After spending hours reading anatomy, watching videos, and examining cadavers, the average student has used up a vast amount of ATP (adenosine triphosphate) and consequently requires sleep. But how exactly does one wake up from a nap; and how is consciousness maintained throughout the day? Scientific literature has pointed to a vast interlacing web of neurons that participate in sustaining arousal and different levels of consciousness.
The reticular (from the Latin reticulum, meaning net) formation is a far-reaching network of neurons extending from the spinal cord to the thalamus, with connections to the medulla oblongata, midbrain (mesencephalon), pons, and diencephalon. These neurons, along with their axons and dendrites, are interspersed between the cranial nerve nuclei and tracts found in the brainstem. It is important to note that although the nuclei of the reticular formation are not as well defined as those of the cranial nerves, they do appear as obvious regions of grey matter with special staining.
The primary goal of this article is to functionally, cytologically and chemically (based on neurotransmitter release) describe the different nuclei of the reticular formation, while pointing out some of its physiological functions. Associated tracts and clinical implications of the reticular system will also be discussed. It should be noted that this is in no way, shape or form, a comprehensive list of nuclei within the reticular formation, as there are over 100 of these nuclei.
The reticular formation nuclei are found deep within the brainstem, along its length. It is easier to appreciate the approximate location of these nuclei if they are superimposed on a posterior view of the brainstem with the cerebellum removed. Topographically, the nuclei can be divided into three groups. There is a lateral, a medial and a median (raphe) group of nuclei. Recall that the brainstem is symmetrically divided by the dorsal median sulcus (continuing from the dorsal surface of the spinal cord). Therefore, the three groups of nuclei described previously are mirrored in each half of the brainstem.
Lateral group of nuclei
The lateral group of nuclei, as the name suggests, occupies the lateral region of the brainstem. When superimposed on the posterior surface of the brainstem, the lateral group extends caudally from the level of the inferior colliculus (lower two bodies of the corpora quadrigemina) to the spinal cord.
The following nuclei are a part of the lateral group of the reticular formation:
- There are three groups of cells found throughout the lateral group of reticular nuclei. Two of these cell groups are catecholamine based and have been classified as noradrenergic cells A1-A7 (excluding A3 in primates) and adrenergic cells C1 and C2. The third are cholinergic cells Ch5 and Ch6.
- The lateral pontine tegmentum is the most rostral aspect of the lateral group of nuclei. It is subdivided into the medial and lateral parabrachial nuclei and the Kölliker-Fuse nucleus. The parabrachial nuclei are found in the inferior aspect of the midbrain, adjacent to the superior cerebellar peduncle and cranial to another reticular nucleus known as the parvocellular area (discussed later). The Kölliker-Fuse nucleus is a ventral continuation of the lateral pontine tegmentum. Sensory fibers associated with these nuclei are associated with the nucleus tractus solitarius and the island of Reil (insula). The medial parabrachial and Kölliker-Fuse nuclei also contain A4, A5 and A7 cells. The area has the responsibility of regulating cardiovascular, digestive and respiratory functions.
- There is another group of reticular nuclei found in the superficial ventrolateral reticular area. These cell bodies, known as the lateral paragigantocellular nucleus, can be found at the level of the facial nucleus, which is located deep to the vestibule of the fourth ventricle (inferolateral to the facial colliculus). They extend as far as the level of the spinomedullary junction, where the medulla oblongata transitions into the spinal cord. It is further subdivided into a caudal portion, called the nucleus retroambiguus, and a cranial segment that integrates with the lateral paragigantocellular nucleus. Catecholaminergic cell types A1, A5 and C1 are also found in this region. It is said to be involved in regulating cardiopulmonary activities and nociceptive response.
- The parvocellular reticular area, also known as the area reticularis parvocellularis, is found deep to the area of the cuneate tubercle, in the caudal aspect of the medulla oblongata. More accurately, the nucleus lies medial to the spinal sensory nucleus of the trigeminal (CN V) nerve. This reticular area contains other nuclei, such as the central nucleus of the medulla oblongata (nucleus reticularis dorsalis), the parvocellular nucleus and the nucleus reticularis ventralis. These nuclei are believed to influence the reflex activity of glossopharyngeal (CN IX) , vagus (CN X), spinal accessory (CN XI) and hypoglossal (XII) nerves.
Medial group of nuclei
Like the lateral group of reticular nuclei, the medial group of nuclei begin rostrally in the mesencephalic midbrain, deep to the level of the superior colliculus. They then extend inferiorly, below the level of the striae medullaris of the fourth ventricle (inferior to the pontomedullary junction). The nuclei contain a mixture of both medium and large neurones; however, the medium sized neurones are of a greater preponderance in the region. The nuclei of the medial reticular group include:
- The nucleus reticularis ventralis (also known as the ventral subnucleus of the medulla oblongata) is the caudal representation of the reticular formation in the medulla oblongata. It continues rostrally as the gigantocellular nucleus (magnocellularis). This nucleus is posterior to the inferior olivary complex, ventrolaterally related to the nuclei of CN XII, and anterior to the CN X nuclei. It is divided into pars alpha and ventral gigantocellular nuclei as the nucleus is traced rostrally. The pars alpha component, which is found lateral to the nucleus raphe magnus (discussed below), contains serotoninergic B3 cells.
- The medial group of reticular cells then transitions from the magnocellularis to the caudal and oral pontine reticular nuclei. The key difference between these groups is that the oral pontine reticular nucleus has small and large cells, but no giant cells; while the caudal pontine reticular nucleus has small and large cells, as well as giant cells. Both the caudal and oral groups of nuclei occupy the space around the motor nucleus of CN V (lateral to the median eminence of the fourth ventricle).
- The cuneiform and subcuneiform nuclei are the mesencephalic midbrain representations of the reticular formation. The latter is situated ventral and lateral to the former; both of which are in the region deep to the corpora quadrigemina. The cuneiform nucleus is made up chiefly of small cells mixed with medium and large cells, while the subcuneiform has a similar composition; however the cells are less tightly packed together when compared to those in the cuneiform nucleus.
Median group of nuclei
The dorsal median sulcus that traverses the dorsal spinal cord and continues cranially to divide the brainstem into symmetrical halves also serves as a landmark for the location of the median group of nuclei. These nuclei are also known as the raphe nuclei, as they are found deep to the level of the midline raphe (or the paramedian zone) from the level of the superior colliculus to the superior two-thirds of the medulla oblongata. The raphe nuclei are divided into nine groups of serotoninergic cell clusters B1-B9 (except B4 cells in primates) that appear almost continuous along the tegmentum.
Included in the group of raphe nuclei are:
- The dorsal raphe (tegmental) nucleus can be found throughout the mesencephalic midbrain. It is the most rostral of the raphe nuclei and contains chiefly B7 cells.
- Inferior to the dorsal raphe nucleus is the superior central nucleus. This nucleus is populated by B6 and B8 cell types.
- The pontine raphe nucleus is located between the superior central nucleus and the nucleus of raphe magnus. The nucleus is made up of B5 cells.
- The nucleus raphes magnus is a B3 filled nucleus that is found inferior to the pontine raphe nucleus, the nuclei raphe obscuris and pallidus.
- The nucleus raphes obscurus and nucleus raphes pallidus reside in the upper two-thirds of the medulla. It crosses the pontomedullary junction and enters the area deep to the obex, and hypoglossal and vagal trigones. Raphe obscuris is mainly populated by B2 cells, while raphe pallidus has mostly B1 cells.
The dendrites and axons of the reticular formation are atypical when compared to those of other neurons. The axons are extremely long and can reach sites far removed from their cell bodies. The dendrites are polysynaptic, giving rise to the reticular formation being described as a non-specific unit. Both efferent and afferent fibers interact with the reticular formation to regulate its own action and the action of other neuronal systems.The reticular formation has afferent sensation from the spinothalamic (temperature sensation, fine touch and pain) and dorsal column-medial lemniscus (proprioception, vibration and position sense, and crude touch) pathways. It modifies information from the vestibular tract, thus assisting with the regulation of antigravity muscle tone while standing.
There are also efferent fibers associated with the reticular formation. These include the reticulobulbar (pain regulation) and reticulospinal (locomotion and postural regulation) tracts that regulate sensory information in the peripheral nervous system.
Circadian cycle and consciousness
The reticular formation is the primary regulator of arousal and consciousness. During sleep, the center normally suppresses the individual’s level of consciousness. Efferent fibers from the reticular formation can convey sensory information to the cortex of a sleeping individual, which would awaken that person.
However, injury or pathological insult to areas of the reticular formation may also result in periods of unconsciousness. In the pathological state, the patient is said to be comatose. If the damage is transient, then the patient may have some degree of consciousness. The patient’s level of awareness can be measured using a Glascow coma scale. The scale measures the degree of consciousness based on the patient’s response to simple instructions regarding three sensory modalities: eye opening (E=4), vocal response (V=5) and motor response (M=6). After adding all three scores, the patient may receive a score ranging from 3 – 15; with 15 indicating that the patient is completely conscious and alert and 3 indicating that the patient is extremely unresponsive or deceased.
Impacts on the endocrine system
The autonomic and endocrine nervous systems, along with the circadian centres of the brain, are all subject to regulation by the reticular formation. The descending reticulospinal and reticulobulbar fibers are involved with the craniosacral (parasympathetic) and thoracolumbar (sympathetic) outflows. The reticular formation indirectly regulates the endocrine nervous system by acting on the hypothalamus to regulate hormonal release. Its action on the circadian rhythm is achieved by an eclectic collection of efferent and afferent projections. Additionally, it modulates somatic and visceral sensation by its action on ascending tracts that project to supraspinal regions. This is particularly important as it relates to the involvement of the reticular formation in the gating mechanism and the regulation of pain perception.
Impacts on muscle activity
The reticulobulbar and reticulospinal tracts also allow the reticular formation to have a wide spread impact on skeletal muscles:
- It coordinates the activity of the respiratory centres that control the muscles of respiration.
- It modifies reflex activity and muscle tone via its actions on gamma and alpha (lower motor neurons of the spinal cord and brainstem) motor neurons.
- The reticular formation also aids in the process of standing by working alongside the vestibular apparatus to preserve muscle tone in the antigravity muscles.
- Finally, it also has an effect on the muscles of facial expression. The reticular formation is found bilaterally in the brain and is therefore able to provide motor control to both sides of the brain when a person laughs or smiles. Since these fibers do not integrate with the corticobulbar fibers (also involved in facial expression), a patient may still smile symmetrically even if they have suffered a cerebrovascular accident (CVA) that has affected the corticobulbar fibers.