Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Mathison Centre for Mental Health, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Neuropsychopharmacology. 2024 Dec;49(13):1989-1999. doi: 10.1038/s41386-024-01927-x. Epub 2024 Aug 9.
The basolateral amygdala (BLA) is reliably activated by psychological stress and hyperactive in conditions of pathological stress or trauma; however, subsets of BLA neurons are also readily activated by rewarding stimuli and can suppress fear and avoidance behaviours. The BLA is highly heterogeneous anatomically, exhibiting continuous molecular and connectivity gradients throughout the entire structure. A critical gap remains in understanding the anatomical specificity of amygdala subregions, circuits, and cell types explicitly activated by acute stress and how they are dynamically activated throughout stimulus exposure. Using a combination of topographical mapping for the activity-responsive protein FOS and fiber photometry to measure calcium transients in real-time, we sought to characterize the spatial and temporal patterns of BLA activation in response to a range of novel stressors (shock, swim, restraint, predator odour) and non-aversive, but novel stimuli (crackers, citral odour). We report four main findings: (1) the BLA exhibits clear spatial activation gradients in response to novel stimuli throughout the medial-lateral and dorsal-ventral axes, with aversive stimuli strongly biasing activation towards medial aspects of the BLA; (2) novel stimuli elicit distinct temporal activation patterns, with stressful stimuli exhibiting particularly enhanced or prolonged temporal activation patterns; (3) changes in BLA activity are associated with changes in behavioural state; and (4) norepinephrine enhances stress-induced activation of BLA neurons via the ß-noradrenergic receptor. Moving forward, it will be imperative to combine our understanding of activation gradients with molecular and circuit-specificity.
外侧杏仁核（BLA）在心理压力下可靠地被激活，并在病理性压力或创伤条件下过度活跃；然而，BLA 的亚群神经元也很容易被奖励刺激激活，并能抑制恐惧和回避行为。BLA 在解剖学上高度异质，在整个结构中表现出连续的分子和连接梯度。一个关键的差距仍然存在于理解杏仁核亚区、回路和细胞类型的解剖特异性，这些亚区、回路和细胞类型被急性应激明确激活，以及它们在整个刺激暴露过程中是如何动态激活的。我们使用活性反应蛋白 FOS 的地形映射和光纤光度法来实时测量钙瞬变的组合，旨在表征 BLA 在一系列新应激源（电击、游泳、束缚、捕食者气味）和非厌恶但新颖刺激（饼干、柠檬醛气味）下的激活的空间和时间模式。我们报告了四个主要发现：（1）BLA 在对整个中-外侧和背-腹轴的新刺激的反应中表现出明显的空间激活梯度，而厌恶刺激强烈地偏向 BLA 的内侧部分激活；（2）新刺激引起不同的时间激活模式，应激刺激表现出特别增强或延长的时间激活模式；（3）BLA 活动的变化与行为状态的变化有关；（4）去甲肾上腺素通过β-肾上腺素能受体增强 BLA 神经元的应激诱导激活。展望未来，将激活梯度与分子和回路特异性相结合将是至关重要的。
