Do stability of hippocampal neuronal excitatory synaptic connectivity and representations support spatial learning?

• Applicants: Dr. Alessio Attardo; Professor Dr. Andreas Kist
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554586006

Hippocampal pyramidal neurons encode spatial locations through localized firing patterns, or place cells. Studies in humans and animals have shown a critical role for the hippocampus in spatial and episodic memory. Several theories have sought to explain how the hippocampus supports these functions and have considered place cells as basic substrates of long-term spatial memory. In many such frameworks, a central tenet is that long-term spatial memory arises from ensembles of cells that retain their spatial coding properties over time periods relevant to long-term memory. However, hippocampal spatial representations exhibit a surprising level of instability, or drift, which seems counterintuitive for a brain region important for memory formation. A few hypotheses exist on the function of this phenomenon, but the cellular and circuit mechanisms underlying hippocampal representational drift representations are completely unknown. By using two-photon time-lapse imaging to track simultaneously excitatory structural plasticity and activity patterns of the same pyramidal neurons over several days in the hippocampus of live mice, we want to shed light on the link between the stability connectivity and the drift of hippocampal representations. Moreover, we will study the relationship between structural plasticity, representation turnover, and learning by using a behavioral learning task, concomitant to imaging, and by perturbing the activity patterns of hippocampal dorsal CA1 pyramidal neurons by increasing local inhibition. In parallel, - and to increase the efficiency and reliability of our data analysis – we will develop a method based on machine and deep learning to consistently and automatically track dendritic spines in two-photon image time lapses and to match these to the activity of single pyramidal neurons in hippocampal dorsal CA1.

• DFG Programme: Research Grants