Departamento de Psicobiologia, Universidade Federal de São Paulo-UNIFESP, São Paulo 04023-062, Brazil.
Universidade Cruzeiro do Sul-UNICSUL, São Paulo 08060-070, Brazil.
Cereb Cortex. 2023 Dec 9;33(24):11456-11470. doi: 10.1093/cercor/bhad375.
In trace fear conditioning, the prelimbic cortex exhibits persistent activity during the interval between the conditioned and unconditioned stimuli, which maintains a conditioned stimulus representation. Regions cooperating for this function or encoding the conditioned stimulus before the interval could send inputs to the prelimbic cortex, supporting learning. The basolateral amygdala has conditioned stimulus- and unconditioned stimulus-responsive neurons, convergently activated. The prelimbic cortex could directly project to the basolateral amygdala to associate the transient memory of the conditioned stimulus with the unconditioned stimulus. We investigated the neuronal circuit supporting temporal associations using contextual fear conditioning with a 5-s interval, in which 5 s separates the contextual conditioned stimulus from the unconditioned stimulus. Injecting retrobeads, we quantified c-Fos in prelimbic cortex- or basolateral amygdala-projecting neurons from 9 regions after contextual fear conditioning with a 5-s interval or contextual fear conditioning, in which the conditioned and unconditioned stimuli overlap. The contextual fear conditioning with a 5-s interval activated ventral CA1 and perirhinal cortex neurons projecting to the prelimbic cortex and prelimbic cortex neurons projecting to basolateral amygdala. Both fear conditioning activated ventral CA1 and lateral entorhinal cortex neurons projecting to basolateral amygdala and basolateral amygdala neurons projecting to prelimbic cortex. The perirhinal cortex → prelimbic cortex and ventral CA1 → prelimbic cortex connections are the first identified prelimbic cortex afferent projections participating in temporal associations. These results help to understand time-linked memories, a process required in episodic and working memories.
在痕迹恐惧条件反射中，边缘前皮质在条件刺激和非条件刺激之间的间隔期间表现出持续的活动，从而维持条件刺激的表示。在该间隔之前，为该功能合作或对条件刺激进行编码的区域可以向边缘前皮质发送输入，以支持学习。基底外侧杏仁核具有条件刺激和非条件刺激反应神经元，它们会聚激活。边缘前皮质可以直接投射到基底外侧杏仁核，将条件刺激的短暂记忆与非条件刺激相关联。我们使用具有 5 秒间隔的上下文恐惧条件反射来研究支持时间关联的神经元回路，在这种情况下，5 秒将上下文条件刺激与非条件刺激分开。通过注射逆行示踪剂，我们在具有 5 秒间隔的上下文恐惧条件反射或上下文恐惧条件反射后，从 9 个区域中量化了边缘前皮质或基底外侧杏仁核投射神经元中的 c-Fos，其中条件刺激和非条件刺激重叠。具有 5 秒间隔的上下文恐惧条件反射激活了向边缘前皮质投射的腹侧 CA1 和边缘旁回神经元，以及向基底外侧杏仁核投射的边缘前皮质神经元。两种恐惧条件反射均激活了向基底外侧杏仁核投射的腹侧 CA1 和外侧内嗅皮质神经元，以及向边缘前皮质投射的基底外侧杏仁核神经元。边缘旁回→边缘前皮质和腹侧 CA1→边缘前皮质的连接是首次确定的参与时间关联的边缘前皮质传入投射。这些结果有助于理解时间相关的记忆，这是情节记忆和工作记忆所必需的过程。
