Absolute Number of Three Populations of Interneurons and All GABAergic Synapses in the Human Hippocampus

The human hippocampus, essential for learning and memory, is implicated in numerous neurological and psychiatric disorders, each linked to specific neuronal subpopulations. Advancing our understanding of hippocampal function requires computational models grounded in precise quantitative neuronal data. While extensive data exist on the neuronal composition and synaptic architecture of the rodent hippocampus, analogous quantitative data for the human hippocampus remain very limited. Given the critical role of local GABAergic interneurons in modulating hippocampal functions, we employed unbiased stereological techniques to estimate the density and total number of three major GABAergic cell types in the male and female human hippocampus: parvalbumin (PV)-expressing, somatostatin (SOM)-positive, and calretinin (CR)-positive interneurons. Our findings reveal an estimated 49,400 PV-positive, 141,500 SOM-positive, and 250,600 CR-positive interneurons per hippocampal hemisphere. Notably, CR-positive interneurons, which are primarily interneuron-selective in rodents, were present in humans at a higher proportion. Additionally, using three-dimensional electron microscopy, we estimated ∼25 billion GABAergic synapses per hippocampal hemisphere, with PV-positive boutons comprising ∼3.5 billion synapses, or 14% of the total GABAergic synapses. These findings contribute crucial quantitative insights for modeling human hippocampal circuits and understanding its complex regulatory dynamics.