Poster Session 3.N - Neurosciences
Velencei, Anna
HUN-REN Institute of Experimental Medicine
Anna Velencei1, Balázs Lükő1, dr. Judit Makara1
1: HUN-REN Institute of Experimental Medicine
Introduction
The ability to form and retrieve memories is fundamental to everyday life. The hippocampus plays a central role in memory processing, with its subregions: the dentate gyrus (DG), CA3, and CA1. The CA3 region is particularly important for associative memory due to its recurrent connectivity. CA3 pyramidal cells (CA3PCs) are interconnected and receive input from DG granule cells via mossy fibers and from the entorhinal cortex. The DG-CA3 circuit is thought to support pattern separation and pattern completion: Pattern separation, mainly attributed to DG, transforms similar inputs into distinct representations that are transferred to CA3 via detonating mossy fibre (MF) synapses of DG granule cells. On the other hand, pattern completion, mediated by CA3 recurrent connections, enables retrieval of stored patterns from partial cues. However, experimental evidence demonstrating the precise role of DG and CA3 in these processes remains limited, with few in vivo studies at cellular resolution.
Aims
This project aims to reveal the cellular and subcellular activity patterns and population function of the DG-CA3 circuit using in vivo two-photon calcium imaging head-fixed behaving mice.
Methods
Activity of DG cells and their MF terminals innervating CA3PCs is measured using in vivo two-photon imaging with genetically encoded Ca²⁺ indicators expressed in CA3PCs and DG granule cells. Mice are head-fixed and navigate in familiar and novel virtual environments while receiving rewards at specific locations. A custom analysis pipeline is developed to quantify behavioral adaptation, reduce motion artifacts and track neurons across sessions.
Results
When switching from familiar to a novel environment, mice learn the location of a reward zone within a few days. Imaged MFs show sparse activity during navigation, with a fraction of axons exhibiting spatial tuning. Learning to navigate in novel environments is accompanied by activity changes in a subpopulation of MFs.
Conclusion
We established methodology to perform subcellular in vivo imaging to study in the functional properties of the unique MF-CA3 connection. This study will provide insights into the cellular mechanisms underlying memory formation.
Funding
The project is conducted as part of a PhD research program of Semmelweis University and is supported by the University Research Scholarship Programme (EKÖP).