Basal ganglia

Summary

Basal ganglia originate from the telencephalon (forebrain) and is a collective name for subcortical nuclei, striatum and pallidum. This structure is developmentally related to the cerebral cortex, the amygdala, the olfactory, and the hippocampal formation. An important role of the basal ganglia is in the control of movement while they are also pivotal in addiction and reward mechanisms.

The transcriptome analysis shows that 73% (n=14736) of all human protein-coding genes (n=20090) are expressed in the human basal ganglia. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 12629 of all mouse one-to-one orthologues (n=16320) are expressed in the mouse basal ganglia and that 13274 of all pig orthologues (n=15829) are expressed in the pig basal ganglia.

Gene classification based on regional RNA expression in human, pig and mouse basal ganglia defines 73 genes as basal ganglia enriched in either of the three species, and 28 out of those genes show highest expression levels in basal ganglia in all three species.

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

Anatomical divisions

Basal ganglia include a collection of subcortical nuclei, striatum, and pallidum. These are subdivisions of the regions included in the collective name of basal ganglia. The caudate nucleus and putamen are often referred to as the striatum and are together with globus pallidus a central relay between the brainstem and cerebral cortex for signals of voluntary movements while the nucleus accumbens plays an important role in addiction and reward systems. The unique look of the striatum is caused by bundles of white matter (myelinated axons densely packed in tracts) surrounded by gray matter, with more neuronal cell bodies. The type of neurons in the gray matter depend on the sub-region of the basal ganglia. The visual effect of white vs gray matter in caudate putamen of the mouse brain is shown by TH in gray matter and CNP in white matter showing the complementary staining pattern.


TH

CNP

Regionally elevated protein expression in human



Figure 2. Schematic drawing of the human brain, indicating the location of basal ganglia from a coronal perspective.

The transcriptome analysis shows that 73% (n=14736) of all human proteins (n=20090) are expressed in basal ganglia. 45 genes show an elevated expression level in basal ganglia compared to other regions of the brain. The human basal ganglia subregions include caudate nucleus, putamen, globus pallidus and nucleus accumbens among others. The highest mean value of the individual sub-regions was used as representation of basal ganglia as one of the 13 brain regions.

  • 2 regionally enriched genes
  • 45 regionally elevated genes in total
  • 15 basal ganglia elevated genes are elevated in other tissues than brain

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

Specificity Number of Human elevated genes
Region enriched 2
Group enriched 5
Region enhanced 38
Elevated 45

Elevated expression in basal ganglia compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in basal ganglia 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 basal ganglia compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 12 genes with the highest level of regional specificity among the 2 enriched genes are listed.

Table 2. The 2 genes with the highest level of enriched expression in human basal ganglia. "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 tissue.

Gene Description Predicted location RS-score
GPR6 G protein-coupled receptor 6 Membrane 4
TRBV24-1 T cell receptor beta variable 24-1 Intracellular 4

Proteins specifically detected in human caudate nucleus

The tissue atlas includes TMA cores from caudate nucleus in standard profiling procedures, enabling high throughput analysis of the protein location in caudate nucleus, here are a few examples of proteins specifically located in human caudate nucleus.


PENK

ADORA2A

CHAT

Regionally elevated protein expression in mouse

The mouse basal ganglia is similar to the human basal ganglia divided into striatum and pallidum, a collection of subcortical nuclei involved in movement control and processing. The subregions of the mouse brain included in this analysis are caudate putamen, septum and ventral forebrain. The transcriptome analysis shows that 63% (n=12629) of all mouse one-to-one human orthologue genes (n=16320) are expressed in the basal ganglia and 183 genes show an elevated expression in basal ganglia compared to other regions of the brain.

Table 3: Number of genes within the different categories of regionally elevated expression, in mouse basal ganglia.

Specificity Number of Mouse elevated genes
Region enriched 48
Group enriched 84
Region enhanced 51
Elevated 183

Elevated expression in basal ganglia compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in basal ganglia 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 basal ganglia compared to the average of all regions), The number of genes in the individual category is shown in Table 3. In Table 4, the 12 genes with the highest level of regional specificity among the 48 enriched genes are listed.


Figure 3. Schematic drawing of the mouse brain, indicating the location of basal ganglia from a sagittal and coronal view.

Table 4: The 12 genes with the highest level of enriched expression in mouse basal ganglia. "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
GPX6 Glutathione peroxidase 6 Secreted 16
SERPINA9 Serpin family A member 9 Intracellular,Secreted 16
CD4 CD4 molecule Intracellular,Membrane 14
SH3RF2 SH3 domain containing ring finger 2 Intracellular 14
IDO1 Indoleamine 2,3-dioxygenase 1 Intracellular 12
GPR6 G protein-coupled receptor 6 Membrane 11
PDE10A Phosphodiesterase 10A Intracellular 11
SCN4B Sodium voltage-gated channel beta subunit 4 Membrane 11
DRD2 Dopamine receptor D2 Intracellular,Membrane 10
GPR88 G protein-coupled receptor 88 Membrane 10
ADORA2A Adenosine A2a receptor Intracellular,Membrane 9
DRD1 Dopamine receptor D1 Membrane 9

Proteins specifically detected in mouse basal ganglia


CHAT

GNG7

RGS9

Regionally elevated protein expression in pig

The pig basal ganglia is similar to the human basal ganglia divided into striatum and pallidum, a collection of subcortical nuclei involved in movement control and processing. The sub regions included in this analysis are four different sub regional areas; caudate nucleus, putamen, septum and ventral pallidum. The transcriptome analysis shows that 66% (n=13274) of all pig genes (n=15829) are expressed in the cerebellum and 143 genes show an elevated expression in cerebellum compared to other regions of the brain.

Table 5: Number of genes within the different categories of regionally elevated expression, in pig basal ganglia

Specificity Number of Pig elevated genes
Region enriched 41
Group enriched 65
Region enhanced 37
Elevated 143


Figure 4. Schematic drawing of the pig brain, indicating the location of basal ganglia from a sagittal view. .

Elevated expression in basal ganglia compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in basal ganglia 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 basal ganglia compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 12 genes with the highest level of regional specificity among the 41 enriched genes are listed.

Table 6: The 12 genes with the highest level of enriched expression in pig basal ganglia. "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
ADORA2A Adenosine A2a receptor Intracellular,Membrane 50
GPR88 G protein-coupled receptor 88 Membrane 42
PRSS21 Serine protease 21 Intracellular 38
PPP1R1B Protein phosphatase 1 regulatory inhibitor subunit 1B Intracellular 26
MUC4 Mucin 4, cell surface associated Membrane,Secreted 16
THEM5 Thioesterase superfamily member 5 Intracellular 15
CHRNE Cholinergic receptor nicotinic epsilon subunit Intracellular,Membrane 14
GNAL G protein subunit alpha L Intracellular 14
DRD1 Dopamine receptor D1 Membrane 13
CCDC27 Coiled-coil domain containing 27 Intracellular 11
MBL2 Mannose binding lectin 2 Secreted 11
DRD3 Dopamine receptor D3 Membrane 10

Extended information

Lateral ventricle wall

Caudate nucleus is a brain region close to the lateral ventricle, which means that although the ventricle wall is not part of the basal ganglia it is often included in the sampling of caudate nucleus, and we are able to see both RNA expression related to location specific cell types as well as proteins with a specific relation to the ependymal cells or subventricular zone.


CFAP53

MGARP

RSPH1

FOXJ1

SPAG6

ENO4

Extended human basal ganglia tissue section

A limited number of targets are selected for a more extensive profiling in human brain, providing a better overview of the regional location in the region of interest. Such is the case for SLC6A3, a protein specifically expressed in Substantia nigra but then transported into caudate nucleus and show variation within the caudate nucleus.


The standard setup in the Tissue Atlas, profiling human tissues, is based on Tissue Micro array technique, saving valuable tissue material as well as reagents but still providing a good tissue representation for protein profiling. However, due to the complex nature of the brain, with different cell types and subfields, sometimes a larger tissue sample is needed to fully understand the protein location. In table 7 the selected targets used for protein profiling on extended tissue material are listed.

Table 7. The following 46 genes have been analyzed using extended basal ganglia samples.

Gene Gene description Staining pattern
AC144573.1 ADRB3-GOT1L1 readthrough Strong neuronal projection positivity.
ADORA2A Adenosine A2a receptor Cytoplasmic positivity in subset of neurons. Synaptic and neuronal projection positivity.
ADRB3 Adrenoceptor beta 3 Strong neuronal projection positivity.
C7orf57 Chromosome 7 open reading frame 57 Cytoplasmic staining in ependymal cells and a subset of astrocytes.
CACNG3 Calcium voltage-gated channel auxiliary subunit gamma 3 Synaptic staining.
CALB1 Calbindin 1 Moderate cytoplasmic positivity was observed in neuronal cells.
CALY Calcyon neuron specific vesicular protein Strong cytoplasmic staining in neurons.
CHAT Choline O-acetyltransferase Nuclear and cytoplasmic staining in a subset of neurons.
CRACDL CRACD like Stains neurons.
DCLK3 Doublecortin like kinase 3 Strong in astrocytes and projections.
DCX Doublecortin Cytoplasmic staining in neuronal cells.
DNAH10 Dynein axonemal heavy chain 10 Weak cytoplasmic positivity in ependymal cells in caudate.
DNAI1 Dynein axonemal intermediate chain 1 Strong cytoplasmic positivity in ependymal cells.
DNER Delta/notch like EGF repeat containing Strong staining in a subset of neurons.
FGF11 Fibroblast growth factor 11 Cytoplasmic staining in neurons.
FGF2 Fibroblast growth factor 2 Nuclear staining in glia and neuropil positivity.
GNAL G protein subunit alpha L Synapse positivity.
GNG12 G protein subunit gamma 12 Axonal positivity.
GNG7 G protein subunit gamma 7 Axonal positivity.
GPRC5B G protein-coupled receptor class C group 5 member B Strong neuropil staining.
GRIK4 Glutamate ionotropic receptor kainate type subunit 4 Moderate staining in neuronal projections.
GRIN1 Glutamate ionotropic receptor NMDA type subunit 1 Moderate cytoplasmic staining in subset of neurons and weak synaptic staining.
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