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

Abstract

ABSTRACTThe human hippocampus plays a central role in learning and memory functions and is implicated in several neurological and psychiatric disorders linked to different subpopulations of its neurons. Understanding the complex workings of the human hippocampus requires computational models with accurate quantitative neuronal data. Although the total number of different hippocampal neurons and their synapses have been extensively described in rodents, most of these data are not available for the human hippocampus. All hippocampal functions are tightly regulated by different classes of local GABAergic interneurons. Therefore, here we used unbiased stereological methods to estimate the density and total number of three major GABAergic cell groups: the parvalbumin (PV)-expressing interneurons, the somatostatin (SOM)-positive interneurons and the calretinin (CR)-positive interneurons. We found that there are approximately 45600 PV-positive, 134500 SOM-positive and 228000 CR-positive interneurons per hippocampal hemisphere. Compared to rodent data, the higher proportion of CR-positive -typically interneuron selective-cells may contribute to a more robust regulation of local interneurons. We also used 3-dimensional electron microscopy to estimate the total number of GABAergic boutons and synapses in the different layers of the hippocampus, and we also quantified those originating from PV-positive neurons. We estimated that there are at least about 1.82 * 1010GABAergic synapses in one hippocampal hemisphere, of which about 2.77 * 109are PV-positive, representing about 15.2% of the total GABAergic synapses of local or afferent neurons.