Processing spatial and non-spatial information during the retrieval of motivated memories (B17#)

动机是成功形成和提取记忆的关键因素之一。内侧颞叶（MTL）包括海马和海马旁皮质区，如外侧和内侧内嗅皮质，在情景记忆中起着至关重要的作用，并接收来自调节动机状态的所有区域的直接/间接输入。一个流行的情景记忆模型，“两流假说”，提出空间和非空间信息的处理是通过分离的皮质通路进行的，这两种信息流在海马体水平上整合到一个情节中。然而，这种整合的经验证据是缺乏的，这些皮质通路在海马体的不同近端远端水平投射，这与信息整合的想法不一致。此外，我们最近提出的证据表明，在使用食欲任务的海马亚区CA1和CA3的近远端轴上存在分离的空间和非空间子网络。这使我们形成了一个全新的概念，描述子网络优先处理海马体内沿这条轴分离的空间或非空间信息。形成/提取记忆的动机已被证明会影响颞叶颞叶区域被用来提取记忆的时间。在目前的建议中，我们建议通过首先测试空间和非空间子网络中的活动是否根据所涉及的动机行为的类型而有所不同来进一步表征这些网络。这将通过检测即时早期基因Arc的产物（用作细胞激活的标记）来完成，通过对大鼠在执行空间或非空间版本的厌恶动机任务（恐惧条件反射）和更中性的任务（自发的物体识别记忆任务）时，CA1和CA3的近端和远端部分引发的细胞水平的大脑活动进行分辨率成像来完成。其次，我们将使用体内电生理学来研究，在执行食欲任务的大鼠中，属于同一个海马体子网络的区域的活动是否同步，这些子网络已被首次描述（与B01项目合作）。第三，使用相同的食欲任务，我们将通过光遗传学评估皮层水平（LEC或MEC）细胞放电抑制对特定子网络募集的影响，来研究这些海马子网络是否是更大的分离MTL子网络的一部分。最后，作为转化的第一步，我们将使用7T功能磁共振成像技术寻找人类中存在这种隔离网络的证据。

Motivation is one of the key elements to successfully forming and retrieving memories. The medial temporal lobe (MTL), which includes the hippocampus and parahippocampal cortical areas such as the lateral and medial entorhinal cortices, plays a crucial role in episodic memory and receives direct/indirect inputs from all areas modulating motivational states. A prevailing model of episodic memory, the ‘two stream hypothesis’, puts forward the processing of spatial and non-spatial information by segregated cortical pathways and the integration of these two information streams at the level of the hippocampus into an episode. Empirical evidence for such an integration is however lacking and these cortical pathways project at distinct proximodistal levels of the hippocampus, which is not consistent with the idea of an integration of the information. Moreover, we have recently brought evidence for the existence of segregated spatial and non-spatial subnetworks along the proximodistal axis of the hippocampal subfields CA1 and CA3 using appetitive tasks. This led us to formulate a completely new concept describing subnetworks preferentially processing spatial or non-spatial information segregated along this axis within the hippocampus. The motivation underlying the memory to be formed/retrieved has been shown to influence at time which MTL area is recruited for the retrieval of memory. In the present proposal, we propose to further characterize these networks by first testing whether activity in the spatial and non-spatial subnetworks differs depending on the type of motivated behavior at stake. This will be done by imaging with resolution to the cell level brain activity elicited in the proximal and distal parts of CA1 and CA3 of rats performing spatial or non-spatial versions of an aversively motivated task (fear conditioning) and a more neutral task (spontaneous object recognition memory task) by detecting the product of the immediate-early gene Arc, used as a marker of cell activation. Second, we will study whether activity in areas belonging to the same hippocampal subnetwork is synchronized using in-vivo electrophysiology in rats performing in the appetitive tasks the subnetworks have been first described with (collaboration with project B01). Third, using the same appetitive tasks, we will investigate whether these hippocampal subnetworks are a part of larger segregated MTL subnetworks by assessing the impact of the inhibition of cell firing at the cortical level (the LEC or the MEC) on the recruitment of the specific subnetworks using optogenetics. Finally, as first translational step, we will look for evidence of the existence of such segregated networks in humans using 7T fMRI techniques.