How does activity of CA3 engram neurons affect CA1 spatial codes?

• Applicants: Dr. Alessio Attardo; Professor Dr. Christian Leibold
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456352444

Hippocampal pyramidal neurons can encode the spatial location of an animal through localized firing patterns, or place cells. Studies on humans and animals have shown a critical role for the hippocampus in spatial and episodic memory. It is largely thought that long-term spatial memory arises from ensembles of cells that retain their spatial coding properties over time periods relevant to long-term memory. Recently, however, a surprising level of instability has been demonstrated in the hippocampus. In fact, hippocampal spatial representations have both dynamic and stable facets. In rodents, there is day-to-day turnover in the set of hippocampal cells representing environments, which might help distinguish the representations of the different visits. However, individual CA1 neural place fields can exhibit long-term stability. Overall, the mechanisms supporting turnover versus stability of hippocampal representations are completely unknown.Ensembles of neurons undergoing coordinated activity-dependent plasticity not only represent experience but are also functional for learning and memory recall, thus they are largely believed to be cellular memory engrams. The activity of engram neurons has a key role in systems memory consolidation. As hippocampal representations are postulated to support memory formation and consolidation, engram neurons should also be important for the dynamics of these representations. Still, this issue is largely unexplored mostly owing to technical difficulties. In this project we propose to combine the complementary expertise of our laboratories to investigate the systems mechanisms that lead to turnover and specificity of representations in hippocampal CA1. Specifically, we will investigate how activity of CA3 engram neurons affects turnover, specificity and directionality of CA1 spatial representations. To achieve these aims we will take advantage of our laboratories’ cutting-edge technologies and analysis frameworks. We will combine Wide Field Head Mounted microscopes - to record neuronal activity in the CA1 of mice as they explore different environments - with optogenetics - to control the activity of CA3 engram neurons – and used advanced analysis tools to investigate the effects of forced re-activation of CA3 engram neurons on activity patters of CA1 neurons.

• DFG Programme: Research Grants