Absolute number of three populations of interneurons and all GABAergic synapses in the human hippocampus

ABSTRACT 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 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, the higher proportion of CR-positive, primarily interneuron-selective, cells in humans, compared to rodents, may enhance local interneuron regulation. Additionally, using 3-dimensional electron microscopy, we estimated approximately 25 billion GABAergic synapses per hippocampal hemisphere, with PV-positive boutons comprising around 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.