Updated Neuronal Numbers of the Rat Hippocampal Formation: Redesigning the Hippocampal Model

The hippocampal formation is a functional entity that includes the hippocampus, subicular complex, and the entorhinal cortex, and has an essential role in learning and memory, emotional processing, and spatial coding. The well-defined structure of hippocampal fields and the segregation of the connections have made this structure a favorite candidate for functional models that rely on fundamental information such as the number of neurons populating the hippocampal fields. Existing models on the rat rely on neuronal populations obtained from single studies, so we aimed to obtain more representative estimates by analyzing all available data. We identified 89 studies using reliable methodology that provided 264 stereological estimates of principal neuron populations. The resulting averages for males showed 1,000,000 neurons for the granule cell layer (GCL); 50,000 for the hilus; 210,000 for CA3; ~30,000 for CA2; 350,000 for CA1; and 300,000 for the Subiculum. Entorhinal cortex (EC) averages for both sexes showed 108,000 neurons in layer II; 270,000 in layer III; and 340,000 in layer V/VI. Most of those estimates are significantly different from those traditionally used in hippocampal models (e.g., ~2-fold difference in EC layer II), revealing an updated architecture of the rat hippocampal formation that might help build more realistic models of hippocampal connectivity and function. Comparisons by age or sex were not reliable given the scarce data available from adolescents or females, while comparisons by strain showed inconsistent results, with similar populations in most fields but significant differences in CA3/CA2. The reliability of this finding is discussed.