CA1 layers · Contribution of distinct pyramidal cell types in hippocampal area CA1 to episodic memory formation
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-06-01 → 2018-05-31
- EU contribution
- €159,461
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Contribution of distinct pyramidal cell types in hippocampal area CA1 to episodic memory formation
One central component of our lives is the ability to find our way around - to work, home, to our favourite restaurant - and to store the events that we experience at those places in our memory. It is known since the 1950s that damage to a collection of brain regions referred to as the hippocampal formation (HF) causes severe deficits in the ability to form new memories in both humans as well as lab animals, such as mice. The overall objective of this project was to elucidate how exactly individual components (or neuronal cell types) of the HF interact in order to create new memories. Performing electrophysiological experiments in genetically modified mice, we were able to demonstrate how different cell types in the HF and a structure referred to as the medial septum interact in order to create a brain clock – a signal which enables our brain to sort memories in the correct temporal order. In a separate project, we focused our investigation on the question of how neurons referred to as grid cells contribute to our ability to navigate. Grid cells are neurons which form a map of the environment and, based on theoretical grounds, were hypothesized to function as the brain’s GPS system. Their importance was recognized with the Nobel Prize 2013. We developed a technique that allowed us to selectively disrupt grid cells. Using this technique, we were able to investigate how grid cells contribute to the function of their communication patterns, and finally, we were the first to provide direct experimental evidence for the theory that grid cells are indeed important for our ability to navigate. The HF is a vulnerable part of the brain and damage to its individual components is observed even in early stages of numerous neurological conditions such as stroke, epilepsy and Alzheimer's disease. Typical symptoms such as loss of memory and spatial navigation skills are likely due to such damage to the HF. The project described here provided us with more detailed information of how exactly the healthy HF functions. Understanding the exact processes of how memories are formed in the healthy brain will allow us to better understand what goes wrong in the diseased brain. This, in turn, will point us towards more directed strategies to slow down or prevent pathological memory loss and to improve memory function in patients with neurological conditions.
Data: CORDIS, © European Union
Project objective
The formation of episodic (unique event) memories is based on the interaction between the hippocampus and the cortical regions that receive its output. The major hippocampal output cells are pyramidal cells (PCs) in area CA1. In rodents, populations of CA1 PCs are known to represent a wide range of aspects associated with an episodic memory: Some cells participate in the formation of a map-like representation of space, while others additionally or exclusively encode items within the environment, represent meaningful locations, or participate in the representation of emotional and behavioural contexts. It is not known so far how heterogeneous CA1 firing patterns are organized and affect memory formation. While CA1 PCs have been traditionally considered a homogeneous cell population, we now have clear evidence for the presence of at least two distinct CA1 PC cell types that differ in their local and long-range connectivity, in their morphology, their molecular makeup and their basic firing patterns. This strongly argues for a functional specialization within the CA1 area. However, a link between the heterogeneous representation of mnemonic information and the presence of anatomically distinct PC types remains to be established. In this proposal I aim to determine whether heterogeneous response properties of CA1 PCs are based on computations in distinct anatomical microcircuits in deep and superficial layers by combining optogenetic and chemogenetic techniques with in vivo recordings in behaving mice. Furthermore, I will seek to obtain detailed knowledge about the functional connectivity between different CA1 PC populations and their target areas. Knowledge about the function of individual CA1 microcircuits and their anatomical connections is the prerequisite to subsequently develop an independent research plan aiming to determine how intra-hippocampal processing affects memory formation in their downstream targets.
Original text from CORDIS.
Participants
- UNIVERSITATSKLINIKUM HEIDELBERG · HeidelbergCoordinatorGermany
Links
Data: CORDIS, © European Union