%0 Generic
%A Barriuso Ortega, Isabel
%C Heidelberg
%D 2023
%F heidok:33200
%R 10.11588/heidok.00033200
%T Space, time and item coding in the lateral entorhinal cortex and the hippocampus
%U https://archiv.ub.uni-heidelberg.de/volltextserver/33200/
%X Episodic memory formation involves encoding information about space, items and time of an experience. In  humans and animals, episodic memory formation depends on the interaction of associative areas with the  hippocampus (HC) and its surrounding parahippocampal areas, in particular the entorhinal cortex (EC). The EC  medial and lateral subdivisions (MEC and LEC), harbour a plethora of spatially and item modulated cell types,  respectively. Thus, MEC and LEC were long considered specialised spatial and item coding centres, respectively,  that conveyed this information to the HC, where it was integrated into one episodic memory. In agreement  with this hypothesis, the firing of neurons in the HC is spatially modulated but is also modified by changes in  contextual and item components of an environment. However, recent studies suggest that both the MEC and  LEC carry out spatial and item coding, albeit the way these elements are encoded may differ. In addition,  temporal coding in the hippocampus requires an intact MEC, however, the specific functional MEC cell types  involved in this process are unknown. Thus, it is currently unclear how space, items and time are encoded in  each of the entorhinal-hippocampal areas, and how the different entorhinal-hippocampal circuits contribute to  the transmission and association of episodic memory components. In this thesis, I explored this question from  three different angles: firstly, I characterized mechanisms of spatial and item coding in the LEC and in the CA1  hippocampal area; secondly, I studied the contribution of a specific MEC-to-LEC pathway to spatial and item  coding in the LEC; thirdly, I evaluated whether the temporal coding process of phase precession in hippocampal  neurons is dependent on a specific MEC functional cell type, namely grid cells. For this purpose, I performed  and analysed in vivo electrophysiological recordings in freely moving mice subjected to a variety of experimental  settings, and combined this with optogenetic tagging of neurons for circuit characterisation. The findings  reported in this thesis fundamentally advance our understanding of the processes underlying episodic memory  encoding in several ways. First, I found that spatial selectivity in the LEC decreases along the anteroposterior  axis, and that spatially modulated neurons remap when the spatial framework changes. In addition, I describe  distinct functional cell types in the LEC encoding for different object features. Importantly, spatial and object  coding neurons appear to be distinct non-overlapping neuronal populations, arguing for a separate processing  of items and space in the LEC. Interestingly, object coding neurons are selectively avoided by long-range  GABAergic projections from MEC to LEC. In the HC, in turn, a subset of spatially modulated neurons also encode  object-related information, suggesting that these two components of episodic memory are integrated, at least  to some extent, in this region. These findings give experimental evidence to the episodic memory encoding  process proposed by the cognitive map theory. Finally, in respect to temporal coding, I demonstrated that phase  precession is intact in the HC when grid cell firing is disrupted in the MEC, indicating that this mechanism may  be dependent on other MEC neurons and/or pathways. Together, these findings uncover new mechanisms of  encoding and transmission of the three episodic memory components in the entorhinal-hippocampal circuits.