Evaluating place cell detection methods in Rats and Humans: Implications for cross-species spatial coding

Place cells, first identified in the rat hippocampus as neurons that fire selectively at specific locations, are central to investigations of the neural underpinnings of spatial navigation. Recent spatial studies in human patients with drug-resistant epilepsy have made identifying and characterizing place cells across species increasingly important for understanding the extent to which decades of rodent research generalize to humans and for uncovering fundamental principles of spatial cognition. One challenge, however, is that detection methods differ: rodent studies often rely on spatial information (SI) in conjunction with place field stability measures, whereas human studies employ analysis of variance (ANOVA) based approaches. These methodological differences may affect the identified place cell populations, which complicates how their properties are interpreted and cross-species comparisons. To address this, we systematically applied multiple detection pipelines to human and rat datasets, supported by simulations that vary place-field properties. Our analyses and simulations demonstrate that spatial information and ANOVA-based approaches are responsive to distinct place field properties: spatial information primarily reflects the contrast between peak and average firing rates, while ANOVA emphasizes consistency across trials. Across species, rodent place cells revealed a broad spectrum of spatial tuning, including strongly tuned neurons with high spatial information and high ANOVA values. In contrast, human place cells lacked this strongly tuned population and exhibited a narrower distribution of tuning scores, concentrated at the lower end of both spatial tuning metrics. Despite these differences, both species had an overlapping population of neurons with weaker yet consistent spatial tuning, which may support important functional roles such as generalization and mixed selectivity. Addressing these analytical differences allows for more direct comparisons between species, though differences in spatial tuning may still relate to variations in experimental paradigms that warrant further investigation. Together, our study provides a roadmap showing how spatial tuning metrics shape place cell detection and interpretation.Author summary: Place cells are neurons that become active in specific locations, and they play a critical role in how the brain supports navigation and memory. Place cells were first discovered in rats and later observed in humans, however, there has been a lack of direct comparisons between species using comparable approaches. Part of the difficulty of doing so is that studies of rodent and human place cells have often relied on different analysis methods, making it difficult to determine if and how place-cell properties differ between species. To address this, in this study, we set out to understand how differences in place cell detection methods affect the identified place cell populations and interpretations of spatial coding across species. To do so, we compared the most prevalent detection methods used in rodent and human research side by side, applying them to datasets from both species and to simulations. We found that different methods emphasize different features of spatial responses, which changes which neurons are identified as place cells. Across species, rat recordings revealed a wide range of spatial responses, from neurons with sharply localized activity to those with broader but reliable patterns. Human recordings, by contrast, were more concentrated at weaker but consistent levels of tuning. Importantly, these weaker but consistent responses reflect an overlapping population of neurons found in both species, which may serve similar functional roles in supporting flexible spatial memory and generalization. By separating methodological effects from biological differences, we lay the groundwork for future cross-species studies for spatial coding.