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

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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.