Nature2014-06-09 4:52 PM

中间神经元在学习中的非抑制行为 Amygdala interneuron subtypes control fear learning through disinhibition 

论文摘要 

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 Lüthi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。

Abstract 

Learning is mediated by experience-dependent plasticity in neuronal circuits. Activity in neuronal circuits is tightly regulated by different subtypes of inhibitory interneurons, 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+ interneurons are excited and indirectly disinhibit the dendrites of basolateral amygdala principal neurons via SOM+ interneurons, 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 interneurons.

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