A universal hippocampal memory code across animals and environments

How learning is affected by context is a fundamental question of neuroscience, as the ability to generalize learning to different contexts is necessary for navigating the world. An example of swift contextual generalization is observed in conditioning tasks, where performance is quickly generalized from one context to another. A key question in identifying the neural substrate underlying this ability is how the hippocampus (HPC) represents task-related stimuli across different environments, given that HPC cells exhibit place-specific activity that changes across contexts (remapping). In this study, we used calcium imaging to monitor hippocampal neuron activity as animals performed a conditioning task across multiple spatial contexts. We investigated whether hippocampal cells, which encode both spatial locations (place cells) and task-related information, could maintain their task representation even when their spatial encoding remapped in a new spatial context. To assess the consistency of task representations, we used advanced dimensionality reduction techniques combined with machine learning to develop manifold representations of population level HPC activity. The results showed that task-related neural representations remained stable even as place cell representations of spatial context changed, thus demonstrating similar embedding geometries of neural representations of the task across different spatial contexts. Notably, these patterns were not only consistent within the same animal across different contexts but also significantly similar across different animals, suggesting a standardized neural encoding or ‘neural syntax’ in the hippocampus. These findings bridge a critical gap between memory and navigation research, revealing how the hippocampus maintains cognitive consistency across different spatial environments. These findings also suggest that hippocampal function is governed by a neural framework shared between animals, an observation that may have broad implications for understanding memory, learning, and related cognitive processes. Looking ahead, this work opens new avenues for exploring the fundamental principles underlying hippocampal encoding strategies.