Department of Psychology, Tulane University, New Orleans, LA 70118.
Tulane Brain Institute, Tulane University, New Orleans, LA 70118.
eNeuro. 2023 Sep 7;10(9). doi: 10.1523/ENEURO.0319-22.2023. Print 2023 Sep.
To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Jikomes et al., 2016; Heinz et al., 2017), these tasks required different behavioral responses to each stimulus. As many brain regions involved in survival behavior process stimuli of opposite valence, we developed a paradigm in which mice perform the same response (nose poke) to distinct auditory cues to obtain a rewarding outcome (palatable food) or avoid an aversive outcome (mild footshoock). This design allows for both within-subject and between-subject comparisons as animals respond to appetitive and aversive cues. The central nucleus of the amygdala (CeA) is implicated in the regulation of responses to stimuli of either valence. Considering its role in threat processing (Wilensky et al., 2006; Haubensak et al., 2010) and regulation of incentive salience (Warlow and Berridge, 2021), it is important to examine the contribution of the CeA to mechanisms potentially underlying comorbid dysregulation of avoidance and reward (Sinha, 2008; Bolton et al., 2009). Using this paradigm, we tested the role of two molecularly defined CeA subtypes previously linked to consummatory and defensive behaviors. Significant strain differences in the acquisition and performance of the task were observed. Bidirectional chemogenetic manipulation of CeA somatostatin (SOM) neurons altered motivation for reward and perseveration of reward-seeking responses on avoidance trials. Manipulation of corticotropin-releasing factor neurons (CRF) had no significant effect on food reward consumption, motivation, or task performance. This paradigm will facilitate investigations into the neuronal mechanisms controlling motivated behavior across valences.
为了生存，动物必须满足其生理需求，同时避免危险。然而，动物的觅食和厌恶性生存行为的神经生物学基础一直是通过单独的行为任务来研究的。虽然最近在小鼠中的研究同时量化了觅食和厌恶性条件反应（Jikomes 等人，2016 年；Heinz 等人，2017 年），但这些任务需要对每个刺激物做出不同的行为反应。由于许多参与生存行为的大脑区域会对具有相反效价的刺激物进行处理，因此我们开发了一种范式，即让小鼠对不同的听觉线索做出相同的反应（鼻触），以获得奖励（美味食物）或避免惩罚（轻度足部电击）。这种设计允许进行个体内和个体间的比较，因为动物会对觅食和厌恶性线索做出反应。杏仁中央核（CeA）参与调节对任何效价刺激物的反应。考虑到它在威胁处理中的作用（Wilensky 等人，2006 年；Haubensak 等人，2010 年）和激励性显著的调节作用（Warlow 和 Berridge，2021 年），研究 CeA 对潜在的回避和奖励调节失调的机制的贡献很重要（Sinha，2008 年；Bolton 等人，2009 年）。使用该范式，我们测试了先前与摄食和防御行为相关的两种分子定义的 CeA 亚型的作用。在任务的获得和表现方面观察到显著的品系差异。CeA 生长抑素（SOM）神经元的双向化学遗传操作改变了回避试验中对奖励的动机和对奖励寻求反应的持续。CRF 神经元的操作对食物奖励消耗、动机或任务表现没有显著影响。该范式将有助于研究控制跨效价动机行为的神经元机制。
