Choice of method of place cell classification determines the population of cells identified

Author summary Place cells are hippocampal cells that have spatially constrained receptive fields, the place field. These cells have been widely studied in the context of navigation, more recently using virtual reality environments in combination with optical methods of recording neuronal activity. However, there is a lack of consensus regarding how to identify place cells in these data. In this study we tested the sensitivity and specificity of four methods of identifying place cells. By comparing these methods and quantifying the populations of place cells they identify, we aimed to increase our understanding of exactly the populations that are currently being studied under the name "place cells". Although the appropriate method may depend on the experimental design, we generally recommend a single method going forward, which will increase consensus within the field about what should be included in a place cell population, and allow us to better compare results between studies. Place cells, spatially responsive hippocampal cells, provide the neural substrate supporting navigation and spatial memory. Historically most studies of these neurons have used electrophysiological recordings from implanted electrodes but optical methods, measuring intracellular calcium, are becoming increasingly common. Several methods have been proposed as a means to identify place cells based on their calcium activity but there is no common standard and it is unclear how reliable different approaches are. Here we tested four methods that have previously been applied to two-photon hippocampal imaging or electrophysiological data, using both model datasets and real imaging data. These methods use different parameters to identify place cells, including the peak activity in the place field, compared to other locations (the Peak method); the stability of cells' activity over repeated traversals of an environment (Stability method); a combination of these parameters with the size of the place field (Combination method); and the spatial information held by the cells (Information method). The methods performed differently from each other on both model and real data. In real datasets, vastly different numbers of place cells were identified using the four methods, with little overlap between the populations identified as place cells. Therefore, choice of place cell detection method dramatically affects the number and properties of identified cells. Ultimately, we recommend the Peak method be used in future studies to identify place cell populations, as this method is robust to moderate variations in place field within a session, and makes no inherent assumptions about the spatial information in place fields, unless there is an explicit theoretical reason for detecting cells with more narrowly defined properties.