Differences in cytoarchitectural organization and connectivity distinguishes granular (or area 29, A29) and dysgranular (or area 30, A30) subdivisions of the retrosplenial cortex (RSC). Although increasing evidence supports the participation of RSC in contextual fear learning and memory, the contribution of each RSC subdivision remains unknown. Here we used orchiectomized rats and intraperitoneal (i.p.) injections of saline (control) or 5 mg/kg MK801, to trigger selective degeneration of pyramidal neurons in layers IV-Va of A29 (A29MK801 neurons). These treatments were applied 3 days before or two days after contextual fear conditioning, and contextual fear memory was evaluated by scoring freezing in the conditioned context five days after training. Afterwards, brains were fixed and c-Fos and Egr-1 expression were assessed as surrogates of neuronal activity elicited by the recall in A29, A30 and in limbic areas. We found that eliminating A29MK801 neurons after training reduces conditioned freezing to 43.1 ± 9.9% respect to control rats. This was associated with a significant reduction of c-Fos and Egr-1 expression in A30, but not in other limbic areas. On the other hand, eliminating A29MK801 neurons before training caused a mild but significant reduction of conditioned freezing to 79.7 ± 6.8%, which was associated to enhanced expression of c-Fos in A29, A30 and CA1 field of hippocampus, while Egr-1 expression in caudomedial (CEnt) entorhinal cortex was not depressed as in control animals. These observations show that severeness of amnesia differs according to whether A29MK801 neurons were eliminated before or after conditioning, likely because loss of A29MK801 neurons after conditioning disrupt memory engram while their elimination before training allow recruitment of other neurons in A29 for partial compensation of contextual fear learning and memory. These observations add further support for the critical role of A29MK801 neurons in contextual fear learning and memory by connecting limbic structures with A30.

中文翻译：

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通过选择性消除颗粒状脾后皮质（A29）中的IV-Va层神经元引起的逆行和顺行上下文恐惧失忆症。

细胞结构组织和连通性的差异区分了脾后皮质（RSC）的细小部分（或区域29，A29）和反义颗粒（或区域30，A30）。尽管越来越多的证据支持RSC参与情境恐惧学习和记忆，但每个RSC细分的贡献仍然未知。在这里，我们使用经睾丸切除的大鼠和腹膜内（ip）注射生理盐水（对照组）或5 mg / kg MK801，以触发A29的IV-Va层（A29MK801神经元）的锥体神经元选择性变性。这些治疗是在情境恐惧条件调理前三天或两天后进行的，并且通过训练后五天在条件环境条件下的冻结得分来评估情境恐惧记忆。之后，大脑被固定，c-Fos和Egr-1表达被评估为A29，A30和边缘区域召回引起的神经元活动的替代物。我们发现，在训练后消除A29MK801神经元，相对于对照大鼠，其条件性冰冻降低至43.1±9.9％。这与A30中c-Fos和Egr-1表达的显着降低有关，而在其他边缘区域则没有。另一方面，在训练前消除A29MK801神经元会导致条件冻结轻微但显着降低至79.7±6.8％，这与海马A29，A30和CA1区域c-Fos表达的增强有关，而Egr-1表达与对照动物相比，在足内侧（CEnt）的内嗅皮层并不压抑。这些观察结果表明，失忆的严重程度取决于是否在调节之前或之后消除了A29MK801神经元，这很可能是因为调节之后的A29MK801神经元丢失会破坏记忆图谱，而在训练前消除它们会允许在A29中募集其他神经元以部分补偿上下文恐惧学习和记忆。这些观察结果通过将边缘结构与A30连接在一起，进一步支持了A29MK801神经元在情境恐惧学习和记忆中的关键作用。