The Amygdala-specific proteome Sub fields of the amygdala Regionally elevated expression in human amygdala Regionally elevated expression in mouse amygdala Regionally elevated expression in pig amygdala

The Amygdala-specific proteome

The amygdala is an almond-shape set of neuronal nuclei located deep within the brain's medial temporal lobe, just anterior to the hippocampus (shown in Figure 1). The amygdala is an important component of the limbic system, a neural network that mediates many aspects of emotional learning and behavior and plays a prominent role in processing of certain emotions, including fear. Abnormal functioning or damage within the amygdala, and the neural circuits that connect it with a variety of cortical and subcortical structures, is thought to contribute to the pathophysiology of a number of neuropsychiatric disorders, such as anxiety, autism and depression.

The transcriptome analysis shows that 83% (n=16248) of all human protein-coding genes (n=19670) are expressed in the human amygdala. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 11653 of all mouse one-to-one orthologues (n=15160) are expressed in the mouse amygdalaand that 12493 of all pig orthologues (n=14656) are expressed in the pig amygdala.

Gene classification based on regional RNA expression in human, pig and mouse amygdala defines 9 genes as amygdala enriched in either of the three species.

Figure 1. Schematic drawing of the human brain, indicating the location of amygdala from a coronal perspective.

Sub fields of the amygdala

The basolateral complex is the largest of the amygdaloid clusters, located roughly within the lateral and middle parts of the amygdala, and includes the lateral and basal nuclei, while the cortical and medial nuclei comprise the cortico-medial amygdaloid group. Interestingly, the basolateral amygdala has been implicated in both mediating the formation of memories related to emotional events and fear extinction (learning process resulting in the elimination of a previously elicited fear response) through interaction with the prefrontal cortex.

SH3GL2
SLC18A3
CCK

Regionally elevated expression in human amygdala

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

Specificity	Number of Human elevated genes
Region enriched	5
Group enriched	55
Region enhanced	4
Elevated	64

The transcriptome analysis shows that 83% (n=16248) of all human proteins (n=19670) are expressed in the amygdala and 64 genes show an elevated expression level in amygdala compared to other regions of the brain.

5 regionally enriched genes
64 regionally elevated genes in total
19 of the amygdala elevated genes are elevated in other tissues than the brain.
45 of the amygdala elevated genes are elevated in the brain.

Elevated expression in amygdala compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in amygdala 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 amygdala compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 5 genes with high level of regional specificity are listed.

Table 2. The 5 genes with the highest level of enriched expression in human amygdala. "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.

Gene	Description	Predicted location	RS-score
UTS2B	Urotensin 2B	Secreted	7
GABRR1	Gamma-aminobutyric acid type A receptor rho1 subunit	Membrane	6
IL31RA	Interleukin 31 receptor A	Intracellular,Membrane	6
DCSTAMP	Dendrocyte expressed seven transmembrane protein	Membrane	4
RAET1L	Retinoic acid early transcript 1L	Membrane	4

Regionally elevated expression in mouse amygdala

The transcriptome analysis shows that 59% (n=11653) of all mouse one-to-one human orthologue genes (n=15160) are expressed in the amygdala. 99 genes show an elevated expression in amygdala compared to other regions of the brain.

Table 3: Number of genes within the different categories of regionally elevated expression, in amygdala amygdala

Specificity	Number of Mouse elevated genes
Region enriched	3
Group enriched	93
Region enhanced	3
Elevated	99

Figure 2. Schematic drawing of the mouse brain, indicating the location of amygdala from a coronal perspective.

Table 4: The 3 genes with the highest level of enriched expression in mouse amygdala. "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 regional.

Gene	Description	Predicted location	RS-score
HPD	4-hydroxyphenylpyruvate dioxygenase	Intracellular	8
MCOLN2	Mucolipin 2	Membrane	5
GRXCR2	Glutaredoxin and cysteine rich domain containing 2	Intracellular	4

Regionally elevated expression in pig amygdala

The transcriptome analysis shows that 64% (n=12493) of all pig one-to-one human orthologue genes (n=14656) are expressed in the amygdala. 61 genes show an elevated expression in amygdala compared to other regions of the brain.

Table 5: Number of genes within the different categories of regionally elevated expression, in amygdala

Specificity	Number of Pig elevated genes
Region enriched	1
Group enriched	58
Region enhanced	2
Elevated	61

Figure 3. Schematic drawing of the pig brain, indicating the location of amygdala from a coronal perspective or sagittal view.

Table 6: GUCA2A is the only gene with enriched expression in pig amygdala. "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.

Gene	Description	Predicted location	RS-score
GUCA2A	Guanylate cyclase activator 2A	Secreted	4