Amygdala interneuron subtypes control fear learning through disinhibition

摘要

Learning is mediated by experience-dependent plasticity in neuronal circuits. Activity in neuronal circuits is tightly regulated by different subtypes of inhibitory intemeurons, yet their role in learning is poorly understood. Using a combination of in vivo single-unit recordings and optogenetic manipulations, we show that in the mouse basolateral amygdala, interneurons expressing parvalbumin (PV) and somatostatin (SOM) bidirectionally control the acquisition of fear conditioning-a simple form of associative learning-through two distinct disinhibitory mechanisms. During an auditory cue, PV~+ intemeurons are excited and indirectly disinhibit the dendrites of basolateral amygdala principal neurons via SOM~+ intemeurons, thereby enhancing auditory responses and promoting cue-shock associations. During an aversive footshock, however, both PV~+ and SOM~+ interneurons are inhibited, which boosts postsynaptic footshock responses and gates learning. These results demonstrate that associative learning is dynamically regulated by the stimulus-specific activation of distinct disinhibitory microcircuits through precise interactions between different subtypes of local intemeurons.%神经微回路内依赖于经验的可塑性据信是学习 和记忆中的一个关键部分,但只是在最近人们 才有可能对这些回路进行详细研究。以小鼠的 经典条件化听觉恐惧为模型系统,Andreas Luethi及同事识别出两个截然不同的与学习相 关的非抑制性机制,涉及截然不同的中间神 经元类群。通过以所识别出的中间神经元类 型为目标对自由活动的小鼠进行活体生理和 光遗传分析,本文作者发现,表达小清蛋白 的中间神经元限制已知会直接键合到主神经 元上的第二个中间神经元类群(表达生长抑制 素)的放电(firing),从而不会抑制杏仁核主神 经元。作者猜测,这一微回路中PV~+和SOM~+ 中间神经元的差异化调制,可能会允许根据 行为情景和实验动物的内在状态来对学习进行 灵活的调控。