Pons is situated inferior to the midbrain, superior to the medulla oblongata and ventral to the fourth ventricle. The pons together with medulla oblongata, midbrain and thalamus comprise the brainstem. Developmentally the pons originates from the third vesicle of the neuronal tube (rhombencephalon). There are several monoamine nuclei situated in the pons, such as noradrenergic locus coeruleus. The pons facilitates connections between medulla and cerebellum, as well as into the thalamus and is important for the control of several of the body’s vital functions. Regulation of the pattern and rate of the respiratory cycle is managed by pons together with the medulla oblongata through a complex network between antagonistic respiratory centres.
The transcriptome analysis shows that 83% (n=16747) of all human protein-coding genes (n=20162) are expressed in the human pons. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 12587 of all mouse one-to-one orthologues (n=16679) are expressed in the mouse pons and that 13950 of all pig orthologues (n=16614) are expressed in the pig pons.
Gene classification based on regional RNA expression in human, pig and mouse pons defines 7 genes as pons enriched in either of the three species, and 0 out of those genes show highest expression levels in pons in all three species.
Figure 1. Schematic drawing of the human brain, indicating the location of pons from a sagittal view.
Pons can be divided into the basilar (ventral) and the pontine tegmentum (dorsal). The basilar division includes the pontine nuclei, a group of several nuclei that are involved in motor function. The cranial nerves trigeminal- (V), abducens- (VI), facial- (VII), and vestibulocochlear (VIII) connect to the pons. Within pontine tegmentum, some nuclei of the cranial nerves are located e.g., the efferent motor facial nucleus and motor trigeminal nucleus and the afferent dorsal cochlear nucleus; posteroventral cochlear nucleus; anterior cochlear nucleus, ventral; principal sensory trigeminal nucleus; spinal trigeminal nucleus, oral; superior vestibular nucleus; and lateral vestibular nucleus. These nerves and nuclei are important for functions such as transmission of sensory information, movement of face and eyes, proprioception, and hearing.
Within the pontine tegmentum, several regions reside that are important for auditory function. For example, the nuclei of the trapezoid body and the superior olive which are a part of the ascending and descending auditory pathway and manage several auditory related functions e.g., the localization of sound, together with the lateral lemniscus nuclei. The superior olive includes areas such as the medial olivary nucleus, medial periolivary nuclei, and the ventral periolivary nuclei. Other nuclei within the pontine tegmentum are the pontine raphe nucleus which contains the serotonergic B5 group of the monoaminergic cell groups defined by Dahlström A, Fuxe K. (1964). The pons situates several monoaminergic groups of cells (as does the midbrain and medulla oblongata) such as the noradrenergic cell groups ventrolateral tegmental area (A5), locus coeruleus (A6) and the subcoeruleus area (A7). The nucleus locus coeruleus is located near the 4th ventricle, right next to the subcoeruleus area. It manages wakefulness and attention and is implicated in Alzheimer’s disease. Noradrenalin is a hormone and neurotransmitter that increases body arousal, and reaches high levels during stress (sympathetic system). The locus coeruleus is the major site of noradrenaline synthesis in the brain and its neurons have projections to all regions of the brain, modulating the brains arousal state.
The dorsal tegmental nucleus and the dorsolateral tegmental nucleus are also situated close to the fourth ventricle in the pontine tegmentum. They are involved in spatial navigation and attention modulation, respectively. Another part of the pons pontine tegmentum is the pontine reticular formation. It includes areas such as lateral parabrachial nucleus; medial parabrachial nucleus; paramedian reticular nucleus; reticular pontine nucleus, caudal; reticular pontine nucleus, oral, and reticulotegmental nucleus. They are involved in several functions, for instance, sleep. Also, the parabrachial nuclear complex and the Kölliker-Fuse nucleus are main areas in the pontine part of the lateral respiratory column. The lateral respiratory column also entails sub-regions within the medulla oblongata and are important for breathing and motor behaviour.
Regionally elevated expression in human
The transcriptome analysis shows that 83% (n=16747) of all human proteins (n=20162) are expressed in the pons. 96 genes show an elevated expression level in pons compared to other regions of the brain.
Elevated expression in pons compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in pons 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 pons compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 6 enriched gene is listed.
Table 2. The 6 gene with the highest level of enriched expression in human pons. "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.
Regionally elevated expression in mouse
For RNAseq, mouse pons and medulla oblongata samples were combined. For more information about the mouse pons click pons and medulla oblongata in mouse.
Regionally elevated expression in pig
Table 3: Number of genes within the different categories of regionally elevated expression, in pig pons.
Table 4: The 3 genes with the highest level of enriched expression in pig pons. "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.
Within the pons resides the locus coeruleus, a nucleus of approximately 40,000 neurons that is the major distributor of noradrenaline in the brain. This region has been implicated in Alzheimer's disease, already in early stages of the disease as described by the Braak stages. A detailed analysis comparing the tau load within iDISCO+ processed and light sheet microscopy scanned locus coeruleus samples of various Braak stages (Gilvesy A et al. (2022)) revealed tau pathology to be more advanced in the dorsal part of the locus coeruleus. The results were irrespective of the Braak stage and suggests a selective vulnerability within the region.
This movie shows the presence and location of amyloid beta plaques and tau tangles in the locus coeruleus and cortex with Alzheimer´s disease. Interview: Prof Tomas Hökfelt, Karolinska Institutet.