Cerebral cortex is the largest region of the human brain and its main function is information processing. Subregions of the cerebral corex are important for generating voluntary motor output, processing of sensory information or are involved in cognitive functions. The cerebral cortex is the dorsal part of the forebrain (telencephalon) and mainly consists of excitatory pyramidal projection neurons organized in 6 distinct layers and inhibitory interneurons that form local networks. The cerebral cortex acts as a relay system, information from subcortical regions is filtered and only selected information is projected back to subcortical regions that generate the behavioral output. Mainy of the human higher cognitive abilities depend on this brain structure and neurodegenerative disease (e.g. Alzheimer's disease) or developmental abnormalities affecting the cerebral cortex often result in cognitive impairments.

The transcriptome analysis shows that 85% (n=16646) of all human protein-coding genes (n=19670) are expressed in the human cerebral cortex. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 11705 of all mouse one-to-one orthologues (n=15160) are expressed in the mouse cerebral cortex and that 12544 of all pig orthologues (n=14656) are expressed in the pig cerebral cortex.

Figure 1. Schematic drawing of the human brain, indicating the location of cerebral cortex from a sagittal view.

Figure 2. Example of tripple labeling of the human cortex indicating cells located in the different layers.Yellow color show staining of TPPP3, green color represent NECAB1, red color is the labeling of PCP4 and blue is DAPI counterstaining.

The main neuronal cell type in the cerebral cortex are glutamatergic pyramidal neurons and inhibitory (mainly GABA-ergic) interneurons. These cells are organized in six cellular layers based on cell densities, morphology electrophysiological properties and connections. The cerebral cortex receives its main excitatory input from the thalamus. The neuronal networks, organized in columns spanning all layers of the cerebral cortex, process this information and output signals are send back to thalamus and other subcortical structures. The white matter, approximately 40% of the cerebral cortex, contains the myelinated input axons originating from subcortical structures and myelinated axons originating from cortical pyramidal neurons projecting to subcortical areas of the brain. In addition the human white matter contains some sparsely distributed neurons including a population of large neurons expressing the calcium binding protein CALHM1.

CALHM1

The transcriptome analysis shows that 85% (n=16646) of all human proteins (n=19670) are expressed in the cerebral cortex and 152 genes show an elevated expression in cerebral cortex compared to other regions of the brain.

• 17 regionally enriched genes
• 152 regionally elevated genes in total
• 67 of the cerebral cortex elevated genes are elevated in other tissues than the brain.
• 85 of the cerebral cortex elevated genes are elevated in the brain.

Table 1: Number of genes within the different categories of regionally elevated expression, in human cerebral cortex

Figure 2. Schematic drawing of the mouse brain, indicating the location of cerebral cortex from a sagittal view and a coronal perspective.

The transcriptome analysis shows that 11709 of all mouse one-to-one orthologues (n=15160) are expressed in the mouse cerebral cortex and 1 genes are classified as regionally enriched genes and in total 114 regionally elevated. Elevated expression in cerebral cortex compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in cerebral cortex 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 cerebral cortex compared to the average of all regions), The number of genes in the individual category is shown in Table 2.

Table 2: Number of genes within the different categories of regionally elevated expression, in mouse cerebral cortex

The expression value representing cerebral cortex in the regional classification is defined as the highest expression (NX) in either of the subregions included. Subregions of the mouse cerebral cortex included in the brain atlas are: frontal cortex (prefrontal and motor cortex sampled together), retrosplenial and cingulate cortex as one sample, somatosensory cortex and visual (occipital) cortex, in total 4 different cortical samples. The entorhinal cortex is also included but grouped together with hippocampus as part of the hippocampal formation.

The transcriptome analysis shows that 12554 of all pig one-to-one orthologues (n=14656) are expressed in the pig cerebral cortex and 1 genes are classified as regionally enriched genes and in total 102 regionally elevated. Elevated expression in cerebral cortex compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in cerebral cortex 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 cerebral cortex compared to the average of all regions), The number of genes in the individual category is shown in Table 3.

Table 3: Number of genes within the different categories of regionally elevated expression, in pig cerebral cortex

Figure 3. Schematic drawing of the pig brain, indicating the location of cerebral cortex from a sagittal view.