Thalamus Anatomical divisions Regionally elevated protein expression in human Regionally elevated protein expression in mouse Regionally elevated protein expression in pig Extended information

Thalamus

The thalamus is a part of the diencephalon, together with the epithalamus, subthalamus, metathalamus, and hypothalamus. The thalamus develops from the embryonic diencephalon. The vast majority of ascending sensory pathways target the cerebral cortex relay in the thalamus, making it a coordination-relay center. The thalamus has multiple functions. It relays sensory information, includes motor signals to the cerebral cortex, and is also involved in the regulation of consciousness, sleep, or alertness, and affects emotions.

The transcriptome analysis shows that 73% (n=14704) of all human protein-coding genes (n=20090) are expressed in the human thalamus. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 12304 of all mouse one-to-one orthologues (n=16320) are expressed in the mouse thalamus and that 12896 of all pig orthologues (n=15829) are expressed in the pig thalamus.

Gene classification based on regional RNA expression in human, pig and mouse thalamus defines 20 genes as thalamus enriched in either of the three species, and 2 out of those genes show highest expression levels in thalamus in all three species.

Figure 1, Schematic drawing of the human brain, indicating the location of thalamus around the third ventricle from a sagittal view.

Anatomical divisions

The paired oval-shaped thalamus is located around the third ventricle in both hemispheres. Its complex structure consists of several groups of nuclei: the anterior nuclei, the medial nuclei (parvocellular, magnocellular, medialis dorsalis, and caudal nuclei), the lateral group of nuclei (involving the complex lateralis and ventralis nuclei), the reticular thalamic nucleus, the intralaminar nuclei (e.g. centromedial nucleus), as well as the metathalamic nuclei (medial and lateral geniculate nuclei). The nuclei of the subthalamus (zona incerta, subthalamic (Luysi) nucleus and Forel-zones) are located between the midbrain and thalamus.

Functionally, the thalamic nuclei can be divided into specific relay and association nuclei and non-specific nuclei. The former receive afferents from certain pathways and project them to certain parts of the cerebral cortex. The latter include the intralaminar and reticular thalamic nuclei; they receive afferents from the brainstem reticular formation and other thalamic nuclei and diffusely project to the cerebral cortex.

In the specific thalamic nuclei, there are basically two type of neurons: (1) projection neurons with long axons, which forward information to the cerebral cortex (thalamo-cortical relay neurons), and (2) Golgi II interneurons, which are GABAergic local circuitry neurons. The axons of interneurons transfer the information to projection neurons in complex synaptic structures called synaptic glomeruli. Certain calcium-binding proteins, like calbindin, calretinin and parvalbumin are prominent neurochemical markers for thalamic neuronal cell populations.

SH3GL2
GABRA3

Regionally elevated protein expression in human

The transcriptome analysis shows that 73% (n=14704) of all human proteins (n=20090) are expressed in the thalamus.

Only 89 genes are classified as regionally elevated in thalamus. The elevated genes are all classified as group enriched, as shown in Table 1. Many group enriched genes are shared with brainstem regions, such as midbrain or pons and medulla.

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

Specificity	Number of Human elevated genes
Region enriched	6
Group enriched	49
Region enhanced	34
Elevated	89

Regionally elevated protein expression in mouse

The mouse thalamus is anatomically similar to the human thalamus, with similar topography of complexes of nuclei.

The transcriptome analysis shows that 61% (n=12304) of all mouse one-to-one homologue genes (n=16320)are expressed in the thalamus and 61 genes show an elevated expression in thalamus compared to other regions of the brain.

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

Specificity	Number of Mouse elevated genes
Region enriched	14
Group enriched	40
Region enhanced	7
Elevated	61

Figure 2. Schematic drawing of the mouse brain, indicating the location of thalamus from a sagittal view.

Elevated expression in thalamus compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in thalamus 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 thalamus compared to the average of all regions), The number of genes in the individual category is shown in Table 2. In Table 3, the 12 genes with the highest level of regional specificity among the 14 enriched genes are listed.

Table 3: The 12 genes with the highest level of enriched expression in mouse thalamus. "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
GPR151	G protein-coupled receptor 151	Membrane	19
TRIM40	Tripartite motif containing 40	Intracellular	18
PPP1R3A	Protein phosphatase 1 regulatory subunit 3A	Intracellular,Membrane	12
ATP2A1	ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1	Intracellular,Membrane	8
WNT9B	Wnt family member 9B	Intracellular,Secreted	7
ABHD12B	Abhydrolase domain containing 12B	Intracellular	5
IRAG1	Inositol 1,4,5-triphosphate receptor associated 1	Intracellular,Membrane	5
MAEL	Maelstrom spermatogenic transposon silencer	Intracellular	5
RGS16	Regulator of G protein signaling 16	Intracellular	5
SNX31	Sorting nexin 31	Intracellular	5
TAFA4	TAFA chemokine like family member 4	Intracellular,Secreted	5
TNNT1	Troponin T1, slow skeletal type	Intracellular	5

Regionally elevated protein expression in pig

The pig thalamus is anatomically similar to the human thalamus, with similar topography of complexes of nuclei.

The transcriptome analysis shows that 64% (n=12896) of all pig one-to-one human orthologue genes (n=15829) are expressed in the thalamus and 25 genes show an elevated expression in thalamus compared to other regions of the brain.

Table 4: Number of genes within the different categories of regionally elevated expression, in pig thalamus.

Specificity	Number of Pig elevated genes
Region enriched	1
Group enriched	18
Region enhanced	6
Elevated	25

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

Table 5: GRP151 is the only gene with enriched expression in pig thalamus. "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
GPR151	G protein-coupled receptor 151	Membrane	9

Extended information

GPR151 G-protein coupled receptor immunostaining in the medial habenula (right) and in the thalamic paraventricular nucleus (left) in mouse brain.

GPR151
GPR151

These short videos demonstrate the 3D distribution of GPR151 immunostaining in the mouse brain:

Full brain scan

Dienchephalon