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Hippocampal formationSummaryThe hippocampal formation is a highly homologous structure across all mammals and, in primates, is located inside the temporal lobe, alongside the amygdala, medial to the inferior horn of the lateral ventricle (shown in Figure 1). The hippocampus is pivotal in recollection of facts and formation of new (including spatial) memories. In fact, long-term potentiation (modifications in synaptic strength as a result of neural activity) in certain parts of the hippocampus has been suggested as a storage mechanism for memory. Information flows into and through the hippocampus through the following principal pathways: 1- the perforant pathway from the entorhinal cortex to granule cells of the dentate gyrus; 2- the mossy fiber pathway from the granule cells of the dentate gyrus to the pyramidal cells of the CA3 region; 3- the Schaffer collateral pathway from the CA3 to the CA1 region. The transcriptome analysis shows that 72% (n=14378) of all human protein-coding genes (n=20090) are expressed in the human hippocampal formation. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 12373 of all mouse one-to-one orthologues (n=16320) are expressed in the mouse hippocampal formation and that 13285 of all pig orthologues (n=15829) are expressed in the pig hippocampal formation.
Figure 1. Schematic drawing of the human brain, indicating the location of hippocampal formation from a coronal perspective. Gene classification based on regional RNA expression in human, pig and mouse hippocampal formation defines 35 genes as hippocampal formation enriched in either of the three species, and 5 out of those genes show highest expression levels in hippocampal formation in all three species. Anatomical divisionsThe hippocampal formation is an inward folded continuation of the cerebral cortex. This brain region includes the entorhinal cortex, subiculum, hippocampus proper cornu ammonis CA1-3 and dentate gyrus. The main cell types of the hippocampal formation are glutamatergic pyramidal neurons located in the cortical areas and CA regions, granule cells located in the dentate gyrus, and interneurons populating different subfields of this brain structure. Pyramidal cells in the CA regions are densely packed in a single layer. The dendrites of these cells receiving input from other regions of the hippocampal formation are located on both sides of the pyramidal cell layer in the oriens layer (superficial) and radiatum layer. The dentate gyrus granule cells are also packed in a single cell layer. These cells have their dendritic trees located in the molecular layer. The axons of these neurons are called mossy fibers and innervate the CA3 pyramidal neurons. The dentate gyrus is one of the brain regions wherein the fully developed brain still new neurons are formed (neurogenesis). These newborn neurons are formed on the interface between the polymorph layer and granular layer. More than 20 different populations of interneurons have been identified based on their location, molecular signature (calcium binding proteins, neuropeptides) and electrophysiological properties. Protein profiles of hippocampus include several interesting patterns, both in human and mouse, either related to certain cell types or selective synaptic fields, where below are a few examples. Regionally elevated protein expression in humanThe transcriptome analysis shows that 72% (n=14378) of all human proteins (n=20090) are expressed in the hippocampal formation. 182 genes show an elevated expression level in the hippocampal formation compared to other regions of the brain.
Elevated expression in hippocampal formation compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in hippocampal formation compared to all other regions), group enriched (at least four-fold higher mRNA levels in a group of 2-5 regions) and regionally enhanced (at least four-fold higher mRNA levels in hippocampal formation compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 8 genes with high level of regional specificity are listed. Table 2. The 8 genes with the highest level of enriched expression in human hippocampal formation. "Predicted localization" shows the classification of each gene into three main classes: Secreted, Membrane, and Intracellular, where the latter consists of genes without any predicted membrane and secreted features. RS-score (Regional Specificity score) corresponds to the score calculated as the fold change to the second highest region.
Hippocampus share many regionally elevated genes with other forebrain regions, such as cerebral cortex, amygdala and basal ganglia. Both neuronal and glial proteins are found among the regionally elevated targets. Regionally elevated protein expression in mouseAlthough the volume of the hippocampus is much smaller in mice than in humans, the basic hippocampal architecture is common to both species. However, substantial species differences exist, which argue against the frequent portrayal of hippocampus as a phylogenetically primitive brain region. The transcriptome analysis shows that 62% (n=12373) of all mouse one-to-one orthologues genes (n=16320) are expressed in the hippocampal formation. 91 genes show an elevated expression in hippocampal formation compared to other regions of the brain. Table 3: Number of genes within the different categories of regionally elevated expression, in mouse hippocampal formation
Figure 2. Schematic drawing of the mouse brain, indicating the location of hippocampal formation from a coronal perspective. Table 4: The 12 genes with the highest level of enriched expression in mouse hippocampal formation. "Predicted localization" shows the classification of each gene into three main classes: Secreted, Membrane, and Intracellular, where the latter consists of genes without any predicted membrane and secreted features. RS-score (Region Specificity score) corresponds to the score calculated as the fold change to the second highest region.
Regionally elevated protein expression in pigThe volume of the pig hippocampus lies between that of mice and humans; however, the basic hippocampal architecture is common to all 3 species. The transcriptome analysis shows that 66% (n=13285) of all pig genes (n=15829) are expressed in the hippocampal formation. 106 genes show an elevated expression in hippocampal formation compared to other regions of the brain.
Figure 3. Schematic drawing of the pig brain, indicating the location of hippocampal formation from a coronal perspective. Elevated expression in hippocampal formation compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in hippocampal formation compared to all other regions), group enriched (at least four-fold higher mRNA levels in a group of 2-5 regions) and regionally enhanced (at least four-fold higher mRNA levels in hippocampal formation compared to the average of all regions), The number of genes in the individual category is shown in Table 5. In Table 6, the 8 enriched genes are listed. Table 6: The 8 genes with the highest level of enriched expression in pig hippocampal formation. "Predicted localization" shows the classification of each gene into three main classes: Secreted, Membrane, and Intracellular, where the latter consists of genes without any predicted membrane and secreted features. RS-score (Regional Specificity score) corresponds to the score calculated as the fold change to the second highest region.
Extended informationExtended human hippocampal formation tissue sectionThe standard setup in the Tissue Atlas, that profiles the human tissues, is based on Tissue Micro array technique, saving valuable tissue material as well as reagents but still provides a good tissue representation for protein profiling. However, due to the complex nature of the hippocampus, with different cell types and subfields, a larger sample to better understand the protein location is used for selected targets. Below, the selected 28 proteins profiled on extended hippocampus tissue material are listed. Table 7. These 28 genes have been analyzed using extended hippocampal formation samples. |
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The Human Protein Atlas
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