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IntraSpace Report Summary

Project ID: 338141
Funded under: FP7-IDEAS-ERC
Country: France

Periodic Report Summary 2 - INTRASPACE (An intracellular approach to spatial coding in the hippocampus)

Humans as many other animals from birds to insects are able to orient themselves and navigate in familiar environments. This ability is thought to rely on the activity of cells in the hippocampal formation, an ensemble of brain structures in the medial temporal lobe in humans. At the core of this network, the hippocampus is important both for spatial navigation and for episodic memory (the memory of our everyday life events). In rodents exploring a new environment, a small ensemble of excitatory cells in the hippocampus, called place cells, will be active in specific locations (their place field) while the majority of hippocampal excitatory cells remain silent. These neurons are thought to represent a cognitive map, a mental representation of that environment, allowing flexible spatial navigation, which will be stored in long-term memory. Understanding the mechanisms involved in the selection of which cells will be active in a particular environment is important to understand the formation of spatial maps and episodic memories. This question is at the core of the InstraSpace project. The ability of a given cell to map an environment could be in part rigidly pre-determined even before spatial exploration (Dragoi and Tonegawa., 2011; Epsztein et al., 2011; Grosmark et al., 2016), maybe through increased intrinsic cellular excitability (Epsztein et al., 2011; Lee et al., 2012) but the mechanisms are unknown. Intrinsic excitability is set by the expression and distribution of voltage-gated channels in a particular cell, which will increase or decrease its ability to respond to incoming inputs. The aim of this project is to further understand the link between intrinsic excitability and mapping.
For this we took advantage of newly developed techniques to perform whole-cell recordings in navigating animals that we contributed to develop together with Dr. A. Lee and Pr. M. Brecht (Lee et al., 2006; Harvey et al., 2009; Lee, Epsztein and Brecht, 2009; Lee et al., 2014). These recordings allow us to monitor the inputs received by a given cell and its outputs thus assessing their input/output function and to stimulate a given cell or inject pharmacological agents in order to induce long-term modifications of its intrinsic excitability.
In a first part of the project we tested several stimulation protocols to selectively induce long-term modifications of the intrinsic excitability of a given cell. We were able to induce a long-term decrease in excitability. We performed several experiments to determine the mechanisms behind these changes. We are now in the process of determining how these long-term changes could modify the ability of a given cell to be activated in the next explored environment.
In a second part of the project we want to see whether the recruitment rule based on intrinsic excitability differed in other part of the hippocampal formation and we started to correlate the level of intrinsic excitability and the recruitment probability of cells in upstream parts of the hippocampal formation.
In a third and last part of the project we wanted to understand the mechanisms behind changes in the coding of place cells that are observed when changes occur in a familiar environment, which is closer to our everyday experience. We often take the same streets to go from home to work but the parked cars have changed, the people in the street are different, the trees have lost their leaves during winter yet we can always find our way. For this we made use of virtual reality to be able to modify instantaneously and in a controlled way the explored environments. The use of virtual reality allowed us to reveal the importance of proximal visual landmarks for the accurate coding of space. We also found that modulating these landmarks could profoundly modify the coding of a familiar environment a process called remapping. The intracellular mechanisms behind these changes are being investigated with whole-cell patch clamp recordings.
Overall this project aims at revealing the cellular mechanisms involved in the formation of spatial memories, which allow us to navigate. This essential function is impaired in several neurological diseases such as Alzheimer disease and temporal lobe epilepsy.


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Record Number: 199494 / Last updated on: 2017-06-21
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