Quantitative assessment of CA1 local circuits: knowledge base for interneuron-pyramidal cell connectivity

Abstract

In this work, through a detailed literature review, data-mining, and extensive calculations, we provide a current, quantitative estimate of the cellular and synaptic constituents of the CA1 region of the rat hippocampus. Beyond estimating the cell numbers of GABAergic interneuron types, we calculate their convergence onto CA1 pyramidal cells and compare it with the known input synapses on CA1 pyramidal cells. The convergence calculation and comparison are also made for excitatory inputs to CA1 pyramidal cells. In addition, we provide a summary of the excitatory and inhibitory convergence onto interneurons. The quantitative knowledge base assembled and synthesized here forms the basis for data-driven, large-scale computational modeling efforts. Additionally, this work highlights specific instances where the available data are incomplete, which should inspire targeted experimental projects toward a more complete quantification of the CA1 neurons and their connectivity.

Keywords: big data; boutons; convergence; divergence; synapses.

Figure 1

Diagram of interneuron types included in this work. The top of the diagram shows shows bar graphs illustrating the relative numbers of interneuronal subtypes. The dendrites and somata of the interneurons are the same color, and the axon is shown in purple with color coded boutons. Pink boutons specify synapses made only onto other interneurons. The legend below the diagram gives the names and numbers of each interneuron type. Groups of neurons (CCK+ misc, other SOM+, other) that cannot be objectively subdivided at this time, due to lack of sufficient data, are not depicted here. Figure adapted from: Klausberger T, Somogyi P. 2008. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321:53–57. Reprinted with permission from AAAS.

Figure 2

Bar graph showing the relative proportion of each category and type of interneuron calculated in this work. * Other SOM+ category does not include bistratified cells, although they are known to express SOM.

Figure 3

Venn diagram showing how the number of COUP-TFII expressing cells in the CA1 was calculated. Known data: 42% of GABAergic cells express COUP-TFII and 98% of COUP-TFII cells are GABAergic (Fuentealba et al., 2010); 38,500 of CA1 cells are GABAergic (Table 2). Derived data: total number of COUPTFII+ cells in the CA1 (16,500). We then used the calculated number of COUP-TFII+ cells to estimate the abundance of other classes of cells.

Figure 4

Venn diagram showing the logic used to obtain the number of nNOS+/NPY+ cells in the CA1 strata oriens, pyramidale, and radiatum. We used the number of COUP-TFII cells in each layer and the percentage of overlap relative to each population (Fuentealba et al., 2010, see their suppl. table 2) to calculate the total number of nNOS+/NPY+/COUP-TFII+ cells and then the number of nNOS+/NPY+ cells (underlined) for each layer.

Figure 5

Venn diagram showing the α-actinin-2-based logic used to obtain the number of neurogliaform cells in the CA1 stratum lacunosum-moleculare. a) Given the number of COUP-TFII cells in the stratum lacunosum and the percentages of overlap (Fuentealba et al., 2010), the total number of α-actinin-2+/COUPTFII+ and α-actinin-2+ cells can be calculated. b) Given the total number of α-actinin-2+ cells and the percentage that are likely to be neurogliaform cells (Price et al., 2005), the total number of neurogliaform cells can be calculated.

Figure 6

Venn diagram showing how the number of CB1R expressing cells in the CA1 was calculated. Known data: 100% of CCK+ cells express CB1R and 86% of CB1R+ cells express CCK (Katona et al., 1999b). Derived data: total number of CB1R+ cells in the CA1 (5,400).

Figure 7

Venn diagram showing the logic used to obtain the number of CR+/VIP- cells in each layer of the CA1. Given the number of COUP-TFII cells in that layer and the percentage of overlap relative to each population (Fuentealba et al., 2010, see their suppl. table 2), the total number of CR+/VIP-/COUP-TFII+ cells and then the number of CR+/VIP- cells (underlined) was calculated for each layer.

Figure 8

Venn diagram showing the logic used to obtain the number of CR-/VIP+ cells in each layer of the CA1. Given the number of COUP-TFII cells in that layer and the percentage of overlap relative to each population (Fuentealba et al., 2010, see their suppl. table 2), the total number of CR-/VIP+/COUP-TFII+ cells and then the number of CR-/VIP+ cells (underlined) was calculated for each layer.

Figure 9

Venn diagram showing the logic used to obtain the number of CR+/VIP+ cells in each layer of the CA1. Given the number of COUP-TFII cells in that layer and the percentage of overlap relative to each population (Fuentealba et al., 2010, see their suppl. table 2), the total number of CR+/VIP+/COUP-TFII+ cells and then the number of CR+/VIP+ cells (underlined) was calculated for each layer.