味觉记忆的获取和检索都是必需的，但对于其维持或消退则不是必需的。此外，当在 CTA（即不适）的无条件刺激的编码期间或之前施加时，该投射的抑制不仅不会影响偶然的味觉学习本身，而且有效地抑制了厌恶味觉记忆的检索。值得注意的是，在没有经历任何内部不适的情况下，在新的味觉消耗后激活该投射足以形成人工的厌恶味觉记忆，从而在检索时引起强烈的厌恶行为。我们的结果表明，投射到 aIC 到 BLA 的神经元是大脑将味觉感觉刺激与负面效价的身体状态相关联并指导在味觉记忆检索时表达效价特异性行为的能力的重要组成部分。在本研究中，我们使小鼠经历条件性味觉厌恶范式，其中动物学会将新的味觉与不适相关联（即，赋予其负面效价）。我们表明，对条件性味觉厌恶做出反应的前脑岛（aIC）中的神经元的激活投射到基底外侧杏仁核（BLA）对于形成对负面味觉的记忆是必需的。此外，在采样味觉后，即使没有任何疼痛的感觉，该途径的人工激活也可以导致这种联想性记忆。因此，激活 aIC 到 BLA 的投射神经元对于形成和检索厌恶味觉记忆是必需和充分的。
