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 82% (n=16612) of all human protein-coding genes (n=20162) are expressed in the human thalamus. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 12557 of all mouse one-to-one orthologues (n=16679) are expressed in the mouse thalamus and that 13915 of all pig orthologues (n=16614) are expressed in the pig thalamus.

Gene classification based on regional RNA expression in human, pig and mouse thalamus defines 18 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 in the epithalamus (that includes the habenula), the ventral thalamus (that includes the subthalamic nucleus and the zona incerta), and the dorsal thalamus (that includes the geniculate bodies, and the centromedial, lateral, mediodorsal and posterior nuclei, among others).

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 82% (n=16612) of all human proteins (n=20162) are expressed in the thalamus.

Only 57 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 4
Group enriched 25
Region enhanced 28
Elevated 57

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 62% (n=12557) of all mouse one-to-one homologue genes (n=16679)are expressed in the thalamus and 60 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 39
Region enhanced 7
Elevated 60


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 Membrane, Intracellular 12
ATP2A1 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 Membrane, Intracellular 8
WNT9B Wnt family member 9B Secreted, Intracellular 7
ABHD12B Abhydrolase domain containing 12B Intracellular 5
IRAG1 Inositol 1,4,5-triphosphate receptor associated 1 Membrane, Intracellular 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 Secreted, Intracellular 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 69% (n=13915) of all pig one-to-one human orthologue genes (n=16614) are expressed in the thalamus and 31 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 20
Region enhanced 10
Elevated 31

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